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Bitter gourd (momordica charantia)
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Zahoor Parray
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This is my first review in the year 2017 and signifies love towards plant medicine.
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Bitter gourd (momordica charantia)
1.
RRJoBT (2017) 1-13
© STM Journals 2017. All Rights Reserved Page 1 Research & Reviews: A Journal of Biotechnology ISSN: 2231-3826 (Online), ISSN: 2347-7245 (Print) Volume 7, Issue 1 www.stmjournals.com Bitter Gourd (Momordica charantia): A Natural Gift in Support of the Research in Medicine and Biotechnology Zahoor Ahmad Parray1 , Shabir Ahmad Parray2, *, Asimul Islam1 1 Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India 2 Department of Ilmus Saidla (Unani Pharmacy), Mohammadia Tibbia College, Mansoora Malegaon, Nashik, India Abstract Bitter gourd (Momordica charantia) is acknowledged to be nature’s silent healer. It is a prospective herbal plant applied world widely in traditional systems of medicine (TSM) to modern medicine. It is medically very effective for various diseases such as diabetes, blood coagulation, cancer, menstrual stimulation and several diseases. Momordica fruit is frequently used in TSM, because it is very potent for cure, multidimensional function and reduces the consequences of diseases. Bitter guard is well-known to have hypoglycemic activity. The endeavor of this review is to comprehend the knowledge of plants used in TSM and in applied biotechnology, for researches in relation to formulate their use by eloquent their pharmacological properties, therapeutic agents so that the data and information of this review could be utilized in drawing approaches for coherent and more systematic and scientific use of medicinal plants in an approach that can be complete point of view for scientific and technical analysis in miscellaneous aspects. Here, we would like to light on its contribution in the field of biotechnology, and few highlights from TSM. In addition, we will uncover the supplementary medicinal properties of M. charantia that will help researchers to pull in concert data regarding the fruit effortlessly. Keywords: Momordica charantia, biotechnology, bitter gourd, traditional system of medicine (TSM) *Author for Correspondence E-mail: saparray@yahoo.co.in INTRODUCTION From ancient days to now a day, medicinal plants have played a potential and useful role for the treatment of several diseases and disorders. One of the common tropical vegetable is Momordica charnatia (MC), also known as nature’s silent healer [1]. Latin name Momordica means “to bite” (referring to the jagged edges of the leaf, which appear as if they have been bitten). MC, bitter gourd or Karela is the member of Cucurbitaceae family, and is a commonly consumed vegetable in India [1, 2]. The additional well-known names are bitter melon, balsam pear, Qisaul Himaar in Arabic, and Karela in Urdu and Hindi, respectively [3, 4]. Plant grows in tropical areas of the Amazon, East Africa, Asia, India, South America and Caribbean; it is used traditionally as both food and medicine. The plant is climbing perennial with elongated fruit that resembles a warty gourd or cucumber. The unripe fruit is white or green in color and has a bitter taste that becomes more pronounced as the fruit ripens [5]. ETHNOMEDICINAL HISTORY AND USES It grows in tropical areas, including parts of the Amazon, East Africa, Asia, and the Caribbean, widely grown in India and other parts of the Indian subcontinent, Southeast Asia, China, Africa, and the Caribbean. Bitter gourd, also known as balsam pear, is a tropical vegetable widely cultivated in Asia, Africa and South America. Bitter melon comes in a variety of shapes and sizes. The typical Chinese phenotype is 20–30 cm long, oblong with bluntly tapering ends and pale green in color, with a gently undulating, warty surface. The bitter melon more typical of India has a
2.
