Alcohol promotes liver fibrosis in high fat diet induced diabetic rats.

OBJECTIVES: Type 2 diabetes (T2DM) and alcoholism are considered to be lifestyle-associated independent risk factors in fatty liver diseases (FLD) mediated cirrhosis and hepatocellular carcinoma (HCC). A combined effect of both these conditions may exacerbate the pathological changes and a pre-clinical exploration of this is expected to provide a mechanical detail of the pathophysiology. The present study aims to understand the effect of alcohol on pre- diabetic and type 2 diabetic female Wistar rats. METHODS: In this experimental study, 12 Wistar rats (180-220 g) were randomly assigned into three groups: Normal (fed normal rat chow), alcohol (20 %) fed diabetic (HFD + STZ), and pre-diabetic rats (HFD alone). After, two months of the experimental period, blood and liver tissues were collected lipid metabolic alteration, liver injury, and fibrosis were determined following biochemical and histological methods. Data were analyzed using one-way ANOVA and Dunnett's Post Hoc test. RESULTS: Significant dyslipidemia was observed in the liver tissues of diabetic and pre-diabetic rats following alcohol ingestion. A significant (p<0.05) increase in lipid peroxidation status, and hepatic marker enzyme activities (p<0.0001) were observed in diabetic animals. In corroborating with these observations, hematoxylin and eosin staining of hepatic tissue revealed the presence of sinusoidal dilation along with heavily damaged hepatocytes and inflammatory cell infiltration. Further, significantly (p<0.001) increased hepatic hydroxyproline content and extended picrosirius red stained areas of collagen in liver tissue indicated initiation of fibrosis in alcohol-fed diabetic rats. CONCLUSIONS: Overall, the results indicate that alcohol consumption in T2DM conditions is more deleterious than pre diabetic conditions in progressing to hepatic fibrosis.

Virgin Coconut Oil Alleviates Dextran Sulphate-Induced Inflammatory Bowel Disease and Modulates Inflammation and Immune Response in Mice.

OBJECTIVE: Virgin coconut oil (VCNO), an unrefined kernel oil from Cocos nucifera L., has considerable medicinal and nutritive value. Experimental evidence suggests its antioxidant, anti-inflammatory, chemoprotective, analgesic, and hypolipidemic effects. Presently, the effect of VCNO on ameliorating dextran sodium sulfate (DSS)-induced inflammatory bowel disease and cyclophosphamide (CTX)-induced immunosuppression in experimental animals was analyzed. METHOD: DSS (4%) was administered to BALB/c mice through drinking water for 12 days to induce inflammatory bowel disease, and VCNO (500, 750, and 1000 mg/kg bwt) was supplemented orally for 12 days. For anti-inflammatory studies, lipopolysaccharide (LPS, 250 µg/animal) was injected into the intraperitoneal cavity of Swiss albino mice followed by 7 days' pretreatment of VCNO (500, 750, and 1000 mg/kg bwt). To understand the mechanism of action, serum from all animals was collected after 6 hours of LPS challenge and levels of proinflammatory cytokines were analyzed using enzyme-inked immunosorbent assay. In addition to this, immunosuppression was induced by CTX (50 mg/kg bwt, po) in Swiss albino mice. RESULTS: Oral administration of VCNO effectively reversed the pathologies associated with inflammatory bowel disease induced by DSS, including loss of body weight, increased disease activity index, shortening of colon length, diarrhea, and rectal bleeding. Histopathological examination showed that VCNO restored the damage in colon tissue induced by DSS. Similar trends were noticed in levels of myeloperoxidase and mRNA expression of proinflammatory cytokines in colon tissue. In addition to this, supplementation of VCNO markedly reduced the hike in the level of serum proinflammatory cytokines in LPS-challenged mice. Further, administration of VCNO effectively increased spleen and thymus indexes and stimulated the production of interferon-γ in serum. CONCLUSIONS: Overall, this study revealed that VCNO alleviates inflammatory bowel disease and inflammation; concurrently, it can revert immunosuppression.

Normolipidic diet containing deep-fried saturated and unsaturated fatty acids rich edible oils promotes metabolic dysregulation and inflammatory microenvironment in Wistar rats.

