K. Akhilender Naidu

Vitamin C in human health and disease is still a mystery ? An overview

Ascorbic acid is one of the important water soluble vitamins. It is essential for collagen, carnitine and neurotransmitters biosynthesis. Most plants and animals synthesize ascorbic acid for their own requirement. However, apes and humans can not synthesize ascorbic acid due to lack of an enzyme gulonolactone oxidase. Hence, ascorbic acid has to be supplemented mainly through fruits, vegetables and tablets. The current US recommended daily allowance (RDA) for ascorbic acid ranges between 100–120 mg/per day for adults. Many health benefits have been attributed to ascorbic acid such as antioxidant, anti-atherogenic, anti-carcinogenic, immunomodulator and prevents cold etc. However, lately the health benefits of ascorbic acid has been the subject of debate and controversies viz., Danger of mega doses of ascorbic acid? Does ascorbic acid act as a antioxidant or pro-oxidant ? Does ascorbic acid cause cancer or may interfere with cancer therapy? However, the Panel on dietary antioxidants and related compounds stated that the in vivo data do not clearly show a relationship between excess ascorbic acid intake and kidney stone formation, pro-oxidant effects, excess iron absorption. A number of clinical and epidemiological studies on anti-carcinogenic effects of ascorbic acid in humans did not show any conclusive beneficial effects on various types of cancer except gastric cancer. Recently, a few derivatives of ascorbic acid were tested on cancer cells, among them ascorbic acid esters showed promising anticancer activity compared to ascorbic acid. Ascorbyl stearate was found to inhibit proliferation of human cancer cells by interfering with cell cycle progression, induced apoptosis by modulation of signal transduction pathways. However, more mechanistic and human in vivo studies are needed to understand and elucidate the molecular mechanism underlying the anti-carcinogenic property of ascorbic acid. Thus, though ascorbic acid was discovered in 17th century, the exact role of this vitamin/nutraceutical in human biology and health is still a mystery in view of many beneficial claims and controversies.

Inhibition of human low density lipoprotein oxidation by active principles from spices.

Spice components and their active principles are potential antioxidants. In this study we examined the effect of phenolic and non-phenolic active principles of common spices on copper ion-induced lipid peroxidation of human low density lipoprotein (LDL) by measuring the formation of thiobarbituric acid reactive substance (TBARS) and relative electrophoretic mobility (REM) of LDL on agarose gel. Curcurriin, capsaicin, quercetin, piperine, eugenol and allyl sulfide inhibited the formation of TBARS effectively through out the incubation period of 12 h and decreased the REM of LDL. Spice phenolic active principles viz. curcumin, quercetin and capsaicin at 10 μM produced 40–85% inhibition of LDL oxidation at different time intervals while non-phenolic antioxidant allyl sulfide was less potent in inhibiting oxidation of LDL. However, allyl sulfide, eugenol and ascorbic acid showed pro-oxidant activity at lower concentrations (10 μM) and antioxidant activity at higher concentrations (50 μM) only. Among the spice principles tested quercetin and curcumin showed the highest inhibitory activity while piperine showed least antioxidant activity at equimolar concentration during initiation phase of oxidation of LDL. The inhibitory effect of curcumin, quercetin and capsaicin was comparable to that of BHA, but relatively more potent than ascorbic acid. Further, the effect of curcurnin, quercetin, capsaicin and BHA on initiation and propagation phases of LDL oxidation showed that curcurnin significantly inhibited both initiation and propagation phases of LDL oxidation, while quercetin was found to be ineffective at propagation phase. These data suggest that the above spice active principles, which constitute about 1–4% of above spices, are effective antioxidants and offer protection against oxidation of human LDL.

Antiproliferative and Proapoptotic Effect of Ascorbyl Stearate in Human Pancreatic Cancer Cells: Association with Decreased Expression of Insulin-Like Growth Factor 1 Receptor

Pancreatic cancer is an aggressive tumor with short median survival and high mortality rate. Alternative therapeutic modalities are currently being evaluated for pancreatic cancer. Here we studied the effects of ascorbyl stearate (Asc-S), a nontoxic, lipophilic derivative of ascorbic acid, on pancreatic cancer. Treatment of human pancreatic carcinoma cells with Asc-S (50–200 μM) resulted in a dose-dependent inhibition of their proliferation. Asc-S slowed down the cell cycle, accumulating, PANC-1 cells in late G2-M phase. Furthermore, Asc-S treatment (150 μM) markedly inhibited growth in soft agar and facilitated apoptosis of PANC-1 cells but not of Capan-2 cells. These effects were accompanied by a significant reduction in insulin-like growth factor 1 receptor (IGF1-R) expression, as compared to untreated controls. Interestingly, Capan-2 cells, the least responsive to Asc-S treatment, did not overexpress the IGF1-R. The results demonstrate the efficacy of Asc-S in inhibing growth of pancreatic cancer cells and warrant additional studies to explore the potential utility of this compound as an alternative and/or adjuvant therapeutic modality for pancreatic cancer.

