Nuclear factor kappa B (NF-κB) refers to a group of five structurally related and conserved proteins in mammals including RelA/p65, Rel/cRel, RelB, NF-κB 1/p50, and NF-κB 2/p52. A major regulation of NF-κB activity is through the control of NF-κΒ migration between nucleus and cytoplasm. Deregulation of NF-κB activation pathway at any stage results in continuous NF-κΒ activation and chronic inflammation and eventually cancer. By trapping NF-kB in cytoplasm, IkB prevents NF-kB/deoxyribonucleic acid complex formation in the nucleus. A chronic inflammation is related to the integral activation of NF-κB because of an imbalance in inflammatory signaling network including defective anti-inflammatory mechanism and tenacious infection with pathogens. Chronic inflammation results in terminal damage to blood vessels, cells, and organs causing multiple health problems such as diabetes, cancers, asthma, cardiovascular diseases, psoriasis, and neurodegenerative diseases as well as joint pains. A number of small molecules from natural resources including fruits, vegetables, and animals could inhibit or prevent chronic inflammation and its related ailments.
Oral-systemic link has been termed Periodontal Medicine. Significance: Periodontal disease is preventable and readily treatable, thus providing many new opportunities for preventing and improving several systemic diseases.
FOCAL INFECTION: Localized or Generalized infection caused by dissemination of microorganisms or toxic products from focus of infection.
FOCUS OF INFECTION Confined area that
(1) contains pathogenic microorganisms
(2) can occur anywhere in body
Diseases/Conditions affected by periodontitis
A PREGNANCY, PREECLAMPSIA
B ISCHEMIC HEART DISEASES, STROKE
C DIABETES MELLITUS
D PNEUMONIA, COPD
E OSTEOPOROSIS
F CANCER
G ALZHEIMER’S DISEASE
H. RHEUMATOID ARTHRITIS
Oral-systemic link has been termed Periodontal Medicine. Significance: Periodontal disease is preventable and readily treatable, thus providing many new opportunities for preventing and improving several systemic diseases.
FOCAL INFECTION: Localized or Generalized infection caused by dissemination of microorganisms or toxic products from focus of infection.
FOCUS OF INFECTION Confined area that
(1) contains pathogenic microorganisms
(2) can occur anywhere in body
Diseases/Conditions affected by periodontitis
A PREGNANCY, PREECLAMPSIA
B ISCHEMIC HEART DISEASES, STROKE
C DIABETES MELLITUS
D PNEUMONIA, COPD
E OSTEOPOROSIS
F CANCER
G ALZHEIMER’S DISEASE
H. RHEUMATOID ARTHRITIS
Stress response caused by events such as surgical trauma includes endocrine, metabolic and immunological changes. Stress hormones and cytokines play a role in these reactions. More reactions are induced by greater stress, ultimately leading to greater catabolic effects. Cuthbertson reported the characteristic response that occurs in trauma patients: protein and fat consumption and protection of body fluids and electrolytes because of hypermetabolism in the early period. The oxygen and energy requirement increases in proportion to the severity of trauma. The awareness of alterations in amino acid, lipid, and carbohydrate metabolism changes in surgical patients is important in determining metabolic and nutritional support. The main metabolic change in response to injury that leads to a series of reactions is the reduction of the normal anabolic effect of insulin, i.e. the development of insulin resistance. Free fatty acids are primary sources of energy after trauma. Triglycerides meet 50 to 80 % of the consumed energy after trauma and in critical illness. Surgical stress and trauma result in a reduction in protein synthesis and moderate protein degradation. Severe trauma, burns and sepsis result in increased protein degradation. The aim of glucose administration to surgical patients during fasting is to reduce proteolysis and to prevent loss of muscle mass. In major stress such as sepsis and trauma, it is important both to reduce the catabolic response that is the key to faster healing after surgery and to obtain a balanced metabolism in the shortest possible time with minimum loss. For these reasons, the details of metabolic response to trauma should be known in managing these situations and patients should be treated accordingly
RECENT ADVANCES IN THE MANAGEMENT OF INFLAMMATORY BOWEL DISEASEPARUL UNIVERSITY
Medical treatment for inflammatory bowel disease (IBD) has progressed significantly over the past decade to achieve and maintain clinical remission in patients & to overcome the side effects of existing drugs for IBD. Conventional therapy for IBD include the use of Amino salicylates, corticosteroids & Anti-microbials. Patients who fail to respond to the conventional therapy are treated with agents such as Calcineurin inhibitor (Cyclosporine), and Biologics like TNF-α inhibitors (Infliximab or Adalimumab) or Anti-cell adhesion molecules (Vedolizumab, natalizumab). These agents are targeted against pro-inflammatory cytokines such as Tumor Necrosis Factor-α (TNF-α), Interleukin-2 (IL-2) and Cell Surface Adhesion Molecules Integrin α4β7. In this review, we provide an overview on the recent advances in the treatment for IBD such as newer Biologics, Small Molecule drugs and Biosimilars effective for IBD and the role of other therapies like Probiotics, Prebiotics, Stem cell transplant and Faecal microbiota transplant and Microbiome targeting diet in the management of IBD
The imbalance between free radical production and endogenous antioxidant defence may result in cellular oxidative stress, causing oxidative damage to various cellular components, such as DNA, proteins and membrane lipids. The human system employs the use of endogenous enzymatic and non-enzymatic antioxidant defence systems against the onslaught of free radicals and oxidative stress.
Unsurprisingly, oxidative damage has been implicated in and is believed to be a key factor causing various pathological conditions, such as cardiovascular disease, neurodegenerative disease, diabetes and cancer. Free radicals can be quenched through a number of mechanisms. Antioxidants directly scavenge free radicals (e.g., via hydrogen atom transfer or electron transfer), prevent free radical formation by chelating metal ions and by interrupting the radical chain reactions of lipid peroxidation, thus retarding its progression. Enzymatic antioxidants include superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. Non-enzymatic antioxidants include vitamins A, C, and E, glutathione, alpha-lipoic acid, carotenoids, and coenzyme Q10. Other antioxidants include polyphenols, minerals (copper, zinc, manganese, and selenium), and cofactors (B-vitamins). Together, antioxidants work synergistically with each other using different mechanisms against different free radicals and stages of oxidative stress.
The benefits associated with antioxidants are numerous and diverse but it can be a minefield when choosing the appropriate antioxidant support for clients. In this hour-long webinar, Dr Nina Bailey discusses the direct and indirect benefits and actions of key antioxidants including (but not limited to) astaxanthin, alpha lipoic acid, polyphenols and co-enzyme Q10, with a focus on:
-Antioxidant sources and benefits
-Mechanisms and actions
-When to combine antioxidants for synergistic effects
-Overcoming bioavailability issues
-Targeted intervention, which antioxidant(s) and why
Stress response caused by events such as surgical trauma includes endocrine, metabolic and immunological changes. Stress hormones and cytokines play a role in these reactions. More reactions are induced by greater stress, ultimately leading to greater catabolic effects. Cuthbertson reported the characteristic response that occurs in trauma patients: protein and fat consumption and protection of body fluids and electrolytes because of hypermetabolism in the early period. The oxygen and energy requirement increases in proportion to the severity of trauma. The awareness of alterations in amino acid, lipid, and carbohydrate metabolism changes in surgical patients is important in determining metabolic and nutritional support. The main metabolic change in response to injury that leads to a series of reactions is the reduction of the normal anabolic effect of insulin, i.e. the development of insulin resistance. Free fatty acids are primary sources of energy after trauma. Triglycerides meet 50 to 80 % of the consumed energy after trauma and in critical illness. Surgical stress and trauma result in a reduction in protein synthesis and moderate protein degradation. Severe trauma, burns and sepsis result in increased protein degradation. The aim of glucose administration to surgical patients during fasting is to reduce proteolysis and to prevent loss of muscle mass. In major stress such as sepsis and trauma, it is important both to reduce the catabolic response that is the key to faster healing after surgery and to obtain a balanced metabolism in the shortest possible time with minimum loss. For these reasons, the details of metabolic response to trauma should be known in managing these situations and patients should be treated accordingly
Similar to Chronic Inflammation: Prospective Prevention and/or Control by the Regulation of Nuclear Factor Kappa B with Natural Products as Dietary Supplements
RECENT ADVANCES IN THE MANAGEMENT OF INFLAMMATORY BOWEL DISEASEPARUL UNIVERSITY
Medical treatment for inflammatory bowel disease (IBD) has progressed significantly over the past decade to achieve and maintain clinical remission in patients & to overcome the side effects of existing drugs for IBD. Conventional therapy for IBD include the use of Amino salicylates, corticosteroids & Anti-microbials. Patients who fail to respond to the conventional therapy are treated with agents such as Calcineurin inhibitor (Cyclosporine), and Biologics like TNF-α inhibitors (Infliximab or Adalimumab) or Anti-cell adhesion molecules (Vedolizumab, natalizumab). These agents are targeted against pro-inflammatory cytokines such as Tumor Necrosis Factor-α (TNF-α), Interleukin-2 (IL-2) and Cell Surface Adhesion Molecules Integrin α4β7. In this review, we provide an overview on the recent advances in the treatment for IBD such as newer Biologics, Small Molecule drugs and Biosimilars effective for IBD and the role of other therapies like Probiotics, Prebiotics, Stem cell transplant and Faecal microbiota transplant and Microbiome targeting diet in the management of IBD
The imbalance between free radical production and endogenous antioxidant defence may result in cellular oxidative stress, causing oxidative damage to various cellular components, such as DNA, proteins and membrane lipids. The human system employs the use of endogenous enzymatic and non-enzymatic antioxidant defence systems against the onslaught of free radicals and oxidative stress.