Bitter Gourd (Momordica
charantia) Parray et al. RRJoBT (2017) 1-13 © STM Journals 2017. All Rights Reserved Page 2 narrower shape with pointed ends, and a surface covered with jagged, triangular "teeth" and ridges [6, 7]. In the Amazon, local people and indigenous tribes grow bitter melon in their gardens for food and medicine. They add the fruit and/or leaves to beans and soup for a bitter or sour flavor; parboiling it first with a dash of salt may remove some of the bitter taste. Medicinally, the plant has a long history of use by the indigenous peoples of the Amazon. A leaf tea is employed for diabetes; as a carminative for colic; topically for sores, wounds, and infections; internally and externally for worms and parasites and as an antiviral agent for measles, hepatitis, and feverish conditions. In Brazilian herbal medicine, bitter melon is used for tumors, wounds, rheumatism, malaria, leucorrhea, inflammation, menstrual problems, diabetes, colic, fevers, worms, to induce abortions, and as an aphrodisiac. It is also employed topically for skin problems, vaginitis, hemorrhoids, scabies, itchy rashes, eczema, and leprosy. In Mexico, the entire plant is used for diabetes and dysentery; the root is a reputed aphrodisiac. In Peruvian herbal medicine, the leaf or aerial parts of the plant are used to treat measles, malaria, and all types of inflammation. In Nicaragua, the leaf is commonly used for stomach pain, diabetes, fevers, colds, coughs, headaches, malaria, skin complaints, menstrual disorders, aches and pains, hypertension, infections, and as an aid in childbirth [2, 6–8]. Momordica charantia (MC) have provided many remedies for various diseases from ancient days to now a day. TRADITIONAL SYSTEM OF MEDICINAL USES It has been used in various Asian traditional medicines [2, 8, 9]. In TSM, especially in Unani and Ayurvedic systems, the fruit is considered as tonic, stomachic, stimulant, emetic, antibilous, laxative and alterative. Like most bitter-tasting foods, bitter melon stimulates digestion, and hence used in dyspepsia, and constipation [2, 9]. In the classical literature of Unani system of medicine, it is mentioned as demulcent, deobstruent, anti-inflammatory and anthelmintic; and used in treatment of cholera, bronchitis, anemia, blood diseases, ulcer, diarrhea, dysentery, gonorrhea rheumatism, gout, worms, colic, disease of liver and spleen [3, 4]. In Ayurvedic medicine, it is used for indigestion, intestinal gas, menstrual stimulation, wound healing, inflammation, fever reduction, gonorrhea, hypertension, as a laxative and emetic [8, 10]. Fruits are used as traditional medication to cure various diseases such as rheumatism, gout, worms, colic, disease of liver and spleen. It is also found useful in the treatment of cancer and diabetes [9, 11, 12]. The medicinal values of bitter melon, lies in the bioactive phytochemical constituents that are nonnutritive chemicals that produce clear-cut physiological effects on human body and protect them from various diseases. Juice of M. charantia leaves is used to treat piles totally [11, 12]. PHYTOCONSTITUENTS AND PHYTOCHEMICAL STUDIES The unripe fruits are a good source of vitamin C and also render vitamin A, phosphorus and iron [13]. Fresh bitter melon is also used as a nourishing food, as it contains 93.8% water, 0.9% protein, 0.1% lipid, 3.3% dietary fiber, 20 kJ energy per 100 g, 0.6% ash, and a small quantity (0.05%) of vitamin C [14]. The fruit bitter melon be full of various compounds that act agonistically to the compounds in body and function correspondingly i.e., contains phytonutrient, polypeptide-P—a plant insulin—known to lower blood sugar levels. In addition it also contain hypoglycemic agent called charantin. Charantin increases glucose uptake and glycogen synthesis in the cells of liver, muscle and adipose tissue. Together, these compounds are thought to be responsible for reduction of blood sugar levels in the treatment of type-2 diabetes [15, 16]. Polypeptide-P, a plant insulin, charantin, vicine, glycosides, and karavilosides improve blood sugar levels by increasing glucose uptake and glycogen synthesis in the liver, muscles, and fat cells [15, 16]. M. charantia is rich in various biologically active chemicals including triterpenes, proteins, and steroids. Triterpenes of M. charantia has the ability to inhibit the enzyme guanylate cyclase that is thought to be linked to the cause of psoriasis. In addition, guanylate cyclase is one of the important enzymes, necessary for the growth of leukemia and other cancer cells. In addition
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Research & Reviews:
A Journal of Biotechnology Volume 7, Issue 1 ISSN: 2231-3826 (Online), ISSN: 2347-7245 (Print) RRJoBT (2017) 1-13 © STM Journals 2017. All Rights Reserved Page 3 to these biologically active triterpenes, M. charantia proteins such as momordin, alpha- and beta-momorcharin and cucurbitacin B were also tested for possible anticancerous effects [17, 18]. BIOLOGICAL ACTIVITIES AND CLINICAL RESEARCH Karela contains an array of biologically active plant chemicals including triterpens, proteins, steroids, alkaloids, saponins, flavonoids and acids due to which plant possesses antifungal, antibacterial, antiparasitic, antiviral, antifertility, anti-inflammatory, antitumorous, hypoglycemic and anticarcinogenic properties [19–22]. Similarly, clinical conditions for which M. charantia extracts (primarily from the fruit) are currently being used include diabetes, dyslipidemia, microbial infections, and potentially as a cytotoxic agent for certain types of cancer [23, 24]. It is well known that dietary fiber rich diets are beneficial in the management of diabetes. The dietary fibers are known to differ from source to source in terms of their chemical nature, functionality and fermentability [25, 26]. Some of the clinical trials have reported that it has highly potential benefits during diabetes [26]. Few important scientific studies are mentioned here: Antidiabetic and Hypoglycaemic Activity It is a potent hypoglycemic agent due to alkaloids and insulin-like peptides and a mixture of steroidal sapogenins known as charantin. Bitter melon's hypoglyecemic ingredients have been shown in animal and human studies [12]. In numerous studies, at least three different groups of constituents found in all parts of Momordica have clinically demonstrated hypoglycemic properties or other actions of potential benefit against diabetes mellitus [27, 28]. Bitter melon has been shown to increase the number of β cells in the pancreas thereby improving the body's ability to produce insulin [27]. The effect of M. charantia fruit juice on the distribution and number of α, β and δ cells in the pancreas of streptozotocin (STZ)-induced diabetic rats using immunohistochemical methods was investigated and the results suggested that oral feeding of M. charantia fruit juice may have a role in the renewal of β cells in STZ-diabetic rats or alternately may permit the recovery of partially destroyed β cells [29]. Studies have shown both the aqueous and alcoholic extracts of the fruit possess hypoglycaemic activity in streptozotocin- induced diabetic rats by inhibiting the enzyme fructose 1, 6-diphosphatase and glucose 6 phosphatase and at the same time stimulating the enzyme glucose 6 phosphate dehydrogenase [28, 30]. This fruit has also shown the ability to enhance cells’ uptake of glucose, to promote insulin release, and to potentiate the effect of insulin [31]. Bitter melon has reduced blood glucose and lipids in both normal and diabetic animals, protected β cells, enhanced insulin sensitivity and reduced oxidative stress [32]. Blood sugar support can be achieved by taking a combination of bitter melon, N-acetyl cysteine, goat’s rue, cinnamon, vanadium, quercetin, vitamin C, vitamin E and B6. Components of bitter melon extract appear to have structural similarities to animal insulin [14]. In rats, oral bitter melon juice has been found to potentiate the glucose-lowering effects of the sulfonylurea tolbutamide [22]. Alcoholic extracted charantin from M. charantia consists of mixed steroids, and in an animal model of diabetes it improved glucose tolerance to a degree similar to the oral hypoglycaemic agent—tolbutamide [15]. A clinical trial of diagnosed type-I diabetes, in which a subcutaneous injection of bitter gourd extract containing crystallized p-insulin, showed statistically significant decrease in blood sugar levels as compared to controls. The onset of p-insulin’s effect was noted 30– 60 min after administration, with peak effect ranging widely from 4–12 h [33]. Another study was carried out to examine the effect of edible portion of bitter gourd at 10% level in the diet of streptozotocin-induced diabetic rats. Different parameters such as diet intake, gain in body weight, water intake, urine sugar, urine volume, glomerular filtration rate and fasting blood glucose profiles were monitored. Renal hypertrophy,
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Bitter Gourd (Momordica
charantia) Parray et al. RRJoBT (2017) 1-13 © STM Journals 2017. All Rights Reserved Page 4 glomerular filtration rate and fasting blood glucose was significantly reduced as 38%, 27%, and 30%, respectively by bitter gourd [27]. Anti-inflammatory Activity Previously, a triterpene 5β, 19-epoxy-25- methoxy-cucurbita-6, 23-diene-3β 19-diol (EMCD), purified from M. charantia L. wild variant WB24, was found to activate AMP- activated protein kinase (AMPK) and have a hypoglycaemic effect in TNF-α-treated FL83B cells. AMPK has been a target for developing antidiabetic medicine and suggested to play a role in anti-inflammation [34]. Consequently, the expression of inflammatory markers including inducible nitric oxide synthase (iNOS), the p65 subunit of nuclear factor-kβ (NF-kβ), protein-tyrosine phosphatase-1B, TNF-α and interleukin-1β were significantly elevated by TNF-α in the cell, and EMCD obviously suppressed the TNF-α-induced expression of these markers. When the effect of EMCD was