Arunaksharan Narayanankutty

Bio: Arunaksharan Narayanankutty is an academic researcher from St. Joseph's College, Bangalore. The author has contributed to research in topics: Antioxidant & Coconut oil. The author has an hindex of 14, co-authored 47 publications receiving 526 citations. Previous affiliations of Arunaksharan Narayanankutty include Malabar Christian College & Saint Joseph's College.

PI3K/ Akt/ mTOR Pathway as a Therapeutic Target for Colorectal Cancer: A Review of Preclinical and Clinical Evidence.

Abstract: Background Phosphoinositide 3-kinase (PI3Ks) is a member of intracellular lipid kinases and involved in the regulation of cellular proliferation, differentiation and survival. Overexpression of the PI3K/Akt/mTOR signalling has been reported in various forms of cancers, especially in colorectal cancers (CRC). Due to their significant roles in the initiation and progression events of colorectal cancer, they are recognized as a striking therapeutic target. Objective The present review is aimed to provide a detailed outline on the role of PI3K/Akt/mTOR pathway in the initiation and progression events of colorectal cancers as well as its function in drug resistance. Further, the role of PI3K/Akt/mTOR inhibitors alone and in combination with other chemotherapeutic drugs, in alleviating colorectal cancer is also discussed. The review contains preclinical and clinical evidence as well as patent literature of the pathway inhibitors which are natural and synthetic in origin. Methods The data were obtained from PubMed/Medline databases, Scopus and Google patent literature. Results PI3K/Akt/mTOR signalling is an important event in colorectal carcinogenesis. In addition, it plays significant roles in acquiring drug resistance as well as metastatic initiation events of CRCs. Several small molecules of natural and synthetic origin have been found to be potent inhibitors of CRCs by effectively downregulating the pathway. Data from various clinical studies also support these pathway inhibitors and several among them are patented. Conclusion Inhibitors of the PI3K/mTOR pathway have been successful for the treatment of primary and metastatic colorectal cancers, rendering the pathway as a promising clinical cancer therapeutic target.

Glutathione, an Antioxidant Tripeptide: Dual Roles in Carcinogenesis and Chemoprevention

Abstract: Glutathione (GSH or reduced glutathione) is a tripeptide of gamma-Glutamyl-cysteinylglycine and the predominant intracellular antioxidant in many organisms including humans. GSH and associated enzymes are controlled by a transcription factor-nuclear factor-2 related erythroid factor-2 (Nrf2). In cellular milieu, GSH protects the cells essentially against a wide variety of free radicals including reactive oxygen species, lipid hydroperoxides, xenobiotic toxicants, and heavy metals. It has two forms, the reduced form or reduced glutathione (GSH) and oxidized form (GSSG), where two GSH moieties combine by sulfhydryl bonds. Glutathione peroxidase (GPx) and glutathione-s-transferase (GST) essentially perform the detoxification reactions using GSH, converting it into GSSG. Glutathione reductase (GR) operates the salvage pathway by converting GSSG to GSH with the expense of NADPH and restores the cellular GSH pool. Hence, GSH and GSH-dependent enzymes are necessary for maintaining the normal redox balance in the body and help in cell survival under stress conditions. In addition, GST removes various carcinogenic compounds offering a chemopreventive property, whereas the GSH system plays a significant role in regulating the cellular survival by offering redox stability in a variety of cancers including prostate, lung, breast, and colon cancer. Studies have also indicated that GSH inhibitors, such as buthionine sulfoximine, improve the chemo-sensitivity in cancer cells. In addition, GSH and dependent enzymes provide a survival advantage for cancer cells against chemotherapeutic drugs and radiotherapy.

Polyphenols of virgin coconut oil prevent pro-oxidant mediated cell death

Abstract: Virgin coconut oil (VCO), extracted from the fresh coconut kernel, is a food supplement enriched with medium chain saturated fatty acids and polyphenolic antioxidants. It is reported to have several health benefits including lipid lowering, antioxidant and anti-inflammatory activities. The pharmacological benefits of VCO have been attributed to its polyphenol content (VCOP), the mechanistic basis of which is less explored. Liquid chromatography/mass spectroscopy (LC/MS) analysis of VCOP documented the presence of gallic acid, ferulic acid (FA), quercetin, methyl catechin, dihydrokaempferol and myricetin glycoside. Pre-treatment of VCOP at different concentrations (25–100 μg/mL) significantly reduced the H2O2 and 2,2′-azobis (2-amidinopropane) dihydrochloride (AAPH) induced cell death in HCT-15 cells. Giving further insight to its mechanistic basis, oxidative stress induced alterations in glutathione (GSH) levels and activities of GR (Glutathione–Reductase), GPx (Glutathione–Peroxidase), GST (Gluta...