Unsurprisingly, oxidative damage has been implicated in and is believed to be a key factor causing various pathological conditions, such as cardiovascular disease, neurodegenerative disease, diabetes and cancer. Free radicals can be quenched through a number of mechanisms. Antioxidants directly scavenge free radicals (e.g., via hydrogen atom transfer or electron transfer), prevent free radical formation by chelating metal ions and by interrupting the radical chain reactions of lipid peroxidation, thus retarding its progression. Enzymatic antioxidants include superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. Non-enzymatic antioxidants include vitamins A, C, and E, glutathione, alpha-lipoic acid, carotenoids, and coenzyme Q10. Other antioxidants include polyphenols, minerals (copper, zinc, manganese, and selenium), and cofactors (B-vitamins). Together, antioxidants work synergistically with each other using different mechanisms against different free radicals and stages of oxidative stress.
The benefits associated with antioxidants are numerous and diverse but it can be a minefield when choosing the appropriate antioxidant support for clients. In this hour-long webinar, Dr Nina Bailey discusses the direct and indirect benefits and actions of key antioxidants including (but not limited to) astaxanthin, alpha lipoic acid, polyphenols and co-enzyme Q10, with a focus on:
-Antioxidant sources and benefits
-Mechanisms and actions
-When to combine antioxidants for synergistic effects
-Overcoming bioavailability issues
-Targeted intervention, which antioxidant(s) and why
Dr William Barnes - The I Factor - Inflammation, Immunity, IllnessDr William Barnes
Immunity and Inflammation
Inflammation and Macrophages
Macrophage Pathology
Foam Cell, Viruses, TAMs
The Brune Theory & Nitric Oxide
Macrophages in Disease States
Treatment Strategies
Colds and Influenza
Treatment Strategies
In the UK, rates of obesity have increased by 30% in women, 40% in men, and 50% in children within the last decade resulting in over 25% of adults classified as obese today.
Obesity, in particular central obesity, is the dominant risk factor for insulin resistance, metabolic syndrome and type II diabetes. Evidence supporting obesity as an inflammation condition continues to grow and this is directly linked to the development of insulin resistance.
This webinar discusses novel approaches for the treatment and prevention of the common morbidities associated with obesity, specifically insulin resistance and type II diabetes, through targeting obesity-induced inflammatory processes.
Type 1 Diabetes (T1D), is a severe disease, representing 5-10% of all reported cases of diabetes worldwide. Fulminant Type 1 Diabetes Mellitus (FT1D) is a subtype of type 1 diabetes mellitus that is largely characterized by the abrupt onset of Diabetic Ketoacidosis (DKA) and severe hyperglycemia without insulin defi ciency. Viral infections have been hypothesized to play a major role in the pathogenesis of Fulminant Type 1 Diabetes Mellitus (FT1D) through the complete and rapid destruction of pancreatic beta cells. Coxsackie viral infection has been detected in islets of 50% of the pancreatic tissue recovered from recent-onset Type 1 Diabetes (T1D) patients. In this report we have highlighted a case where the patient developed a Group B Coxsackie virus infection culminating in the development of Fulminant Type 1 Diabetes Mellitus (FT1D).
critical illness and metabolism ICRC 2012.pptxssuser6aa7a3
critical illnes and metablism
Similar to Chronic Inflammation: Prospective Prevention and/or Control by the Regulation of Nuclear Factor Kappa B with Natural Products as Dietary Supplements (20)
Convalescent Plasma and COVID-19: Ancient Therapy Re-emergedasclepiuspdfs
Convalescent plasma has again re-emerged as a therapy during coronavirus disease (COVID-19) outbreaks currently use as a prophylactic or an interventional treatment in infected patients. Convalescent plasma has been used in the 20th century confronting different infectious diseases where there was no other therapy available. Conceivably, this convalescent plasma therapy tends to be proving a game-changing treatment in some COVID-19 patients and could support treatment, in addition to the current interventions before other developed therapies are available for the population.
The Negative Clinical Consequences Due to the Lack of the Elaboration of a Sc...asclepiuspdfs
Until a few years ago, the immune system was considered as responsible for the only defense against microbial infections and other external agents. On the contrary, the immune cells have been proven to be linked not only through cell-cell contact but also by releasing proteins capable of influencing the immune-inflammatory response, the so-called cytokines or interleukins. Moreover, the cytokines have appeared to play not only immune activities but also metabolic and systemic effects influencing the overall biological systems, including the nervous, the endocrine, and the cardiovascular systems, by representing the main endogenous molecules responsible for the maintenance of the unity of the biological life. Therefore, only the systematic clinical consideration of cytokine effects may allow the generation of real future holistic medicine.
The great benefit of blood/blood constitutes therapy is the ability to provide transfusion support for patients with many unique hematologic conditions. For some patients, such as patients with sickle cell disease, thalassemia major, immune hemolytic anemia, anemia of kidney disease, and aplastic anemia may need for this consolidation extends throughout their life. By knowing the alteration mechanisms of these conditions, we can appreciate the stationary, urgency, and the value of the transfused red blood cell (RBC).
Decreasing or Increasing Role of Autologous Stem Cell Transplantation in Mult...asclepiuspdfs
During the past four decades, autologous stem cell transplantation (ASCT) has been the first choice and the standard option for the treatment of newly diagnosed patients with multiple myeloma. The introduction of new agents such as thalidomide, lenalidomide, and bortezomib has led to a clear improvement in basic approach and those agents became the standard of care in the induction phase; however, they were not able to play the role of ASCT in term of progression-free survival and overall survival. Debate continues about the best induction, consolidation, and maintenance taking into account the toxicities of these new agents. The new monoclonal antibody (anti CD38) starts to take its place in the induction setting and it seems to be a promising agent in the high-risk group. Until recently, ASCT is the standard treatment for newly diagnosed patients.
Comparison of the Hypocalcemic Effects of Erythropoietin and U-74389Gasclepiuspdfs
Aim: This study calculated the effects on serum calcium (Ca) levels, after treatment with either of two drugs: The erythropoietin (Epo) and the antioxidant lazaroid (L) drug U-74389G. The calculation was based on the results of two preliminary studies, each one of which estimated the certain influence, after the respective drug usage in an induced ischemia-reperfusion animal experiment. Materials and Methods: The two main experimental endpoints at which the serum Ca levels were evaluated were the 60th reperfusion min (for the Groups A, C, and E) and the 120th reperfusion min (for the Groups B, D, and F). Especially, the Groups A and B were processed without drugs, Groups C and D after Epo administration, whereas Groups E and F after the L administration. Results: The first preliminary study of Epo presented a non-significant hypocalcemic effect by 0.34% ± 0.68% (P = 0.6095). However, the second preliminary study of U-74389G presented a non-significant hypercalcemic effect by 0.14% ± 0.66% (P = 0.8245). These two studies were coevaluated since they came from the same experimental setting. The outcome of the coevaluation was that L is 2.3623042-fold (2.3482723–2.3764196) more hypercalcemic than Epo (P = 0.0000). Conclusions: The antioxidant capacities of U-74389G ascribe 2.3623042-fold more hypercalcemic effects than Epo (P = 0.0000).
The term refractory anemia (RA) may be confusing to those who are not hematologists. RA should be well defined because it means more than what it says. RA is defined as anemia that is not responsive to therapy except transfusion.[1] The term RA is used to rule out those types of anemia with a known cause such as anemia of systemic diseases (liver and kidney) and anemia of inflammation even though they are considered refractory to therapy.[2] RA with cellular or hypercellular bone marrow was formerly used to exclude aplastic anemia.