Deleterious health impacts of high dietary intake of deep-fried edible oils have been reported however, their health impacts at normal dietary levels are yet to be evaluated. This study investigated the influence of prolonged consumption of thermally oxidised long-chain saturated and unsaturated edible oils on metabolic dysregulation and inflammation. The thermally oxidised oils used in the study possess higher p-anisidine values and free fatty acid contents compared to unoxidised oils. Fourier transform infrared spectroscopy and fatty acid methyl ester analysis confirmed the presence of free fatty acids, hydroperoxides, and aldehydes, formed during thermal oxidation. The study analysed the effects of dietary intake of 5% sunflower oil, palm oil, and their thermally-oxidised forms in male Wistar rats for six months. Unoxidised and thermally oxidised palm oil-fed animals experienced metabolic syndrome with obesity-associated inflammatory changes. However, sunflower oil-fed animals exhibited increased inflammation, as evidenced by enhanced C-reactive protein, IL-6, and lipoprotein-associated phospholipase A2 activity and hepatosteatosis condition. This study indicates that prolonged consumption of thermally oxidised oil leads to the dysregulation of carbohydrate and lipid metabolism andpromotes inflammatory microenvironment in Wistar rats that may contribute to metabolic syndrome associated with obesity and hepatic steatosis.

A High-Fructose Diet Formulated with Thermally Oxidized Monounsaturated Fat Aggravates Metabolic Dysregulation in Colon Epithelial Tissues of Rats.

BACKGROUND: Various epidemiological and clinical studies have indicated a positive association of colon cancer with high sugar and thermally oxidized fats consumption. The present study evaluated the effects of fresh and thermally oxidized coconut (CO) and mustard oils (MO) along with a high-sugar diet in the rat colon mucosa. METHODS: The animals were fed with a modified diet containing high-fructose and different edible oils as fatty acids sources over a period of 30 weeks. Further, the development of insulin resistance and hyperglycemia were estimated biochemically. The changes in the redox status were estimated in terms of reduced glutathione (GSH), antioxidant enzymes and thiobarbituric acid reactive substances (TBARS). Changes in the expression of genes associated with inflammation and cell proliferation were evaluated by qPCR. RESULTS: The animals fed with high-fructose developed hyperglycemia and insulin resistance over 30 weeks. These animals had diminished GSH level, SOD activity and a concomitant increase in the TBARS level in the colon epithelial tissues. In addition, the expression of pro-inflammatory cytokines (IL-6 and TNF-α) was elevated while P53 and PPARγ were down-regulated. This heightened body metabolic dysregulation and associated oxidative damage and inflammation in the colon were exacerbated by thermally oxidized edible oils incorporated in the diet, with a more prominent effect was observed with TMO. CONCLUSION: Feeding high-fructose diet with TMO increases the oxidative and inflammatory damages in the colon epithelium of Wistar rats. Therefore, the study cautions the prolonged consumption of thermally oxidized monounsaturated fat-rich edible oils, especially by individuals with type 2 diabetes.

Hot-processed virgin coconut oil abrogates cisplatin-induced nephrotoxicity by restoring redox balance in rats compared to fermentation-processed virgin coconut oil.

Virgin coconut oil (VCO) is a functional food oil prepared from fresh coconut kernel either by hot-processed (HPVCO) or fermentation-processed (FPVCO). The FPVCO has been widely explored for its pharmacological efficacy; while HPVCO, which has traditional uses, is less explored. The present study compared the phenolic content and nephroprotective effect of both these oils in male Wistar rats. In vitro antioxidant activity was estimated in terms of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, ferric reducing antioxidant power and ex vivo lipid peroxidation inhibition. In in vivo models, the rats were pretreated orally with of FPVCO or HPVCO (doses 2 and 4 mL/kg) for seven days and nephrotoxicity was induced by the single intraperitoneal injection of cisplatin (10 mg/kg). The results indicated significantly higher polyphenol content in HPVCO (400.3 ± 5.8 µg/mL) than that of FPVCO (255.5 ± 5.8 µg/mL). Corroborating with the increased levels of polyphenols, the in vitro antioxidant potential was significantly higher in the HPVCO. Further, pretreatment with these VCO preparations protected the rats against the cisplatin-induced nephrotoxicity, with higher extent by HPVCO. The renal function markers like urea, creatinine and total bilirubin were significantly reduced (p < 0.05) with HPVCO pretreatment. Apart from the nephroprotective effects, HPVCO also abrogated the cisplatin-induced myelosuppression and hepatotoxicity. The restoration of hepato-renal function by the pretreatment of HPVCO was well corroborated with the improvement in functional antioxidants and subsequent reduction in renal lipid peroxidation. Supporting these observations, renal histology revealed reduced glomerular/tubular congestion and necrosis. Thus, the study concludes that HPVCO may be better functional food than FPVCO.