tested simultaneously with epigallocatechin-3-gallate (EGCG)—a catechin from green tea reported to be anti- inflammatory—EMCD showed a more obvious anti-inflammatory activity than EGCG does [35]. Anticancer Activity MC extracts in cancer patients, in vitro studies indicate bitter melon fruit and seed extracts inhibit the growth of several cancer cell lines, including prostate adenocarcinoma [36], human colon cancer (Caco-2 cells) [37], and the highly metastatic breast cancer cell line MDA-MB-231 [38]. A research indicated that MC extracts modify the immune response in cancer patients via decreased intestinal secretion of interleukin-7, reduced lymphocyte number, and increased T- helper and natural killer cell populations [39]. The characterization of the compounds from bitter gourd and their inhibitory effects on the activation of Epstein-Barr virus early antigen (EBV-EA) by 12-O-tetradecanoylphorbol-13- acetate (TPA) in Raji cells by compounds 1-18 (MeOH extract) of M. charantia fruit. In addition, the other extracted compounds showed inhibitory effect on cancer; two-stage mouse skin carcinogenesis tests were reported [40]. It was reported that M. charantia fractions were also rich in different types of phenolic compounds that have strong antioxidant activity as well as perform as antimutagenic and antitumor compounds [41]. Momordin is another phytochemical that has clinically demonstrated anticancerous activity against Hodgkin’s lymphoma in vivo and several other in vivo studies have shown the cytostatic and antitumor activity of the entire plant of bitter melon [42]. Antihyperlipidemic Activity Five compounds in bitter melon increases the activity of adenosine-5-monophosphate kinase (AMPK)—an enzyme that facilitates cellular glucose uptake and fatty acid oxidation. Hypoglycaemic agents in bitter melon promotes efficient oxidation of glucose into fuel, and conversion into starch [17]. The compounds in bitter melon improves lipid profile and reduces liver secretion of apolipoprotein B (Apo B) and apolipoprotein C- III expression; and increases the expression of apolipoprotein A-1 (ApoA1) and hence increase the HDL ratio. It also lowers cellular triglyceride content. In another in vivo study, bitter melon fruit and/or seed have been shown to reduce total cholesterol and triglyceride both in the presence and absence of dietary cholesterol. The fruit and seed of bitter melon have demonstrated (in animal studies) to lower blood cholesterol levels [19]. Hepatoprotective and Antioxidative Activity A carcinogen-induced lipid peroxidation in liver and DNA damage in lympocytes were studied by the treatment of M. charantia. The fruit extract was found to significantly activate liver enzymes glutathione S-transferase, glutathione peroxidase and catalase, which showed a depression following exposure to the carcinogen. The result suggested the preventive role of water soluble constituents of M.charantia fruit during carcinogenesis, which is mediated possibly by their modulatory effect on enzymes of biotransformation and detoxification system of host [10]. Semis et al. reported antioxidants and chemoprotective action of M. charantia fruit extracts [43].
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A Journal of Biotechnology Volume 7, Issue 1 ISSN: 2231-3826 (Online), ISSN: 2347-7245 (Print) RRJoBT (2017) 1-13 © STM Journals 2017. All Rights Reserved Page 5 In vivo immunological responses oxidative stress of M. charantia plant extract on rats showed decrease in the intestinal secretion of Interleukin (IL)-7 and an increase in the secretion of transforming growth factor (TGF)-β and IL-10 and also inhibits the degenerative process of oxidative stress [44]. Antifertility Effect Bitter melon seeds contain momorcharin, shown to have antifertility effects in female mice. Bitter melon seed consumption is not recommended in those seeking to become pregnant [45]. Other studies showed ethanol and water extracts of the fruit and leaf (ingested orally) to be safe during pregnancy. The seeds, however, have demonstrated the ability to induce abortions in rats and mice, and the root has been documented with a uterine stimulant effect in animals. The fruit and leaf of bitter melon has demonstrated an in vivo antifertility effect in female animals; in male animals, it was reported to affect the production of sperm negatively. This plant has been documented to reduce fertility in both males and females and should therefore not be used by those undergoing fertility treatment or seeking pregnancy [46]. Antiviral and Anti HIV Studies The extract of M. charantia contain α and β momorcharin, lecithin and MAP30. They have been documented to have in vitro antiviral activity against Epstein barr, herpes, HIV [47], Coxsackie virus B3 and polio viruses [48]. In vitro studies have shown that bitter melon extracts and the MAP30 protein analog— isolated from the seeds of bitter gourd extracts—possess broad-spectrum antimicrobial activity; also inhibit the infection and growth of