Management of Immunogenic Heparin-induced Thrombocytopeniaasclepiuspdfs
Immunogenic heparin-induced thrombocytopenia (HIT) is an immune response to heparin associated with significant morbidity and mortality in hospitalized patients if unidentified as soon as possible, due to thromboembolic complications involving both arterial and venous systems. Early diagnoses based on a comprehensive interpretation of clinical and laboratory information improve clinical outcomes. Management principles of strongly suspected HIT should not be delayed for laboratory result confirmation. Treatment strategies have been introduced including new, safe, and effective agents. This review summarizes the clinical therapeutic options for HIT addressing the use of parenteral direct thrombin inhibitors and indirect factor Xa inhibitors as well as the potential non-Vitamin K antagonist oral anticoagulants.
73-year-old woman without any pertinent history was admitted to the hospital due to remittent fever with erythema. She showed itching and linearly arranged erythema on the chest, back, and abdomen [Figure 1a and b]. As she had been taking daily cefditoren pivoxil for the 4 days before her admission, she was diagnosed as having drug-related scratch dermatitis, and the antibiotic treatment was stopped. Her fever remained. Laboratory data showed elevated levels of white blood cells (14,800/μl, normal range 4000–7000) and liver enzymes such as aspartate aminotransferase (AST) 138 IU/L (normal range 5–40), alanine aminotransferase 97 IU/L (normal range 5–35), and ferritin (17469.5 ng/mL, normal range 5–152).
Bone Marrow Histology is a Pathognomonic Clue to Each of the JAK2V617F, MPL,5...asclepiuspdfs
According to the World Health Organization and Clinical Laboratory Molecular and Pathological criteria bone marrow pathology in JAK2V617F mutated trilinear myeloproliferative neoplasm (MPN) patients essential thrombocythemia (ET) and polycythemia vera are indistinguishably featured by clustered medium to large pleomorphic megakaryocytes and increased cellularity (60–90%) due to increased erythropoiesis and megakaryopoiesis. MPL515 mutated ET is the second distinct clonal MPN characterized by thrombocythemia in a normocellular bone marrow showing clustered increased large to giant mature megakaryocytes with staghorn-like hyperlobulated nuclei. Calreticulin (CALR) mutated hypercellular thrombocythemia associated with prefibrotic megakaryocytic, granulocytic myeloproliferation (MGM) recently became the third distinct MPN featured by dense clusters of immature megakaryocytes with cloud-like nuclei. Bone marrow pathology in newly diagnosed MPN patients appears to be a pathognomonic clue for diagnostic differentiation between JAK2V617F mutated trilinear MPN, MPL515 normocellular thrombocythemia, and CALR thrombocythemia with MGM characteristics followed by secondary reticulin fibrosis. Their natural histories clearly differ featured by an increase of erythro/granulopoiesis and cellularity in JAK2V617F, decrease of erythropoiesis and cellularity in MPL515 and increase of dual megakaryo/granulopoiesis and cellularity in CALR mutated MPN.
Helicobacter pylori Frequency in Polycythemia Vera Patients without Dyspeptic...asclepiuspdfs
Introduction: In polycythemia vera (PV) patients, peptic ulcer and gastroduodenal erosions are more common than the general population, but there are insufficient data on the frequency of Helicobacter pylori (HP) and its role in etiopathogenesis. In this study, we aimed to compare the prevalence of HP infection in PV patients without dyspeptic complaints with a healthy control group without dyspeptic complaints. Materials and Methods: Fifty patients with PV without dyspeptic complaints and 50 controls without dyspeptic complaints were enrolled in this study after informed consent obtained. Stool samples of selected patients were analyzed using HP stool antigen test (True Line®). Results: There was surprisingly striking difference between HP prevalence in PV patients without dyspeptic complaints and asymptomatic healthy controls (64% vs. 2%) (P < 0.05). There was no significant relationship found between HP presence and age, gender, treatment modalities, complete blood count, positivity of JAK2 V617F, serum erythropoietin level, and splenomegaly in PV patients (P > 0.05). Conclusion: As the susceptibility of HP infections in PV patients are higher, it is recommended to have close surveillance of these patients by screening HP presence. In addition, when HP positivity is determined, the eradication of HP is essential to prevent possible future gastrointestinal lesions in patients with PV.
Lymphoma of the Tonsil in a Developing Communityasclepiuspdfs
The lymphoma of the tonsil is a rarity. Single case reports have appeared in countries as disparate as China, Greece, India, Japan, and Turkey. Therefore, this paper presents cases found in Nigeria among the Ibo ethnic group. The epidemiological comparisons are deemed to be worthy of documentation such as age ranges and sides of involvement.
Should Metformin Be Continued after Hospital Admission in Patients with Coron...asclepiuspdfs
Background: In most patients with diabetes, guidelines recommend discontinuation of oral anti-diabetic agents. Preliminary data suggest that pre-admission metformin use may have a mortality benefit in patients with coronavirus disease (COVID)-19 admitted to the hospital. Objective: The objective of the study was to review the impact of metformin on morbidity and mortality among hospitalized patients with COVID-19. Methods: Review of English literature by PUBMED search until November 10, 2020. Search terms included diabetes, COVID-19, metformin, retrospective studies, meta-analyses, pertinent reviews, pre-print articles, and consensus guidelines are reviewed.
Clinical Significance of Hypocalcemia in COVID-19asclepiuspdfs
Background: Preliminary data suggest that hypocalcemia is common among patients with COVID-19 admitted to the hospital. Objective: The objective of the study was to examine the clinical significance of hypocalcemia in the setting of COVID-19. Methods: Literature search (PubMed) until August 5, 2020. Search terms include hypocalcemia, COVID-19, mortality, and complications. Retrospective studies are reviewed due to a lack of randomized trials. Results: Prevalence of hypocalcemia among hospitalized patients with COVID-19 ranges from 62% to 78%, depending on the definition of hypocalcemia and patients’ characteristics. In most cases, hypocalcemia is mild to moderate biochemically. Hypocalcemia is a risk factor for hospitalization of patients with COVID-19. In already hospitalized patients, hypocalcemia is significantly associated with increase severity of COVID-19 and its complications, including multiorgan failure, acute respiratory distress syndrome, and death. Hypocalcemia is significantly correlated with inflammatory markers of COVID-19. Causes of hypocalcemia in COVID-19 patients are unclear, but Vitamin D deficiency may be a contributing factor. Conclusion: Hypocalcemia is common in hospitalized patients with COVID-19 and carries unfavorable outcomes. Further studies are needed to examine the causes of hypocalcemia in COVID-19 and to see whether normalization of circulating calcium levels improves prognosis.
Excess of Maternal Transmission of Type 2 Diabetes: Is there a Role of Bioche...asclepiuspdfs
Objective: An excess of maternal transmission of Type 2 diabetes (T2D) has been reported in some populations but not confirmed in other studies. Mitochondrial inheritance has been proposed to explain such excess. In the present paper, we have considered the presence of T2D in the mother and/or in the father in relation to the risk of T2D and to age at onset of the disease in the offspring. The distribution of two genetic polymorphisms involved in glucose metabolism in relation to the presence of T2D in the mother has been also considered. Materials and Methods: Two hundred and seventy-nine participants with T2D were studied in the population of Penne, a small rural town in the eastern side of central Italy. Adenosine deaminase locus 1 (ADA1) and phosphoglucomutase locus 1 (PGM1) phenotypes were determined by starch gel electrophoresis. Statistical analyses were carried out using commercial software (SPSS). Results: The proportion of patients from T2D mothers is much greater as compared to the proportion of the patients from T2D fathers (P < 0.0001). Age at onset of the disease in patients in whom one or both parents are T2D is lower as compared to other patients. The distribution of ADA1 and PGM1 phenotypes in participants with T2D depends on the presence of diabetes in the mother. Conclusions: About the transmission of T2D, our data confirm the high proportion of maternal T2D and show the role of two common biochemical polymorphisms involved in glucose metabolism.
The Effect of Demographic Data and Hemoglobin A 1c on Treatment Outcomes in P...asclepiuspdfs
Objective: Diabetes mellitus, the most common cause of non-traumatic foot amputations, is a life-threatening condition due to its high mortality and morbidity. In our study, we retrospectively evaluated our patients with diabetic foot syndrome in our clinic. Materials and Methods: The demographic data, duration of diabetes, Wagner classification, haemoglobin A 1c (HbA1c) levels, white blood cell, C-reactive protein sedimentation levels, hospital stay, and treatment results were evaluated retrospectively in 14 patients with diabetic foot between January 2017 and December 2018. Results: The mean age of the patients was 62.43 ± 7.7 years. Of the 14 patients, 3 were females and 11 were males. All 14 patients were type 2 diabetes mellitus. When diabetic foot Wagner classification was performed, 6 patients were evaluated as Wagner 2, five patients were Wagner 3, and three patients were evaluated as Wagner 4. Nine patients had complete amputation and 3 had vascular surgery. Conclusion: Although the level of HbA1c is below the target level, the risk of diabetic foot is increased when there is no adequate diabetes mellitus foot training. Inadequate diabetic patient education and hospitalization of patients after infection progress the amputation rate.
