n-Hexane Insoluble Fraction of Plantago lanceolata Exerts Anti-Inflammatory Activity in Mice by Inhibiting Cyclooxygenase-2 and Reducing Chemokines Levels
Inflammation is involved in the progression of many disorders, such as tumors, arthritis, gastritis, and atherosclerosis. Thus, the development of new agents targeting inflammation is still challenging. Medicinal plants have been used traditionally to treat various diseases including inflammation. A previous study has indicated that dichloromethane extract of P. lanceolata leaves exerts anti-inflammatory activity in an in vitro model. Here, we examined the in vivo anti-inflammatory activities of a n-hexane insoluble fraction of P. lanceolata leaves dichloromethane extract (HIFPL). We first evaluated its potency to reduce paw edema induced by carrageenan, and the expression of the proinflammatory enzyme, cyclooxygenase (COX)-2, in mice. The efficacy of HIFPL to inhibit COX-2 was also evaluated in an in vitro enzymatic assay. We further studied the
effect of HIFPL on leukocytes migration in mice induced by thioglycollate. The level of chemokines facilitating the migration of leukocytes was also measured. We found that HIFPL (40, 80, 160 mg/kg) demonstrated anti-inflammatory activities in mice. The HIFPL reduced the volume of paw edema and COX-2 expression. However, HIFPL acts as an unselective COX-2 inhibitor as it inhibited COX-1 with a slightly higher potency. Interestingly, HIFPL strongly inhibited leukocyte migration by reducing the level of chemokines, Interleukine-8 (IL-8) and Monocyte chemoattractant protein-1 (MCP-1).
Evaluation of anti-inflammatory activity of selected medicinal plants used in...Mohd Aijaz
This document discusses the evaluation of the anti-inflammatory activity of selected medicinal plants used in Indian traditional medicine. It describes in vitro and in vivo studies conducted to test extracts of Cissus quadrangularis, Plumbago zeylanica, Terminalia bellerica, and Terminalia chebulla for cyclooxygenase (COX) inhibition and ability to reduce carrageenan-induced rat paw edema. The results showed that ethanol extracts of T. bellarica and T. chebulla exhibited the highest COX-1 and COX-2 inhibition. In vivo, oral administration of extracts of P. zeylanica, T. bellarica and T. chebulla reduced
Phytochemical Profile and in vitro and in vivo Anticonvulsant and Antioxidant...Self-employed researcher
This study presents the phytochemical profile and in vitro and in
vivo anticonvulsant and antioxidant activities of Epilobium hirsutum, which
has been traditionally used in the treatment of epilepsy by local people of
Turkey. In vitro studies revealed that the extract contained a pronounced
amount of phenolics (206.3±0.9 mg Gallic acid Eq/g extract) and exhibited
significant levels of antioxidant (FRAP; 6226 µmol Fe2+/g extract, ORAC;
6593 µmol Trolox Eq/g extract, DPPH; IC50:33.8 ug/mL and metal chelation;
IC50:114 ug/mL) and anticonvulsant (AChE; IC50:71.2 ug/mL, BChE; IC50:92.5
ug/mL, GABA-T; IC50:94.7 ug/mL) activities. In vivo studies shown that the
the extract exhibited high anticonvulsant activities. In addition, the extracts
regulated the behavior, locomotion, and mental activities of the mice tested.
Biochemical evaluation of the brain tissue revealed that the extract inhibited
the production of MDA and stimulated the increase of antioxidant enzyme
levels, which suggest the possible antioxidative role of the extract that worked
as neuroprotective agents by scarfing the free radicals produced through PTZ
seizure inducer and attenuate convulsions. Moreover the extract regulated
serum biochemical parameters, total antioxidants, total oxidant, and ischemia modified albumin levels. Chromatographic studies were revealed that gallic
acid principally might be the major contributor of anticonvulsant and
antioxidant activities with the additive contributions of fatty acids and mineral
compounds. Findings obtained from this study partially justified the traditional
use of Epilobium hirsutum in the treatment of epilepsy and suggest potential
use of the extract as an industrial or pharmaceutical agent.
In Vitro Anti Inflammatory and Anti Arthritic Activity of Commelina benghalen...SriramNagarajan16
Introduction
Commelina benghalensis L. commonly known as Benghal dayflower, belongs to the family Commelinaceae. It
is widely used for the treatment of wounds and skin diseases.
Aim
The current study focuses on the evaluation of in vitro anti-inflammatory and antiarthritic property of the leaf
extracts ofCommelina benghalensis L.
Methods
The hydroalcoholic extract (70%) of Commelina benghalensis L. (Leaf) was subjected to anti-inflammatory and
anti arthritic activity by membrane stabilisation and inhibition of protein denaturation method were determined.
Results
The inhibitory concentration (IC50) of HAECB in HRBC membrane stabilization study was found to be 69µg/ml in
comparison with diclofenac sodium 57µg/ml. It showed moderate anti-inflammatory activity. The inhibitory
concentration (IC50) of HAECB in protein denaturation was found to be 17µg/ml in comparison with diclofenac
sodium 14µg/ml. It showed moderate anti-arthritic activity.
Conclusion
HAECB showed moderate anti-inflammatory activity which may be due to the strong occurrence of
polyphenolic compounds such as flavonoids, tannins and phenols. HAECB has shown moderate anti-arthritic
activity which may be due to the phenolic constituent.
Isolation, in vitro antidiabetic, antioxidant activity and molecular docking ...iosrjce
The document describes the isolation and characterization of two pentacyclic triterpenoids, friedelin and 3β-friedelinol, from the stem bark of Syzygium alternifolium. The compounds were tested for their antidiabetic and antioxidant activities. Friedelin and 3β-friedelinol showed significant inhibition of α-glucosidase and α-amylase enzymes, decreasing plasma glucose levels and demonstrating antidiabetic effects. They also exhibited antioxidant properties by scavenging free radicals in the DPPH inhibition assay. Molecular docking studies confirmed the binding of friedelin and 3β-friedelinol to α-glucosidase and
Preliminary phytochemical studies and evaluation of Antipyretic property of t...researchplantsciences
Purpose-The root of Ritchiea longipedicellata was claimed to have anti pyretic, analgesic and antimicrobial properties. The people of Idemili area in Anambra State of Nigeria use the decoction of it to treat wounds, running stomach, aches and pains as well as fever. It is to this backdrop that this investigation was carried out to ascertain the veracity of the claim.
Methodology-The root of Ritchiea longipedicellata was collected and dried at ambient temperature. It was pulverized into powder. 500 gm of the powdered drug was placed into a two litre beaker containing one litre of methanol. It was allowed to stand with occasional shaking for 48 h. The content was filtered and the filtrate was concentrated using rotary evaporator. The extract contains the following secondary metabolites-alkaloids, flavonoids, terpenoids, saponins and glycosides. The antipyretic activity was investigated using brewer’s yeast to induce pyrexia.
Result -The root of Ritchiea longipedicellata exhibited significant (p<0.05) antipyretic effect at 600 mg/kg from 1 h to 4 h and at 3 h to 4 h at 300 mg/kg compared with the control.
Conclusion-The claim of Idemili people of Anambra State Nigeria on the use of Ritchiea longipedicellata appears to be obvious in line with the results of the investigation.
Article Citation:
Chinedu Fred Anowi, Ezugwu CO, Ilodigwe EE, Ajaghaku DL.
Preliminary Phytochemical Studies and Evaluation of Antipyretic Property of the Methanol Extract of the Rootbark of Ritchiea longipedicellata Gilg (capparidaceae)
Journal of Research in Plant Sciences (2013) 2(2): 192-195.
Full Text:
http://plantsciences.co.in/documents/PS0048.pdf
Preliminary Studies on Antidiabetic, Antimicrobial and Antioxidant Activities...IJARIIT
Pharmaceutical industries are still in the hunt of effective scavengers for free radicals from the unexplored
medicinal plants. About 80,000 species of plants are utilized for treating various diseases in different systems of Indian
medicine. Many pharmaceutical companies giving importance in plant-derived drugs mainly due to the current widespread
belief that 'Green Medicine' is safe and more dependable than the costly synthetic drugs, which have adverse side effects.
The objective of the study is isolation of Phytochemical active constituents, Antidiabetic, antimicrobial and
antioxidant activities of the rare Antidiabetic medicinal plant Epaltes divaricata (Linn.) since the selected plant has varied
medicinal properties used in Ayurveda. This valuable plant is used in traditional Ayurvedic medicine to alleviate jaundice,
diabetes mellitus, urethral discharges and acute dyspepsia. It is also regarded as a diaphoretic, diuretic and a stimulating
expectorant.
The methanol extract of Epaltes divaricata L. showed excellent antimicrobial activity against bacteria and fungi.
Phytochemical analysis was carried out for the same extract by two different standard methods and which confirmed the
presence of steroids, triterpenoids and phenolic compounds. Decreasing of postprandial hyperglycemia is a therapeutic
approach for treating diabetes mellitus. This can be achieved in current trends through the inhibition of carbohydrate
hydrolyzing enzymes such as alpha glucosidase and alpha amylase. Agents with α-amylase and α-glucosidase inhibitory
activity are very useful as oral anti hypoglycemic agents for the control of hyperglycemia in patients who have diabetes
mellitus. In this study the methanol extract exhibited above 50% of inhibition in all standard concentration.
The study investigated the antimicrobial activity of petroleum ether, chloroform, and hydroalcoholic extracts of Pandanus odoratissimus leaf. All three extracts showed inhibition against gram-positive bacteria Bacillus subtilis and Staphylococcus aureus, but not against gram-negative bacteria or the yeast Candida albicans. The hydroalcoholic extract demonstrated the strongest antimicrobial activity with a minimum inhibitory concentration of 25mg/ml against gram-positives. Phytochemical analysis revealed this extract contained alkaloids and flavonoids, compounds possibly responsible for its antimicrobial effects.
Evaluation of anti-inflammatory activity of selected medicinal plants used in...Mohd Aijaz
This document discusses the evaluation of the anti-inflammatory activity of selected medicinal plants used in Indian traditional medicine. It describes in vitro and in vivo studies conducted to test extracts of Cissus quadrangularis, Plumbago zeylanica, Terminalia bellerica, and Terminalia chebulla for cyclooxygenase (COX) inhibition and ability to reduce carrageenan-induced rat paw edema. The results showed that ethanol extracts of T. bellarica and T. chebulla exhibited the highest COX-1 and COX-2 inhibition. In vivo, oral administration of extracts of P. zeylanica, T. bellarica and T. chebulla reduced
Phytochemical Profile and in vitro and in vivo Anticonvulsant and Antioxidant...Self-employed researcher
This study presents the phytochemical profile and in vitro and in
vivo anticonvulsant and antioxidant activities of Epilobium hirsutum, which
has been traditionally used in the treatment of epilepsy by local people of
Turkey. In vitro studies revealed that the extract contained a pronounced
amount of phenolics (206.3±0.9 mg Gallic acid Eq/g extract) and exhibited
significant levels of antioxidant (FRAP; 6226 µmol Fe2+/g extract, ORAC;
6593 µmol Trolox Eq/g extract, DPPH; IC50:33.8 ug/mL and metal chelation;
IC50:114 ug/mL) and anticonvulsant (AChE; IC50:71.2 ug/mL, BChE; IC50:92.5
ug/mL, GABA-T; IC50:94.7 ug/mL) activities. In vivo studies shown that the
the extract exhibited high anticonvulsant activities. In addition, the extracts
regulated the behavior, locomotion, and mental activities of the mice tested.
Biochemical evaluation of the brain tissue revealed that the extract inhibited
the production of MDA and stimulated the increase of antioxidant enzyme
levels, which suggest the possible antioxidative role of the extract that worked
as neuroprotective agents by scarfing the free radicals produced through PTZ
seizure inducer and attenuate convulsions. Moreover the extract regulated
serum biochemical parameters, total antioxidants, total oxidant, and ischemia modified albumin levels. Chromatographic studies were revealed that gallic
acid principally might be the major contributor of anticonvulsant and
antioxidant activities with the additive contributions of fatty acids and mineral
compounds. Findings obtained from this study partially justified the traditional
use of Epilobium hirsutum in the treatment of epilepsy and suggest potential
use of the extract as an industrial or pharmaceutical agent.
In Vitro Anti Inflammatory and Anti Arthritic Activity of Commelina benghalen...SriramNagarajan16
Introduction
Commelina benghalensis L. commonly known as Benghal dayflower, belongs to the family Commelinaceae. It
is widely used for the treatment of wounds and skin diseases.
Aim
The current study focuses on the evaluation of in vitro anti-inflammatory and antiarthritic property of the leaf
extracts ofCommelina benghalensis L.
Methods
The hydroalcoholic extract (70%) of Commelina benghalensis L. (Leaf) was subjected to anti-inflammatory and
anti arthritic activity by membrane stabilisation and inhibition of protein denaturation method were determined.
Results
The inhibitory concentration (IC50) of HAECB in HRBC membrane stabilization study was found to be 69µg/ml in
comparison with diclofenac sodium 57µg/ml. It showed moderate anti-inflammatory activity. The inhibitory
concentration (IC50) of HAECB in protein denaturation was found to be 17µg/ml in comparison with diclofenac
sodium 14µg/ml. It showed moderate anti-arthritic activity.
Conclusion
HAECB showed moderate anti-inflammatory activity which may be due to the strong occurrence of
polyphenolic compounds such as flavonoids, tannins and phenols. HAECB has shown moderate anti-arthritic
activity which may be due to the phenolic constituent.
Isolation, in vitro antidiabetic, antioxidant activity and molecular docking ...iosrjce
The document describes the isolation and characterization of two pentacyclic triterpenoids, friedelin and 3β-friedelinol, from the stem bark of Syzygium alternifolium. The compounds were tested for their antidiabetic and antioxidant activities. Friedelin and 3β-friedelinol showed significant inhibition of α-glucosidase and α-amylase enzymes, decreasing plasma glucose levels and demonstrating antidiabetic effects. They also exhibited antioxidant properties by scavenging free radicals in the DPPH inhibition assay. Molecular docking studies confirmed the binding of friedelin and 3β-friedelinol to α-glucosidase and
Preliminary phytochemical studies and evaluation of Antipyretic property of t...researchplantsciences
Purpose-The root of Ritchiea longipedicellata was claimed to have anti pyretic, analgesic and antimicrobial properties. The people of Idemili area in Anambra State of Nigeria use the decoction of it to treat wounds, running stomach, aches and pains as well as fever. It is to this backdrop that this investigation was carried out to ascertain the veracity of the claim.
Methodology-The root of Ritchiea longipedicellata was collected and dried at ambient temperature. It was pulverized into powder. 500 gm of the powdered drug was placed into a two litre beaker containing one litre of methanol. It was allowed to stand with occasional shaking for 48 h. The content was filtered and the filtrate was concentrated using rotary evaporator. The extract contains the following secondary metabolites-alkaloids, flavonoids, terpenoids, saponins and glycosides. The antipyretic activity was investigated using brewer’s yeast to induce pyrexia.
Result -The root of Ritchiea longipedicellata exhibited significant (p<0.05) antipyretic effect at 600 mg/kg from 1 h to 4 h and at 3 h to 4 h at 300 mg/kg compared with the control.
Conclusion-The claim of Idemili people of Anambra State Nigeria on the use of Ritchiea longipedicellata appears to be obvious in line with the results of the investigation.
Article Citation:
Chinedu Fred Anowi, Ezugwu CO, Ilodigwe EE, Ajaghaku DL.
Preliminary Phytochemical Studies and Evaluation of Antipyretic Property of the Methanol Extract of the Rootbark of Ritchiea longipedicellata Gilg (capparidaceae)
Journal of Research in Plant Sciences (2013) 2(2): 192-195.
Full Text:
http://plantsciences.co.in/documents/PS0048.pdf
Preliminary Studies on Antidiabetic, Antimicrobial and Antioxidant Activities...IJARIIT
Pharmaceutical industries are still in the hunt of effective scavengers for free radicals from the unexplored
medicinal plants. About 80,000 species of plants are utilized for treating various diseases in different systems of Indian
medicine. Many pharmaceutical companies giving importance in plant-derived drugs mainly due to the current widespread
belief that 'Green Medicine' is safe and more dependable than the costly synthetic drugs, which have adverse side effects.
The objective of the study is isolation of Phytochemical active constituents, Antidiabetic, antimicrobial and
antioxidant activities of the rare Antidiabetic medicinal plant Epaltes divaricata (Linn.) since the selected plant has varied
medicinal properties used in Ayurveda. This valuable plant is used in traditional Ayurvedic medicine to alleviate jaundice,
diabetes mellitus, urethral discharges and acute dyspepsia. It is also regarded as a diaphoretic, diuretic and a stimulating
expectorant.
The methanol extract of Epaltes divaricata L. showed excellent antimicrobial activity against bacteria and fungi.
Phytochemical analysis was carried out for the same extract by two different standard methods and which confirmed the
presence of steroids, triterpenoids and phenolic compounds. Decreasing of postprandial hyperglycemia is a therapeutic
approach for treating diabetes mellitus. This can be achieved in current trends through the inhibition of carbohydrate
hydrolyzing enzymes such as alpha glucosidase and alpha amylase. Agents with α-amylase and α-glucosidase inhibitory
activity are very useful as oral anti hypoglycemic agents for the control of hyperglycemia in patients who have diabetes
mellitus. In this study the methanol extract exhibited above 50% of inhibition in all standard concentration.