several viruses, including HIV [44, 49, 50], Herpes simplex [51, 52]. A preliminary report on the effect of MC extract in three HIV patients showed a normalization of CD4/CD8 ratios with MC treatment. It is believed that MC extracts inhibit HIV replication by preventing syncytial formation and cell-to-cell infection [53]. Another study explained that HIV-infected cells treated with alpha- and beta-momorcharin showed a nearly complete loss of viral antigen while healthy cells were largely unaffected. “In treating HIV infections the protein is administered alone or in conjunction with conventional AIDS therapies” stated by inventors of MAP-30 protein analog in U.S. Patent. The proteins (alpha and beta momorcharin) appeared to modulate the activity of both T and B lymphocytes and significantly suppressed the macrophage activity [54]. Bitter melon has also been suggested as a treatment for AIDS, but the evidence thus far is too weak to even mention. Laboratory tests suggest that compounds in bitter melon might be effective for treating HIV infection. As most compounds isolated from bitter melon that impact HIV have either been proteins or glycoproteins (lectins), neither of which are well-absorbed, it is unlikely that oral intake of bitter melon will slow HIV in infected people. Clearly more research is necessary before this could be recommended. Antimicrobial and Antiprotozoal Activities MC extracts also appear to inhibit the growth of numerous gram-negative and gram-positive bacteria, including Escherichia coli, Salmonella, Shigella [55], Staphylococcus, Pseudomonas, Streptococcus, and Helicobacter pylori, and parasitic organisms Entamoeba histolytica and Plasmodium falciparum [56]. M. charantia leaves have been shown to have antiprotozoal activity against Trypanosoma brucei brucei and Trypanosoma cruzi [57]. Antimicrobial activity was evaluated for Pseudomonas aeruginosa, E. coli, Klebsiella pneumoniae and Bacillus subtilis by using stokes disc diffusion and well diffusion methods. Methanolic plant extract showed a maximum zone of inhibition in E.coli by disc method but in well diffusion method Bacilli and Klebsiella showed maximum inhibitory activity. The evaluation of antimicrobial efficacy and antioxidant activity of methanol and aqueous extract of M. charantia was carried out, which helps in the development of new, novel drugs [58]. It was clinically demonstrated that broad spectrum antimicrobial activity of leaf extracts of bitter gourd, have reported in vitro antibacterial activities of water, ethanol, and methanol against E. coli, Staphylococcus, Pseudomonas, Salmonella, Streptobacillus and Streptococcus. An extract of the entire plant
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charantia) Parray et al. RRJoBT (2017) 1-13 © STM Journals 2017. All Rights Reserved Page 6 have shown antiprotozoal activity against E. histolytica [59]. In another study, a fruit extract of Karela has demonstrated antibacterial activity against the stomach ulcer-causing bacteria H. pylori [60]. Antimalarial and Leishmaniasis Activity According to the research findings of Waako et al., M. charantia has antimalarial activity and can thus be used in the prevention and treatment of malaria. Other findings on crude extracts of M. charantia showed significant antiplasmodial activity [61, 62]. However, the findings by Temitope et al., had shown that M. charantia cause a significant decrease in mean haemoglobin concentration in test animals [63]. In view of the above studies, the use of M. charantia as a therapy for malaria could come with a serious consequence, because a decrease in haemoglobin concentration in already-anaemic and malaria-infected patients will be aggregated. In this aspect, future investigations should be done for clear findings and conclusion. Aqueous extract of the green fruits of the Indian plant M. charantia and purified Momordicatin structurally established as 4-(o- carboethoxyphenyl) butanol were evaluated in vitro and in vivo against kalaazar caused by Leishmania donovani. 50% inhibitory concentration (IC50) against Leishmania promastigotes in vitro for the crude extract and Momordicatin were 0.6 mg/L and 0.02 mg/L, respectively. When administered in the hamster model of visceral leishmaniasis, 100% parasite clearance was achieved at a dose of 300 mg/kg body weight of crude extract and 10 mg/kg body weight of Momordicatin [64]. Wound Healing Activity Researchers found that M. charantia Linn. fruit powder, in the form of an ointment (10% w/w dried powder in simple ointment base), showed a statistically significant response (P < 0.01), in terms of wound contracting ability, wound closure time, period of mepithelization, tensile strength of the wound and regeneration of tissues at wound site when compared with the control group. These results were comparable with standard drug povidone iodine ointment in an excision, incision and dead space wound model in rats [59, 65]. BITTER GOURD IN THE FIELD OF BIOTECHNOLOGY Biotechnology is a very