Safety evaluation of Monascus purpureus red mould rice in albino rats

Monascus purpureus MTCC 410-fermented rice (red mould rice) is one of the food supplements to lower blood-lipid levels and monacolins have been proven to be the main active constituents in red mould rice (RMR). In this study, we have assessed the safety of RMR by conducting toxicological studies in albino rats. Acute and sub-chronic toxicity studies were conducted on both sexes of albino rats. Feeding acute doses of RMR at 0.5, 1.0, 2.5 and 5.0 g/kg body weight to rats did not cause any symptoms of toxicity or mortality. Similarly, dietary feeding of RMR at 2.0%, 4.0%, 8.0% and 12.0% level (w/w) for 14 weeks did not produce any significant changes in food intake or gain in body weight of the experimental rats compared to control rats. There were no significant differences in the relative weight of vital organs, hematological parameters, macroscopic and microscopic changes in vital organs and serum clinical enzyme levels between the experimental and control groups. Moreover, the rats fed with RMR showed a significant reduction in cholesterol and triglyceride levels in both serum and liver. The results showed that toxicity studies with RMR of M. purpureus did not cause any toxic effects in albino rats.

Spice active principles as the inhibitors of human platelet aggregation and thromboxane biosynthesis.

Spice active principles are reported to have anti-diabetic, anti-hypercholesterolemic, antilithogenic, anti-inflammatory, anti-microbial and anti-cancer properties. In our previous report we have shown that spices and their active principles inhibit 5-lipoxygenase and also formation of leukotriene C4. In this study, we report the modulatory effect of spice active principles viz., eugenol, capsaicin, piperine, quercetin, curcumin, cinnamaldehyde and allyl sulphide on in vitro human platelet aggregation. We have demonstrated that spice active principles inhibit platelet aggregation induced by different agonists, namely ADP (50microM), collagen (500microg/ml), arachidonic acid (AA) (1.0mM) and calcium ionophore A-23187 (20microM). Spice active principles showed preferential inhibition of arachidonic acid-induced platelet aggregation compared to other agonists. Among the spice active principles tested, eugenol and capsaicin are found to be most potent inhibitors of AA-induced platelet aggregation with IC50 values of 0.5 and 14.6microM, respectively. The order of potency of spice principles in inhibiting AA-induced platelet aggregation is eugenol>capsaicin>curcumin>cinnamaldehyde>piperine>allyl sulphide>quercetin. Eugenol is found to be 29-fold more potent than aspirin in inhibiting AA-induced human platelet aggregation. Eugenol and capsaicin inhibited thromboxane B2 (TXB2) formation in platelets in a dose-dependent manner challenged with AA apparently by the inhibition of the cyclooxygenase (COX-1). Eugenol-mediated inhibition of platelet aggregation is further confirmed by dose-dependent decrease in malondialdehyde (MDA) in platelets. Further, eugenol and capsaicin inhibited platelet aggregation induced by agonists-collagen, ADP and calcium ionophore but to a lesser degree compared to AA. These results clearly suggest that spice principles have beneficial effects in modulating human platelet aggregation.

Toxicity Assessment Of Phycocyanin - A Blue Colorant From Blue Green Alga Spirulina platensis

Abstract Phycocyanin, a blue colorant from the cyanobacterium (blue green alga) Spirulina platensis was evaluated for its safety as a natural food colour by toxicity evaluation studies in albino rats. Acute and subchronic studies on phycocyanin were conducted on both sexes of albino rats. Phycocyanin at high concentrations‐ 0.25 to 5.0 g/kg body weight (w/w) did not induce any symptoms of toxicity nor mortality of the animals. Feeding of low concentrations of phycocyanin at 0.5 to 4.0 g/kg in the diet for 14 weeks did not affect food intake or body weight gain of phycocyanin‐fed rats compared to control animals. Terminal values on absolute and relative weights of vital organs, hematology and serum enzymes did not reveal any differences between phycocyanin‐fed and control groups. Histological examination of vital organs did not show any remarkable differences between treated and control groups. Overall, consumption of phycocyanin, a natural colorant from Spirulina platensis did not result in adverse effect...