The study investigated the antimicrobial activity of petroleum ether, chloroform, and hydroalcoholic extracts of Pandanus odoratissimus leaf. All three extracts showed inhibition against gram-positive bacteria Bacillus subtilis and Staphylococcus aureus, but not against gram-negative bacteria or the yeast Candida albicans. The hydroalcoholic extract demonstrated the strongest antimicrobial activity with a minimum inhibitory concentration of 25mg/ml against gram-positives. Phytochemical analysis revealed this extract contained alkaloids and flavonoids, compounds possibly responsible for its antimicrobial effects.
Evaluation of analgesic and anti inflammatory activity of different fractions...pharmaindexing
This document describes a study that evaluated the analgesic and anti-inflammatory activity of different fractions of the plant Leucas cephalotes. The fractions were tested in various in vivo animal models and the ethyl acetate fraction was found to be the most potent. Specifically, at a dose of 150mg/kg, the ethyl acetate fraction significantly inhibited writhing response in mice by 68.98% and formalin-induced pain by 73.52-76.03%. It also inhibited carrageenan-induced rat paw edema by 65.35% and reduced cotton pellet granuloma formation in rats by 43.87-40.64%. The results suggest that fractions of L. cephalotes have analgesic and
Screening of phytochemicals and anti inflammatory property of berginiaNeeraj Ojha
This document summarizes a research project on screening the phytochemicals and anti-inflammatory properties of Berginia ciliata (Dhungeful), a medicinal plant used in Pyuthan district of Nepal. The objectives are to identify phytochemicals present in Dhungeful extracts and test its anti-inflammatory activity in vitro and in vivo. Methods proposed include extracting rhizomes with methanol, ether and hexane, qualitative phytochemical analysis, and testing anti-inflammatory effects using HRBC membrane stabilization, lipid peroxidation inhibition, protein denaturation inhibition, and carrageenan-induced paw edema in rats. A timeline is provided and chemicals/materials estimated to cost 30740
Background: Dennentia tripetalla (Pepper Fruit) belongs to the Annonaceae family and is abundant in Nigeria. Its
fruit in folklore medicine is used for treatment of varying ailments. While ample research evidence exists on the
plants fruit and seed, no current study exists on the toxicological profile of the plant leaves.
Methods: qualitative and quantitative phytochemicals and In vitro antioxidant assays were carried out using
standard methods. The acute toxicity study indicates that the LD50 was higher than 2000 mg/Kg body weight. Subchronic
toxicity studies was carried out using five groups of rats. Group 1 served as control, 2–5 received 100 mg/
Kg, 200 mg/Kg, 500 mg/Kg and 1000 mg/Kg body weight orally for 28 days.
Results: Post-administration biochemical analysis indicates there was increased weight in rats administered 100
mg/kg and 200 mg/kg while it reduced in the 500 mg/kg group. Significant elevations of liver function markers
were reported for 200 mg/kg and 500 mg/kg respectively. Serum and hepatic protein profiles remained unaltered.
Renal function analysis revealed elevated serum urea and creatinine for 200 and 500 mg/kg groups, elevated serum
Na+ and Ca+ and reduced serum Cl− for the 500 mg/Kg group. Elevated Kidney K+ and Ca+ levels, reduced Cl−
were significantly observed in 500 mg/Kg group. Significant rise in hepatic and renal lipid peroxidation was
observed in 200 and 500 mg/Kg groups. There were observed disarmament of the antioxidant defense systems
occasioned by rise and drop in tissue (hepatic, renal, testes, heart) Superoxide dismutase (SOD), Catalase (Cat),
Glutathione-s-transferase (GST), Glutathione peroxidase (GPx) activities in the test groups relative to control.
Histopathological examination indicated architectural aberrations at 500 and 1000 mg/kg.
Conclusions: It concluded that the plant had significant phytochemical and antioxidant properties of medical
interest and possessed toxic properties in rats when administered at a dose above 200 mg/Kg over a prolonged
period of time.
Anthelmintic activity of leaves of different extracts of Gossypium herbaceum ...SriramNagarajan16
The N-hexane, ethyl ether and ethanol extracts of leaves of Gossypium herbaceum L was investigated for
anthelmintic activity using earthworms (Pheretimaposthuma). Various concentrations (10,20,40,60,80 &100
mg/ml) of plant extracts were tested in the bioassay. Albendazole (10 mg/ml) was used as reference standard drug
whereas 1% v/v tween 80 as control. Determination of paralysis time and death time of the worms were recorded.
Theethyl ether and ethanol extracts exhibited significant anthelmintic activity at highest concentration of 60, 80 &
100 mg/ml compared to standard drug. The result shows that ethyl ether extract possesses potent vermicidal
activity and found to be effective as an anthelmintic compared to ethanolic extract
In-vivo anthelmintic evaluation of a processed herbal drug from Entada leptos...IOSR Journals
The document describes an in vivo study that evaluated the anthelmintic activity of a processed herbal drug from Entada leptostachya and Prosopis juliflora against gastrointestinal nematodes in sheep. The herbal drug showed maximum egg count reduction of 80.95% at a dose of 250 mg/kg body weight on day 11 post-treatment. Phytochemical analysis revealed the presence of compounds including alkaloids, steroids, phenolic compounds, tannins and flavonoids that may contribute to the anthelmintic effects. The study suggests the herbal drug has comparable anthelmintic activity to the conventional drug levamisole and could be used as an alternative de
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
All manuscripts are subject to rapid peer review. Those of high quality (not previously published and not under consideration for publication in another journal) will be published without delay.
The Central and Peripheral effects of the methanol extract of Fadogia cienkow...iosrjce
The methanol extract of Fadogia cienkowskii schweinf. var cienkowskii leaves was investigated for its central and peripheral nervous system effects. Oral administration of the extract up to 4000 mg/kg did not cause any mortality or clinical signs of toxicity in mice. The extract significantly prolonged phenobarbitone-induced sleeping times in mice, indicating a central nervous system effect. It also demonstrated local anesthetic and analgesic effects peripherally by reducing pain responses, though with lower potency than lignocaine. The extract did not show any muscle relaxant effects. Thus, the extract exhibited both central and peripheral nervous system activities, suggesting potential as a source of novel analgesic and anesthetic agents.
The document summarizes a study that evaluated the antipyretic (fever-reducing) activity of methanolic extracts of the root and leaves of Morinda angustifolia Roxb. in mice. Yeast was injected in mice to induce pyrexia (fever). The mice were divided into groups that received extracts of the root or leaves at 500 mg/kg, paracetamol (standard drug) at 150 mg/kg, or a control vehicle. Rectal temperatures were measured before and for 3 hours after treatment. Both extracts and paracetamol significantly reduced fever compared to the control and showed maximum reduction within 2 hours, indicating antipyretic effects comparable to paracetamol. The ant
1) The study examines the anti-HIV activity and cytotoxicity of extracts and isolated compounds from Wrightia tomentosa leaf against HIV-1 and HIV-2.
2) All extracts and compounds showed cytotoxic effects against MT-4 cells with CC50 values ranging from 8-117 μg/ml. Indirubin displayed the strongest cytotoxicity with a CC50 of 8.32 μg/ml.
3) The extracts and compounds did not show strong anti-HIV activity, with IC50 values all being greater than 50 μg/ml. However, indirubin provided some protection against viral infection at lower concentrations.
International Journal of Pharmaceutical Science Invention (IJPSI) is an international journal intended for professionals and researchers in all fields of Pahrmaceutical Science. IJPSI publishes research articles and reviews within the whole field Pharmacy and Pharmaceutical Science, new teaching methods, assessment, validation and the impact of new technologies and it will continue to provide information on the latest trends and developments in this ever-expanding subject. The publications of papers are selected through double peer reviewed to ensure originality, relevance, and readability. The articles published in our journal can be accessed online.
This document presents the results of a study analyzing the phytochemical composition and biological activities of extracts from different parts of Rheum ribes L. Qualitative tests showed the presence of phenolics and tannins in all parts tested. Quantitatively, the macerated flowers extract had the highest total phenolic and tannin contents. In antioxidant assays, the macerated flowers extract showed the strongest ABTS radical scavenging and ferric reducing activity, while the macerated leaves and Soxhlet radix extracts exhibited the strongest DPPH scavenging and cupric reducing activity respectively. The Soxhlet young shoots extracts displayed the highest anticholinesterase activity. All extracts showed low anti-urease
This study investigated the effects of parietin, an anthraquinone compound isolated from Rheum ribes L, on an in vitro wound model using human dermal fibroblast cells. Parietin was isolated from Rheum ribes L and its antioxidant properties were determined using the DPPH method. An in vitro wound model was created using human dermal fibroblast cells, and different concentrations of parietin and zinc were added to test their effects on cell proliferation and viability. Parietin showed antioxidant activity and significantly increased cell viability and proliferation at concentrations of 5 to 10 μM, similar to the effects of 50 μM zinc. The results suggest that parietin may promote wound healing at low doses by inducing dermal fibro
Synthesis, Characterization, and Biological Evaluation of Some Novel Phthalim...BRNSS Publication Hub
Objective: Different Phthalimide derivatives (4,5,6,7-tetrachloro-2-[1,2,4]triazol-4-yl]-isoindole-1,3-dione derivatives) were synthesized and biological activities of them were evaluated. Materials and Methods: In the present study, four new phthalimide derivatives were synthesized. The structures of final compounds were characterized on the basis of spectral data. Then, biological evaluation of all the synthesized compounds means in vivo anticancer activity was evaluated on the Ehrlich ascites carcinoma (EAC) bearing Swiss albino mice model, and in vitro antioxidant activity was assessed using 1,1-diphenyl-2-picryl hydrazine (DPPH) radical scavenging assay. Results: The titled compounds (2A-2D) were found to reduce tumor volume, viable cell count and increase non-viable cell count, and percentage increase in life span. All compounds showed significant activity in quenching DPPH free radical. Conclusion: All compounds showed significant (P<0.01) anticancer activity compared to EAC control group. All synthesized compound exhibited considerable antioxidant activity against free radicals, and they showed significant IC50 values and can, thus, ensure protection against oxidative stress.
The document summarizes a study that examined the inhibitory effects of extracts from Rheum ribes (rhubarb) roots and stems on pathogenic fungi and cancer cell lines. Phytochemical screening of the plant extracts found secondary metabolites including flavonoids, phenols, and fatty acids. The aqueous and alcoholic extracts were tested for their antioxidant effects in vitro. The alcoholic extracts showed greater inhibition of fungal growth than the aqueous extracts in a dose-dependent manner. Both root and stem extracts appeared to effectively inhibit fungal growth, though the stem extracts showed greater efficacy. The study evaluated the extracts' potential as natural antifungal and anticancer agents.
The use of medicinal plants in the treatment of harmful impacts of xenobiotics in animals is attracting an increasing attention in recent times. The aim of the current study is to assess the preventive potential of Costus afer aqueous leaves extract (CAAE) in treating metabolic aberrations imposed by crude oil contaminated diet in Wistar albino rats. Six groups of rats were treated as follows: A = Normal diet; B= Normal diet + 100 mg/kg body weight of CAAE; C =Normal diet + 200 mg/kg body weight of CAAE; D= Crude oil contaminated diet; E= crude oil contaminated diet + 100 mg/kg body weight of CAAE, F = crude oil contaminated diet + 200 mg/kg body weight of CAAE. After thirty days of exposure to the diet and administration of the corresponding plant extracts, the rats were sacrificed with chloroform and the required organs were excised. The hematological indices, as well as function indicators and levels of drug metabolizing enzymes in the liver and kidney, were investigated with standard protocols. The results indicated that the hematological parameters and kidney and liver function indices were altered in rats fed with crude oil contaminated diet. However, the values came close to those in control rats when Costus afer aqueous extracts were administered. Similarly, the activities of oxidase enzymes (aldehyde oxidase, monoamine oxidase, xanthine oxidase, and sulphite oxidase), following their inhibition by the ingestion of crude oil contaminated diet, equally restored close to control values upon treatment with Costus afer aqueous extract. This study, therefore, was able to establish an aqueous extract of Costus afer leave as an antidote for crude oil intoxication.
DEVELOPMENT AND EVALUATION OF ANTI- INFLAMMATORY HERBAL FORMULATIONVikram Choudhary
This document summarizes a research article that developed and evaluated an anti-inflammatory herbal gel formulation. The gel was formulated using extracts of Vitex negundo leaves, Boswellia serrata gum resin, Berberis aristata roots, and wintergreen oil. Three gel formulations (F1-F3) were prepared with increasing concentrations of the herbal extracts. The formulations were evaluated for parameters like appearance, pH, viscosity, spreadability, extrudability, and drug content. Formulation F3 was found to be optimal based on evaluation. In vitro drug release studies were also conducted using a Franz diffusion cell to assess drug release from the gel formulations over 6 hours.
Background: The probable mechanism of an earlier reported capacity of palm oil extracts to confer protection
against high dose cadmium poisoning in rats was reported in this study. Similar experimental design earlier reported
by us was retained. Rats therefore were sacrificed at intervals of twelve; twenty four and forty eight hours post CdCl2
insult.
Results: Oxidative stress and antioxidant status (malondialdehyde, superoxide dismutase, catalase and glutathione)
were assessed in tissues (liver, kidney, heart, brain, muscle) and serum. Oxidative stress indicators showed a significantly
(p < 0.05) increased lipid peroxidation and alterations in antioxidant defence systems occasioned by drop in
catalase and superoxide dismutase enzymes (serum, liver, heart, brain and kidneys) of the rats. Also observed were
significant (p < 0.05) reduction in the non-enzymatic antioxidant reduced glutathione over time. Pre-administration of
rats with the crude palm oil and its extracts modulated cadmium mediated depletion of the antioxidant capacities of
rats acutely exposed to cadmium and rising lipid peroxidation profile.
Conclusions: Regulation of stress and antioxidant response was the underlying mechanism by which the extracts
conferred protection against high dose cadmium insult thus suggesting its potential as a viable therapeutic target
against its deleterious effects.
This study evaluated the immunostimulatory and antioxidant properties of Phoenix dactylifera, commonly known as dates. Mice were injected with various concentrations of a Phoenix dactylifera extract. Results showed that the extract significantly increased phagocytic activity and reduced the half-life of carbon in the blood, indicating enhanced function of the reticuloendothelial system. The extract also significantly increased levels of the antioxidant glutathione in the liver. The concentration of 50 mg/kg produced the highest effects on phagocytosis and glutathione. Therefore, the study suggests that Phoenix dactylifera has immune-stimulating and antioxidant activities, with 50 mg/kg having the strongest impact.
ABSTRACT
Background- The mainstay of the treatment of pain and inflammation are opioids, steroids, and non-steroidal anti-inflammatory drugs. Though, they are effective and readily available with negative and unpleasant effects, more importantly, hepatotoxicity and nephrotoxicity. Thus, the need for safer and effective therapy in the management of pain and inflammation. Objective- The work sought to investigate the anti-nociceptive and anti-inflammatory activities of the hydro-ethanolic leaf extract of Clerodendrum polycephalum (HeCP) in animals. Methods- HeCP (100, 200 or 400 mg/kg, p.o.) given to mice, 1 h before administer of acetic acid (0.6% v/v, i.p.), formalin (1%v/v, intraplantar) or capsaicin (1% w/v, intraplantar) for nociceptive behavior in mice while carrageenan (1% w/v in saline, intraplantar) or cotton pellet (20 mg implanted into both groin) to induce acute or chronic inflammation in rats. Results- HeCP (100 – 400 mg/kg, p.o.) reduced mean writhes number, duration of paw licking or biting in the acetic acid, formalin and capsaicin models, respectively, in mice. However, the initial treatment of mice with L-NNA (neuronal nitric oxide synthase inhibitor), naloxone (opioid receptor antagonist), or glibenclamide (ATP-sensitive K+ channel blocker) prevented HeCP induced anti-nociception in mice. In contrast, the initial treatment of mice with, sulpiride (dopamine D2-receptor antagonist) failed to reverse HeCP-induced antinociception. In the aspect of anti-inflammatory activity, HeCP caused significantly but not dose-dependent inhibition of edema development in carrageenan-induced inflammation and cotton pellet-induced granuloma formation in rats. Conclusion- Findings from this work indicates that the hydroethanolic leaf extract of Clerodendrum polycephalum has anti-nociceptive and anti-inflammatory possibly due to its polyphenolic constituents.
Key-words: ATP-sensitive K+ channel, Capsaicin, Glibenclamide, Nociception, Inflammation
Antioxidants are substances which are capable to protect the body from damages caused by free radical. A variety of free radical scavenging antioxidants exists in the body and many of them are derived from plant sources. The aim of the present study was to investigate the antioxidant activity of the absolute ethanolic extract of Enantia chlorantha stem bark on typhoid fever induced rats. Salmonella typhi infected rats were treated every day between 7 to 9 AM with different doses of plant extract (9.16, 36.5 and 73 mg/kg or oxytetracyclin 20 mg/ kg). After 09 days of treatment, the results show that the different doses of this extract have all contributed to the cure of the infected rats, healing marked by the absence of salmonella in animal’s blood cultured on ss agar. In the other hand, treatment with different doses of plant extract result in a relative and signifi cant (p < 0.05) increase in the level of some blood and tissues antioxidant parameters such as CAT, SOD and POD while the level of alkaline phosphatase, malondialdehyde and nitric oxide as compared to untreated control group animal as compared to the untreated control group animals. Whereas, the level of ALP, MDA and NO were signifi cantly decreased (p < 0.05). These results showed that the absolute ethanolic extract of E. chlorantha stem bark possess antioxidant and antityphoid properties necessary to eradicate the free radical produced during typhoid fever infection.