Virgin coconut oil complements with its polyphenol components mitigate sodium fluoride toxicity in vitro and in vivo.

Virgin coconut oil (VCO), prepared from fresh coconut kernel without any chemical refining, is an emerging functional food. The pharmacological benefits of VCO are believed to be due to the natural combination of phenolics. Although cell culture studies have demonstrated the antioxidant activity of VCO under different oxidative stress conditions, a valid in vivo demonstration of the antioxidant activity of VCO is yet to come. Sodium fluoride (NaF), an environmental pollutant, is widely used to induce oxidative stress in cell culture models and rodents to test the antioxidant potential of several compounds. Herein, VCO and its polyphenolic (VCOP) and non-phenolic oil fraction (VCOF) were individually tested in fluoride-exposed normal intestinal cells (IEC-6) and mice to address their contribution to the documented antioxidant potential. It was found that pretreatment of VCOP (40 µg/mL) was effective in mitigating the fluoride-induced cell death when compared to VCO (200 µg/mL) and VCOF (160 µg/mL). Further, exposure to fluoride (10 mM), increased the intracellular ROS measured based on the dichlorofluorescein (DCF) fluorescence, and this, in turn, was significantly reduced when the cells were supplemented with VCOP. Oral administration of VCO (2 mL/kg bwt) reversed the drop in the hepatic catalase and SOD activities to near normal with a minimal level of lipid peroxidation in fluoride intoxicated mice. However, VCOP and VCOF were less effective in lowering the fluoride-induced increase in hepatic oxidative stress markers. It is reasoned that the oil components of VCO complement the natural antioxidant molecules resulting in an overall increase in their bioavailability.

Amelioration of sodium fluoride induced oxidative stress by Cynometra travancorica Bedd in mice.

OBJECTIVES: Cynometra travancorica, endemic to Western Ghats of India is pharmacologically similar to Saraca asoca and occasionally used as substitute in a well-known Ayurvedic uterine tonic Asokarishta. S. asoca possess various biological properties, but there are no reports on C. travancorica. The present study evaluated the pharmacological properties of C. travancorica and its efficacy in attenuating the sodium fluoride (NaF) induced oxidative stress in mice. METHODS: Antioxidant potential of methanolic extract of C. travancorica (CTE) stem bark was evaluated using DPPH, superoxide radical scavenging and total antioxidant assays. The effect of CTE on mitigating NaF deteriorated redox status in the liver tissue of mice was evaluated. Functional groups in CTE were analyzed by FTIR analysis. RESULTS: CTE effectively scavenged the free radicals in in vitro condition. CTE could augment catalase (46.6%), superoxide dismutase (53.8%) activities and GSH level (48.1%) against NaF induced decline in the liver tissue of mice. The peroxidation of lipids was found to be decreased by 44.9% and tissue damage abated as inferred by histopathology. FTIR analysis revealed the presence of biologically active functional groups in CTE. CONCLUSIONS: The study revealed the ameliorative effect of C. travancorica against NaF induced deleterious effect in experimental animals by its potent antioxidant potential.

Atherogenic oxoaldehyde of cholesterol induces innate immune response in monocytes and macrophages.