Self-efficacy Impact Adherence in Diabetes Mellitusasclepiuspdfs
The aim of the paper is to explore how self-efficacy (SE) is associated with adherence among adults with diabetes mellitus (DM). Methods: The search of electronic databases identified 564 records from 2007 to 2017 on SE and adherence from different perspectives and its effect on adults with DM. Discussions: SE increases the confidence in adults in their self-care behaviors. Non-adherence continues to be a significant barrier to SE. SE and adherence should be informed by an understanding of theoretical frameworks and the individual characteristics. Conclusion: Adherence is likely among adults with better SE to empower them to make valid decisions about their health. Interventions to improve SE should be tailored based on different types of non-adherence such as intentional and unintentional non-adherence. Implications: An intercollaborative professional practice approach is crucial to improve SE and adherence for sound judgment and valid decision-making.
Uncoiling the Tightening Obesity Spiralasclepiuspdfs
While an underweight prevalence was once more than twice that of obesity, now more people are obese than underweight. Obesity is one of the leading causes of preventable death in the world. There are an estimated 2,100,000,000 obese people worldwide and that number is forecast to grow to 51% of the world’s population by 2030. Escalating obesity-related disease costs threaten to bankrupt the world’s health-care systems.
Prevalence of Chronic Kidney disease in Patients with Metabolic Syndrome in S...asclepiuspdfs
Background and Objective: Chronic kidney disease (CKD) which is an increasingly important clinical and public health issue is associated with cardiovascular disease. Epidemiologic studies have also linked metabolic syndrome (MetS) with an increased risk of incident CKD. Therefore, the present study was designed retrospectively to find the prevalence and potential risk factors of CKD in patients with MetS in Saudi Arabia.
Management Of Hypoglycemia In Patients With Type 2 Diabetesasclepiuspdfs
Hypoglycemia is the rate-limiting step of intensive management in patients with diabetes. Lowering one’s A1C to a prescribed target is expected to mitigate one’s risk of developing long- and short-term diabetes-related complications. Several of the less expensive and commonly prescribed glucose lowering agents favored by practitioners result in weight gain, hypoglycemia, and even an increased risk of cardiovascular (CV) mortality. Although achieving a targeted A1C of <7 % is the standard of care, clinicians often fail to evaluate patients for glycemic variability which can increase oxidative stress driving long-term diabetes-related complications including CV death. The use of concentrated insulins and glucagon-like peptide-1 receptor agonists separately or in combination with each other reduces glycemic variability and one’s risk of hypoglycemia. Pharmaceutical agents which allow patients to safely achieve their targeted A1C without weight gain and hypoglycemia should be preferred in patients with type 2 diabetes.
Predictive and Preventive Care: Metabolic Diseasesasclepiuspdfs
South Asians have a very high incidence of ischemic heart disease and stroke. In addition, they also have a very high incidence of metabolic diseases such as prehypertension, hypertension, visceral obesity, metabolic syndrome, prediabetes, type-2 diabetes, and its clinical complications. Currently, there are over 75 million diabetic subjects in India and an equal number of prediabetics. Republic of China has taken over India as the diabetes capital of the world, with over 115 million diabetics. Modern medicine is disease focused and has failed to address the prevention of these chronic diseases. According to the reports from the United Nations (Millennium Development Goals [MDGs], the World Health Organization, Global Health Initiatives, and the non-communicable disease risk task force), obesity has increased by 2-fold and type-2 diabetes by 4-fold worldwide. Experts in this field predict that chances of meeting the MDGs set by the UN members of reducing the incidence of these diseases at 2025 to the level of 2020 are very little. Western medicine has failed to reduce or reverse the trend in the incidence of these diseases. We feel that an integrated approach to health care may be a better option, to reduce the disease burden in developing and resource-poor countries. Having said that, one cannot prevent something that one is not aware of, as such it is the need of the hour for us, to develop a robust predictive and preventive health-care platform. In an earlier article, we presented our views on reducing or reversing cardiometabolic diseases. There is great enthusiasm among the health-care providers and professional bodies that integration of emerging technologies will help develop personalized, precision medicine, as well as reduce the cost of health-care worldwide.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
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Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
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2. Vadapalli, et al.: Chronic Inflammation: Prospective Prevention and/or Control by the Regulation of Nuclear Factor Kappa B
with Natural Products as Dietary Supplements.
2 Journal of Community and Preventive Medicine • Vol 1 • Issue 1 • 2018
and ultimately attack cells and tissues of internal organs. In
general, chronic inflammation did not reveal any symptoms
but only could be detected by elevated C-reactive protein
levels (CRP).[1-3]
CHRONIC
INFLAMMATION‑ASSOCIATED
AILMENTS
Heart disease
In cardiovascular diseases, cholesterol gets deposited in the
blood vessel lining acting as an insult leading to systematic
inflammation, resulting in blockages and blood clots causing
heart attacks. Hence, people with chronic inflammation from
an autoimmune disorder might be at greater risk for heart
disease. In addition, bacteria from gum disease reached blood
vessels and heart causing inflammation that elevated the
chance of heart attack. The increased levels of some nuclear
factor kappa B (NF-κB) activators such as osteoprotegerin
were linked to cardiac disease-related mortalities.[4,5]
Diabetes
In diabetes, nuclear factor kappa-light-chain-enhancer of
activated beta cells (NF-κB) was activated by multiple pro-
inflammatory cytokines for normal survival and death of
β-cells. β-cells were destroyed with the activation of inducible
nitric oxide synthase (iNOS) gene expression and successive
formation of NO. Interleukin-1 β (IL-1β)-induced NF-κB
activation resulted in apoptosis of β-cells in the pancreas,
in type-1 diabetes, whereas, in type-2 diabetes, activated
NF-κB induced apoptosis and insulin resistance. NF-κB was
upregulated with interactions of advanced glycation end
products and their receptor advanced glycation end products.
Uninterrupted activation of NF-κB stimulated a systemic
inflammation, a contributory factor for the development of
multiple diabetic ailments such as diabetic cardiomyopathy,
retinopathy, nephropathy, and neuropathy, suggesting a need
for NF-κB-based therapeutic approach.[6]
Lung tissues
Chronic inflammation in lungs was associated with various
problems such as chronic obstructive pulmonary disease
(COPD) and asthma. Inflammation of the lungs resulted in
fluid accumulation, thereby narrowing the airways making
breathing arduous. COPD developed as a chronic and
significant inflammatory response to inhaled irritants. COPD
was a third most common cause of death in the United
States.[7,8]
Anger disorder and aggressive behavior
Individuals with high aggressive behavior displayed elevated
inflammatory cytokine levels and deregulated immune
responses including slower wound healing. Cytokines
produce sickness behaviors including reduced activity, food
intake, and social interaction together with increased sleep
and anhedonia. Higher levels of inflammatory markers
such as tumor necrosis factor alpha (TNF-α), CRP and IL-6
were found in people with intermittent explosive disorder
appeared to be related to the aggressive behavioral aspect in
humans. Increased NF-κB inflammatory signaling included
the elevated expression of pro-inflammatory cytokines.[9,10]
Bone health
Chronic inflammation was linked to increased bone loss and
lack of bone growth where cytokines in the blood interfered
with bone renovation, a process in which damaged old bones
were replaced with the new. In addition, inflammation in gut
decreased the absorption of nutrients such as calcium and
vitamin D which were essential to bone health.[11]
Cancer
When immune cells infiltrated the tumor in an inflammatory
response, tumor grows utilizing those immune cell nutrients
and oxygen instead of getting destroyed. Gene mutations
occurred as a result of chronic inflammatory response which
triggered the loss of proteins involved in deoxyribonucleic
acid (DNA) repair. Occasionally, chronic inflammation might
serve as a precursor to certain cancers associated with DNA
damage which could lead to cancer. People with chronic
inflammatory bowel diseases, ulcerative colitis, and Crohn’s
disease were at an increased risk of colon cancer.[12]
It has long been assumed that NF-κB signaling played
an important role in chronic inflammation-associated
malignancies and other inflammation-associated disorders
although genetic evidence for this hypothesis had been
lacking. However, recent studies suggested the vitality of
NF-κB activation in tumor cell survival, angiogenesis, and
metastatic potential. NF-κB activation of tumor-associated
leukocytes and macrophages, in particular, resulted in
tumorogenesis through the upregulation of tumor-promoting
pro-inflammatory proteins, emphasizing the importance of
NF-κB inhibitors as immunotherapeutic agents to reduce
or prevent chronic inflammation. Therefore, it was obvious
that NF-κB inhibitors might inhibit or prevent chronic
inflammation-related tumorogenesis as well as angiogenesis
and metastasis.[13,14]
CELLULAR MECHANISMS
OF NF-ΚB ASSOCIATED
INFLAMMATION
A number of inflammatory mechanisms occurred by the
activation of inflammatory factor, NF-κB, a protein complex
controlled transcription of DNA, cytokines production, and
cell survival. In addition, NF-κB was involved in cellular
responses to inflammation stimuli caused by cytokines,
heavy metals, ultraviolet irradiation free radicles, bacterial
3. Vadapalli, et al.: Chronic Inflammation: Prospective Prevention and/or Control by the Regulation of Nuclear Factor Kappa B
with Natural Products as Dietary Supplements.