This document summarizes a study that evaluated the antidiabetic effects of different extracts of Jatropha curcas leaves in rats with streptozotocin-induced type 2 diabetes. Rats were treated with petroleum ether, ethyl acetate, successive or crude methanolic extracts of J. curcas leaves for 30 days. The extracts were found to improve glucose, liver enzymes, lipids, oxidative stress markers, and pancreatic and liver histopathology in diabetic rats. Three flavonoid glycosides were isolated from the ethyl acetate extract and identified, which may contribute to the antidiabetic effects. The study demonstrates the antioxidant and anti-hyperglycemic properties of J. curcas extracts, indicating their potential
ANTI-INFLAMMATORY AND ANALGESIC EFFECTS OF METHANOLIC EXTRACT OF Afrofritomia...paperpublications3
Abstract: Methanolic extract of the leaf of Afrofritomia sylvestris was investigated for its anti-inflammatory and analgesic effects. The extract was evaluated using carragenaan-induced paw oedema in rats (anti-inflammatory effect) as well as acetic acid-induced writhing (analgesic effect) in mice, after intra-peritoneal injection of the extract (250mg/kg, 500mg/kg and 1000mg/kg). The negative control animals were given normal saline (10ml/kg) and the effects were compared with that of Acetylsalicylic acid (100mg/kg), as a positive control drug. Each experiment consisted of twenty five animals divided into 5 groups of 5 animals each. Tail immersion reaction time and Naloxone antagonism of the extracts and morphine were further used to investigate the mode of action of the analgesic activity of the leaf. The extract significantly inhibited carageenan-induced hind paw inflammation in rats (P<0.05-0.01)><0.01). The methanolic extract failed to raise the pain threshold of mice towards heat stimulus and Naloxone did not show any significant antagonism (blocking effect) against the extract in the tail immersion experiment, thus ruling out the involvement of opioid receptors in the mechanism of analgesic action of the extract. Phytochemical analyses of the plant show the presence of flavonoids, alkaloids, saponins, tannins, steroids, triterpenes and cyanogenic glycosides. The LD50 of the extract was determined to be 3050+223.65mg/kg using the method of Tainter and Miller.In this study, methanolic extract of Afrofritomia sylvestris leaf was found to possess significant anti-inflammatory and analgesic effects in the tested models.
Evaluation of analgesic and anti inflammatory activity of different fractions...pharmaindexing
This document describes a study that evaluated the analgesic and anti-inflammatory activity of different fractions of the plant Leucas cephalotes. The fractions were tested in various in vivo animal models and the ethyl acetate fraction was found to be the most potent. Specifically, at a dose of 150mg/kg, the ethyl acetate fraction significantly inhibited writhing response in mice by 68.98% and formalin-induced pain by 73.52-76.03%. It also inhibited carrageenan-induced rat paw edema by 65.35% and reduced cotton pellet granuloma formation in rats by 43.87-40.64%. The results suggest that fractions of L. cephalotes have analgesic and
Screening of phytochemicals and anti inflammatory property of berginiaNeeraj Ojha
This document summarizes a research project on screening the phytochemicals and anti-inflammatory properties of Berginia ciliata (Dhungeful), a medicinal plant used in Pyuthan district of Nepal. The objectives are to identify phytochemicals present in Dhungeful extracts and test its anti-inflammatory activity in vitro and in vivo. Methods proposed include extracting rhizomes with methanol, ether and hexane, qualitative phytochemical analysis, and testing anti-inflammatory effects using HRBC membrane stabilization, lipid peroxidation inhibition, protein denaturation inhibition, and carrageenan-induced paw edema in rats. A timeline is provided and chemicals/materials estimated to cost 30740
Background: Dennentia tripetalla (Pepper Fruit) belongs to the Annonaceae family and is abundant in Nigeria. Its
fruit in folklore medicine is used for treatment of varying ailments. While ample research evidence exists on the
plants fruit and seed, no current study exists on the toxicological profile of the plant leaves.
Methods: qualitative and quantitative phytochemicals and In vitro antioxidant assays were carried out using
standard methods. The acute toxicity study indicates that the LD50 was higher than 2000 mg/Kg body weight. Subchronic
toxicity studies was carried out using five groups of rats. Group 1 served as control, 2–5 received 100 mg/
Kg, 200 mg/Kg, 500 mg/Kg and 1000 mg/Kg body weight orally for 28 days.
Results: Post-administration biochemical analysis indicates there was increased weight in rats administered 100
mg/kg and 200 mg/kg while it reduced in the 500 mg/kg group. Significant elevations of liver function markers
were reported for 200 mg/kg and 500 mg/kg respectively. Serum and hepatic protein profiles remained unaltered.
Renal function analysis revealed elevated serum urea and creatinine for 200 and 500 mg/kg groups, elevated serum
Na+ and Ca+ and reduced serum Cl− for the 500 mg/Kg group. Elevated Kidney K+ and Ca+ levels, reduced Cl−
were significantly observed in 500 mg/Kg group. Significant rise in hepatic and renal lipid peroxidation was
observed in 200 and 500 mg/Kg groups. There were observed disarmament of the antioxidant defense systems
occasioned by rise and drop in tissue (hepatic, renal, testes, heart) Superoxide dismutase (SOD), Catalase (Cat),
Glutathione-s-transferase (GST), Glutathione peroxidase (GPx) activities in the test groups relative to control.
Histopathological examination indicated architectural aberrations at 500 and 1000 mg/kg.
Conclusions: It concluded that the plant had significant phytochemical and antioxidant properties of medical
interest and possessed toxic properties in rats when administered at a dose above 200 mg/Kg over a prolonged
period of time.
Anthelmintic activity of leaves of different extracts of Gossypium herbaceum ...SriramNagarajan16
The N-hexane, ethyl ether and ethanol extracts of leaves of Gossypium herbaceum L was investigated for
anthelmintic activity using earthworms (Pheretimaposthuma). Various concentrations (10,20,40,60,80 &100
mg/ml) of plant extracts were tested in the bioassay. Albendazole (10 mg/ml) was used as reference standard drug
whereas 1% v/v tween 80 as control. Determination of paralysis time and death time of the worms were recorded.
Theethyl ether and ethanol extracts exhibited significant anthelmintic activity at highest concentration of 60, 80 &
100 mg/ml compared to standard drug. The result shows that ethyl ether extract possesses potent vermicidal
activity and found to be effective as an anthelmintic compared to ethanolic extract
In-vivo anthelmintic evaluation of a processed herbal drug from Entada leptos...IOSR Journals
The document describes an in vivo study that evaluated the anthelmintic activity of a processed herbal drug from Entada leptostachya and Prosopis juliflora against gastrointestinal nematodes in sheep. The herbal drug showed maximum egg count reduction of 80.95% at a dose of 250 mg/kg body weight on day 11 post-treatment. Phytochemical analysis revealed the presence of compounds including alkaloids, steroids, phenolic compounds, tannins and flavonoids that may contribute to the anthelmintic effects. The study suggests the herbal drug has comparable anthelmintic activity to the conventional drug levamisole and could be used as an alternative de
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
All manuscripts are subject to rapid peer review. Those of high quality (not previously published and not under consideration for publication in another journal) will be published without delay.
The Central and Peripheral effects of the methanol extract of Fadogia cienkow...iosrjce
The methanol extract of Fadogia cienkowskii schweinf. var cienkowskii leaves was investigated for its central and peripheral nervous system effects. Oral administration of the extract up to 4000 mg/kg did not cause any mortality or clinical signs of toxicity in mice. The extract significantly prolonged phenobarbitone-induced sleeping times in mice, indicating a central nervous system effect. It also demonstrated local anesthetic and analgesic effects peripherally by reducing pain responses, though with lower potency than lignocaine. The extract did not show any muscle relaxant effects. Thus, the extract exhibited both central and peripheral nervous system activities, suggesting potential as a source of novel analgesic and anesthetic agents.
The document summarizes a study that evaluated the antipyretic (fever-reducing) activity of methanolic extracts of the root and leaves of Morinda angustifolia Roxb. in mice. Yeast was injected in mice to induce pyrexia (fever). The mice were divided into groups that received extracts of the root or leaves at 500 mg/kg, paracetamol (standard drug) at 150 mg/kg, or a control vehicle. Rectal temperatures were measured before and for 3 hours after treatment. Both extracts and paracetamol significantly reduced fever compared to the control and showed maximum reduction within 2 hours, indicating antipyretic effects comparable to paracetamol. The ant
1) The study examines the anti-HIV activity and cytotoxicity of extracts and isolated compounds from Wrightia tomentosa leaf against HIV-1 and HIV-2.
2) All extracts and compounds showed cytotoxic effects against MT-4 cells with CC50 values ranging from 8-117 μg/ml. Indirubin displayed the strongest cytotoxicity with a CC50 of 8.32 μg/ml.
3) The extracts and compounds did not show strong anti-HIV activity, with IC50 values all being greater than 50 μg/ml. However, indirubin provided some protection against viral infection at lower concentrations.
International Journal of Pharmaceutical Science Invention (IJPSI) is an international journal intended for professionals and researchers in all fields of Pahrmaceutical Science. IJPSI publishes research articles and reviews within the whole field Pharmacy and Pharmaceutical Science, new teaching methods, assessment, validation and the impact of new technologies and it will continue to provide information on the latest trends and developments in this ever-expanding subject. The publications of papers are selected through double peer reviewed to ensure originality, relevance, and readability. The articles published in our journal can be accessed online.
This document presents the results of a study analyzing the phytochemical composition and biological activities of extracts from different parts of Rheum ribes L. Qualitative tests showed the presence of phenolics and tannins in all parts tested. Quantitatively, the macerated flowers extract had the highest total phenolic and tannin contents. In antioxidant assays, the macerated flowers extract showed the strongest ABTS radical scavenging and ferric reducing activity, while the macerated leaves and Soxhlet radix extracts exhibited the strongest DPPH scavenging and cupric reducing activity respectively. The Soxhlet young shoots extracts displayed the highest anticholinesterase activity. All extracts showed low anti-urease
This study investigated the effects of parietin, an anthraquinone compound isolated from Rheum ribes L, on an in vitro wound model using human dermal fibroblast cells. Parietin was isolated from Rheum ribes L and its antioxidant properties were determined using the DPPH method. An in vitro wound model was created using human dermal fibroblast cells, and different concentrations of parietin and zinc were added to test their effects on cell proliferation and viability. Parietin showed antioxidant activity and significantly increased cell viability and proliferation at concentrations of 5 to 10 μM, similar to the effects of 50 μM zinc. The results suggest that parietin may promote wound healing at low doses by inducing dermal fibro
Synthesis, Characterization, and Biological Evaluation of Some Novel Phthalim...BRNSS Publication Hub
Objective: Different Phthalimide derivatives (4,5,6,7-tetrachloro-2-[1,2,4]triazol-4-yl]-isoindole-1,3-dione derivatives) were synthesized and biological activities of them were evaluated. Materials and Methods: In the present study, four new phthalimide derivatives were synthesized. The structures of final compounds were characterized on the basis of spectral data. Then, biological evaluation of all the synthesized compounds means in vivo anticancer activity was evaluated on the Ehrlich ascites carcinoma (EAC) bearing Swiss albino mice model, and in vitro antioxidant activity was assessed using 1,1-diphenyl-2-picryl hydrazine (DPPH) radical scavenging assay. Results: The titled compounds (2A-2D) were found to reduce tumor volume, viable cell count and increase non-viable cell count, and percentage increase in life span. All compounds showed significant activity in quenching DPPH free radical. Conclusion: All compounds showed significant (P<0.01) anticancer activity compared to EAC control group. All synthesized compound exhibited considerable antioxidant activity against free radicals, and they showed significant IC50 values and can, thus, ensure protection against oxidative stress.
The document summarizes a study that examined the inhibitory effects of extracts from Rheum ribes (rhubarb) roots and stems on pathogenic fungi and cancer cell lines. Phytochemical screening of the plant extracts found secondary metabolites including flavonoids, phenols, and fatty acids. The aqueous and alcoholic extracts were tested for their antioxidant effects in vitro. The alcoholic extracts showed greater inhibition of fungal growth than the aqueous extracts in a dose-dependent manner. Both root and stem extracts appeared to effectively inhibit fungal growth, though the stem extracts showed greater efficacy. The study evaluated the extracts' potential as natural antifungal and anticancer agents.
The use of medicinal plants in the treatment of harmful impacts of xenobiotics in animals is attracting an increasing attention in recent times. The aim of the current study is to assess the preventive potential of Costus afer aqueous leaves extract (CAAE) in treating metabolic aberrations imposed by crude oil contaminated diet in Wistar albino rats. Six groups of rats were treated as follows: A = Normal diet; B= Normal diet + 100 mg/kg body weight of CAAE; C =Normal diet + 200 mg/kg body weight of CAAE; D= Crude oil contaminated diet; E= crude oil contaminated diet + 100 mg/kg body weight of CAAE, F = crude oil contaminated diet + 200 mg/kg body weight of CAAE. After thirty days of exposure to the diet and administration of the corresponding plant extracts, the rats were sacrificed with chloroform and the required organs were excised. The hematological indices, as well as function indicators and levels of drug metabolizing enzymes in the liver and kidney, were investigated with standard protocols. The results indicated that the hematological parameters and kidney and liver function indices were altered in rats fed with crude oil contaminated diet. However, the values came close to those in control rats when Costus afer aqueous extracts were administered. Similarly, the activities of oxidase enzymes (aldehyde oxidase, monoamine oxidase, xanthine oxidase, and sulphite oxidase), following their inhibition by the ingestion of crude oil contaminated diet, equally restored close to control values upon treatment with Costus afer aqueous extract. This study, therefore, was able to establish an aqueous extract of Costus afer leave as an antidote for crude oil intoxication.
DEVELOPMENT AND EVALUATION OF ANTI- INFLAMMATORY HERBAL FORMULATIONVikram Choudhary
This document summarizes a research article that developed and evaluated an anti-inflammatory herbal gel formulation. The gel was formulated using extracts of Vitex negundo leaves, Boswellia serrata gum resin, Berberis aristata roots, and wintergreen oil. Three gel formulations (F1-F3) were prepared with increasing concentrations of the herbal extracts. The formulations were evaluated for parameters like appearance, pH, viscosity, spreadability, extrudability, and drug content. Formulation F3 was found to be optimal based on evaluation. In vitro drug release studies were also conducted using a Franz diffusion cell to assess drug release from the gel formulations over 6 hours.
Background: The probable mechanism of an earlier reported capacity of palm oil extracts to confer protection
against high dose cadmium poisoning in rats was reported in this study. Similar experimental design earlier reported
by us was retained. Rats therefore were sacrificed at intervals of twelve; twenty four and forty eight hours post CdCl2
insult.
Results: Oxidative stress and antioxidant status (malondialdehyde, superoxide dismutase, catalase and glutathione)
were assessed in tissues (liver, kidney, heart, brain, muscle) and serum. Oxidative stress indicators showed a significantly
(p < 0.05) increased lipid peroxidation and alterations in antioxidant defence systems occasioned by drop in
catalase and superoxide dismutase enzymes (serum, liver, heart, brain and kidneys) of the rats. Also observed were
significant (p < 0.05) reduction in the non-enzymatic antioxidant reduced glutathione over time. Pre-administration of
rats with the crude palm oil and its extracts modulated cadmium mediated depletion of the antioxidant capacities of
rats acutely exposed to cadmium and rising lipid peroxidation profile.
Conclusions: Regulation of stress and antioxidant response was the underlying mechanism by which the extracts
conferred protection against high dose cadmium insult thus suggesting its potential as a viable therapeutic target
against its deleterious effects.
Palm oil extracts protected against cadmium chloride poisoning via inhibition...
Similar to n-Hexane Insoluble Fraction of Plantago lanceolata Exerts Anti-Inflammatory Activity in Mice by Inhibiting Cyclooxygenase-2 and Reducing Chemokines Levels
This study evaluated the immunostimulatory and antioxidant properties of Phoenix dactylifera, commonly known as dates. Mice were injected with various concentrations of a Phoenix dactylifera extract. Results showed that the extract significantly increased phagocytic activity and reduced the half-life of carbon in the blood, indicating enhanced function of the reticuloendothelial system. The extract also significantly increased levels of the antioxidant glutathione in the liver. The concentration of 50 mg/kg produced the highest effects on phagocytosis and glutathione. Therefore, the study suggests that Phoenix dactylifera has immune-stimulating and antioxidant activities, with 50 mg/kg having the strongest impact.