Cholesterol oxidation product, 3ß-hydroxy-5-oxo-5,6-secocholestan-6-al (cholesterol 5,6-secosterol, ChSeco or Atheronal-A), formed at inflammatory sites, has been shown to promote monocyte differentiation into macrophages and cause elevated expression of macrophage scavenger receptors. Since inflammation is a key event at all stages of atherosclerotic plaque formation, the pro-inflammatory actions of ChSeco in human THP-1 monocytes and mouse J774 macrophages were investigated in the present study by employing ELISA, qRT-PCR, and functional assays. An increase in the secretion of interleukin-8 and platelet-derived growth factor (PDGF) isoform AA and, to a limited extent, PDGF isoform BB was observed into the culture medium of THP-1 monocytes exposed to ChSeco. However, no changes were seen in the secretion of tumor necrosis factor-alpha. In J774 macrophages treated with ChSeco, there was an upregulation of gene expression of several pro-inflammatory cytokines and their receptors. Concomitantly, there was down-regulation of gene expression of interleukin-1ß, interleukin-10, and lymphotoxin-beta. An increase in the release of interleukin-18 and chemokine (C-C motif) ligand-20 from J774 macrophages (which corroborated well with their gene expression profiles) and increased binding of THP-1 monocytes to ChSeco-exposed human aortic endothelial cells were observed. The results of the present study, for the first time, demonstrate the pro-inflammatory action of ChSeco and suggest the underlying pro-atherogenic mechanisms. These could be mediated through enhanced monocyte recruitment into the sub-endothelial space and subsequent proliferation of smooth muscle cells under the influence of monocyte-derived PDGF.

Targeting Histone Onco- Modifications Using Plant-Derived Products.

The regulatory mechanisms lying over the genome that determines the differential expression of genes are termed epigenetic mechanisms. DNA methylation, acetylation, and phosphorylation of histone proteins and RNAi are typical examples. These epigenetic modifications are important determinants of normal growth and metabolism; at the same time, aberrant histone modifications play a major role in pathological conditions and are emerging as a new area of research for the last decades. Histone onco-modification is a term introduced by the scientific world to denote histone post-translational modifications that are associated with cancer development and progression. These modifications are likely to act in certain conditions as adaptive mechanisms to environmental and social factors. The enzymes that regulate DNA methylation as well as histone modifications are thus become a target for cancer therapy and chemoprevention. Since oxidative stress has been shown to modulate epigenetic changes, and phytocompounds with powerful antioxidant properties have a significant role in disease prevention. Nowadays, "nutri- epigenetics" is becoming an emerging area of research that deals with the influence of dietary compounds in epigenetics. This review aims to discuss the biological efficacy of promising phytocompounds that are able to counteract deleterious epigenetic modifications, especially histone onco- modifications.

Curcumin Enriched VCO Protects against 7,12-Dimethyl Benz[a] Anthracene-Induced Skin Papilloma in Mice.

Virgin coconut oil (VCO) and turmeric are traditionally being used in Indian cuisine systems; VCO is a natural combination of medium-chain triglyceride and polyphenols with established pharmacological potential. Curcumin isolated from turmeric is renowned for its anticancer properties, however, with limited clinical success due to poor bioavailability. Considering the lipophilic nature of VCO, curcumin added to VCO is expected to have synergistic/additive actions. In this study, the chemopreventive potential of curcumin enriched VCO (VCr) (4 and 8 mL/Kg orally) was analyzed in 7,12-dimethyl benz[a]anthracene (DMBA;470 nmoles/200 µL/week for two weeks topical)/croton oil (3% v/v in 200 µL acetone twice a week for 6 weeks topical) induced skin papilloma. In DMBA control animals, an average incidence of 13 papilloma/mice (latency period of 11.6 ± 1.5 weeks) was recorded. Pretreatment with VCrH (8 mL/kg) had a 60% inhibition of tumor index, and an increased latency period (12.5 ± 0.9 weeks). Additionally, DMBA/croton oil-induced reduction in glutathione levels and concomitant increase in thiobarbituric acid reactive substance (TBARS) in the skin microenvironment were restored by VCr. The study thus suggests that the VCr promotes antioxidant status in vivo and imparts an improved anticarcinogenic potential. However, further studies are necessary to ascertain the improvement in bioavailability of curcumin .