Vegetable oil blends with α-linolenic acid rich Garden cress oil modulate lipid metabolism in experimental rats.

Vegetable oil blends with modified fatty acid profile are being developed to improve n-6/n-3 polyunsaturated fatty acid (PUFAs) ratio in edible oils. The objective of this study is to develop vegetable oil blends with α-linolenic acid (ALA) rich Garden cress oil (GCO) and assess their modulatory effect on lipid metabolism. Sunflower oil (SFO), Rice bran oil (RBO), Sesame oil (SESO) were blended with GCO at different ratios to obtain n-6/n-3 PUFA ratio of 2.3-2.6. Native and GCO blended oils were fed to Wistar rats at 10% level in the diet for 60 days. Serum and liver lipids showed significant decrease in Total cholesterol (TC), Triglyceride (TG), LDL-C levels in GCO and GCO blended oil fed rats compared to native oil fed rats. ALA, EPA, DHA contents were significantly increased while linoleic acid (LA), arachidonic acid (AA) levels decreased in different tissues of GCO and GCO blended oils fed rats. In conclusion, blending of vegetable oils with GCO increases ALA, decreases n-6 to n-3 PUFA ratio and beneficially modulates lipid profile.

Inhibition of monoamine oxidase by the fungicide metalaxyl.

The in vitro effect of metalaxyl on monoamine oxidase (MAO) activity in rat heart was studied. Metalaxyl decreased MAO activity in a dose-dependent manner. The inhibitory concentration (IC50) for metalaxyl was found to be 19 mumol. Substrate-dependent kinetic studies demonstrated noncompetitive inhibition as evidenced by decreased velocity of enzyme activity (Vmax) without significant change in enzyme-substrate affinity (Km). The inhibition of MAO activity by metalaxyl suggests interference with amine metabolism.

Oleic acid, hydroxytyrosol and n-3 fatty acids collectively modulate colitis through reduction of oxidative stress and IL-8 synthesis; in vitro and in vivo studies.

Our recent study has demonstrated that medium chain triglycerides (MCT) and monounsaturated fatty acids potentiate the beneficial effects of fish oil on risk factors of cardiovascular disease. In the present study, we have investigated the influence of MCT or olive oil on the protective and mucosal healing ability of fish oil in ulcerative colitis using cell simulation and animal models. Caco-2 cells grown in medium chain fatty acids enriched medium has exaggerated t-butyl hydroperoxide induced cell damage, GSH depletion, and IL-1β induced IL-8 synthesis, compared to the cells grown in oleic acid & hydroxytyrosol (OT) enriched medium. Further, combined treatment of cells with eicosapentaenoic acid, docosahexaenoic acid, and OT has remarkably attenuated the cell damage, and IL-8 synthesis, compared to individual treatments. To evaluate the effect of these lipid formulations in vivo, adult Wistar rats were fed diet enriched with high amount of medium chain triglycerides (MCT), virgin olive oil, or their combination with fish oil. Colitis was induced in rats using dextran sulfate sodium (DSS) for 7days followed by 10-days of recovery period. Rats of MCT group exhibit severe disease activity, higher levels of inflammatory cytokines in the colon compared to the olive oil group. Furthermore, there was persistent body weight loss, loose stools, higher levels of inflammatory cytokines in the rats of MCT group, even after DSS was withdrawn from drinking water. Conversely, fish oil has remarkably attenuated the DSS induced alterations in both MCT and olive oil diet groups with significantly greater effect in the olive oil group. Thus, MCT increase the susceptibility to colitis through oxidative damage and IL-8 synthesis in intestinal epithelial cells. The beneficial effects of virgin olive oil could be partially attributed to hydroxytyrosol. Combined treatment of hydroxytyrosol, oleic acid and n-3 fatty acids exhibit huge therapeutic benefits in colitis.

Rice bran oil and n-3 fatty acid-rich garden cress (Lepidium sativum) seed oil attenuate murine model of ulcerative colitis

Dear Editor:Ulcerative colitis (UC) is an autoimmune disease of humanscharacterizedbychronicinflammationinthecolonandrectum.AlthoughtheetiologyandpathogenesisofUCremainunclear, there is increasing evidence that the dysregulation ofmucosal immunological function plays a major role in theinitiationandpropagationofthisdisease.Dataonthepreviousstudies suggest that the overproduction of pro-inflammatorycytokines such as interleukin-1 β (IL-1β), interferon-γ,andtumornecrosisfactor-α(TNF-α)andinflammatorymediatorssuch as nitric oxide (NO), superoxide, and leukotriene B