ABSTRACT
Background- The mainstay of the treatment of pain and inflammation are opioids, steroids, and non-steroidal anti-inflammatory drugs. Though, they are effective and readily available with negative and unpleasant effects, more importantly, hepatotoxicity and nephrotoxicity. Thus, the need for safer and effective therapy in the management of pain and inflammation. Objective- The work sought to investigate the anti-nociceptive and anti-inflammatory activities of the hydro-ethanolic leaf extract of Clerodendrum polycephalum (HeCP) in animals. Methods- HeCP (100, 200 or 400 mg/kg, p.o.) given to mice, 1 h before administer of acetic acid (0.6% v/v, i.p.), formalin (1%v/v, intraplantar) or capsaicin (1% w/v, intraplantar) for nociceptive behavior in mice while carrageenan (1% w/v in saline, intraplantar) or cotton pellet (20 mg implanted into both groin) to induce acute or chronic inflammation in rats. Results- HeCP (100 – 400 mg/kg, p.o.) reduced mean writhes number, duration of paw licking or biting in the acetic acid, formalin and capsaicin models, respectively, in mice. However, the initial treatment of mice with L-NNA (neuronal nitric oxide synthase inhibitor), naloxone (opioid receptor antagonist), or glibenclamide (ATP-sensitive K+ channel blocker) prevented HeCP induced anti-nociception in mice. In contrast, the initial treatment of mice with, sulpiride (dopamine D2-receptor antagonist) failed to reverse HeCP-induced antinociception. In the aspect of anti-inflammatory activity, HeCP caused significantly but not dose-dependent inhibition of edema development in carrageenan-induced inflammation and cotton pellet-induced granuloma formation in rats. Conclusion- Findings from this work indicates that the hydroethanolic leaf extract of Clerodendrum polycephalum has anti-nociceptive and anti-inflammatory possibly due to its polyphenolic constituents.
Key-words: ATP-sensitive K+ channel, Capsaicin, Glibenclamide, Nociception, Inflammation
Antioxidants are substances which are capable to protect the body from damages caused by free radical. A variety of free radical scavenging antioxidants exists in the body and many of them are derived from plant sources. The aim of the present study was to investigate the antioxidant activity of the absolute ethanolic extract of Enantia chlorantha stem bark on typhoid fever induced rats. Salmonella typhi infected rats were treated every day between 7 to 9 AM with different doses of plant extract (9.16, 36.5 and 73 mg/kg or oxytetracyclin 20 mg/ kg). After 09 days of treatment, the results show that the different doses of this extract have all contributed to the cure of the infected rats, healing marked by the absence of salmonella in animal’s blood cultured on ss agar. In the other hand, treatment with different doses of plant extract result in a relative and signifi cant (p < 0.05) increase in the level of some blood and tissues antioxidant parameters such as CAT, SOD and POD while the level of alkaline phosphatase, malondialdehyde and nitric oxide as compared to untreated control group animal as compared to the untreated control group animals. Whereas, the level of ALP, MDA and NO were signifi cantly decreased (p < 0.05). These results showed that the absolute ethanolic extract of E. chlorantha stem bark possess antioxidant and antityphoid properties necessary to eradicate the free radical produced during typhoid fever infection.
This document summarizes a study that evaluated the antidiabetic effects of different extracts of Jatropha curcas leaves in rats with streptozotocin-induced type 2 diabetes. Rats were treated with petroleum ether, ethyl acetate, successive or crude methanolic extracts of J. curcas leaves for 30 days. The extracts were found to improve glucose, liver enzymes, lipids, oxidative stress markers, and pancreatic and liver histopathology in diabetic rats. Three flavonoid glycosides were isolated from the ethyl acetate extract and identified, which may contribute to the antidiabetic effects. The study demonstrates the antioxidant and anti-hyperglycemic properties of J. curcas extracts, indicating their potential
ANTI-INFLAMMATORY AND ANALGESIC EFFECTS OF METHANOLIC EXTRACT OF Afrofritomia...paperpublications3
Abstract: Methanolic extract of the leaf of Afrofritomia sylvestris was investigated for its anti-inflammatory and analgesic effects. The extract was evaluated using carragenaan-induced paw oedema in rats (anti-inflammatory effect) as well as acetic acid-induced writhing (analgesic effect) in mice, after intra-peritoneal injection of the extract (250mg/kg, 500mg/kg and 1000mg/kg). The negative control animals were given normal saline (10ml/kg) and the effects were compared with that of Acetylsalicylic acid (100mg/kg), as a positive control drug. Each experiment consisted of twenty five animals divided into 5 groups of 5 animals each. Tail immersion reaction time and Naloxone antagonism of the extracts and morphine were further used to investigate the mode of action of the analgesic activity of the leaf. The extract significantly inhibited carageenan-induced hind paw inflammation in rats (P<0.05-0.01)><0.01). The methanolic extract failed to raise the pain threshold of mice towards heat stimulus and Naloxone did not show any significant antagonism (blocking effect) against the extract in the tail immersion experiment, thus ruling out the involvement of opioid receptors in the mechanism of analgesic action of the extract. Phytochemical analyses of the plant show the presence of flavonoids, alkaloids, saponins, tannins, steroids, triterpenes and cyanogenic glycosides. The LD50 of the extract was determined to be 3050+223.65mg/kg using the method of Tainter and Miller.In this study, methanolic extract of Afrofritomia sylvestris leaf was found to possess significant anti-inflammatory and analgesic effects in the tested models.
1) A study investigated the vasodilatory and toxic effects of a crude extract of Ruta graveolens (Ruta) on rat aortas and CRL1730 endothelial cells.
2) The Ruta extract generated vasodilation in rat aortas at subtoxic concentrations, partially dependent on the endothelium. It caused a loss of cell viability in CRL1730 cells at high concentrations but did not induce oxidative stress or DNA fragmentation.
3) The results suggest Ruta extract regulates vascular tone through a complex, partially endothelium-dependent mechanism and has vasodilatory activity at subtoxic levels without damaging cell membranes or viability.
Hepatoprotective Activity of Methanolic Extract of Whole Plant of Pulicaria W...IOSRJPBS
Natural remedies from medicinal plants are considered to be effective and safe alternative treatment for liver injury. The present study was conducted to evaluate the hepatoprotective activity of methanolic extract of whole plant of Pulicaria wightiana in wistar rats. The studies were conducted using the two popular inducing agents Paracetamol (2 g/kg, p.o.) in 1% NaCMC and Carbon tetrachloride (1 ml/kg). Silymarin (100 mg/kg, p.o.) was used as reference drug in the respective models. The effect was estimated by measuring the enzymatic levels and histo- pathological studies. The methanolic extract of whole plant of Pulicaria wightiana has shown very significant hepatoprotection against both Paracetamol and CCl4 - induced hepatotoxicity study models in wistar rats. This was evidenced by marked reduction in marker enzymes in serum. Histopathological studies also confirmed the hepatoprotective nature of the extract
This study examined the effects of desloratadine on ovarian ischemia-reperfusion injury in rats. Rats were divided into three groups: an ischemia-reperfusion injury group, an ischemia-reperfusion injury group treated with desloratadine, and a sham group. Ovarian tissue was analyzed for markers of oxidative stress and inflammation after ischemia and reperfusion. Results showed that desloratadine significantly reduced oxidative stress markers like MDA and increased antioxidant markers like GSH compared to the ischemia-reperfusion injury group. Desloratadine also decreased levels of proinflammatory cytokines like NF-κB, IL-1β, and TNF-α. Histological analysis revealed that desl
Evaluation of Protective Efficacy of Hydro Alcoholic Extract and Methanol Fra...paperpublications3
Abstract: The objective of the study was to investigate and compare the radioprotective effect of hydroalcoholic extract (HAE) and methanol fraction (MF) of Tamarindus indica pod in mice against electron beam radiation. Animals were treated with 100 mg/Kg body weight of HAE and MF of T. indica for 15 consecutive days before exposing to 6Gy (sublethal dose) whole body EBR. The irradiation of animals resulted in an elevation in lipid peroxidation and reduction in glutathione, total antioxidants and antioxidant enzymes such as superoxide dismutase, glutathione peroxidase and catalase activities. Irradiated group had shown micronucleus in the bone marrow cells. Treatment of mice with HAE and MF before irradiation, reduced the symptoms of radiation sickness when compared with the irradiated group. Pretreated mice showed a significant reduction in lipid peroxidation followed by elevation in reduced glutathione, total antioxidants and antioxidant enzymes such as superoxide dismutase, glutathione peroxidase and catalase. It also showed a reduction in the micronucleus formation in bone marrow cells. The findings of our study indicate the protective efficacy of HAE and MF on radiation induced biochemical and chromosomal changes in mice may be due to its free radical scavenging and increased antioxidant levels. It also reveals MF, a better protective agent than that of HAE of T. indica.
Hepatoprotective and Antioxidant Effects of the Flavonoid-rich Fraction of th...IOSRJPBS
The leaves of Jatropha tanjorensis are edible and used in herbal medicine in the treatment of diseases associated with oxidative stress. The present study demonstrates the antioxidative effect of the flavonoid-rich fraction of the methanol extract of Jatropha tanjorensis leaves (FRJT) against CCl4-induced hepatotoxicity in rats. Hepatoprotective and antioxidant properties of FRJT were determined by serum biochemical enzymes; alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), antioxidant enzymes (SOD, CAT and GPx), heamatological pararmeters (PCV, Hb and WBC) and histology study. The results obtained showed a significant reduction (p < 0.05) in the activities of liver marker enzymes across the pre-treated groups compared with the untreated rats. Assay of antioxidant enzymes showed that the extract significantly (p < 0.05) enhanced SOD and GPx activities whereas CAT activity was non-significantly (p ˃ 0.05) increased when compared with the untreated animals. PCV, Hb and WBC levels were significantly (p < 0.05) lower in the untreated group. However, supplementation with FRJT and Silymarin ameliorated the induced depletion of blood in the pre-treated animals. Histological examination of the liver tissue showed marked reduction in fatty degeneration across the pre-treated groups when compared with the untreated group. The results in this study indicate that FRJT exhibited varying levels of protection against CCl4-induced oxidative stress in rat models. These results also indicate that the flavonoid-rich fraction contains antioxidants, which mop up free radicals in the system and support its use in the treatment of diseases resulting from oxidative damage.
This document summarizes a study comparing the anti-inflammatory effects of the medicinal plant Azadirachta indica (neem) and the drug diclofenac. Rats were injected with carrageenan to induce paw edema and inflammation. Groups received neem extract, diclofenac, a combination, or saline control. Diclofenac showed the best anti-inflammatory effect as measured by decreased paw swelling compared to the neem extract. However, the neem extract did show anti-inflammatory properties, though not as strong as diclofenac. The study concludes diclofenac is a more effective anti-inflammatory treatment than neem leaves extract for acute inflammation in rats.
Evaluation of In-vitro neuroprotective effect of Ethanolic extract of Canariu...AI Publications
The ethanolic extract of canarium solomonense leaves (ecsl) was studied for its neuroprotective activity. The neuroprotective activity of ECSL was found to have a significant impact on neuronal cell death triggered by hydrogen peroxide (MTT assay) in human SH-SY5Y neuroblastoma cells. Scopolamine, a muscarinic receptor blocker, is frequently used to induce cognitive impairment in laboratory animals. Injections of scopolamine influence multiple cognitive functions, including motor function, short-term memory, and attention. Using the Morris water maze, the Y maze, and the passive avoidance paradigm, memory enhancing activity in scopolamine-induced amnesic rats was evaluated. Using the Morris water maze, the Y maze, and the passive avoidance paradigm, ECSL was found to have a substantial effect on the memory of scopolamine- induced amnesic rats. Our experimental data indicated that ECSL can reverse scopolamine induced amnesia and assist with memory issues.
Toxicological profile of Grewia bicolor root extractIOSRJPBS
The document summarizes a study on the toxicological profile of Grewia bicolor root extract. The study found:
1) The tolerated dose of the extract in rats was 800mg/kg while the toxic dose was 1600mg/kg, with behavioral and neurological signs observed at toxic doses.
2) The median lethal dose (LD50) of the extract was calculated to be 2663.92 mg/kg in acute toxicity testing.
3) In a 28-day sub-acute toxicity study, rats administered 800mg/kg of the extract daily showed no changes in body weight, hematological, or biochemical parameters compared to controls.
The document summarizes a study that evaluated the antihyperglycemic and antinociceptive activities of the methanolic extract of Kaempferia rotunda rhizomes. In glucose tolerance tests in mice, the extract significantly lowered serum glucose levels in a dose-dependent manner, with the highest dose of 400 mg/kg reducing glucose by 39.6%. In antinociceptive tests using acetic acid-induced writhing in mice, the extract significantly reduced the number of writhes in a dose-dependent manner, with the highest dose of 400 mg/kg reducing writhes by 69.4%. The extract demonstrated significant antihyperglycemic and antinociceptive effects,
Diabetes mellitus was induced in rats using streptozotocin. Creatinine, urea, and inflammatory biomarkers were measured in the rats' blood serum. Creatinine and urea levels were significantly increased in diabetic rats, while an inflammatory marker (IL-10) decreased. Administration of Jatropha curcas extracts to diabetic rats resulted in reductions in creatinine, urea, and inflammatory biomarkers, similar to effects of the antidiabetic drug glibenclamide. The extracts showed protective effects against kidney disorders associated with diabetes mellitus.
ABSTRACT- Plants contain various phytocompounds that shows different interactions with various proteins involved in
several diseases. The ethanolic rhizome extract of K. galanga was shown a phytocompound (2e, 4e, 6e)-11-methyl
dodeca-2, 4, 6, 10-tetraenoic acid. Various biological activities like antioxidant, antimicrobial, protease inhibition and
anti-proliferation activities were tested for (2e, 4e, 6e)-11-methyl dodeca-2, 4, 6, 10-tetraenoic acid. The antioxidant
activities with IC50 for (2e, 4e, 6e)-11-methyl dodeca-2, 4, 6, 10-tetraenoic acid was shown 39.5 μg/ml and IC50 for
standard (Ascorbic acid) was shown as 24.5μg/ml. The (2e, 4e, 6e)-11-methyl dodeca-2, 4, 6, 10-tetraenoic acid were
shown good antifungal activities (11 to 12 mm) along with antibacterial activities (11 to 13 mm). The bacterial standard
like Tetracyclin shown zone of inhibitions as 10 to 14 mm and for fungi standard as Fluconazole shown zone of inhibition
from 13 to 16 mm. The compound (2e, 4e, 6e)-11-methyl dodeca-2, 4, 6, 10-tetraenoic acid were shown the good
inhibition activity with enzymes like protease k and trypsin when compared with chymotrypsin. The standard tetracycline
had shown the complete inhibition with proteolytic enzymes and control not shown the inhibition with proteolytic
enzymes with X-ray photographic film. Dose Response of (2e, 4e, 6e)-11-methyl dodeca-2, 4, 6, 10-tetraenoic acid from
K. galanga on MCF-7 (Breast Cancer) cell line shown very less activity 80 μg/ml when compared with the standard
tamoxifen 12.5 μgm/ml. Hence the experimentations concluded that a phytocompound, 1-(5-hydroxypentyloxy) propan-2-
one from ethanolic rhizome extract of K. galanga shown good biological activities.
Key Words- (2e, 4e, 6e)-11-methyl dodeca-2, 4, 6, 10-tetraenoic acid, Kaempferia galanga, Antioxidant activity,
Antimicrobial activity, Protease inhibition and antiproliferative activities
Genotoxicity of Goji Berry (Lyciumbarbarum) In Vivo Mammalian Cellsinventionjournals
Lyciumbarbarum (Gojji berry) belongs to family Salonaceae which is found in China and Himalayan. This herb is used to prevent various diseases and in medical treatments as an alternative medicine being widely used for its antioxidant and revitalizing potential effects. In recent years, Gojji has become increasingly popular in Europe and North America as a "superfruit" and dietary supplement. The belief that herbal products do not bring any risk to health, is part of popular culture. However the term "natural" assigned to many products cannot assure no health risk. The aim of this study was to evaluate the possible genotoxic effects of aqueous extract of Lyciumbarbarum (Gojji berry) by micronucleus test and comet assay. Thirty Rattus norvegicus were divided into three equal groups: 1) experimental group, submitted to Gojji berry (200mg/kg orally); 2) positive control group (cyclophosphamide), and; 3) negative control group (distilled water). Micronucleus Tests were done by smear method of bone marrow cells performed after 48h for acute, and 72h for chronic exposure. The comet assay was performed on peripheral blood taken from the tail of each animal 4h, and 24h after intervention. Cytotoxicity was assessed by observing the DNA damage measuring the percentage of DNA in the tail (% DNA- measurement of the proportion of the total DNA present in the tail) and the tail moment (TM-tail length times the percentage of DNA in the tail), calculated by 100 nucleoids per animal and the presence of micronuclei in 2,000 polychromatic erythrocytes per animal. Analysis of variance (ANOVA) followed by Tukey test at 5% significance was used comparing the results. The data showed no significant difference in the frequency of DNA damage and the number of micronuclei between the experimental group and the negative control group. The results also suggest that the aqueous extract of Lyciumbarbarum (Gojji berry) at the dose of 200 mg/kg showed no genotoxic effect, which could, to a certain point, justifies its use.
