Department of Pharmacy
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Item Natural HDAC Inhibitors: Nature’s Answer to the Cancer(NMIMS, 2015) Gaikwad, Anil BhanudasPost translational modifications of histones play a significant role in regulation of physiological and pathological processes in the body. Acetylation is one of the most important chromatin modifying mechanisms being controlled by histone acetyl transferases and histone deacetylases. The histone deacetylases (HDAC) are basically responsible for silencing of gene transcription. Cancer involves silencing of a large number of genes. Inhibition of such gene silencing could possibly lead us to alleviatin or control of cancer progression. Natural HDAC inhibitors, a highly researched topic thus seems an attractive method to conquer the kingdom of cancer and thus prove to be the ‘bull’s eye’ like target for cancer treatmentItem Recent developments in using plant-derived natural products as tubulin inhibitors for the management of cancer(Elsevier, 2016) Gaikwad, Anil BhanudasDefeating cancer has become a global battle calling for development of new treatment options. Better understanding of the biological processes involved in development of cancer has made it possible to screen various drugs against a wide range of targets. Targeting of microtubule dynamics has remained one of the favorite targets for researchers. Tubulin inhibitors are drugs of choice in many of the treatment strategies employed by the oncologists. Tubulin inhibitors are classified under two types as microtubule stabilizers or destabilizers. Three different sites are identified where these inhibitors binds. Natural sources have played an important role in development of modern medicines for treating various diseases including cancer. Vinca alkaloids, colchicine, and taxane are the first drugs in these categories which are named after different binding sites. Drugs binding to vinca domain and colchicine domain fall under microtubule destabilizers; and those binding to taxane domain fall under microtubule stabilizers. These drugs have served as prototypes for the development of their semisynthetic derivatives which are having wide range of anticancer activities. In present review, various aspects of the natural tubulin inhibitors and their role in development of chemotherapeutic agents for cancer treatment are discussed.Item Folic Acid in Pain: An Epigenetic Link(Elsevier, 2017) Gaikwad, Anil BhanudasPain, due to its variability and lack of clear definition, forms one of the biggest challenges being faced by the physicians globally. The current therapeutic interventions being used to treat or reduce pain seem to be insufficient to solve the problem. Although the mechanisms underlying pain and associated with “killing pain” have been in limelight since time immemorial, the exact mechanisms have not yet been delineated. The genetic and epigenetic basis of pain and its treatment are emerging as potential answers to the unsolved queries associated with pain. Folic acid (vitamin B9) has been reported to show a potential role in treatment of various types of pains including joint pain (rheumatoid arthritis), myofascial pain, and cancer-associated pain. This pharmacological property displayed by folic acid could rightly be linked to the epigenetic alterations associated with folic acid administration. This review attempts to link the analgesic effect of folic acid with its deoxyribonucleic acid (DNA) methylation property (a major epigenetic alteration), which may help us understand the molecular basis of analgesic effect of folic acid in a more appropriate manner.Item Curcumin: The epigenetic therapy(Elsevier, 2016) Gaikwad, Anil BhanudasThe process of gene expression is tightly regulated by a series of interconnected epigenetic alterations including DNA methylation, covalent modifications of histones, or altered microRNA. The food components which are taken regularly play a significant role in altering the epigenetic modifications, and associated gene expression may act as important tools in curbing the diseases which involve epigenetic alterations. The polyphenolic compound curcumin (diferuloylmethane), possesses a large number of biological activities owing to which its use has been implicated in various diseases including cancer, respiratory diseases, metabolic disorders, and neurodegenerative disorders. These activities could be attributed partially to its DNA hypomethylating and histone acetylating property. In conclusion, curcumin is able to restore the epigenetic regulation balance and appears as an attractive preventive and/or therapeutic approach, and hence there is a need to study the epigenetic modifications promoted by its treatment.Item Biomarkers of Multiple Sclerosis and Their Modulation by Natural Products(Elsevier, 2017) Gaikwad, Anil BhanudasMultiple sclerosis (MS) is one of the leading causes of neurological disabilities and can be explained as a chronic, inflammatory, and autoimmune disease related to the central nervous system. Biomarkers play an important role in defining and understanding the various mechanisms involved in the progression of disease. The success of therapeutic treatment of MS can be measured by evaluating biomarkers, which can serve as a “surrogate end point” of clinical outcomes. Biomarkers of MS can be categorized as immune system biomarkers, blood–brain barrier disruption biomarkers, demyelination biomarkers, oxidative stress and excitotoxicity biomarkers, axonal/neuronal damage biomarkers, and remyelination and repair biomarkers. Studies have shown that natural products can modulate biomarkers of MS and can be used for its treatment. Polyunsaturated fatty acids, vitamins (specifically vitamin D), minerals, and trace elements all have promising effects on biomarkers of MS. Phytochemicals like adenanthin, cannabinoids, curcumin, epigallocatechin gallate, glucoraphanin, sulforaphane, hyperforin, matrine, plumbagin, and quercetin have also shown promise as potential treatments for MS. There is a wide scope for research in the domain of multiple sclerosis biomarkers and their modulation by natural products.Item Nutraceuticals as therapeutic agents for inflammation(Elsevier, 2016) Gaikwad, Anil BhanudasNutraceutical is a broad term