broad field of biology including plant biotechnology, plant genetics, recombinant DNA technology, microbiology, immunology, molecular biology, molecular genetics and supplementary subjects associated within the subject all are reliant of each other. Bitter gourd is a highly potent herb, applied in the field of medical as well as biotechnology. Bitter gourd serve as a potential source of a functional protein isolate as its seeds are rich in protein sources. Soy protein isolates (SPI) and bitter melon seed protein isolate (BMSPI) are high quality protein because of presence of most essential amino acids isolated. The functionalities of these proteins were known that they comprise emulsifying properties and foaming properties [66]. Moreover, the high expression of permeability-glycoproteins, P-gp (ATP- binding cassette [ABC] transporter super family), was observed which flushes out hydrophobic drugs from a cell by using energy obtained by hydrolyzing ATP in the cell membrane of tumor cells. Higher intracellular P-gp concentration will lower the intracellular drug concentration. M. charantia active compounds such as 1-monopalmitin and its related compounds inhibit the P-gp activity in the tumor cells [20, 21, 67–69]. In addition, it has been seen that M. charantia decreased the genotoxic activity of methylnitrosamine, methanesulfonate and tetracycline, as shown by the decrease in chromosome breakage [70]. Already mentioned regarding polypeptide –p or p-insulin is an insulin-like hypoglycaemic protein, shown to lower blood glucose levels in gerbils, langurs and humans when injected subcutaneously [71]. The p-insulin works by mimicking the action of human insulin in the body and thus may be used as plant-based insulin replacement in patients with type-1 diabetes [72]. The research on nanoparticles in a number of crops has evidenced for enhanced germination and seedling growth, physiological activities including photosynthetic activity and nitrogen metabolism, mRNA expression and protein level, and also positive changes in gene expression indicating their potential use in crop improvement. Nanobiotechnology can boost crop production and quality of plant fruit
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A Journal of Biotechnology Volume 7, Issue 1 ISSN: 2231-3826 (Online), ISSN: 2347-7245 (Print) RRJoBT (2017) 1-13 © STM Journals 2017. All Rights Reserved Page 7 and the first evidence from increased plant biomass, fruit yield and phytomedicine content in bitter melon (M. charantia) was observed [73]. Bitter melon was studied as a model to evaluate the effects of seed treatment with a carbon-based nanoparticle, fullerol [C60(OH)20], on yield of plant biomass, fruit characters and phytomedicine contents in fruits. Fullerol-treatment resulted in increase of up to 54% in biomass yield and 24% in water content. Increases of up to 20% in fruit length, 59% in fruit number, and 70% in fruit weight led to an improvement up to 128% in fruit yield. Contents of two anticancer phytomedicines—cucurbitacin-B and lycopene—were enhanced up to 74% and 82%, respectively; contents of two antidiabetic phytomedicines— charantin and insulin— were augmented up to 20% and 91%, respectively [73]. Two comprehensive reviews have presented evaluation of a variety of nanomaterials (NMs), mostly metal-based (MBNMs) and carbon-based (CBNMs), for their absorption, translocation, accumulation, and importantly, effects on growth and development in an array of crop plants [74, 75]. Hence, demonstration of any increase of its fruit yield and/or phytomedicine content through nanobiotechnological intervention could be useful to follow as a model for other crops. Production of higher plant biomass as a feedstock for bioenergy production has recently emerged as an important target in agriculture [76]. GENETIC ENGINEERING OF BITTER GOURD Genetic engineering can be used to produce desirable agronomic characteristics quickly and efficiently. Most plant transformation procedures require a plant regeneration system for efficient gene transfer, selection, and regeneration of transgenic plants [77]. M. charantia has shown the efficient regeneration protocol for direct organogenesis [78, 79] and somatic embryogenesis [80, 81]. Gene transfer studies in cucurbits such as Cucumis melo [82, 83], Crocus sativus [84, 85] and Colocynthis citrullus [86] have been reported. Agrobacterium-mediated β-glucuronidase expression was detected in explants of immature cotyledonary nodes in M. charantia [87]. Recently tumor research centre has reported Agrobacterium-mediated genetic transformation from cotyledonary nodes of bitter melon. For genetic transformation of bitter melon, it is necessary to established stable plant regeneration protocol from leaf explants of M. charantia via organogenesis [88]. An efficient and a simple protocol for Agrobacterium tumefaciens-mediated genetic transformation of bitter melon using leaf disc as explants had been developed. This optimized transformation system could be used