Journal of Community and Preventive Medicine • Vol 1 • Issue 1 • 2018 30
or viral antigens, and oxidized low-density lipids including
stress. The unwanted inflammation process could be reduced
by switching off NF-κB actions thereby minimizing damage
to cells, tissues, and organs. Recognized inducers of NF-κB
activity were TNF interleukin 1-β (IL-1β), reactive oxygen
species (ROS), osteoprotegerin, isoproterenol, bacterial
lipopolysaccharides (LPS), cocaine, and ionizing radiation.
The recognized activity of NF-κB was associated with the
regulation of inflammatory responses as well as activation,
differentiation, and effective function of inflammatory
T-cells. The increased levels of TNF-α regulated protein
kinase B (AKT)/mammalian target of rapamycin pathway
were essential for the management of skeletal muscle
hypertrophy. NF-κB pathway regulated pro-inflammatory
cytokine production and leucocyte recruitment which were
primary contributors to inflammatory response. NF-κB
reduction contributed to the control of multiple inflammatory
mechanisms thereby diminishes enormity and duration of
inflammatory response.[15,16]
[Figure 1].
NF-κB was a central regulator of distinctive immune
response. Usually, NF-κB was activated as host protective
mechanism, and long-term activation of NF-κB was
tumorigenic in nature. Furthermore, NF-κB recurrent
activation obstructed the activities of inflammatory mediator,
resulting in tumor progression. Multiple small molecules
from natural or synthetic origin targeted different signaling
pathways including NF-κB pathway and p53 protein (p53),
thereby establishing a prominent change in cancer treatment
and management. The anticancer activity of various NF-κB
inhibitors was partly due to their capacity to induce p53 in
cancer cell.[17]
Selective natural products were inhibitors of NF-κB signaling
by intercalating to the enhancer sequences of heavy chain of
immunoglobulin and gene kappa light chain. NF-κB was
a group of interrelated transcription factors including five
genes: NF-κB1 (p50/p105), NF-κB2 (p52/p100), RelA (p65),
c-Rel, and RelB. In cancers, inflammatory stimuli controlled
the mechanisms of gene expression. In this process, the
cells ceased to relate their existence with underlying
mechanisms, coordinating their phenotype and functions.
NF-κB activation was triggered by two separate pathways
such as canonical and non-canonical (alternative) pathways.
The canonical pathway was activated by toll-like receptors
and pro-inflammatory cytokines (TNFα and IL-1), directing
the activation of Re1A that controlled the expression of pro-
inflammatory and cell survival genes. The alternative NF-κB
pathway was activated by lymphotoxin β (LΤ β), CD40
ligand, B-cell activating factor belonging to the TNF family
(BAFF), and receptor activator of NF-κB ligand (RANKL)
resulting in activation of RelB/p52 complexes. Alternative
pathway activation regulated genes that were required for
lymph-organogenesis and B-cell activation. A variety of
cytokines, growth factors, and kinases involved in signaling
pathways triggered the activation of NF-κB, key protein,
a major therapeutic target for drug discovery in cancer
inflammation and progression.[18-21]
NF-κB signaling system
had been established to be a mediator of inducible and tissue-
specific gene control. Nonetheless, NF-κB/REL complexes
contained homoor heterodimers of the proteins of NF-κB and
Rel families. The Rel family included RelA p65, c-Rel, and
RelB proteins, whereas NF-κB family comprised p50 (p105)
and p52 proteins (p100). Usually, NF-κB complexes were
localized in cytoplasm by binding to inhibitory IkB proteins.
(IκBα a, IκBß, IκBγ, IkBε and Bcl3). Phosphorylation
of IkB proteins transpired through activation of either
external or internal signals. Later, they were ubiquitinated
and destroyed in proteasomes. IkB protein release from
Rel homology domain of Rel protein disclosed nuclear
localization sequence domain. Furthermore, NF-κB-complex
migrated into nucleus and activated the transcription of genes
including inflammatory genes. There were variations in the
activation of NF-κB-complex signaling pathways upstream.
Furthermore, there were alterations in transactivation ability
of NF-κB-complexes at the transcription level. The protein
kinases that phosphorylated IkB proteins were I-kappa B
kinases (IKKs) (IkB kinases α and β). NF-κB-signaling
pathway is NF-κB-essential modulator and regulatory
subunit of IKK complex. IKKs were controlled by various
interacting proteins by connecting IKK complex to canonical
pathway thereby regulating the activation of IKK. The other
non-canonical NF-κB pathway was activated by NF-κB-
inducing kinase (NIK) which facilitated signals from CD40,
lymphotoxin, and BAFF/BLys receptors. This pathway was
IKK dependent and however, IκB-independent. Furthermore,
non-canonical NF-κB pathway regulated NF-κB-activation
through p100 (NF-κB-p52) subunit handling.. IKKα/IKKβ
was a junction for NF-κB-mediated inflammatory signaling.
Furthermore, several cytokine receptors were connected to
NF-κB-signaling to increase and enumerate the inflammatory
responses. NF-κB-system was a cytoplasmic sensor that
Figure 1: Inflammation associated nuclear factor kappa beta
signaling mechanism
4. Vadapalli, et al.: Chronic Inflammation: Prospective Prevention and/or Control by the Regulation of Nuclear Factor Kappa B
with Natural Products as Dietary Supplements.
31 Journal of Community and Preventive Medicine • Vol 1 • Issue 1 • 2018
responded to immune assaults as well as to various external
and internal hazard signals such as hypoxia, oxidative, and
genotoxic stress. NF-κB-signaling signified the connection
between inflammation and cancer. The genes responsible
for inflammation contributing to the activation of NF-κB-
signaling were important targets for drug discovery.[22-25]
[Figure 2].
Natural products as anti-inflammatory activators through the
suppression of NF-κB signaling.
Several herbal remedies proved to be potent drugs against
various NF-κB - associated inflammatory ailments and
cancer. Selective inhibition of IKKβ, a mediator of innate
immune responses and cancer, proved to be a proper strategy
to block NF-κB - signaling. Various plant-derived products
had been established as possible inhibitors of NF-κB-pathway
including lignans, polyphenols, and terpenoids.[26]
Various
natural products inhibited inducible as well as constitutively
active NF-κB-activities, and some of these compounds
with specificity toward IKK or IKKK, IκBα stability, p65
translocation, and DNAbinding in NF-κB-activation pathway
have been reported.[27]
Astaxanthin, (1) a xanthophyll mostly present in salmon,
shrimp, and crab, blocked the activation of IKKα kinase and
IκBα protein degradation as well as nuclear movement of
NF-κB-p65 subunit in addition to inflammatory NF-κB-
dependent gene expression, thereby reducing inflammation
through its antioxidant activity.[28,29]
β-carotene (2) suppressed
LPS-induced NF-κB-signaling and expression of
inflammatory genes by blocking the degradation of IκBα
protein, nuclear migration of p65 protein, DNA binding of
NF-κB-complex, LPS-induced expression iNOS,
cyclooxygenase-2 (COX-2), TNF-α, and IL-1β expression.[30]
Capsaicin (3), a known inhibitor of NF-κB, from chili peppers
(Capsicum species) prevented IκBα degradation and nuclear
translocation of p65. Moreover, capsaicin (3) prevented
NF-κB-activity by blocking the degradation and
phosphorylation of IκBα. Capsaicin (3) inhibited production
of LPS-induced prostaglandin E2 (PGE2) and curbed COX-2
enzyme activity as well as the expression of iNOS protein.