Genotoxicity of Goji Berry (Lyciumbarbarum) In Vivo Mammalian Cellsinventionjournals
Lyciumbarbarum (Gojji berry) belongs to family Salonaceae which is found in China and Himalayan. This herb is used to prevent various diseases and in medical treatments as an alternative medicine being widely used for its antioxidant and revitalizing potential effects. In recent years, Gojji has become increasingly popular in Europe and North America as a "superfruit" and dietary supplement. The belief that herbal products do not bring any risk to health, is part of popular culture. However the term "natural" assigned to many products cannot assure no health risk. The aim of this study was to evaluate the possible genotoxic effects of aqueous extract of Lyciumbarbarum (Gojji berry) by micronucleus test and comet assay. Thirty Rattus norvegicus were divided into three equal groups: 1) experimental group, submitted to Gojji berry (200mg/kg orally); 2) positive control group (cyclophosphamide), and; 3) negative control group (distilled water). Micronucleus Tests were done by smear method of bone marrow cells performed after 48h for acute, and 72h for chronic exposure. The comet assay was performed on peripheral blood taken from the tail of each animal 4h, and 24h after intervention. Cytotoxicity was assessed by observing the DNA damage measuring the percentage of DNA in the tail (% DNA- measurement of the proportion of the total DNA present in the tail) and the tail moment (TM-tail length times the percentage of DNA in the tail), calculated by 100 nucleoids per animal and the presence of micronuclei in 2,000 polychromatic erythrocytes per animal. Analysis of variance (ANOVA) followed by Tukey test at 5% significance was used comparing the results. The data showed no significant difference in the frequency of DNA damage and the number of micronuclei between the experimental group and the negative control group. The results also suggest that the aqueous extract of Lyciumbarbarum (Gojji berry) at the dose of 200 mg/kg showed no genotoxic effect, which could, to a certain point, justifies its use.
Similar to n-Hexane Insoluble Fraction of Plantago lanceolata Exerts Anti-Inflammatory Activity in Mice by Inhibiting Cyclooxygenase-2 and Reducing Chemokines Levels (20)
ON OPTIMALITY OF THE INDEX OF SUM, PRODUCT, MAXIMUM, AND MINIMUM OF FINITE BA...UniversitasGadjahMada
Chaatit, Mascioni, and Rosenthal de ned nite Baire index for a bounded real-valued function f on a separable metric space, denoted by i(f), and proved that for any bounded functions f and g of nite Baire index, i(h) i(f) + i(g), where h is any of the functions f + g, fg, f ˅g, f ^ g. In this paper, we prove that the result is optimal in the following sense : for each n; k < ω, there exist functions f; g such that i(f) = n, i(g) = k, and i(h) = i(f) + i(g).
Toward a framework for an undergraduate academic tourism curriculum in Indone...UniversitasGadjahMada
We analyse policy documents as well opinions of stakeholders contributing to the development of the undergraduate academic tourism curriculum, namely: The Government which develops the general framework for curriculum development in Indonesian universities; non-governmental tourism associations which assist universities with opinions and guidance; tourism academics who develop and implement the curriculum in the classroom; and tourism trade associations. Two issues characterize the development of the tourism curriculum namely: determining the appropriate balance between vocational and academic frameworks, and an aspiration to move from inter- to mono-disciplinary instruction.
Association of the HLA-B alleles with carbamazepine-induced Stevens–Johnson s...UniversitasGadjahMada
Carbamazepine (CBZ) is a common cause of life-threatening cutaneous adverse drug reactions such as Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Previous studies have reported a strong association between the HLA genotype and CBZ-induced SJS/TEN.We investigated the association between the HLA genotype and CBZ-induced SJS/TEN in Javanese and Sundanese patients in Indonesia. Nine unrelated patients with CBZ-induced SJS/TEN and 236 healthy Javanese and Sundanese controls were genotyped for HLA-B and their allele frequencies were compared. The HLA-B*15:02 allele was found in 66.7% of the patients with CBZ-induced SJS/TEN, but only in 29.4% of tolerant control (p = 0.029; odds ratio [OR]: 6.5; 95% CI: 1.2–33.57) and 22.9% of healthy controls (p = 0.0021; OR: 6.78; 95% CI: 1.96– 23.38). These findings support the involvement of HLA-B*15:02 in CBZ-induced SJS/TEN reported in other Asian populations. Interestingly, we also observed the presence of the HLA-B*15:21 allele. HLA-B*15:02 and HLA-B*15:21 are members of the HLA-B75 serotype, for which a greater frequency was observed in CBZ-induced SJS/TEN (vs tolerant control [p = 0.0078; OR: 12; 95% CI: 1.90–75.72] and vs normal control [p = 0.0018; OR: 8.56; 95% CI: 1.83–40]). Our findings suggest that screening for the HLA-B75 serotype can predict the risk of CBZ-induced SJS/TEN more accurately than screening for a specific allele.
Characteristics of glucomannan isolated from fresh tuber of Porang (Amorphoph...UniversitasGadjahMada
Porang is a potential source of glucomannan. This research objective was to find a direct glucomannan isolation method from fresh porang corm to produce high purity glucomannan. Two isolation methods were performed. In first method, sample was water dissolved using Al2(SO4)3 as flocculant for 15 (AA15) or 30 (AA30) minutes with purification. In second method, sample was repeatedly milled using ethanol as solvent and filtered for 5 (EtOH5) or 7 (EtOH7) times without purification. The characteristics of obtained glucomannan were compared to those of commercial porang flour (CPF) and purified konjac glucomannan (PKG). High purity (90.98%), viscosity (27,940 cps) and transparency (57.74 %) of amorphous glucomannan were isolated by EtOH7. Ash and protein level significantly reduced to 0.57% and 0.31%, respectively, with no starch content. Water holding capacity (WHC) of EtOH7 glucomannan significantly enhanced, whereas its solubility was lower than those of PKG due to its ungrounded native granular form.
Phylogenetic Analysis of Newcastle Disease Virus from Indonesian Isolates Bas...UniversitasGadjahMada
This study was conducted to analyze phylogenetic of Indonesian newcastle disease virus(NDV) isolates based on fusion (F) protein-encoding gene, with aim to determine which genotype group of Indonesian NDV isolates, compared to vaccine strain that circulating in Indonesia.
Land Capability for Cattle-Farming in the Merapi Volcanic Slope of Sleman Reg...UniversitasGadjahMada
This research carried out to study the cattle farming development based on the land capability in rural areas of the Merapi Volcanic slope of Sleman Regency Yogyakarta after eruption 2010. Samples taken were Glagaharjo village (Cangkringan Sub-District) as impacted area and Wonokerto village (Turi Sub-District) as unimpacted area. Survey method used were to land evaluation analysis supported by Geographic Information System (GIS) software. Materials used were Indonesian topographical basemap (RBI) in 1:25000 scale, IKONOS image [2015], land use map, landform map, and slope map as supple- ments. Potential analysis of land capability for cattle forage using the production unit in kg of TDN per AU. The result showed that based on the land capability class map, both villages had potential of carrying capacity for forage feed that could still be increased as much as 1,661.32 AU in Glagaharjo and 1,948.13 AU in Wonokerto.
When anti-corruption norms lead to undesirable results: learning from the Ind...UniversitasGadjahMada
This paper analyzes how and why adverse side-effects have occurred in the implementation of two articles of Indonesia’s anti-corruption law. These articles prohibit unlawful acts which may be detrimental to the finances of the state. Indeed, the lawmakers had good intentions when they drafted the two articles. They wanted to make it easier to convict corrupt individuals by lowering the standard of evidence required to prove criminal liability. The implementation of these articles has raised legal uncertainty. The loose definition of the elements of the crime enables negligence and imperfection of (public) contracts to be considered as corruption. The Constitutional Court has issued two rulings to restrict and guide the interpretation of these articles. However, law enforcement agencies (Supreme Court and public prosecutors) have been unwilling to adhere to the rulings. There are two possible reasons for this. First, as has been argued by several commentators, the law enforcement agencies have misinterpreted the concept of Bunlawfulness^. Besides, the law enforcement agencies wish to be seen to be committed to prosecuting and delivering convictions in corruption cases. To do so, they need to maintain looser definitions of the elements of the offence. This paper endorses the Constitutional Court rulings and provides additional reasons in support of their stance. The paper can be considered as a case study for other countries that may be contemplating similar legislation.
Receptor binding and antigenic site analysis of hemagglutinin gene fragments ...UniversitasGadjahMada
We reported a retrospective study on hemagglutinin (HA) gene fragments of Avian Influenza (AI) viruses recovered between 2010 to 2012, using reverse transcriptase polymerase chain reaction (RT-PCR) followed by sequencing. The results provide information about the receptor binding sites (RBS) and antigenic sites character of HA gene of AI viruses in Indonesia. Viral RNA was extracted from allantoic fluid of specific pathogen free (SPF) of chicken embryonated eggs inoculated by AI suspected samples. Amplification was performed by using H5 specific primers to produce amplification target of 544 bp. The resulting sequences were analyzed with MEGA-5 consisting of multiple alignment, deductive amino acid prediction, and phylogenetic tree analysis. The results showed that out of the 12 samples amplified using RT-PCR technique, only 7 were detected to be avian influenza serotype H5 viruses. Sequence analysis of AIV H5 positive samples, showed a binding preference towards avian type receptors. Antigenic site analysis is consistent with the previous report, however, the antigenic site B at position 189 showed that the residue had undergone mutation from arginine to methionine. Phylogenetic tree analysis showed that these viruses were clustered into clade 2.1.3. Our report supports the importance of the previous study of RBS and antigenic properties of HPAI H5N1 in Indonesia.
Sustaining the unsustainable? Environmental impact assessment and overdevelop...UniversitasGadjahMada
Bali faces serious environmental crises arising from overdevelopment of the tourism and real estate industry, including water shortage, rapid conversion of agricultural land, pollution, and economic and cultural displacement. This article traces continuities and discontinuities in the role of Indonesian environmental impact assessment (EIA) during and since the authoritarian ‘New Order’ period. Following the fall of the Suharto regime in 1998, the ‘Reform Era’ brought dramatic changes, democratizing and decentralizing Indonesia’s governing institutions. Focusing on case studies of resort development projects in Bali from the 1990s to the present, this study examines the ongoing capture of legal processes by vested interests at the expense of prospects for sustainable development. Two particularly controversial projects in Benoa Bay, proposed in the different historical and structural settings of the two eras—the Bali Turtle Island Development (BTID) at Serangan Island in the Suharto era and the Tirta Wahana Bali Internasional (TWBI) proposal for the other side of Benoa in the ‘Reform Era’—enable instructive comparison. The study finds that despite significant changes in the environmental law regime, the EIA process still finds itself a tool of powerful interests in the efforts of political and economic elites to maintain control of decision-making and to displace popular opposition forces to the margins.
Magnetogama is an open schematic handassembled fluxgate magnetometer. Compared to another magnetometer, Magnetogama has more benefit concerning its price and its ease of use. Practically Magnetogama can be utilized either in land or attached to an unmanned aerial vehicle (UAV). Magnetogama was designed to give open access to a cheap and accurate alternative to magnetometer sensor. Therefore it can be used as a standard design which is directly applicable to the low-budget company or education purposes. Schematic, code and several verification tests were presented in this article ensuring its reproducibility. Magnetogama has been tested with two kind of tests: a comparison with two nearest observatories at Learmonth (LRM) and Kakadu (KDU) and the response of magnetic substance.
Limitations in the screening of potentially anti-cryptosporidial agents using...UniversitasGadjahMada
The emergence of cryptosporidiosis, a zoonotic disease of the gastrointestinal and respiratory tract caused by Cryptosporidium Tyzzer, 1907, triggered numerous screening studies of various compounds for potential anti-cryptosporidial activity, the majority of which proved ineffective. Extracts of Indonesian plants, Piper betle and Diospyros sumatrana, were tested for potential anticryptosporidial activity using Mastomys coucha (Smith), experimentally inoculated with Cryptosporidium proliferans Kváč, Havrdová, Hlásková, Daňková, Kanděra, Ježková, Vítovec, Sak, Ortega, Xiao, Modrý, Chelladurai, Prantlová et McEvoy, 2016. None of the plant extracts tested showed significant activity against cryptosporidia; however, the results indicate that the following issues should be addressed in similar experimental studies. The monitoring of oocyst shedding during the entire experimental trial, supplemented with histological examination of affected gastric tissue at the time of treatment termination, revealed that similar studies are generally unreliable if evaluations of drug efficacy are based exclusively on oocyst shedding. Moreover, the reduction of oocyst shedding did not guarantee the eradication of cryptosporidia in treated individuals. For treatment trials performed on experimentally inoculated laboratory rodents, only animals in the advanced phase of cryptosporidiosis should be used for the correct interpretation of pathological alterations observed in affected tissue. All the solvents used (methanol, methanol-tetrahydrofuran and dimethylsulfoxid) were shown to be suitable for these studies, i.e. they did not exhibit negative effects on the subjects. The halofuginone lactate, routinely administered in intestinal cryptosporidiosis in calves, was shown to be ineffective against gastric cryptosporidiosis in mice caused by C. proliferans. In contrast, the control application of extract Arabidopsis thaliana, from which we had expected a neutral effect, turned out to have some positive impact on affected gastric tissue.
Self-nanoemulsifying drug delivery system (SNEDDS) of Amomum compactum essent...UniversitasGadjahMada
This document summarizes research on the development of a self-nanoemulsifying drug delivery system (SNEDDS) for Amomum compactum essential oil. Key points:
- Virgin coconut oil was selected as the carrier oil due to its high solubility of the essential oil compared to other oils tested.
- A D-optimal mixture design was used to optimize the SNEDDS formulation, with emulsification time and transmittance as the response variables.
- The optimized formulation contained 10% Amomum compactum essential oil, 10% virgin coconut oil, 65.71% Tween 80 surfactant, and 14.29% PEG 400 co-surfactant.
Attenuation of Pseudomonas aeruginosa Virulence by Some Indonesian Medicinal ...UniversitasGadjahMada
This study aims to discover quorum sensing inhibitors (QSI) from some Indonesian medicinal plants ethanol extract to analyze their inhibitory activities against QS-mediated virulence factors in P. aeruginosa using in-vitro experimental study-laboratory setting. Indonesian medicinal plant ethanolic extracts were tested for their capability to inhibit P. aeruginosa motility, biofilm formation using microtiter plate method, pyocyanin and LasA production using LasA staphylolytic assay. Statistical significance of the data were determined using one way ANOVA, followed by Dunnett’s test. Differences were considered significant with P values of 0.05 or less. The findings obtained showed that Ethanolic extract of T. catappa leaves and A. alitilis flower capable to inhibit P. aeruginosa motility as well as pyocyanin production and biofilm formation. Both extracts also showed capability in reducing LasA protease production. It is concluded that T. catappa and A. alitilis are an interesting sources of innovative plant derived quorum quenching compound(s), thus can be used in the development of new antipathogenic drug.
Short-chain alcohols are a group of volatile organic compounds (VOCs) that are often found in workplaces and laboratories, as well as medical, pharmaceutical, and food industries. Realtime monitoring of alcohol vapors is essential because exposure to alcohol vapors with concentrations of 0.15–0.30 mg·L−1 may be harmful to human health. This study aims to improve the detection capabilities of quartz crystal microbalance (QCM)-based sensors for the analysis of alcohol vapors. The active layer of chitosan was immobilized onto the QCM substrate through a selfassembled monolayer of L-cysteine using glutaraldehyde as a cross-linking agent. Before alcohol analysis, the QCM sensing chip was exposed to humidity because water vapor significantly interferes with QCM gas sensing. The prepared QCM sensor chip was tested for the detection of four different alcohols: n-propanol, ethanol, isoamyl alcohol, and n-amyl alcohol. For comparison, a non-alcohol of acetone was also tested. The prepared QCM sensing chip is selective to alcohols because of hydrogen bond formation between the hydroxyl groups of chitosan and the analyte. The highest response was achieved when the QCM sensing chip was exposed to n-amyl alcohol vapor, with a sensitivity of about 4.4 Hz·mg−1·L. Generally, the sensitivity of the QCM sensing chip is dependent on the molecular weight of alcohol. Moreover, the developed QCM sensing chips are stable after 10 days of repeated measurements, with a rapid response time of only 26 s. The QCM sensing chip provides an alternative method to established analytical methods such as gas chromatography for the detection of short-chain alcohol vapors.
APPLICATION OF CLONAL SELECTION IMMUNE SYSTEM METHOD FOR OPTIMIZATION OF DIST...UniversitasGadjahMada
This paper proposes an application of clonal selection immune system method for optimization of distribution network. The distribution network with high-performance is a network that has a low power loss, better voltage profile, and loading balance among feeders. The task for improving the performance of the distribution network is optimization of network configuration. The optimization has become a necessary study with the presence of DG in entire networks. In this work, optimization of network configuration is based on an AIS algorithm. The methodology has been tested in a model of 33 bus IEEE radial distribution networks with and without DG integration. The results have been showed that the optimal configuration of the distribution network is able to reduce power loss and to improve the voltage profile of the distribution network significantly.
Screening of resistant Indonesian black rice cultivars against bacterial leaf...UniversitasGadjahMada
The document summarizes a study that screened Indonesian black rice cultivars for resistance to bacterial leaf blight caused by Xanthomonas oryzae pv. oryzae. Five black rice cultivars and four white rice cultivars were inoculated with the bacteria and their resistance was evaluated based on disease symptoms and gene expression. The cultivar showing the best resistance was Cempo Ireng, which had the lowest disease intensity and expressed resistance genes xa5, Xa10, Xa21, and RPP13-like after inoculation. Cempo Ireng was identified as the most resistant cultivar and potential source of resistance genes for breeding programs.