for the genetic improvement of bitter melon [80]. M. charantia has been used as an alternative therapy for diabetes mellitus as described above. The study was analyzed and elucidated that therapeutic targets contributing to the hypoglycaemic effect of aqueous extract of MC seeds (MCSE) by transcriptomic analysis. Protein ingredients aimed at the hypoglycaemic target were further identified by proteomic, docking, and receptor binding assays. The data showed that MSCE (1 g/kg) significantly lowered the blood glucose level in normal and diabetic mice. Moreover, MCSE primarily regulated the insulin signaling pathway in muscles and adipose tissues, suggesting that MCSE might target insulin receptor (IR), stimulate the IR-downstream pathway, and subsequently display hypoglycaemic activity in mice [89]. RNA-degrading enzymes, better known as ribonucleases (RNases), have been studied in eukaryotic cells for many years. According to Farkas [90] and Wilson [91] plant ribonucleases were studied actively before the 1980s. S-glycoproteins, now called S-RNases, are secreted into the style mucilage where they are thought to abort the growth of pollen bearing the same S-allele [92–94]. Interest began to wane subsequently because little correlation was found between total RNase activity and RNA content in most plant samples and because experiments to determine the function of individual enzymes were not feasible at the time. RNase MC is from the seeds of the bitter gourd M. charantia [94], which is also self-compatible in addition was recently crystallized [95]. RNase LE and LX, isolated from cultured cells of Lycopersicon esculentum [96, 97] and RNase MC are all S- like RNases because they exhibit sequence homology to the S- and the fungal T2-type
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Bitter Gourd (Momordica
charantia) Parray et al. RRJoBT (2017) 1-13 © STM Journals 2017. All Rights Reserved Page 8 RNases [98]. Those plant products which possess ribonucleases (RNases) are promising drugs for different cancers based on their concrete antitumor activities in vitro and in vivo. The first time purification and characterization of a 14-kDa RNase, designated as RNase MC2, in the seeds of bitter gourd (M. charantia) was carried out [99]. RNase MC2 manifested potent RNA- cleavage activity toward baker’s yeast tRNA, tumor cell rRNA, and an absolute specificity for uridine. RNase MC2 demonstrated both cytostatic and cytotoxic activities against MCF-7 breast cancer cells. Treatment of MCF-7 cells with RNase MC2 caused nuclear damage (karyorrhexis, chromatin condensation, and DNA fragmentation), ultimately resulting in early/late apoptosis. Further molecular studies unveiled that RNase MC2 induced differential activation of MAPKs and Akt. On the other hand, RNase MC2 exposure activated caspase-8, caspase-9, and caspase-7, increased the production of Bak and cleaved PARP, which in turn contributed to the apoptotic response. In conclusion, RNase MC2 is a potential agent which can be exploited in the worldwide fight against breast cancer [99]. RAPD markers have been used to analyze the genetic diversity among 12 different accessions of M. charantia, collected from different districts of West Bengal, India. The presence of SCAR markers in the two varieties of M. charantia namely var. muricata and var. charantia has been determined so that nutritional and medicinal properties could be exploited judiciously [72]. Molecular markers such as RAPD and SCAR could be used to explore the genes associated with medicinal properties of M. charantia. Genetic diversity among populations can be determined using molecular markers. Different types of molecular markers which has been used to assess the genetic diversity of M. charantia are mentioned [72], RAPD markers have been used extensively in bitter gourd to classify accessions identify cultivars and analyze genetic diversity. Changyuan et al. (2005) have employed RAPD markers in order to detect genetic relationship in 45 bitter gourd cultivars, collected from different parts of South East Asia [100]. Infact, recently, Wang et al. had cloned and expressed the 498 bp gene sequence coding for the M. charantia polypeptide p-gene and have also proved that it has the hypoglycaemic effect of the recombinant polypeptide in alloxan-induced diabetic mice [101]. CONCLUSION Medicinal plants based on TSM are playing imperative role in providing healthcare to large section of population, especially in developing countries. M. charantia have been providing many remedies for different diseases from ancient days to nowadays. It has been used in various TSM for the treatment of diverse pathological conditions and diseases. The main aim of this review was to provide the link between TSM (especially with reference to Ayurveda and Unani) and biotechnology with respect to this fruit/vegetable. The contribution of the fruit in crop improvement, biomass of plant, medicinal uses, and a lead for new drug discoveries will be more widespread and improve their effectiveness against diseases when biotechnology and genetic engineering will be there. There are still some qualities in it which are unwrapped and can be surveyed and incessantly, and the surprises conceal in the fruit will be materialized. REFERENCES 1. Gupta M, Sharma S, Gautam AK, et al. Momordica charantia linn. (karela): nature’s silent healer. Int J Pharmal Sci Rev Res. 2011; 11: 32–7p. 2. Kirtikar KR, Basu BD. Indian medicinal plant. Dehra Dun, India: Bishen Singh Mahendra Pal Singh; 1987. 