Natural combination of phenolic glycosides from fruits resists pro-oxidant insults to colon cells and enhances intrinsic antioxidant status in mice.

A combination of fresh fruits adequately supplying required nutrients is likely to have better health benefits by virtue of the synergistic/additive effect of its natural constituents. With this view and aiming to obtain phenolic glycosides in combination, fresh apple, grape, orange, pomegranate, and sapota fruit juices were combined and lyophilized. An aqueous extract of this fruit combination (AEFC) had polyphenols as a major constituent (47.36 µg GAE/mL) and LC-MS analysis documented the presence of cyanidin and pallidol 3-O-glucosides, phloridzin, delphinidin-3-O-rutinoside, kaempferol-3-O-pentoside, quercetin-3-O-rutinoside, trans-caffeic acid. Corroborating this, AEFC exhibited significant DPPH and superoxide radical scavenging activities (IC50values 43.63 and 49.01 µg/mL) and protected colon epithelial cells (HCT-15) against H2O2 and AAPH induced cell death by 40 and 72.62% and buthionine sulfoximine (BSO) induced GSH depletion by 52.43%. In normal Swiss albino mice, administration of AEFC for over 30 days improved hepatic and renal GPx, SOD, and catalase activities and GSH levels. The study thus suggests the combinatorial effects of natural phenolic glycosides from fruits in resisting oxidative insults and associated disease pathology.

Non-polar lipid carbonyls of thermally oxidized coconut oil induce hepatotoxicity mediated by redox imbalance.

Thermal oxidation products of edible oils including aldehydes, peroxides and polymerized triglycerides formed during the cooking process are increasingly debated as contributory to chronic degenerative diseases. Depending on the oil used for cooking, the source of fatty acids and its oxidation products may vary and would have a differential influence on the physiological process. Coconut oil (CO) is a medium chain triglyceride-rich edible oil used in South India and other Asia Pacific countries for cooking purposes. The present study evaluated the biological effects of thermally oxidized coconut oil (TCO) as well as its non- polar hexane (TCOH) and polar methanol (TCO-M) sub-fractions in male Wistar rats. Results showed an increase in the thiobarbituric acid reactive substances (TBARs) and conjugated diene levels in TCO, which was extracted to TCOH fraction. The animals consumed TCO and its hexane and methanol fractions had a considerable increase in weight gain. However, serum and hepatic triglycerides were increased only in animals with TCO and TCOH administration. In these animals, the hepatic redox balance was disturbed, with a reduction in GSH and a concomitant increase in thiobarbituric acid reactive substances (TBARs). Increased incidence of microvesicles in hepatic histological observations also supported this assumption. Together, the study shows that TCO consumption is unhealthy, where the nonpolar compounds generated during thermal oxidation may be involved in the toxic insults.

Non-enzymatic conversion of primary oxidation products of Docosahexaenoic acid into less toxic acid molecules.

Docosahexaenoic acid (DHA) is long chain omega-3 fatty acid with known health benefits and clinical significance. However, 4-hydroxy hexenal (HHE), an enzymatic oxidation product of DHA has recently been reported to have health-damaging effects. This conflict raises major concern on the long-term clinical use of these fatty acids. Even though the enzymatic and non-enzymatic conversion of HHE to nontoxic acid molecules is possible by the aldehyde detoxification systems, it has not yet studied. To address this, primary oxidation products of DHA in lipoxidase system were subjected to non-enzymatic conversion at physiological temperature over a period of 1 week. The reaction was monitored using HPLC, IR spectroscopy and biochemical assays (based on the loss of conjugated dienes, lipid peroxides aldehydes). Short term and long term cytotoxicity of the compounds generated at various time points were analyzed. IR and HPLC spectra revealed that the level of aldehydes in the primary oxidation products reduced over time, generating acids and acid derivatives within a week period. In short term and long term cytotoxicity analysis, initial decomposition products were found more toxic than the 1-week decomposition products. Further, when primary oxidation products were subjected to aldehyde dehydrogenase mediated oxidation, it generated products that are also less toxic. The study suggests the possible non-enzymatic conversion of primary oxidation products of DHA to less cytotoxic acid molecules. Exploration of the physiological roles of these acid molecules may explain the biological potential of omega-3 fatty acids.