Capsaicin (3) entirely blocked LPS-induced disappearance of
IkB-α and inactivated NF-κB. Capsaicin (3) inhibited
constitutive as well as IL-1β-induced and TNF-α-induced
IL-8 expression.[31,32]
Curcumin (4), a major constituent of
Curcuma longa (turmeric) rhizomes, inhibited IKK, pro-
inflammatory TNF-2α, COX-1, COX-2, and p53 activation
by inhibiting mouse double minute 2 homologue and
regulating other signaling pathways. Curcumin (4) inhibited
the expression of COX-2 gene induced by phorbol 12-m/
restate 13-acetate and TNF-α or fecapentaene-12 in human
colon epithelial cells. Curcumin (4) wedged tumor promoter-
mediated NF-κB-transactivation through inhibition of NIK/
IKK signaling complex. Furthermore, curcumin (4)
suppressed IKK and inhibited constitutive and inducible
NF-κB-activation as well as strengthened TNF-α-apoptosis.
Curcumin (4) curbed Ras/mitogen-activated protein kinase
(MAPK) and phosphoinositide 3-kinase/AKT signaling
pathways that were involved in the activation of NF-κB.[33-36]
Resveratrol (5) obstructed NF-κB/p65 and p53transcriptional
functions by the deacetylation of specific residues.
Resveratrol (5) treatment increased chromatin-associated
sirtuin 1 (SIRT1), cellular inhibitor of apoptosis 2 promoter
regions in the cells. This effect correlated with the loss of
NF-κB-regulated gene expression and cell sensitivity to
TNFα induced apoptosis suggesting that SIRT1 activity
increased apoptosis in response to TNFα with decatalyse
capacity to inhibit the transactivation capacity of RelA/p65
protein.[37-40]
Apigenin (6) present in parsley, thyme, and
peppermint intercepted p65 phosphorylation by inhibiting
IKK functions. In addition, apigenin (6) suppressed NF-κB-
translocation to nucleus which resulted in the inhibition of
IκBα degradation and phosphorylation. Apigenin (6)
regulated NF-κB-activity through hypophosphorylation of
Ser 536 in P65 subunit, in non-canonical pathway.
Furthermore, apigenin (6) inactivated IKK complex
stimulated by LPS. In addition, apigenin (6) inhibited LPS-
induced TNF in vivo. Besides, apigenin (6) inhibited mortality
induced by lethal doses of LPS suggesting a molecular
mechanism of apigenin (6) in inflammation suppression and
modulation of immune response.[41]
Apigenin (6) strengthened
activation-induced cell death by inhibiting NF-κB-activation
and supressing NF-κB-regulated antiapoptotic molecules
(cFLIP, Bcl-x (L), Mcl-1, XIAP, and IAP) and supressed
NF-κB-translocation to nucleus. Moreover, apigenin (6)
inhibited IκBα phosphorylation and degradation as a response
to T-cell receptor (TCR) stimulation in reactivated peripheral
blood CD4-positive T-lymphocyte (CD4 T cells). Besides,
apigenin (6) suppressed the expression of COX-2 protein in
Figure 2: Canonical and non-canonical (alternative) pathways
of nuclear factor kappa beta signaling activation
5. Vadapalli, et al.: Chronic Inflammation: Prospective Prevention and/or Control by the Regulation of Nuclear Factor Kappa B
with Natural Products as Dietary Supplements.
Journal of Community and Preventive Medicine • Vol 1 • Issue 1 • 2018 32
activated human T-cells.[42]
Genistein (7) from soybeans and
fava beans obstructed the activation of NF-κB-and
degradation of IκBα as well as inhibited NF-κB-signaling
through AKT pathway. Genistein (7) treatment of human
myeloid cells, T-cells, and epithelial cells completely
suppressed TNF-induced NF-κB-activation correlated with
protein tyrosine kinase activity. In addition, genistein (7)
inhibited the activation of NF-κB-and AKT signaling
pathways which maintained the balance between cell survival
and programmed cell death (apoptosis), angiogenesis, and
metastasis.[43,44]
Luteolin (8) present in celery, broccoli, green
pepper, parsley, and thyme prevented NF-κB-activity through
the accumulation of ROS. Luteolin (8) markedly controlled
NF-κB-activation while potentiated c-jun amino-terminal
kinase c-jun N-terminal kinase (JNK) to increase apoptosis
induced by TNF in lung cancer cells. Furthermore, luteolin
(8) induced an early phase of ROS segregation through
suppression of cellular superoxide dismutase (SOD) activity.
Therefore, accumulating ROS induced by luteolin (8) played
an important role in the suppression of NF-κB-and
potentiation of JNK to sensitize lung cancer cells to go
through TNF-induced apoptosis.[45]
Epi-catechin (9) an
important constituent of green tea, coco, and grapes stalled
the constitutive NF-κB-activity by obstructing p65 nuclear
translocation and inhibited NF-κB DNA-binding activity.
Epi-catechin (9) inhibited NF-κB-DNAbinding by preventing
NF-κB-as well as NF-κB-dependent gene expression in
L-428 and KM-H2 cells.[46]
Epi-gallocatechin-3-gallate (10),
a constituent of green tea, reduced IKK activation, IκBα
degradation, NF-κB-activation, and phosphorylation of p65
subunit of NF-κB-and prevented nuclear translocation of
p65. Epi-gallocatechin-3-gallate (10) reduced IL-1
β-mediated IL-1β receptor-associated kinase (IRAK)
degradation and the subsequent downstream of signaling
episodes, IKK activation, IκBα degradation and NF-κB-
activation. Besides Epi-gallocatechin-3-gallate (10) curbed
phosphorylation of p65 subunit of NF-κB-which was evident
by the inhibition of IL-8 gene expression. Epi-gallocatechin-
3-gallate (10) inhibited prototype tumor promoter
12-O-tetradecanoylphorbol-13-acetate (TPA)-induced DNA
binding of NF-κB-and cyclic adenosine 3’,5’-monophosphate
response element binding protein (CREB) in mouse skin.
Furthermore, epi-gallocatechin-3-gallate (10) repressed TPA-
induced phosphorylation and the consequent degradation of
IκBα and simultaneously restricted nuclear translocation of
p65. Epi-gallocatechin-3-gallate (10) inhibited TPA-induced
DNA binding of NF-κB-and CREB by blocking activation of
p38 MAPK. suggesting a molecular basis of COX-2 inhibition
by epi-gallocatechin-3-gallate (10) in mouse skin. Epi-
gallocatechin-3-gallate (10) inhibited build-up of LPS-
induced IL-12p40, IL-6, monocyte chemoattractant protein-1,
intercellular adhesion molecule 1 (ICAM-1), vascular cell
adhesion protein, and mRNA in bone marrow-derived
macrophages. Moreover, epi-gallocatechin-3-gallate (10)
restricted LPS-induced IκBα degradation as well as RelA
nuclear translocation. Consequently, epi-gallocatechin-3-
gallate (10) could prevent LPS-induced pro-inflammatory
gene expression through the restriction of NF-κB-and MAPK
signaling pathways.[47-49]
Saxifragin (11) (quercetin
5-glycoside) is widely distributed in plants as well as insects
and displayed peroxynitrite-scavenging effects. Saxifragin
(11) suppressed the production of NO and PGE2
in LPS-
activated RAW 264.7 macrophages by suppressing the level
of protein and mRNA expression of iNOS and COX-2,
respectively. In addition, saxifragin (11) inhibited the mRNA
expression of pro-inflammatory cytokines comprising TNF-
α, IL-6, and IL-1β. The inhibitory effects of saxifragin (11)
on NF-κB were a result of activation of caspase-1 and
phosphorylation of Jun-N-terminal kinase (JNK) and
extracellular signal-regulated kinase (ERK). Moreover,
pretreatment with saxifragin (11) increased the survival rate
of mice with LPS-induced septic death. Thus, saxifragin (11)
displayed anti-inflammatory activity through the inhibition
of NF-κB, caspase-1, and MAPK activation.[50]
Sesamin (12)
from the bark of Fagara species and sesame oil prevented
TNF-induced IKK activation. IκBα degradation and
phosphorylation; down-regulated constitutive and inducible
NF-κB-activation and suppressed P65 phosphorylation and
nuclear translocation. Sesamin (12) assisted in the prevention
of hyperlipidemia, hypertension, and carcinogenesis and
inhibited the proliferation of wide variety of tumor cells
including leukemia, cancers of colon, pancreas, lung,
prostate, and breast as well as multiple myeloma. In addition,
sesamin (12) increased TNFα induced apoptosis associated
with suppression of gene products related to cell survival
(Bcl-2 (B-cell leukemia/lymphoma 2 protein Bcl-2)),
proliferation bcl-1 proto-oncogene product (cyclin D1)),
inflammation(COX-2),invasion(matrixmetalloproteinases-9
[MMP-9] and ICAM-1), and angiogenesis. Sesamin (12)
reduced constitutive and inducible NF-κB-activation which
was initiated by multiple inflammatory stimuli and
carcinogens. Furthermore, sesamin (12) reduced the
degradation of IκBα by supressing phosphorylation of IκBα
there by inhibiting the activation of clampdown of p65
phosphorylation and nuclear translocation as well as NF-κB-
mediated reporter gene transcription. Moreover, sesamin (12)
markedly reduced LPS-stimulated IL-6 mRNA and protein in
microglia cells (BV-2). Sesamin (12) decreased LPS-
activated p38 MAPK and NF-κB-activation. Furthermore,
SB203580 (inhibitor of p38 MAP kinase) inhibited LPS-
induced IL-6 production.[51,52]
Xantholhumol (13) (Hops)
controlled T cell-mediated immune responses by inhibiting
NF-κB-transcription factor through the suppression of
phosphorylation of IκBα (inhibitor of NF-κB) [Figure 3].[53]
A number of monoterpenoids, sesquiterpenoids, and
diterpenoids displayed anti-inflammatory activity by
intercepting NF-κB-signaling pathways. Humulene (14)
present in Humulus lupulus (hops) significantly reduced LPS-
induced NF-κB-activation as well as inflammatory response.