which encompasses foods/products obtained from foods with beneficial health effects. Nutraceuticals focus on prevention rather than cure. This category of products has gained much attention due to their safe therapeutic effects other than their nutritional benefits. They may be used to prevent the onset of many life-threatening diseases like diabetes, cancer, neurodegenerative disorders, etc. Nutraceuticals range from dietary supplements (proteins, vitamins, and minerals), pure compounds to components derived from natural sources. Inflammation is the biological response to a harmful stimulus. While being helpful to remove the foreign object, inflammation also damages the body’s own cells. Inflammation is believed to be the cause for many chronic diseases like rheumatoid arthritis, diabetes, atherosclerosis, obesity, and cancer. In this chapter we have elaborated the purified extracts and isolated phytoconstituents from plants as source of nutraceutical used specifically for the prevention/treatment of inflammation.Item Fibromyalgia Syndrome: Role of Obesity and Nutrients(Elsevier, 2017) Gaikwad, Anil BhanudasFibromyalgia syndrome (FMS) is a devastating musculoskeletal disorder with characteristic symptoms of fatigue, chronic pain, headache, anxiety, morning stiffness, and memory loss that ultimately affects the quality of life. Although the clear pathogenesis of FMS is unknown, multiple lines of evidence propose a link between obesity, diet, nutritional status, and FMS. Several studies have reported that overweight and obese people have higher incidence of FMS, and weight reduction in these patients seems to be effective in improving symptoms. Vegetarian and vegan diets were reported to have beneficial effects on FMS due to the high amounts of antioxidants consumed. Nutritional deficiencies of magnesium, iron, iodine, selenium, thiamine, and manganese have been described, but there are no detailed studies available that show a direct relationship between FMS and deficiencies of these micronutrients. Extremely limited data is available about the nutritional supplements in FMS which indicates that more studies are needed to determine the types of nutritional supplements that could help reduce the symptoms of FMS. In conclusion, physical exercise, weight control, and dietary supplements, including antioxidants and micronutrients, are important in improving FMS patients’ quality of life.Item Natural Remedies for Treatment of Cancer Pain(Elsevier, 2017) Gaikwad, Anil BhanudasPain is one of the most critical indications related with cancer. Intensity of cancer pain increases with advancement in stage of cancer. More than one third patients of cancer suffer from moderate to severe pain. World Health Organization (WHO) has developed a three step analgesic ladder for treatment of cancer pain. Natural drugs are being used for treatment of cancer but very less natural drugs are used in cancer pain. Morphine, a naturally occurring opioid is considered as a gold standard for treatment of cancer pain. Another natural opioid codeine is also being successfully used for the management of cancer pain. Cannabis, also known as marijuana, is used for treatment of moderate to severe cancer pain. Tetrodotoxin, a sodium channel blocker, of marine origin is in clinical trial for its use in cancer pain management. Vitamin supplementation is proving effective in decreasing the intensity of pain, as well as the dose of opioid analgesics. Many other natural drugs are being used as supportive treatments in cancer pain management.Item PARG inhibitors’ success: a long way to go!(Bentham Science, 2014) Gaikwad, Anil BhanudasPoly(ADP-ribosyl)ation is one of the most pertinent post translational modifications involved in regulation of chromatin structure, cell cycle progression, tissue development and differentiation and other vital biological phenomena. The enzymes that catalyze the synthesis and degradation of poly(ADP) ribose polymers are PARP and PARG, respectively. The role of PARP has been implicated in development of various diseases since a long time and hence it has evolved as an important pharmacological target but a plethora of drawbacks associated with PARP inhibitors compelled the shift of focus towards PARG. Recently PARG has evolved as an alternative target to overcome the hurdles being faced in the treatment of various conditions like multiple organ failure, ischemic organ damage, diabetic nephropathy, neurodegenerative diseases and cancer. The review provides a compendium on PARG, its mode of action, inhibitors, and its therapeutic applications and also discusses the reasons due to which PARG inhibitors have not been able to reach the clinical trials. PARG inhibitors, though far from success, definitely appear as alluring topics for further research as PARG emerges out as an eminent pharmacological target in making which can shape the future of medicines to provide better therapy with reduced side effects and more efficiency.Item Disparity in actions of rosiglitazone against cisplatin-induced nephrotoxicity in female Sprague-Dawley rats(Elsevier, 2013-11) Gaikwad, Anil BhanudasCisplatin is one of the most common chemotherapeutic drugs used against various solid, tumours. Despite of its therapeutic benefits, its use in clinical practice is often limited because of dose, related toxicity. The nephrotoxic potential of cisplatin has been ascribed to its accumulation in the, renal tubular cells generating reactive oxygen species (ROS), activation of Bax, increased secretion of, TNFα and activation of certain inflammatory mediators like cytokines. The present investigation was, undertaken with an objective to study the effect of rosiglitazone against cisplatin induced, nephrotoxicity. Pretreatment of rosiglitazone prevents cisplatin induced nephrotoxicity which was, clearly evident from the renal biochemical parameters like reduced BUN, creatinine and TNFα levels, and increased albumin levels, which was also supported by histopathological studies of the kidneys. In contrast, posttreatment of rosiglitazone was not able to protect the renal damage in cisplatin induced, renal toxicity. These results showed the variation of pre & posttreatment effects of rosiglitazone, against the cisplatin induced nephrotoxicity.