This article analyzes the life of young millennial Salafi-niqabi in Surakarta and their strategies in dealing with power relations in their everyday lives. Studies on Salafi in Indonesia have focused more on global Salafimovements, power politics, links with fundamentalist-radical movements, state security and criticism of Salafi religious doctrine. Although there are several studies that try to portray the daily life of this religious group, the majority of previous studies focused on formal institutions and male Salafi. Very few studies have addressed the lives of Salafi women. This is likely due to the difficulty of approaching this group because of their exclusivity, and their restrictions on interacting with the outside world. Using Macleod’s theory of ‘accommodating protest’ within the framework of everyday politics, agency, and power relations, this research found that young millennial Salafi-niqabi have a unique method of negotiating with the modern and globalized world. Through what Macleod calls an accommodation which is at the same time a protest, young Salafi-niqabi have experienced hijrah as a form of negotiation of their millennial identity.
Application of arbuscular mycorrhizal fungi accelerates the growth of shoot r...UniversitasGadjahMada
This document summarizes a study that examined the effects of applying different doses of arbuscular mycorrhizal fungi (AMF) inoculum on shoot root growth of five sugarcane clones. The key findings are:
1) Application of 2-3 g of AMF inoculum/bud chips resulted in faster and greater root colonization compared to the control, reaching 57-100% colonization within 5 days.
2) AMF inoculation significantly increased shoot root traits like root length, surface area, and number of shoot roots, especially for clones BL, VMC, and PS864.
3) AMF application of 2-3 g/bud chips also significantly increased seedling
SHAME AS A CULTURAL INDEX OF ILLNESS AND RECOVERY FROM PSYCHOTIC ILLNESS IN JAVAUniversitasGadjahMada
Most studies of shame have focused on stigma as a form of social response and a socio-psychological consequence of mental illness. This study aims at exploring more complex Javanese meanings of shame in relation to psychotic illness. Six psychotic patients and their family members participated in this research. Ethnographic fieldwork was conducted in Yogyakarta, Indonesia. Thematic analysis of the data showed that participants used shame in three different ways. First, as a cultural index of illness and recovery. Family members identified their member as being ill when they had lost their sense of shame. If a patient exhibited behavior that indicated the reemergence of shame, the family saw this as an indication of recovery. Second, as an indication of relapse. Third, as a barrier toward recovery. In conclusion, shame is used as a cultural index of illness and recovery because it associated with the moral-behavioral control. Shame may also be regarded as a form of consciousness associated with the emergence of insight. Further study with a larger group of sample is needed to explore shame as a ‘socio-cultural marker’ for psychotic illness in Java.
Frequency and Risk-Factors Analysis of Escherichia coli O157:H7 in Bali-CattleUniversitasGadjahMada
Cattle are known as the main reservoir of zoonotic agents verocytotoxin producing Escherichia coli. These bacteria are usually isolated from calves with diarrhea and / or mucus and blood. Tolerance of these agents to the environmental conditions will strengthen of their transmission among livestock. A total of 238 cattle fecal samples from four sub-districts in Badung, Bali were used in this study. Epidemiological data observed include cattle age, sex, cattle rearing system, the source of drinking water, weather, altitude, and type of cage floor, the cleanliness of cage floor, the slope of cage floor, and the level of cattle cleanliness. The study was initiated by culturing of samples onto eosin methylene blue agar, then Gram stained, and tested for indole, methyl-red, voges proskauer, and citrate, Potential E.coli isolates were then cultured onto sorbitol MacConkey agar, and further tested using O157 latex agglutination test and H7 antisera. Molecular identification was performed by analysis of the 16S rRNA gene, and epidemiological data was analyzed using
STATA 12.0 software. The results showed, the prevalence of E. coli O157:H7 in cattle at Badung regency was 6.30% (15/238) covering four sub districts i.e. Petang, Abiansemal, Mengwi, and Kuta which their prevalence was 8.62%(5/58), 10%(6/60), 3.33%(2/60), and 3.33(2/60)%, respectively. The analysis of 16S rRNA gene confirmed of isolates as an E. coli O157:H7 strain with 99% similarities. Furthermore, the risk factors analysis showed that the slope of the cage floor has a highly significant effect (P<0.05) to the distribution of infection. Consequently, implementing this factor must be concerned in order to decrease of infection.
Phenomics assisted breeding in crop improvementIshaGoswami9
As the population is increasing and will reach about 9 billion upto 2050. Also due to climate change, it is difficult to meet the food requirement of such a large population. Facing the challenges presented by resource shortages, climate
change, and increasing global population, crop yield and quality need to be improved in a sustainable way over the coming decades. Genetic improvement by breeding is the best way to increase crop productivity. With the rapid progression of functional
genomics, an increasing number of crop genomes have been sequenced and dozens of genes influencing key agronomic traits have been identified. However, current genome sequence information has not been adequately exploited for understanding
the complex characteristics of multiple gene, owing to a lack of crop phenotypic data. Efficient, automatic, and accurate technologies and platforms that can capture phenotypic data that can
be linked to genomics information for crop improvement at all growth stages have become as important as genotyping. Thus,
high-throughput phenotyping has become the major bottleneck restricting crop breeding. Plant phenomics has been defined as the high-throughput, accurate acquisition and analysis of multi-dimensional phenotypes
during crop growing stages at the organism level, including the cell, tissue, organ, individual plant, plot, and field levels. With the rapid development of novel sensors, imaging technology,
and analysis methods, numerous infrastructure platforms have been developed for phenotyping.
ESR spectroscopy in liquid food and beverages.pptxPRIYANKA PATEL
With increasing population, people need to rely on packaged food stuffs. Packaging of food materials requires the preservation of food. There are various methods for the treatment of food to preserve them and irradiation treatment of food is one of them. It is the most common and the most harmless method for the food preservation as it does not alter the necessary micronutrients of food materials. Although irradiated food doesn’t cause any harm to the human health but still the quality assessment of food is required to provide consumers with necessary information about the food. ESR spectroscopy is the most sophisticated way to investigate the quality of the food and the free radicals induced during the processing of the food. ESR spin trapping technique is useful for the detection of highly unstable radicals in the food. The antioxidant capability of liquid food and beverages in mainly performed by spin trapping technique.
Authoring a personal GPT for your research and practice: How we created the Q...Leonel Morgado
Thematic analysis in qualitative research is a time-consuming and systematic task, typically done using teams. Team members must ground their activities on common understandings of the major concepts underlying the thematic analysis, and define criteria for its development. However, conceptual misunderstandings, equivocations, and lack of adherence to criteria are challenges to the quality and speed of this process. Given the distributed and uncertain nature of this process, we wondered if the tasks in thematic analysis could be supported by readily available artificial intelligence chatbots. Our early efforts point to potential benefits: not just saving time in the coding process but better adherence to criteria and grounding, by increasing triangulation between humans and artificial intelligence. This tutorial will provide a description and demonstration of the process we followed, as two academic researchers, to develop a custom ChatGPT to assist with qualitative coding in the thematic data analysis process of immersive learning accounts in a survey of the academic literature: QUAL-E Immersive Learning Thematic Analysis Helper. In the hands-on time, participants will try out QUAL-E and develop their ideas for their own qualitative coding ChatGPT. Participants that have the paid ChatGPT Plus subscription can create a draft of their assistants. The organizers will provide course materials and slide deck that participants will be able to utilize to continue development of their custom GPT. The paid subscription to ChatGPT Plus is not required to participate in this workshop, just for trying out personal GPTs during it.
When I was asked to give a companion lecture in support of ‘The Philosophy of Science’ (https://shorturl.at/4pUXz) I decided not to walk through the detail of the many methodologies in order of use. Instead, I chose to employ a long standing, and ongoing, scientific development as an exemplar. And so, I chose the ever evolving story of Thermodynamics as a scientific investigation at its best.
Conducted over a period of >200 years, Thermodynamics R&D, and application, benefitted from the highest levels of professionalism, collaboration, and technical thoroughness. New layers of application, methodology, and practice were made possible by the progressive advance of technology. In turn, this has seen measurement and modelling accuracy continually improved at a micro and macro level.
Perhaps most importantly, Thermodynamics rapidly became a primary tool in the advance of applied science/engineering/technology, spanning micro-tech, to aerospace and cosmology. I can think of no better a story to illustrate the breadth of scientific methodologies and applications at their best.
The ability to recreate computational results with minimal effort and actionable metrics provides a solid foundation for scientific research and software development. When people can replicate an analysis at the touch of a button using open-source software, open data, and methods to assess and compare proposals, it significantly eases verification of results, engagement with a diverse range of contributors, and progress. However, we have yet to fully achieve this; there are still many sociotechnical frictions.
Inspired by David Donoho's vision, this talk aims to revisit the three crucial pillars of frictionless reproducibility (data sharing, code sharing, and competitive challenges) with the perspective of deep software variability.
Our observation is that multiple layers — hardware, operating systems, third-party libraries, software versions, input data, compile-time options, and parameters — are subject to variability that exacerbates frictions but is also essential for achieving robust, generalizable results and fostering innovation. I will first review the literature, providing evidence of how the complex variability interactions across these layers affect qualitative and quantitative software properties, thereby complicating the reproduction and replication of scientific studies in various fields.
I will then present some software engineering and AI techniques that can support the strategic exploration of variability spaces. These include the use of abstractions and models (e.g., feature models), sampling strategies (e.g., uniform, random), cost-effective measurements (e.g., incremental build of software configurations), and dimensionality reduction methods (e.g., transfer learning, feature selection, software debloating).
I will finally argue that deep variability is both the problem and solution of frictionless reproducibility, calling the software science community to develop new methods and tools to manage variability and foster reproducibility in software systems.
Exposé invité Journées Nationales du GDR GPL 2024
The binding of cosmological structures by massless topological defectsSérgio Sacani
Assuming spherical symmetry and weak field, it is shown that if one solves the Poisson equation or the Einstein field
equations sourced by a topological defect, i.e. a singularity of a very specific form, the result is a localized gravitational
field capable of driving flat rotation (i.e. Keplerian circular orbits at a constant speed for all radii) of test masses on a thin
spherical shell without any underlying mass. Moreover, a large-scale structure which exploits this solution by assembling
concentrically a number of such topological defects can establish a flat stellar or galactic rotation curve, and can also deflect
light in the same manner as an equipotential (isothermal) sphere. Thus, the need for dark matter or modified gravity theory is
mitigated, at least in part.
EWOCS-I: The catalog of X-ray sources in Westerlund 1 from the Extended Weste...Sérgio Sacani
Context. With a mass exceeding several 104 M⊙ and a rich and dense population of massive stars, supermassive young star clusters
represent the most massive star-forming environment that is dominated by the feedback from massive stars and gravitational interactions
among stars.
Aims. In this paper we present the Extended Westerlund 1 and 2 Open Clusters Survey (EWOCS) project, which aims to investigate
the influence of the starburst environment on the formation of stars and planets, and on the evolution of both low and high mass stars.
The primary targets of this project are Westerlund 1 and 2, the closest supermassive star clusters to the Sun.
Methods. The project is based primarily on recent observations conducted with the Chandra and JWST observatories. Specifically,
the Chandra survey of Westerlund 1 consists of 36 new ACIS-I observations, nearly co-pointed, for a total exposure time of 1 Msec.
Additionally, we included 8 archival Chandra/ACIS-S observations. This paper presents the resulting catalog of X-ray sources within
and around Westerlund 1. Sources were detected by combining various existing methods, and photon extraction and source validation
were carried out using the ACIS-Extract software.
Results. The EWOCS X-ray catalog comprises 5963 validated sources out of the 9420 initially provided to ACIS-Extract, reaching a
photon flux threshold of approximately 2 × 10−8 photons cm−2
s
−1
. The X-ray sources exhibit a highly concentrated spatial distribution,
with 1075 sources located within the central 1 arcmin. We have successfully detected X-ray emissions from 126 out of the 166 known
massive stars of the cluster, and we have collected over 71 000 photons from the magnetar CXO J164710.20-455217.
Or: Beyond linear.
Abstract: Equivariant neural networks are neural networks that incorporate symmetries. The nonlinear activation functions in these networks result in interesting nonlinear equivariant maps between simple representations, and motivate the key player of this talk: piecewise linear representation theory.
Disclaimer: No one is perfect, so please mind that there might be mistakes and typos.
dtubbenhauer@gmail.com
Corrected slides: dtubbenhauer.com/talks.html
n-Hexane Insoluble Fraction of Plantago lanceolata Exerts Anti-Inflammatory Activity in Mice by Inhibiting Cyclooxygenase-2 and Reducing Chemokines Levels
1. Scientia
Pharmaceutica
Article
n-Hexane Insoluble Fraction of Plantago lanceolata
Exerts Anti-Inflammatory Activity in Mice by
Inhibiting Cyclooxygenase-2 and Reducing
Chemokines Levels
Nanang Fakhrudin 1,2,*, Eny Dwi Astuti 1, Rini Sulistyawati 1,4, Djoko Santosa 1,2,
Ratna Susandarini 3, Arief Nurrochmad 1 and Subagus Wahyuono 1,2
1 Faculty of Pharmacy, Universitas Gadjah Mada, Sekip Utara, Yogyakarta 55281, Indonesia;
aenydwi10@gmail.com (E.D.A.); sulistyawati.rini@yahoo.co.id (R.S.); djoko5346@ugm.ac.id (D.S.);
ariefnr@ugm.ac.id (A.N.); subagusw@yahoo.com (S.W.)
2 Center for Natural Antiinfective Research, Faculty of Pharmacy, Universitas Gadjah Mada, Sekip Utara,
Yogyakarta 55281, Indonesia
3 Faculty of Biology, Universitas Gadjah Mada, Sekip Utara, Yogyakarta 55281, Indonesia;
rsusandarini@gmail.com
4 Akademi Analis Farmasi Al Islam Yogyakarta, Gedongkiwo, Mantrijeron, Yogyakarta 55142, Indonesia
* Correspondence: nanangf@ugm.ac.id; Tel.: +62-858-7850-2778
Academic Editor: Gernot Eller
Received: 7 February 2017; Accepted: 8 March 2017; Published: 13 March 2017
Abstract: Inflammation is involved in the progression of many disorders, such as tumors, arthritis,
gastritis, and atherosclerosis. Thus, the development of new agents targeting inflammation is still
challenging. Medicinal plants have been used traditionally to treat various diseases including
inflammation. A previous study has indicated that dichloromethane extract of P. lanceolata
leaves exerts anti-inflammatory activity in an in vitro model. Here, we examined the in vivo
anti-inflammatory activities of a n-hexane insoluble fraction of P. lanceolata leaves dichloromethane
extract (HIFPL). We first evaluated its potency to reduce paw edema induced by carrageenan,
and the expression of the proinflammatory enzyme, cyclooxygenase (COX)-2, in mice. The efficacy of
HIFPL to inhibit COX-2 was also evaluated in an in vitro enzymatic assay. We further studied the
effect of HIFPL on leukocytes migration in mice induced by thioglycollate. The level of chemokines
facilitating the migration of leukocytes was also measured. We found that HIFPL (40, 80, 160 mg/kg)
demonstrated anti-inflammatory activities in mice. The HIFPL reduced the volume of paw edema and
COX-2 expression. However, HIFPL acts as an unselective COX-2 inhibitor as it inhibited COX-1 with
a slightly higher potency. Interestingly, HIFPL strongly inhibited leukocyte migration by reducing
the level of chemokines, Interleukine-8 (IL-8) and Monocyte chemoattractant protein-1 (MCP-1).
Keywords: Plantago lanceolata; anti-inflammation; chemokines
1. Introduction
Inflammation is a biological process disrupting tissue homeostasis that involves the accumulation
and recruitment of blood-derived products (leukocytes, fluid, plasma protein) into perturbed tissue
and induces vasodilatation, vascular permeability and augmented blood flow [1]. Inflammation
is also related with various pathological conditions such as arthritis, cancer, sepsis, metabolic,
neurodegenerative and cardiovascular diseases [2,3]. To date, corticosteroids and non-steroidal
anti-inflammatory drugs (NSAID) are available in clinical practices. These drugs remain the common
choice to cure inflammatory diseases. However, severe side effects and lack of potency in reducing
Sci. Pharm. 2017, 85, 12; doi:10.3390/scipharm85010012 www.mdpi.com/journal/scipharm
2. Sci. Pharm. 2017, 85, 12 2 of 12
a specific inflammatory symptom restricted the usage of these drugs. Furthermore, gastrointestinal
tract-related toxicity often occurs because of high-dose NSAID consumption, whereas long-term
medication using corticosteroids anti-inflammatory drugs could lead to osteoporosis, weight gain,
and immunosuppressive effects [4]. Many efforts have been made to identify potential targets of
anti-inflammation and to find promising anti-inflammatory agents from various sources [5,6].
One of the most important and well-established therapeutic targets is cyclooxygenase (COX).
This enzyme is responsible for the biosynthesis of the inflammatory mediator, prostanoids from
arachidonic acid, and displays a role for therapeutic intervention in pain and inflammation [7,8].
COX-1 is constitutively expressed and facilitates the production of prostaglandins and thromboxane
A2. It is also involved in the regulation of vascular, renal, gastrointestinal and various physiological
functions. COX-2 is an inducible enzyme expressed during the inflammatory processes [9].
