Molecular mechanisms of the antiglycative and cardioprotective activities of Psidium guajava leaves in the rat diabetic myocardium.

CONTEXT: Antiglycative potential of Psidium guajava L. (Myrtaceae) leaves has been established. However, the molecular basis of its antiglycative potential remains unknown. OBJECTIVE: The ethyl acetate fraction of P. guajava leaves (PGEt) was evaluated to determine the cardioprotective effect and its mechanism of action compared to quercetin. MATERIALS AND METHODS: After the induction of diabetes by streptozotocin (55 mg/kg body weight), PGEt and quercetin (50 mg/kg body weight) was administered for 60 days. Rats were grouped as follows: Group C: Control, Group D: Diabetic, Group D + E: Diabetic rats treated with PGEt, Group D + Q: Diabetic rats treated with quercetin. The antiglycative potential was evaluated by assaying glycosylated haemoglobin, serum fructosamine and advanced glycation end product levels. The differential receptor for advanced glycation end products and nuclear factor kappa B (NFκB) protein levels was determined by western blot and the transcript level changes of connective tissue growth factor (CTGF), brain natriuretic peptide (BNP) and TGF-ß1 in heart tissue were assessed by RT-PCR analysis. RESULTS: Glycated haemoglobin and serum fructosamine levels were found to be enhanced in diabetic rats when compared with control. Administration of PGEt significantly reduced the glycated haemoglobin and fructosamine levels to a larger extent than quercetin treated diabetic rats. PGEt reduced the translocation of NFκB from cytosol to nucleus when compared with diabetic rats. Expression of TGF-ß1, CTGF and BNP was downregulated in PGEt treated groups compared with diabetic controls. DISCUSSION AND CONCLUSION: Administration of PGEt ameliorated diabetes associated changes in the myocardium to a greater extent than quercetin.

The Ayurvedic drug Ksheerabala (101) ameliorates alcohol-induced neurotoxicity by down-regulating the expression of transcription factor (NFkB) in rat brain.

INTRODUCTION: Most of the pharmaceutical effects of alcohol are due to its accumulation in the brain. Ksheerabala (101) an Ayurvedic formulation mainly used against central nervous system disorders. AIM: To determine the antioxidant and neuroprotective effect of Ksheerabala (101) on alcohol-induced oxidative stress in rats. MATERIALS AND METHODS: Male Albino rats of Sprague-Dawley strain were grouped into four; control, alcohol (4 g/kg), Ksheerabala (15 µL/1 ml milk/100 g) and Ksheerabala (15 µL/1 ml milk/100 g) + alcohol (4 g/kg). After the experimental period (90 days), the animals were sacrificed and the effect of Ksheerabala (101) was studied on oxidative stress, inflammatory markers, and induction of transcription factor in brain. Results were statistically analyzed by one-way ANOVA. RESULTS: The activities of antioxidant enzymes and reduced glutathione which were decreased in alcohol-treated rats, increased significantly in co-administered groups. The lipid peroxidation products and protein carbonyls which were increased significantly in alcohol-treated rats decreased significantly in co-administered groups. The expression of gamma-glutamyl cysteine synthase decreased significantly in alcohol-treated rats and increased significantly in co-administered groups. The transcription factor nuclear factor-κB (NFκB) which was up-regulated in alcohol-treated rats was down-regulated in co-administered rats. The histopathology reinforced these results. CONCLUSION: Ksheerabala (101) attenuates alcohol-induced oxidative stress and down-regulates the expression of NFκB in rat brain.

Reversal of alcohol induced testicular hyperlipidemia by supplementation of ascorbic acid and its comparison with abstention in male guinea pigs.

BACKGROUND: Chronic ethanol exposure causes hyperlipidemia. The present study was designed to investigate the impact of ascorbic acid supplementation on ethanol induced hyperlipidemia in testis and to compare it with that of abstinence from taking alcohol. METHODS: Thirty-six male guinea pigs were divided into two groups and were maintained for 90 days as follows (1) control (C) (2) ethanol treated group (E) (4 g/kg body wt/day). Ethanol was administered for 90 days and on 90th day, alanine amino transaminase (ALT), aspartate amino transaminase (AST) and γ-glutamyltransferase (GGT) in serum was assayed. The animals in the ethanol group were further divided into an ascorbic acid supplemented group (25 mg/100 g body wt/day) (E+AA) and an ethanol abstention group (EAG) and those in the control group were divided into a control group and a control+ascorbic acid group (C+AA). RESULTS: There was significant increase in levels of testicular cholesterol, free fatty acid, phospholipids and triglycerides in the ethanol group. There was also a significant increase in the activity of HMG CoA reductase and decrease in activity of testicular glucose-6-phosphate dehydrogenase (G6PDH) and malic enzyme in ethanol-ingested animals that further led to decreased levels of serum testosterone. Alcohol administration also enhanced the activity of testicular alcohol dehydrogenase (ADH). Ascorbic acid supplementation and abstention altered all these parameters induced by chronic alcohol administration. Histological studies were also in line with the above results. CONCLUSIONS: Ascorbic acid was able to reinstate the cholesterol homeostasis in testis which could have further restored the testicular steroidogenesis. The present study demonstrated that ascorbic acid is effective in reducing the hyperlipidemia induced by chronic alcohol administration and produced a better recovery than abstention.