Health impacts of different edible oils prepared from coconut (Cocos nucifera): A comprehensive review

Abstract: Background Edible oils, preferably plant origin are rich sources of fatty acids and other lipophilic antioxidants to the body. Among these, oils derived from the coconut kernel (Cocos nucifera) are widely used in India and the Asia Pacific, which includes copra oil (CO), virgin coconut oil (VCO) and refined, bleached and deodorized (RBD) oil. Based on the mode of preparation, their composition and biological effects vary. Scope and approach This review compares the physicochemical and biological properties of coconut oils prepared by different methods. The metabolism of coconut oil and its predominant content lauric acid is also explained. This review emphasizes the use of VCO in the prevention and amelioration of several degenerative diseases, including cardiovascular disease and cancers, over CO or RBD oils. Key findings and Conclusion There are no evident differences in the fatty acid profiles of CO, VCO and RBD oils. However, they differ in their polyphenol contents, which are reported to be high in VCO, possibly due to less harsh treatment during its preparation. Various epidemiological and clinical reports indicating the health risk of coconut oils could be pertinent to the data on the individuals consumed CO/RBD oil, which lacks polyphenols. Whereas, VCO have antioxidant, anti-inflammatory, lipid-lowering and cytoprotective efficacies, which may be attributed to its higher polyphenolics. Further, emerging studies have indicated that hot-extracted VCO (H-VCO) have a pharmacological advantage over VCO prepared by fermentation. At this juncture, further explorations on the biopharmaceutical potential of VCO have to be undertaken through clinical studies.

Virgin coconut oil maintains redox status and improves glycemic conditions in high fructose fed rats

Abstract: Virgin Coconut Oil (VCO), extracted from fresh coconut kernel possess similar fatty acid composition to that of Copra Oil (CO), a product of dried kernel. Although CO forms the predominant dietary constituent in south India, VCO is being promoted for healthy life due to its constituent antioxidant molecules. High fructose containing CO is an established model for insulin resistance and steatohepatitis in rodents. In this study, replacement of CO with VCO in high fructose diet markedly improved the glucose metabolism and dyslipidemia. The animals fed VCO diet had only 17 % increase in blood glucose level compared to CO fed animals (46 %). Increased level of GSH and antioxidant enzyme activities in VCO fed rats indicate improved hepatic redox status. Reduced lipid peroxidation and carbonyl adducts in VCO fed rats well corroborate with the histopathological findings that hepatic damage and steatosis were comparatively reduced than the CO fed animals. These results suggest that VCO could be an efficient nutraceutical in preventing the development of diet induced insulin resistance and associated complications possibly through its antioxidant efficacy.

Influence of Resveratrol on the Immune Response

Abstract: Resveratrol is the most well-known polyphenolic stilbenoid, present in grapes, mulberries, peanuts, rhubarb, and in several other plants. Resveratrol can play a beneficial role in the prevention and in the progression of chronic diseases related to inflammation such as diabetes, obesity, cardiovascular diseases, neurodegeneration, and cancers among other conditions. Moreover, resveratrol regulates immunity by interfering with immune cell regulation, proinflammatory cytokines’ synthesis, and gene expression. At the molecular level, it targets sirtuin, adenosine monophosphate kinase, nuclear factor-κB, inflammatory cytokines, anti-oxidant enzymes along with cellular processes such as gluconeogenesis, lipid metabolism, mitochondrial biogenesis, angiogenesis, and apoptosis. Resveratrol can suppress the toll-like receptor (TLR) and pro-inflammatory genes’ expression. The antioxidant activity of resveratrol and the ability to inhibit enzymes involved in the production of eicosanoids contribute to its anti-inflammation properties. The effects of this biologically active compound on the immune system are associated with widespread health benefits for different autoimmune and chronic inflammatory diseases. This review offers a systematic understanding of how resveratrol targets multiple inflammatory components and exerts immune-regulatory effects on immune cells.