Partially Purified Aqueous Fraction of Desmodium gyrans DC Improves Reverse Cholesterol Transport and Lipoprotein Metabolism in Wistar Rats Fed with High Fat Diet.

Apart from the conventional hypolipidemic therapy, plaque regression through enhanced reverse cholesterol transport (RCT) has emerged as novel approach in atherosclerotic drug development. High-density lipoprotein (HDL) mimetics as well as agents that augment the functional HDL and RCT pathways are under intense exploration. Desmodium gyrans (Fabacea) has been shown to have hypolipidemic efficacy, with an HDL-enhancing property. In this study, a chromatographically purified active fraction of D. gyrans (DGMAF) significantly decreased the serum and lipid profiles as well as lipotoxicity in liver in Wistar rats fed with high-fat diet (HFD). Except for the marginal deposition of liver lipids, all other organs showed no weight gain due to lipid accumulation. A lower level of lipid peroxidation and a reduced atherogenic index suggests the hypolipidemic efficacy of DGMAF, which was comparatively higher than clinically used atorvastatin. Furthermore, the DGMAF-treated animals had enhanced levels of HDL, associated ApoA-1, and paraoxonase activity. The mRNA levels of ApoA-1 and SR-B1 were upregulated, and cholesteryl ester transfer protein (CETP) was downregulated. Overall, the results of this study indicate that D. gyrans augments the RCT pathway and improves the lipid metabolism in rats fed an HFD.

EGFR gene regulation in colorectal cancer cells by garlic phytocompounds with special emphasis on S-Allyl-L-Cysteine Sulfoxide.

Colorectal cancer is one among the most common cancers in the world and a major cause of cancer related deaths. Similar to other cancers, colorectal carcinogenesis is often associated with over expression of genes related to cell growth and proliferation, especially Epidermal Growth Factor Receptor (EGFR). There is an increasing attention towards the plant derived compounds in prevention of colorectal carcinogenesis by downregulating EGFR. Among plants, garlic (Allium sativum L.) is emerging with anticancer properties by virtue of its organosulfur compounds. The present study was aimed to analyze the interaction ability of garlic compounds in the active region of EGFR gene by in silico molecular docking studies and in vitro validation. This was conducted using the Discovery studio software version 4.0. Among the tested compounds, s-allyl-l-cysteine-sulfoxide (SACS)/alliin showed higher affinity towards EGFR. Furthermore, wet lab analysis using cell viability test and EGFR expression analysis in colorectal cancer cells confirmed its efficacy as a potent anticancer agent.

Virgin coconut oil reverses hepatic steatosis by restoring redox homeostasis and lipid metabolism in male Wistar rats.

BACKGROUND: Hepatosteatosis, a form of nonalcoholic fatty liver disease (NAFLD), is being increasingly recognized as a major health burden worldwide. Insulin resistance, dyslipidemia and imbalances in adipokine/cytokine interplay are reported to be involved in the onset and progression of this disease. Use of dietary nutraceuticals in prevention and treatment of NAFLD is emerging. Virgin coconut oil (VCO), a fermented product of fresh coconut kernel, has been shown to impede the development of hepatosteatosis in rats. This study analyzes the potential of VCO to reverse the already developed hepatosteatosis condition. RESULTS: Hyperglycemia, reduced glucose tolerance, dyslipidemia, and hepatic macrovesicles in high-fructose-diet-fed rats (4 weeks) confirmed the development of hepatosteatosis. Natural reversion in these parameters was observed upon shifting to normal diet in untreated control animals. Administration of VCO, however, increased this natural reversion by improving high-density lipoprotein cholesterol level (53.5%) and reducing hepatic and serum triacylglycerols (78.0 and 51.7%). Increased hepatic glutathione level (P < 0.01), antioxidant enzyme activities (P < 0.05) and reduced lipid peroxidation were also noticed in these animals. These observations were in concordance with reduced liver enzyme activities (P < 0.01) and restoration of altered hepatic architecture. CONCLUSION: The study indicates that VCO can be used as a nutraceutical against hepatosteatosis. © 2017 Society of Chemical Industry.