This enzyme facilitates prostaglandins production and mediates fever, pain and inflammatory
processes [7,9,10]. Although COX-2 is one of the best-characterized therapeutic targets [10,11],
COX-2 inhibition is often accompanied with undesired side effects, such as renal and gastrointestinal
toxicities [11,12]. Selective COX-2 inhibitors “Coxibs” derivatives, for instance valdecoxib and rofecoxib,
have been developed, but they have been withdrawn due to serious skin reactions and increased risks
of heart attack and stroke, respectively [13,14]. Thus, the exploration and development of alternative
anti-inflammatory agents from different sources is still a challenging area of research.
Medicinal plants provide abundant biodiversity of natural compounds with a huge structural
variety and represent a potential source for drug discovery and development. One of the promising
plants with anti-inflammatory activity is Plantago lanceolata L. (Plantaginaceae). The leaves of
P. lanceolata have been traditionally used to cure inflammatory disorders, such as inflammation of
skin, oral, pharyngeal mucosa, respiratory tract, mouth and the throat [15]. In a previous study [16],
the corresponding author focussed on the ethnopharmacological in vitro studies on folk medicine
for anti-inflammation by performing a screening for anti-inflammatory activity from a collection
of medicinal plants traditionally used to cure inflammatory diseases. The study found that the
dichloromethane extract of P. lanceolata leaves inhibited nuclear factor-kappa B (NF-κB) activation
induced by tumour necrosis factor-alpha (TNF-α). Here, we further investigated the anti-inflammatory
effect of dichloromethane extracts of P. lanceolata leaves on mice. Chlorophylls and other non-polar inert
constituents were separated by n-hexane partition to give a n-hexane insoluble fraction of P. lanceolata
leaves extract (HIFPL) containing the more polar constituents of dichloromethane extract.
2. Materials and Methods
2.1. Plant Material
Plantago lanceolata leaves were collected from Tawangmangu, Karanganyar, Jawa Tengah, Indonesia.
Plant species determination was done by the botanist (Djoko Santosa) and the voucher specimen
(number NF-01-02-TM-14) was deposited at the Dept. of Pharmaceutical Biology, Faculty of Pharmacy,
Universitas Gadjah Mada, Indonesia. The fresh leaves were dried in the oven set at 50 ◦C for 48 h.
The dried leaves were ground and stored at 4 ◦C until used for extraction.
2.2. Extraction and Fractionation
The powdered plant material (1000 g) was macerated with dichloromethane (5 L) at room
temperature for 24 h. After filtration, the residue was remacerated with dichloromethane in a similar
procedure. The filtrates were combined and evaporated at reduced pressure using a rotary evaporator
for drying. The dried extract (13.8 g) was then dissolved in 69 mL n-hexane to produce n-hexane soluble
and insoluble (HIFPL) fractions. The fractionation process was repeated five times until colorless
n-hexane soluble fraction was obtained. This method yielded 8.6 g and 4.9 g of n-hexane soluble and
insoluble fractions, respectively. The HIFPL was subjected to anti-inflammatory activity assays.
3. Sci. Pharm. 2017, 85, 12 3 of 12
2.3. Animal Experiments
2.3.1. Animal
The animals used for the anti-inflammatory study were mice (Mus musculus, BALB/c strain, 20–30 g
of weight). The mice were maintained in an animal house with a controlled environment. They were
fed with a standard pellet diet, and water was given ad libitum. Before the experiment, the mice
were acclimatized in the animal house for a week, randomized and further divided into five groups.
The experiment procedures were approved by Institutional Animal Ethic Committee at the Integrated
Research and Testing Laboratory, Universitas Gadjah Mada (number 191/KEC-LPPT/IX/2014).
2.3.2. Carrageenan-Induced Paw Edema in Mice
A carrageenan-induced mice paw edema assay was done as previously described [17] to study
the inflammatory potency of HIFPL. The right hind paw of the mice was injected (sub plantar) with
0.2 mL carrageenan 1% (freshly prepared). The mice were divided randomly into five different groups
(five mice in each group). Thirty minutes prior to the injection of carrageenan, the HIFPL-treated
groups received orally a single dose of 0.1 mL HIFPL (40, 80 or 160 mg/kg) whereas the solvent- and
indomethacin-treated groups were orally given 0.1 mL solvent (DMSO) and indomethacin (5 mg/kg),
respectively. After carrageenan injection, the volume of the edema was measured every 30 min for
6 h using a plethysmometer instrument. The anti-inflammatory activity was determined with the
trapezoidal method [18] by plotting the time of induction (from 0 to 6 h) versus paw edema to obtain
the area under the curve (AUC). The anti-inflammatory activity of HIFPL was based on the percentage
of the AUC compared to the solvent-treated group.
2.3.3. Immunohistochemistry
After determination of the volume of the edema, the mice were sacrificed and the hind
paw (soft plantar region sections) were cut and fixed [19]. The paraffin-embedded sections were
deparaffinized, dehydrated, washed in a phosphate buffered saline solution (PBS) and then incubated
in a peroxidase blocking solution followed with mice primary antibody (anti COX-2; 1:250) at 4 ◦C
overnight. After washing, the diluted secondary biotinylated universal antibody (antiIgG; 1:200) was
added, incubated at room temperature for 5 min and a conjugated-streptavidin peroxidase complex
was added. The sections were stained with peroxidase substrate solution and then counter-stained
with hematoxylin. For immunohistochemistry analysis, the mounting media was added and the
sections were embedded in the microscope slides. COX-2 expression was detected if the cytoplasm was
stained brown, thus, the cells were considered positive. The level of COX-2 expression was determined
based on the number of positive cells according to the previous methods [19,20]. A light microscope
with a 1000× magnification was used to calculate the number of cells at five different fields.
2.3.4. Thioglycollate-Induced Leukocytes Migration
This method was performed according to the previous studies [21,22]. HIFPL was tested in
the dose of 40, 80 and 160 mg/kg whereas indomethacin was tested at 5 mg/kg. Both HIFPL
and indomethacin were dissolved in DMSO to obtain the desired concentrations, and then orally
administered (0.2 mL) 30 min prior to the induction of leukocytes migration with 0.5 mL of sterile
thioglycollate 4% (intra peritoneal). After 4.5 h, the animals were sacrificed and the peritoneal lavage
was collected and further spun in a centrifuge (Sartorius Centrisart G-16C; Goettingen, Germany)
at 1200 rpm for 10 min to obtain the cells pellet. The cells pellet was suspended in PBS for
total leukocytes counting and cytokines level analysis. The number of cells was counted using
a haemocytometer (Assistent; Sandheim, Germany) after staining with methylene blue.
4. Sci. Pharm. 2017, 85, 12 4 of 12
2.3.5. Analysis of Chemokines Level
The amount of chemokines, Interleukine-8 (IL-8) and Monocyte chemoattractant protein-1 (MCP-1)
produced in the peritoneum lavage supernatant was quantified using ELISA kit (Cusabio CSB-E07430m
and CSB-E07274m, respectively; Cusabio, College Park, MD, USA) according to the protocol from the
manufacturers. The activity of HIFPL in reducing the chemokines level was compared to the solvent
(DMSO) treatment and presented as percent inhibition.
2.4. Cyclooxygenase Enzymatic Assays
A COX Inhibitor Screening Assay kit (Caymann 760111; Cayman Chemical, Ann Arbor, MI, USA) was
used to determine the in vitro activity of the HIFPL to inhibit cyclooxygenase enzymes. HIFPL (17.6 mg)
was dissolved in 5 mL DMSO to give a stock solution of 3.52 mg/mL. Serial concentrations of HIFPL
were prepared by dilution from the stock solution to give final concentrations of 10, 20 and 40 µg/mL
in a 96-well plate. Indomethacin stock solution (8.8 mg/10 mL) was prepared in DMSO and tested
at final concentrations of 5, 10 and 20 µg/mL. The experiment protocol was done according to
the manufacturer’s instructions. This kit was based on colorimetric measurement that included the
peroxidase component of cyclooxygenase. The activity of peroxidase is determined by quantification
of oxidized tetramethyl-p-phenylenediamine (TMPD) generated in the enzymatic reaction at 590 nm
in an ELISA reader (Pioway RT-2100C; Nanjing, China) [23]. The percent inhibition was calculated
by comparing the inhibitory activity of the test sample-treated group to the inhibitory activity of the
solvent-treated group.
2.5. Statistical Analysis
The results were presented as a mean ± standard error of mean (SEM) and the statistical analysis
was performed to determine the significance of the effects. The data was analyzed using one-way
analysis of variance (ANOVA) followed by a post hoc test (Dunnet).
3. Results
In this study, we investigated the anti-inflammatory effects of HIFPL using two acute experimental
models of inflammation in mice. First, we performed a carrageenan-induced paw edema which
represents a common method for an acute anti-inflammatory evaluation. The second in vivo
experiment model utilized mice induced by thioglycollate to evaluate the effect of HIFPL on the
leukocytes’ migration and chemokines level.
3.1. Anti-Inflammatory Activity in Carrageenan-Induced Paw Edema
HIFPL and indomethacin (positive control) were given orally 30 min prior to carrageenan
stimulation. HIFPL was able to reduce the edema volume compared to that of the solvent-treated
group (Figure 1) in a dose-dependent manner. This result indicates that HIFPL exerts anti-inflammatory
activity in carrageenan-induced paw edema in mice (IC50: 21.76 mg/kg). As expected, indomethacin,
the reference drug, demonstrated a potent anti-inflammatory activity indicating the sensitivity of this
animal experimental model to detect the activity of anti-inflammatory agents.
5. Sci. Pharm. 2017, 85, 12 5 of 12
COX-2 expression. The amount of COX-2 expressing cells was quantified and the result was
presented in Figure 3. This figure indicates that pretreatment with HIFPL inhibited COX-2
expression in a dose-dependent manner, suggesting that HIFPL exerts anti-inflammatory activity,
partly by inhibiting the expression of COX-2. Consistent with the reduction of paw edema,
indomethacin exerts a potent reduction of COX-2 expression.
Figure 1. Anti-inflammatory activity of HIFPL on carrageenan-induced paw edema in mice. HIFPL
was tested at 40, 80 and 160 mg/kg; indomethacin (5 mg/kg) was used as a reference drug. HIFPL,
indomethacin or solvent was given orally 30 min prior to the injection of carrageenan injection (sub
plantar). (A) Paw edemas were measured every 30 min for 6 h; (B) The anti-inflammatory activity of
HIFPL was based on the area under the curve (AUC) of each group after 6 h compared to the
solvent-treated group. The values are relative AUC ± standard errors. * p < 0.05; ** p < 0.01
(ANOVA/Dunnett), compared to the solvent-treated group.
Figure 1. Anti-inflammatory activity of HIFPL on carrageenan-induced paw edema in mice. HIFPL was
tested at 40, 80 and 160 mg/kg; indomethacin (5 mg/kg) was used as a reference drug.
HIFPL, indomethacin or solvent was given orally 30 min prior to the injection of carrageenan injection
(sub plantar). (A) Paw edemas were measured every 30 min for 6 h; (B) The anti-inflammatory
activity of HIFPL was based on the area under the curve (AUC) of each group after 6 h compared
to the solvent-treated group. The values are relative AUC ± standard errors. * p < 0.05; ** p < 0.01
(ANOVA/Dunnett), compared to the solvent-treated group.
3.2. Analysis of COX-2 Expression
COX-2 is involved in the production of proinflammatory mediators and involved in the
development of paw edema. In order to assess whether the reduction of the paw edema upon HIFPL
treatment is due to the inhibition of COX-2, we measured the expression level of COX-2 in the
paw edema. The expression of COX-2 was assessed using immunohistochemistry from soft plantar
region sections of the hind paw. The COX-2 expression was considered positive if the cytoplasm
was stained brown. Figure 2 shows the comparison of COX-2 expression cells (stained dark-brown)
in the mice treated with HIFPL, solvent or indomethacin. These photos clearly showed that COX-2
was expressed in the paw edema and the treatment with HIFPL or indomethacin was able to reduce
the COX-2 expression. The amount of COX-2 expressing cells was quantified and the result was
presented in Figure 3. This figure indicates that pretreatment with HIFPL inhibited COX-2 expression
in a dose-dependent manner, suggesting that HIFPL exerts anti-inflammatory activity, partly by
inhibiting the expression of COX-2. Consistent with the reduction of paw edema, indomethacin exerts
a potent reduction of COX-2 expression.
6. Sci. Pharm. 2017, 85, 12 6 of 12
Sci. Pharm. 2017, 85, 12 6 of 12
Figure 2. Representative photos showing the cyclooxygenase (COX)-2 expressing cells (stained
dark-brown) of the paw edema. (a) Solvent-treated group; (b) Indomethacin-treated group; (c–e)
HIFPL-treated group at 160, 80 and 40 mg/kg (per oral), respectively. The soft plantar region sections of
the hind paw were cut and fixed, COX-2 expression was detected using immonohistochemisty. The
number of COX-2 expressing cells were counted in a light microscope with a 1000× magnification at five
different fields. Scale bar: 10 μm.
Figure 3. The effect of HIFPL on COX-2 expression in carrageenan-induced paw edema. Mice paws
were cut and fixed in buffered formalin and COX-2 expression was quantified. HIFPL was tested at 40,
80 or 160 mg/kg (per oral), and indomethacin (5 mg/kg, per oral) was used as a reference drug. The
values are mean ± standard errors. * p < 0.05; ** p < 0.01 (ANOVA/Dunnett), compared to the
solvent-treated group (set as 100% of COX-2 expression).
3.3. Cyclooxygenases Inhibition Enzymatic Assays
Not only was the expression of COX-2 investigated, but we also evaluated the effect of HIFPL
on COX-2 activity. To determine the selectivity, the effect on the COX-1 was also evaluated. To
investigate whether HIFPL also affected the activity of COX-2, in vitro enzymatic assays were
performed. We found that HIFPL not only reduced COX-2 expression, but also inhibited the activity
Figure 2. Representative photos showing the cyclooxygenase (COX)-2 expressing cells (stained dark-brown)
of the paw edema. (a) Solvent-treated group; (b) Indomethacin-treated group; (c–e) HIFPL-treated
group at 160, 80 and 40 mg/kg (per oral), respectively. The soft plantar region sections of the hind
paw were cut and fixed, COX-2 expression was detected using immonohistochemisty. The number of
COX-2 expressing cells were counted in a light microscope with a 1000× magnification at five different
fields. Scale bar: 10 µm.
Sci. Pharm. 2017, 85, 12 6 of 12
Figure 2. Representative photos showing the cyclooxygenase (COX)-2 expressing cells (stained
dark-brown) of the paw edema. (a) Solvent-treated group; (b) Indomethacin-treated group; (c–e)
HIFPL-treated group at 160, 80 and 40 mg/kg (per oral), respectively. The soft plantar region sections of
the hind paw were cut and fixed, COX-2 expression was detected using immonohistochemisty. The
number of COX-2 expressing cells were counted in a light microscope with a 1000× magnification at five
different fields. Scale bar: 10 μm.
Figure 3. The effect of HIFPL on COX-2 expression in carrageenan-induced paw edema. Mice paws
were cut and fixed in buffered formalin and COX-2 expression was quantified. HIFPL was tested at 40,
80 or 160 mg/kg (per oral), and indomethacin (5 mg/kg, per oral) was used as a reference drug. The
values are mean ± standard errors. * p < 0.05; ** p < 0.01 (ANOVA/Dunnett), compared to the
solvent-treated group (set as 100% of COX-2 expression).
3.3. Cyclooxygenases Inhibition Enzymatic Assays
Not only was the expression of COX-2 investigated, but we also evaluated the effect of HIFPL
on COX-2 activity. To determine the selectivity, the effect on the COX-1 was also evaluated. To
investigate whether HIFPL also affected the activity of COX-2, in vitro enzymatic assays were
performed. We found that HIFPL not only reduced COX-2 expression, but also inhibited the activity
Figure 3. The effect of HIFPL on COX-2 expression in carrageenan-induced paw edema. Mice paws
were cut and fixed in buffered formalin and COX-2 expression was quantified. HIFPL was tested at
40, 80 or 160 mg/kg (per oral), and indomethacin (5 mg/kg, per oral) was used as a reference drug.
The values are mean ± standard errors. * p < 0.05; ** p < 0.01 (ANOVA/Dunnett), compared to the
solvent-treated group (set as 100% of COX-2 expression).
3.3. Cyclooxygenases Inhibition Enzymatic Assays
Not only was the expression of COX-2 investigated, but we also evaluated the effect of HIFPL on
COX-2 activity. To determine the selectivity, the effect on the COX-1 was also evaluated. To investigate
7. Sci. Pharm. 2017, 85, 12 7 of 12
whether HIFPL also affected the activity of COX-2, in vitro enzymatic assays were performed.
We found that HIFPL not only reduced COX-2 expression, but also inhibited the activity of COX-2 in
a concentration-dependent manner (Figure 4). To determine the selectivity, HIFPL was also tested for
the COX-1 inhibition assay. Our study indicated that HIFPL acted as an unselective COX-2 inhibitor
with a higher affinity against COX-1 (IC50: 8.13 µg/mL) compared to COX-2 (IC50: 35.27 µg/mL).
Sci. Pharm. 2017, 85, 12 7 of 12
of COX-2 in a concentration-dependent manner (Figure 4). To determine the selectivity, HIFPL was
also tested for the COX-1 inhibition assay. Our study indicated that HIFPL acted as an unselective
COX-2 inhibitor with a higher affinity against COX-1 (IC50: 8.13 µg/mL) compared to COX-2
(IC50: 35.27 µg/mL).