3. Ghani N. Khazainul Advia. New Delhi: Idara Kitabul Shifa YNM; 2014. 4. Kabiruddin M. Makhzan ul Mufradat. New Delhi: Idara Kitabul Shifa; 2007. 5. Chandarshekar B, Mukherjee B, Mukerjee SK. Blood sugar lowering potentiality of selected Cucurbitaceae plants of Indian origin. Ind J Med Res. 1989; 90: 300–5p. 6. Vaidyaratnam PS, Varier S. Indian Medicinal Plants: A Compendium of 500 Species. Madras, India: Orient Longman Ltd.; 1994. 7. Meena AK, Bansal P, Kumar S. Plants- herbal wealth as a potential source of
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A Journal of Biotechnology Volume 7, Issue 1 ISSN: 2231-3826 (Online), ISSN: 2347-7245 (Print) RRJoBT (2017) 1-13 © STM Journals 2017. All Rights Reserved Page 9 ayurvedic drugs. Asian Journal of Traditional Medicines. 2009; 4: 152–70p. 8. Nadkarni KM. Indian Materia Medica. India: Popular Prakashan; 1993. 9. Duke JA. Handbook of Medicinal Herbs. Boca Raton FL: CRC Press; 1985. 10. Kumar DS, Sharathnath KV, Yogeswaran P, et al. A medicinal potency of momordica charantia. Int J Pharma Sci Rev Res. 2010; 1: 95–100p. 11. Ahmad N, Hasan N, Ahmad Z, et al. Momordica charantia: for traditional uses and pharmacological actions. Journal of Drug Delivery & Therapeutics. 2016; 6(2): 40–4p. 12. Altinterim B. Bitter Melon (Momordica charantia) and the Effects of Diabetes Disease. J Agriculture Faculty of Uludag University. 2012; 26: 65–9p. 13. Raman A, Lau C. Anti-diabetic properties and phytochemistry of Momordica charantia L. (Cucurbitaceae). Phytomedicine. 1996; 2: 349–62p. 14. Basch E, Gabardi S, Ulbricht C. Bitter melon (Momordica charantia): a review of efficacy and safety. Am J Health Syst Pharm. 2003; 60: 356–9p. 15. Sarkar S, Pranava M, Marita R. Demonstration of the hypoglycemioc action of Momordica charantia in a validate animal model of diabetes. Pharmacol Res. 1996; 33: 1–4p. 16. Grover JK, Yadav SP. Pharmacological actions and potential uses of Momordica charantia; a review. J Ethanopharmacol. 2004; 93: 123–32p. 17. Yadav UCS, Moorthy K, Baquer NZ. Combined treatment of sodium orthovanadate and Momordica charantia fruit extract prevents alterations in lipid profile and lipogenic enzymes in alloxan diabetic rats. Mol Cell Biochem. 2005; 268: 111–20p. 18. Ambasta SP. The useful plants of India, publications and information directorate. New Delhi, India: Publication & Information Directorate, CSIR; 1986. 19. Nerurkar PV, Pearson L, Efird JT, et al. Microsomal Triglyceride Transfer Protein Gene Expression and ApoB Secretion are Inhibited by Bitter Melon in HepG2 Cells. J Nutr. 2005; 135: 702–6p. 20. Beloin N, Gbeassor M, Akpagana K, et al. Ethnomedicinal uses of Momordica charantia (Cucurbitaceae) in Togo and relation to its phytochemistry and biological activity. A Rev J Ethnopharmacol. 2005; 96: 49–55p. 21. Ng TB, Chan WY, Yeung HW. Proteins with abortifacient, ribosome inactivating, immunomodulatory, antitumor and anti- AIDS activities from Cucurbitaceae plants. Gen Pharmacol. 1992; 23: 579– 90p. 22. Cummings E, Hundal H, Wackerhage H, et al. Momordica charantia fruit juice stimulates glucose and amino acid uptakes in L6 myotubes. Mol Cell Biochem. 2004; 261: 99–104p. 23. Oishi Y, Sakamoto T, Udagawa H, et al. Inhibition of increases in blood glucose and serum neutral fat by Momordica charantia saponin fraction. Biosci Biotechnol Biochem. 2007; 71: 735–40p. 24. [24] Chaturvedi P, George S, Milinganyo M, et al. Effect of Momordica charantia on lipid profile and oral glucose tolerance in diabetic rats. Phytother Res. 2004; 18: 954–6p. 25. Ahmed I, Lakhani MS, Gillett M, et al. Hypotriglyceridemic and hypocholesterolemic effects of anti- diabetic Momordica charantia (karela) fruit extract in streptozotocin-induced diabetic rats. Diabetes Res Clin Pract. 2001; 51: 155–61p. 26. Trowell HC. Dietary fibre hypothesis of the etiology of diabetes mellitus. Diabetes. 1975; 24: 762–5p. 27. Shetty AK, Kumar GS, Sambaiah KK, et al. Effect of bitter gourd (Momordica charantia) on glycaemic status in streptozotocin induced diabetic rats. Plant Foods Hum Nutr. 2005; 60: 109–12p. 28. Day C. Hypoglycaemic compounds from plants. In: Bailey CJ, Flatt PR (Eds.). New Antidiabetic Drugs. Japan: Nishimura Publication Ltd,; 1990. 267–78p. 29. Ahmed I, Adeghate E, Sharma AK, et al. Effects of Momordica charantia fruit juice on islet morphology in the pancreas of the streptozotocin-diabetic rat. Diabetes Research and Clinical Practice. 1998; 40: 145–51p.
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