6. Vadapalli, et al.: Chronic Inflammation: Prospective Prevention and/or Control by the Regulation of Nuclear Factor Kappa B
with Natural Products as Dietary Supplements.
33 Journal of Community and Preventive Medicine • Vol 1 • Issue 1 • 2018
However, humulene (14) did not alter the activation of ERK,
p38, and JNK.[54]
Zerumbone (15), a potent anti-inflammatory
andanticanceragentisolatedfromZingiberzerumbet(ginger),
curbed the function of IKK complex as a result of reduced
protein phosphorylation and degradation of IκBα) proteins,
consequently resulting in a decrease in nuclear translocation
of NF-κB-complex and gene expression.[55,56]
Carnosol (16)
from Rosmarinus officinalis (Rosemary) curbed the activation
of NF-κB-system through inhibiting IκBα phosphorylation
and reducing the expression of iNOS and NO production.
Metastasis was suppressed by carnosol (16) through the
blockade of MMP-9 expression with the downregulation of
NF-κB-and c-Jun protein-mediated signaling as a result of
its antioxidant capacity.[57,58]
Inflammatory responses were
suppressed by huperzine A (17) from Huperzia serrata with
the restriction of NF-κB-signaling.[59]
Costunolide (18) from
Saussurea lappa (costus root oil) inhibited phosphorylation
of IkB proteins, resulting in nuclear localization of
NF-κB‑complex. Furthermore, costunolide (18) inhibited
LPS-induced inflammatory signaling pathway by curbing
NF-κB-activation and downstream gene expression.[60]
Ergolide (19) from Inula britannica (British yellowhead
and Meadow fleabane) constrained NF-κB-activation in
LPS-stimulated RAW 264.7 macrophages through inhibition
of nuclear translocation of NF-κB-complex and degradation
of IkB protein.[61]
Helenalin A (20) from Arnica montana
(wolf’s bane, Leopard’s bane, Mountain tobacco, and
Mountain arnica) and Arnica chamissonis (Chamisso arnica)
inhibited NF-κB-signaling through alkylation of p65 subunit
of NF-κB complex, thereby inhibiting the complex DNA
binding and transcription of NF-κB-dependent genes.[62]
Nepalolide A (21) from Carpesium nepalense displayed anti-
inflammatory activity through the inhibition of LPS- and
cytokine- inducedactivationofNF-κB-signalinginC6glioma
cells. The suppression of NF-κB-signaling occurred due to
the inhibition of IkB protein phosphorylation in stimulated
cells.[63]
Parthenolide (22) of Tanacetum parthenium
(feverfew) repressed the activity of IKKβ, a kinase subunit
that played a vital function in cytokine-mediated signaling.
Mutation of cysteine 179 in activation loop of IKKβ resulted
in elimination of IKKβ binding sensitivity to parthenolide
(22). Furthermore, anti-inflammatory activity of parthenolide
(22) was facilitated through α-methylene γ-lactone moiety
present in other sesquiterpene lactones. Parthenolide (22)
alkylated cysteine-38 in p65 subunit of NF-κB-and inhibited
DNA binding of NF-κB-complex.[64]
Iso-deoxyelephantopin
(23) from Elephantopus scaber inhibited osteoclastogenesis
by suppressing NF-κB-activation and potentiated apoptosis.
Furthermore, iso-deoxyelephantopin (23) reduced cytokine-
induced NF-κB-activation by suppressing IKK complex
activity.[65]
Hypoestoxide (24) from Hypoestes rosea inhibited
IKKβ activation and inflammatory responses including
colorectal cancer.[66,67]
Genipin (25), from Gardenia fruit
extract, displayed anti-inflammatory activity by inhibiting
the expression of iNOS and NO production in RAW 264.7
macrophages. Genipin (25) restricted the degradation of IkBb
protein that led to inhibition of NF-κB-signaling.[68]
Aucubin
(26), an iridoid glycoside from Rehmannia glutinosa,
exhibited its anti-inflammatory activity by inhibiting the
degradation of IκBα protein and prevented the nuclear
translocation of p65 subunit of NF-κB-complex. In addition,
aucubin (26) acted as anti-inflammatory agent protecting
against hepatotoxicity. Besides, aucubin (26) exhibited
antitumor activity.[69,70]
Acanthoic acid (27) from the bark of
Acanthopanax koreanum curbed LPS-induced activation of
IκBα phosphorylation and nuclear DNA binding of NF-κB-
complex in addition to the reduction in LPS-induced cytokine
synthesis and pro-inflammatory response.[71]
Kahweol
(28) present in Coffea arabica (coffee beans) suppressed
NF-κB-related transcriptional activation through inhibition
of nuclear DNA binding of NF-κB-complex, IKK activity
and prevented degradation of IkB proteins.[72,73]
Catalposide
(29) from Catalpa ovata (yellow catalpa. Chinese catalpa)
curbed the activation of NF-κB, IκBα protein degradation
and translocation of P65 sub-unit to the nuclei. Furthermore,
catalposide (26) decreased TNF-α induced p38 and ERK
phosphorylation through up-regulation of cytokine signaling
thereby reducing intestinal inflammation.[74]
Tanshinone IIA
Figure 3: Carotenoids and phenols
7. Vadapalli, et al.: Chronic Inflammation: Prospective Prevention and/or Control by the Regulation of Nuclear Factor Kappa B
with Natural Products as Dietary Supplements.
Journal of Community and Preventive Medicine • Vol 1 • Issue 1 • 2018 34
(30) from Salvia miltiorrhiza suppressed NF-κB-signaling
and inhibited IKKα/β and NIK activation, consequently
inhibiting the phosphorylation of IκBα protein as well as
nuclear migration NF-κB-complex.[75]
Triptolide (31) from
Tripterygium wilfordii inhibited the phosphorylation of
NF-κB-complex into nuclei and ultimately DNA binding
of the complex. Furthermore, triptolide 32 curbed NF-κB-
signaling in T-lymphocytes by upregulating IκBα protein
expression.[76,77]
[Figure 4].