Figure 4. HIFPL inhibited COXs activity in in vitro enzymatic assays. HIFPL was dissolved in DMSO
and prepared in three different concentrations (10, 20 and 40 µg/mL). The values are means ±
standard errors, * p < 0.05; n.s.: not significant (ANOVA/Dunnett), compared to the solvent-treated
group.
3.4. Leukocytes Migration Assay
Leukocytes migration plays a crucial role in inflammation. To assess the effect of HIFPL on the
early stage of inflammation, we evaluated the effectivity of HIFPL to inhibit leukocytes migration in
mice induced by thioglycollate. In this experiment, thioglycollate was able to stimulate the massive
migration of leukocytes from the blood circulation to the site of injury located in the peritoneum
(Figure 5). The treatment with indomethacin potently reduced leukocytes migration, indicating that
this bioassay represents a sensitive method to assess the anti-inflammatory activity of test samples.
Consistent with the anti-inflammatory activity in the previous in vivo experiment employing the
carrageenan-induced paw edema, HIFPL inhibited leukocytes migration (IC50: 61.74 mg/kg) induced
by thioglycollate in a concentration-dependent manner. A higher concentration of HIFPL was required
to completely inhibit the leukocytes migration to a level similar to the untreated mice.
Figure 5. HIFPL inhibited the migration of leukocytes induced by thioglycollate (five mice per group).
HIFPL was tested at 40, 80 and 160 mg/kg (per oral) and indomethacin (5 mg/kg, per oral) was used as
a reference drug. The values are mean ± standard errors. * p < 0.05; ** p < 0.01 (ANOVA/Dunnett),
compared to the solvent-treated group.
Figure 4. HIFPL inhibited COXs activity in in vitro enzymatic assays. HIFPL was dissolved in DMSO
and prepared in three different concentrations (10, 20 and 40 µg/mL). The values are means ± standard
errors, * p < 0.05; n.s.: not significant (ANOVA/Dunnett), compared to the solvent-treated group.
3.4. Leukocytes Migration Assay
Leukocytes migration plays a crucial role in inflammation. To assess the effect of HIFPL on the
early stage of inflammation, we evaluated the effectivity of HIFPL to inhibit leukocytes migration in
mice induced by thioglycollate. In this experiment, thioglycollate was able to stimulate the massive
migration of leukocytes from the blood circulation to the site of injury located in the peritoneum
(Figure 5). The treatment with indomethacin potently reduced leukocytes migration, indicating that
this bioassay represents a sensitive method to assess the anti-inflammatory activity of test samples.
Consistent with the anti-inflammatory activity in the previous in vivo experiment employing the
carrageenan-induced paw edema, HIFPL inhibited leukocytes migration (IC50: 61.74 mg/kg) induced
by thioglycollate in a concentration-dependent manner. A higher concentration of HIFPL was required
to completely inhibit the leukocytes migration to a level similar to the untreated mice.
Sci. Pharm. 2017, 85, 12 7 of 12
of COX-2 in a concentration-dependent manner (Figure 4). To determine the selectivity, HIFPL was
also tested for the COX-1 inhibition assay. Our study indicated that HIFPL acted as an unselective
COX-2 inhibitor with a higher affinity against COX-1 (IC50: 8.13 µg/mL) compared to COX-2
(IC50: 35.27 µg/mL).
Figure 4. HIFPL inhibited COXs activity in in vitro enzymatic assays. HIFPL was dissolved in DMSO
and prepared in three different concentrations (10, 20 and 40 µg/mL). The values are means ±
standard errors, * p < 0.05; n.s.: not significant (ANOVA/Dunnett), compared to the solvent-treated
group.
3.4. Leukocytes Migration Assay
Leukocytes migration plays a crucial role in inflammation. To assess the effect of HIFPL on the
early stage of inflammation, we evaluated the effectivity of HIFPL to inhibit leukocytes migration in
mice induced by thioglycollate. In this experiment, thioglycollate was able to stimulate the massive
migration of leukocytes from the blood circulation to the site of injury located in the peritoneum
(Figure 5). The treatment with indomethacin potently reduced leukocytes migration, indicating that
this bioassay represents a sensitive method to assess the anti-inflammatory activity of test samples.
Consistent with the anti-inflammatory activity in the previous in vivo experiment employing the
carrageenan-induced paw edema, HIFPL inhibited leukocytes migration (IC50: 61.74 mg/kg) induced
by thioglycollate in a concentration-dependent manner. A higher concentration of HIFPL was required
to completely inhibit the leukocytes migration to a level similar to the untreated mice.
Figure 5. HIFPL inhibited the migration of leukocytes induced by thioglycollate (five mice per group).
HIFPL was tested at 40, 80 and 160 mg/kg (per oral) and indomethacin (5 mg/kg, per oral) was used as
a reference drug. The values are mean ± standard errors. * p < 0.05; ** p < 0.01 (ANOVA/Dunnett),
compared to the solvent-treated group.
Figure 5. HIFPL inhibited the migration of leukocytes induced by thioglycollate (five mice per group).
HIFPL was tested at 40, 80 and 160 mg/kg (per oral) and indomethacin (5 mg/kg, per oral) was used
as a reference drug. The values are mean ± standard errors. * p < 0.05; ** p < 0.01 (ANOVA/Dunnett),
compared to the solvent-treated group.
8. Sci. Pharm. 2017, 85, 12 8 of 12
3.5. Analysis of Chemokines Level
In the inflamed tissues, chemotactic cytokines or chemokines are required for the trafficking of
leukocytes. The migration of mice leukocytes induced by thioglycollate was driven by the presence
of chemokines such as MCP-1 and IL-8. Thus, we investigated the level of MCP-1 and IL-8 in the
mice peritoneum cavity induced by thioglicollate. To evaluate the effect of the tested extract on the
chemokine expression, we measured the level of MCP-1 and IL-8 in the HIFPL-treated compared
with the solvent-treated mice. Figure 6 demonstrates that the levels of MCP-1 and IL-8 were increased
upon thioglycollate induction and the treatment with indomethacin significantly reduced the level
of the chemokines. This indicated that these two chemokines were involved in the leukocytes
migration process. In line with the ability of HIFPL to inhibit leukocytes migration, the levels of
MCP-1 and IL-8 were also decreased upon HIFPL treatment. This suggests that HIFPL inhibited the
thioglycollate-induced leukocytes migration in mice peritoneum, at least partly through lowering the
level of the chemokines MCP-1 and IL-8.
Sci. Pharm. 2017, 85, 12 8 of 12
3.5. Analysis of Chemokines Level
In the inflamed tissues, chemotactic cytokines or chemokines are required for the trafficking of
leukocytes. The migration of mice leukocytes induced by thioglycollate was driven by the presence
of chemokines such as MCP-1 and IL-8. Thus, we investigated the level of MCP-1 and IL-8 in the
mice peritoneum cavity induced by thioglicollate. To evaluate the effect of the tested extract on the
chemokine expression, we measured the level of MCP-1 and IL-8 in the HIFPL-treated compared
with the solvent-treated mice. Figure 6 demonstrates that the levels of MCP-1 and IL-8 were
increased upon thioglycollate induction and the treatment with indomethacin significantly reduced
the level of the chemokines. This indicated that these two chemokines were involved in the
leukocytes migration process. In line with the ability of HIFPL to inhibit leukocytes migration, the
levels of MCP-1 and IL-8 were also decreased upon HIFPL treatment. This suggests that HIFPL
inhibited the thioglycollate-induced leukocytes migration in mice peritoneum, at least partly
through lowering the level of the chemokines MCP-1 and IL-8.
Figure 6. Effect of HIFPL on MCP-1 and IL-8 levels in carrageenan-induced paw edema in mice.
HIFPL was tested at 40, 80 and 160 mg/kg (oral administration) and indomethacin (5 mg/kg, oral
administration) was used as a reference drug. The values are mean ± standard errors. * p < 0.05; ** p <
0.01; n.s.: not significant (ANOVA/Dunnett), compared to the solvent-treated group.
4. Discussion
Plantago lanceolata has been widely used worldwide for decades in the preparation of herbal
medicine to treat various disorders including inflammatory diseases. Even though the dried leaves
were traditionally prepared as a decoct dosage form, previous studies indicated that the
dichloromethane extract of the leaves demonstrated a potent inhibition against the main
transcription factor in inflammatory events, NF-κB, more potent that the polar extract. To enrich the
secondary metabolite components which might be responsible for the activity, the chlorophyll
content was removed from the dichloromethane extract of P. lanceolata leaves by partition using
n-hexane to yield a n-hexane-insoluble fraction of P. lanceolata (HIFPL; Thin layer chromatography
profile is shown in Supplementary materials Figure S1). In this study, we investigated the
anti-inflammatory activities of HIFPL in mice models to strengthen the scientific evidence regarding
the anti-inflammatory activity of this plant. We performed two acute experimental models of
inflammation. In the first experiment, we employed a carrageenan-induced paw edema as a
common simple method to evaluate the acute anti-inflammatory activity. In this model, the effect of
HIFPL on the expression of the enzyme responsible for generating inflammatory mediators, COX-2,
was also evaluated. The second experiment model employed the thioglycollate-induced leukocytes
migration to confirm the anti-inflammatory efficacy and to get insight into the effect on the
proinflammatory chemokines.
We found that HIFPL demonstrates a significant anti-inflammatory effect by reducing paw
edema volume in a dose-dependent manner after 6 h of observation, confirming its efficacy as an
Figure 6. Effect of HIFPL on MCP-1 and IL-8 levels in carrageenan-induced paw edema in mice.
HIFPL was tested at 40, 80 and 160 mg/kg (oral administration) and indomethacin (5 mg/kg,
oral administration) was used as a reference drug. The values are mean ± standard errors. * p < 0.05;
n.s.: not significant (ANOVA/Dunnett), compared to the solvent-treated group.
4. Discussion
Plantago lanceolata has been widely used worldwide for decades in the preparation of herbal
medicine to treat various disorders including inflammatory diseases. Even though the dried leaves were
traditionally prepared as a decoct dosage form, previous studies indicated that the dichloromethane
extract of the leaves demonstrated a potent inhibition against the main transcription factor in
inflammatory events, NF-κB, more potent that the polar extract. To enrich the secondary metabolite
components which might be responsible for the activity, the chlorophyll content was removed from the
dichloromethane extract of P. lanceolata leaves by partition using n-hexane to yield a n-hexane-insoluble
fraction of P. lanceolata (HIFPL; Thin layer chromatography profile is shown in Supplementary
materials Figure S1). In this study, we investigated the anti-inflammatory activities of HIFPL
in mice models to strengthen the scientific evidence regarding the anti-inflammatory activity of
this plant. We performed two acute experimental models of inflammation. In the first experiment,
we employed a carrageenan-induced paw edema as a common simple method to evaluate the acute
anti-inflammatory activity. In this model, the effect of HIFPL on the expression of the enzyme
responsible for generating inflammatory mediators, COX-2, was also evaluated. The second experiment
model employed the thioglycollate-induced leukocytes migration to confirm the anti-inflammatory
efficacy and to get insight into the effect on the proinflammatory chemokines.
We found that HIFPL demonstrates a significant anti-inflammatory effect by reducing paw
edema volume in a dose-dependent manner after 6 h of observation, confirming its efficacy as
9. Sci. Pharm. 2017, 85, 12 9 of 12
an anti-inflammatory remedy. As edema is one of the common features of an acute inflammatory
process [24], the ability of HIFPL to reduce paw edema volume suggested that it has an acute
anti-inflammatory activity in mice. However, the activity of HIFPL is still low compared to the
reference drug, indomethacin. Further separation of the fraction might be required to obtain a single
active compound with stronger anti-inflammatory activity.
The key enzyme in the inflammatory process is COX-2. This inducible enzyme is responsible for
generating inflammatory mediators including prostaglandins and leukotrienes from arachidonic acid.
In inflammatory condition, COX-2 is over expressed and contributes to the development of
inflammatory events. HIFPL significantly reduced COX-2 expression in a dose-dependent manner.
However, a higher dose of HIFPL was required to reduce COX-2 expression to the basal level.
As expected, indomethacin, the anti-inflammatory drug targeting COXs, demonstrated higher activity.
Not only was the expression of COX-2 investigated, but the effect of HIFPL on COX-1 and -2 activities
was also determined. Indeed, HIFPL was able to inhibit both COX-2 and COX-1 activities with a high
potency. Nevertheless, it demonstrated an unselective COX-2 inhibitor as it also inhibited COX-1
with a higher potency. Previous studies indicated that not only COX-2, but also COX-1 is involved in
the progression of neuroinflammation (Alzeimer’s disease) [25,26]. HIFPL can still be considered as
a potential source to be developed as a therapeutic agent to prevent or treat neurodegenerative diseases
in which neuroinflammation is the underlying pathological mechanism. Interestingly, P. lanceolata
also inhibits 12-lipooxygenase activity [27], another key enzyme in inflammation, suggesting that
P. lanceolata has a considerable anti-inflammatory effect and represents a potential plant source of
anti-inflammatory compounds.
One of the key events in the progression of acute inflammatory responses is leukocytes
migration [28,29]. Thus, inhibition of leukocytes migration is an important approach in
combating inflammation [30]. Interestingly, HIFPL effectively inhibited the migration of leukocytes.
Again, this confirmed the effectiveness of HIFPL in acute inflammation in vivo experiment models.
However, the method used in this study counted the entire leukocytes migration, not a specific type of
leukocytes. Thus, further study to differentiate the subset of migrated leukocytes, especially neutrophil,
might be necessary. Among the other leukocytes, neutrophil is a main subset that plays a key role in
the development of inflammatory processes as well as in various inflammatory-related disorders [31].
The migration of leukocytes to the site of inflammation induced by pro-inflammatory agents such
as thioglycollate was driven by the presence of chemokines including IL-8 and MCP-1. HIFPL inhibited
the expression level of MCP-1 and IL-8. This finding suggests that HIFPL exerts anti-inflammatory
activity in the thioglycollate-induced leukocytes migration in mice, at least partly by lowering
the level of MCP-1 and IL-8. As the binding of MCP-1 and IL-8 to their receptors is a crucial
event in inflammation and it also represents a potential therapeutic target [32–34], the reduction
of MCP-1 and IL-8 levels upon HIFPL treatment makes P. lanceolata leaves a potential source of
natural compounds with promising anti-inflammatory activity. HIFPL exerted a stronger inhibition
against MCP-1 compared to IL-1. Considerable data suggested that MCP-1, by its chemotactic
activity, contributes to many inflammatory diseases, such as atherosclerosis [35], nephritis [36],
periodontitis [37] and arthritis [38]. Therefore, P. lanceolata represents a plausible source of bioactive
compounds for therapeutic purposes.
Our findings are in line with previous studies showing that P. lanceolata leaves exerted
anti-inflammatory activity in various models [39–41]. Ursolic acid, a major triterpenoid compound
of P. lanceolata leaves, was likely to be an active compound responsible for the anti-inflammatory
activities [42]. Ursolic acid inhibited the activation of transcription factors involved in the inflammation,
such as NF-κB, AP-1 (Activator Protein-1), NF-AT (Nuclear Factor of Activated T cells) and STAT3
(Signal Transducer and Activator of Transcription 3) [42,43]. In addition, it was also known to exert
anti-inflammatory activities on adjuvant-induced chronic arthritis and zymosan-induced inflammation
in mice [44]. In addition, ursolic acid has also been reported as a selective COX-2 inhibitor [45].
Other compounds that might contribute to the anti-inflammatory activity of HIFPL are oleanolic acid,
10. Sci. Pharm. 2017, 85, 12 10 of 12
the structural isomer of ursolic acid [45], and the phenylethanoid compounds, plantamajoside and
acteoside [46]. These compounds exhibited anti-inflammatory activities in different models.
5. Conclusions
We demonstrated that HIFPL exhibited anti-inflammatory activity in in vivo experimental models.
It reduced paw edema volume in the carrageenan-induced mice and inhibited the expression and
activity of the proinflammatory enzyme COX-2. However, it acts as an unselective COX-2 inhibitor.
Interestingly, HIFPL inhibited the migration of leukocytes by reducing the level of chemokines
(MCP-1 and IL-8). Our finding is in line with previous studies and correlates with the traditional use
of P. lanceolata leaves as an anti-inflammatory remedy; this suggests that this plant could be further
developed for the discovery of novel leads or dietary supplements targeting inflammation.
Supplementary Materials: The following are available online at http://www.mdpi.com/2218-0532/85/1/12/s1,
Figure S1: Chromatogram (TLC profile) of P. lanceolata extract after chlorophyl removal using n-hexane partition.
Acknowledgments: This research project was supported by Insentif Riset Unggulan Klaster UGM, (Grant number
LPPM-UGM/1665/BID.III/2012 and by Hibah Penguatan UPR (Grant number: LPPM-UGM/1169/LIT/2013)
from the Directorate General of Higher Education, Ministry of Education and Culture, Republic of Indonesia.
Author Contributions: N.F. performed the experiments, analyzed the data and wrote the paper; R.S. and E.D.A
performed the experiments; D.S., A.N. and R.S. performed the experiments and contributed materials and analysis
tool; S.W. analyzed the data and wrote the paper.
Conflicts of Interest: The authors declare no conflict of interest.
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