Coconut phytocompounds inhibits polyol pathway enzymes: Implication in prevention of microvascular diabetic complications.

Coconut oil (CO), the primary choice of cooking purposes in the south Asian countries, is rich in medium chain saturated fatty acids, especially lauric acid (50-52%). The oil has high medicinal use in Ayurvedic system and known to contain polyphenolic antioxidants. Studies have reported that CO improves insulin sensitivity and shows hypoglycemic effect. However, there is no information regarding its effect on chronic diabetic complications including retinopathy and nephropathy is available. The secondary diabetic complications are mediated by the activation of polyol pathway, where aldose reductase (AR) plays crucial role. In this study, in silico analysis has been used to screen the effect of CO as well as its constituents, MCFAs and phenolic compounds, for targeting the molecules in polyol pathway. The study revealed that lauric acid (LA) interacts with AR and DPP-IV of polyol pathway and inhibits the activity of these enzymes. Validation studies using animal models confirmed the inhibition of AR and SDH in wistar rats. Further, the LA dose dependently reduced the expression of AR in HCT-15 cells. Together, the study suggests the possible role of CO, particularly LA in reducing secondary diabetic complications.

Epithelial Mesenchymal Transition in Cancer Progression: Prev entive Phytochemicals.

BACKGROUND: Epithelial-Mesenchymal Transition (EMT) is the conversion of epithelial cells into mesenchymal phenotype generally observed during embryogenesis and wound healing as well as in malignant transformation. Several signaling pathways and transcription factors associated with EMT have been explored. Dietary phytochemicals that are multi-targeted agents which interfere with these pathways, assume preventive potential against pathologic EMT. OBJECTIVE: The present review aims to provide a detailed description of the nature and characteristics of EMT in physiological and pathophysiological conditions and the scope of phytochemicals in its prevention. METHOD: Details regarding the initiation, progression as well as prevention of pathologic EMT and metastasis and recent patents on preventive phytochemicals were obtained from PubMed literatures and patent databases. RESULTS: The phenotypic changes during EMT are regulated by transcription factors like Snail, Slug, Twist and Zeb, which are activated through diverse signaling pathways of TGF-ß, NF-kB, Wnt and Notch. s phytocompounds that are potent enough to interfere with these signaling pathways, which in turn prevent pathological implications of EMT. Present review also discusses 28 recent patents on those phytocompounds. CONCLUSION: EMT is a significant pharmacological target for developing preventive agents to combat pathological conditions like malignancy. Many of the phytochemicals cited in this review are being enrolled for different phases of clinical trials for their efficacy. In spite of the major limitations regarding bioavailability, sensitivity and tolerance of these compounds, their synthetic analogs, formulations and efficient drug delivery systems are also being attempted which will hopefully generate productive and promising results in near future.

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

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 (Glutathione-S-Transferase) and catalase (CAT) were restored to near-normal by VCOP, concomitantly reducing lipid peroxidation. The efficacy of VCOP was similar to that of Trolox and FA added in culture. The study thus suggests that VCOP protects cells from pro-oxidant insults by modulating cellular antioxidant status.

Vitamin E supplementation modulates the biological effects of omega-3 fatty acids in naturally aged rats.

Omega-3 fatty acids are well-known class of nutraceuticals with established health benefits. Recently, the oxidation products of these fatty acids are gaining attention, as they are likely to disturb body redox balance. Therefore, the efficacy of omega-3 fats under conditions of diminished antioxidant status, such as aging, is always a concern. Present study assessed the effects of omega-3 fats (DHA and EPA) together with or without vitamin-E in naturally aged rats. It was found that in omega-3 fats alone consumed rats the lipid profile was improved, while in omega-3 fat with vitamin-E-consumed group (OMVE), the hepato protective and antioxidant properties were pronounced, especially the redox status of brain tissue. It is possible that vitamin-E might have reduced the peroxidation of omega-3 fats, thereby allowing their synergistic effects. Hence, the use of vitamin-E along with omega-3 fat may be beneficial under aged conditions.