Several triterpenoids and their glycosides displayed anti-
inflammatory activity by interfering with NF-κB signaling
pathway reducing inflammation. Betulinic acid (32)
(pentacyclic triterpenoid), naturally occurring and widely
distributed in plants such as Ancistrocladus heyneanus,
Diospyros leucomelas, Prunella vulgaris (common selfheal),
Pseudocydonia sinensis (Chinese quince), Pulsatilla
chinensis, R. officinalis (rosemary), Syzygium formosanum
(jambul), Tetracera boiviniana, Triphyophyllum peltatum,
and Ziziphus mauritiana displayed anti-inflammatory
activity by the suppression of IKKα activation which was
initiated by certain typical NF-κB-activators followed by
the downregulation of NF-κB-dependent gene expression.[78]
Glycyrrhizin (33) from Glycyrrhiza glabra (liquorice) with
the help of glycyrrhizic acid inhibited NF-κB-signaling. The
calcium-mediated activation of NF-κB-system was blocked
by glycyrrhizic acid. However, excessive use of liquorice
could result in hypertension.[79]
Lupeol (34) present in
various fruits, vegetables, and several herbs inhibited NF-κB-
signaling including phosphorylation of IκBα protein, DNA
binding of NF-κB-complex as well as NF-κB-related gene
activity. Furthermore, lupeol (30) inhibited various signaling
pathways such as AKT-dependent pathways, reducing the
inflammation.[80-82]
Acetyl-11-keto-ß-boswellic acid (35)
from Boswellia serrata curbed constitutively activated
NF-κB-signaling by inhibiting IKK activity. Psoriasis
vulgaris is a chronic inflammatory skin disease involving
cytokines and activated cellular immune system where
psoriatic skin lesions display potent activation of NF-κB,
mainly confined to dermal macrophages. Severe psoriasis
lesion topical treatment with IKKβ inhibitor and acetyl-11-
keto-ß-boswellic acid (35) resulted in profound suppression
of TNFα production of macrophages.[83]
Celastrol (36)
from Celastrus, tripterygium wilfordii, C. orbiculatus, and
C. regelii intercepted the systolic I-Bα degradation and
nuclear translocation of RelA and blocked IKK function
together with IKKβ activity. Celastrol (36) inhibited
numerous stimuli-induced NF-κB-regulated gene expression
and DNA-binding of NF-κB-without affecting DNA-binding
activity of activator protein-1 (AP-1). Celastrol (36) pre-
incubation entirely blocked LPS-, TNF-α−, or phorbol
12-myristate 13-acetate (PMA)-induced degradation and
phosphorylation of IκBα. Celastrol (36) primarily inhibited
IKK and constitutively active IKKβ activities. Furthermore,
NF-κB-activation was suppressed by celasterol (36) through
targeting cysteine 179 in IKK. Celastrol (36) prevented LPS-
induced messenger ribonucleic acid (mRNA) expression
iNOS and TNF--α as well as TNFα-induced antiapoptotic
protein-BfI-1/A1 BfI-1/A1 expression. Celastrol (36)
suppressed proliferation, invasion, and angiogenesis through
the induction of apoptotic factors and reducing constitutive
NF-κB-activity.[27,84]
Ursolic acid (37), a natural pentacyclic
triterpenoid carboxylic acid present in wide variety of plants,
including apples, basil, bilberries, cranberries, peppermint,
rosemary, and oregano inhibited the activation of NF-κB-
signaling initiated by different carcinogenic factors in various
cell lines. Ursolic acid (37) restricted IκBα kinase activation,
IkBα protein phosphorylation and degradation, p65 migration
to nucleus and DNA binding of NF-κB-complex including
NF-κB-related gene expression.[85]
Escin (38), a constituent
of Aesculus hippocastanum (horse chestnut), restricted
TNF-induced IKK activation as well as I- Bα degradation
and phosphorylation. Escin (38) strengthened TNF-
induced apoptosis and inhibited tumor cell invasion. This
process was associated with the downregulation of B-cell
leukemia/lymphoma 2 protein (Bcl-2) cellular inhibitor of
apoptosis bcl-1 proto-oncogene product (cyclin D1), COX-
2, intercellular adhesion molecule-1, MMP-9, and vascular
endothelial growth factor (VEGF) which were regulated
by t NF-κB-activation. Accordingly, escin (38) inhibited
the activation of NF-κB-through IKK inhibition resulting
Figure 4: Mono-, sesqui- and di-terpenoids
8. Vadapalli, et al.: Chronic Inflammation: Prospective Prevention and/or Control by the Regulation of Nuclear Factor Kappa B
with Natural Products as Dietary Supplements.
35 Journal of Community and Preventive Medicine • Vol 1 • Issue 1 • 2018
in sensitization of cells to cytokines and chemotherapeutic
agents.[86]
Saikosaponin D (39) from Bupleurum curbed
NF-κB-signaling along with T-cell activation and apoptosis
of cancer cells including inflammation. Saikosaponin D (39)
blocked the phosphorylation of IκBα protein and increased
protein level of inhibitory IκBα protein. In addition,
saikosaponin D (39) constrained Jun-N-terminal kinase (JNK.
c-jun amino-terminal kinase) signaling through upstream
regulation of IKK and NF-κB-complexes [Figure 5].[87]
Avicin G (40), a triterpenoid glycoside from Acacia
victoria (gundabluie and bardi bush), inhibited DNA
binding of NF-κB-complex and expression of N-kB-
dependent genes, resulting in the reduction of inflammation
[Figure 5].[88]
Ginsenosides, a mixture of saponins of Panax
species (ginseng) prevented the activation of IKKα kinase
and phosphorylation and degradation of IκBα protein
thereby inhibiting NF-κB - signaling either directly or
indirectly. Ginsenosides, the main components of Panax
ginseng, were well known for their anti-inflammatory and
antiproliferative activities. Ginsenoside Rb 1 (42) was
converted by intestinal bacteria to compound K (41). This
metabolite showed a significant inhibitory effect on TNF-
α-induced expression of intercellular adhesion molecule-1
in human astroglial cells. Pretreatment with compound K
(41) suppressed TNF-α-induced phosphorylation of ΙκΒα
kinase and the subsequent phosphorylation and degradation
of IkBα. In addition, the treatment inhibited TNF-α-induced
phosphorylation of mitogen-activated protein kinase
kinase 4 and subsequent activation of JNK-activating
protein kinase 1 (JNK-AP-1) pathway, suggesting that
ginsenoside metabolite compound K (41) displayed anti-
inflammatory effect through the inhibition of both NF-κB-
and JNK pathways in a cell-specific manner.[89]
Pregnane
X receptor (PXR) activation displayed anti-inflammatory
effects by blocking NF-κB. However, overactivation of
PXR might disturb the homeostasis of multiple enzymes
and transporters. Ginsenosides curbed NF-κB activation and
reinstated the expression of PXR target genes in TNF-α-
stimulated LS174T cells. In addition, ginsenosides restrained
NF-κB activation in a PXR-dependent manner and increased
interaction between PXR and NF-κB p65 subunit and thus
decreased the nuclear translocation of p65. Ginsenoside Rb1
and compound K (41) were major bioactive compounds in
controlling PXR/NF-κB signaling pathway. Ginsenosides
attenuated dextran sulfate sodium-induced experimental
colitis, associated with restored PXR/NF-κB signaling,
suggesting that ginsenosides might cause anti-inflammatory
effects by targeting PXR/NF-κB interaction without
disrupting PXR function [Figure 6].[90]
In another study, compound Rb1 and its metabolite compound
K (41) could inhibit colitis injury. Compound K (41) lessened
colitis histopathology injury and improved myeloperoxidase
activity. Furthermore, compound K (41) reduced pro-
inflammatory cytokines production, such as IL-6, IL-1β,
TNF-α, and elevated anti-inflammatory cytokine IL-10
production. Compound K (41) inhibited NF-κB p65 nuclear
translocation, downregulated p-IκBα, and upregulated IκBα,
Figure 5: Triterpenoids and glycosides
Figure 6: Triterpenoid glycosides, avicin G (40), compound K
(41)and ginsenoside Rb1 (42)
9. Vadapalli, et al.: Chronic Inflammation: Prospective Prevention and/or Control by the Regulation of Nuclear Factor Kappa B
with Natural Products as Dietary Supplements.
Journal of Community and Preventive Medicine • Vol 1 • Issue 1 • 2018 36
suggesting that compound K (41) suppressed the activation
of NF-κB pathway in the progression of colitis [Figure 6].[91]
Several secondary metabolites regulated the defect in
inflammatory pathways by suppressing NF-κB-activity with
high selectivity. Epidemiological data suggested that intake
of small amounts of polyphenols from foods and beverages
exerts a strong effect in the reduction of inflammation and
chronic diseases. It had been widely acknowledged that
many plant-derived compounds exhibited significant anti-
inflammatory effects. These naturally occurring compounds
displayed anti-inflammatory properties by their actions with
the modulation of cytokines and associated intracellular
signaling pathways.[92,93]
CONCLUSION
Plant and animal-derived constituents could prevent or inhibit
NF-κB-signaling system, displaying therapeutic effects
against inflammatory ailments including cancer. NF-κB, a key
regulator of internal immune response, is activated as a host
protection. However, chronic inflammation is tumorigenic
and blocking the activities by inflammatory mediators
suppresses tumor regression and its aggressiveness. Two
separate pathways for NF-κB-activation include canonical
pathway and non-canonical (alternative) pathway. These
pathways are identified by differential requirement for
IKK subunits. Several secondary metabolites of natural
origin as well as small synthetic molecules target multiple
signaling pathways including NF-κB-and p53. A number of
natural constituents present in fruits, vegetables, and natural
supplements could help in reducing or preventing chronic
inflammation and related diseases.
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How to cite this article: Vadapalli J, Vanam A,
Motohashi N, Gollapudi R. Chronic Inflammation:
ProspectivePreventionand/orControlbytheRegulationof
Nuclear Factor Kappa B with Natural Products as Dietary
Supplements. J 28-39.