Comparative study of the efficacy of ascorbic acid, quercetin, and thiamine for reversing ethanol-induced toxicity.

This study compares the curative effect of three antioxidants-ascorbic acid, quercetin, and thiamine-on ethanol-induced toxicity in rats. Administration of ethanol at a dose of 4 g/kg of body weight/day for 90 days initiated chronic alcohol-induced oxidative stress as shown by increased malondialdehyde level and DNA fragmentation in liver and brain. Ethanol administration also led to a decrease in DNA content. Activities of toxicity marker enzymes-alanine aminotransferase, aspartate aminotransferase, and γ-glutamyltranspeptidase-in liver and serum increased progressively upon ethanol administration. After ethanol administration for 90 days, the efficacy of antioxidant treatment of the alcohol-induced toxicity was studied by supplementing ascorbic acid (200 mg/100 g of body weight/day), quercetin (50 mg/kg of body weight/day), and thiamine (25 mg/kg of body weight/day) for 30 days. These groups were compared with the abstention group (not treated with ethanol). All the alterations induced by alcohol were reduced significantly by the supplementation of antioxidants and also with abstention. The regression by antioxidants was greater that of abstention. Antioxidants significantly reduced the oxidative stress induced by ethanol intoxication, increased membrane integrity, and also increased organ regeneration. Ascorbic acid was shown to be more effective than quercetin and thiamine in treating both hepatotoxicity and neurotoxicity induced by alcohol administration. This may be due to the higher antioxidant potential of ascorbic acid in physiological conditions.

Spermatotoxicity of a protein isolated from the root of Achyranthes aspera: a comparative study with gossypol.

BACKGROUND: A previous study showed that 50% ethanolic extracts of the roots of Achyranthes aspera possess spermatotoxic effects. STUDY DESIGN: A 58-kDa protein (Ap) was isolated, and its spermatotoxic effects were studied in comparison with gossypol. Ap (25 mg/kg body weight a day) and gossypol (40 mg/kg body weight a day) were administered orally to Swiss male albino mice for 35 days. Sperm motility, sperm count, sperm abnormality, toxicity markers such as aspartate aminotransferase (AST), alanine aminotransferase (ALT) in the liver and serum, testicular activities of hydroxyl methyl glutaryl CoA reductase (HMG CoA reductase), 3ß-hydroxysteroid dehydrogenase (3ß-HSD), 17ß-hydroxysteroid dehydrogenase(17ß-HSD), glucose-6-phosphate dehydrogenase, cholesterol level and serum testosterone were assayed. Spermicidal action of the proteolytic digests of Ap was also studied in vitro. RESULTS: Treated mice showed significant spermatotoxicity. Significant differences were also observed in the testicular activities of HMG CoA reductase, 3ß-HSD, 17ß-HSD and glucose-6-phosphate dehydrogenase and in the levels of cholesterol and serum testosterone. The nontoxic nature of Ap was indicated by the insignificant alterations in the activities of AST and ALT. Ap possessed spermicidal activity even after proteolysis. CONCLUSION: The 58-kDa protein isolated from A. aspera possesses spermatotoxic effects comparable to gossypol.

Impact of selenium on NFκB translocation in isoproterenol-induced myocardial infarction in rats.

NFκB is a major transcription factor that controls the expression of various genes. Its activation is a complex process that can be triggered by many agents and one among them is reactive oxygen species. The aim of this study was to investigate the effect of selenium on NFκB activation in rats induced with myocardial infarction by isoproterenol (ISP). The markers of myocardial infarction showed increased activity in the serum of rats induced with ISP compared to the group that was pretreated with selenium along with ISP. Cellular selenium status was also found to be very low in the ISP-induced group of rats. The concentration of cytosolic NFκB was comparatively lower in the ISP group than in the group treated with selenium and ISP. Whereas higher levels of NFκB were found in the nuclear extract of the ISP-treated animals than in the selenium + ISP group. Elevated levels of malondialdehyde, hydroperoxides, and conjugated diens in the ISP-treated rats revealed the higher levels of oxidative stress in this group. Thus, our studies reveal the inhibitory effect of selenium in the nuclear translocation of NFκB during myocardial infarction. Histopathological studies of the heart also support the cardioprotective role of selenium.

Spermatotoxic effects of Cananga odorata (Lam): a comparison with gossypol.

OBJECTIVE: To compare the antifertility effects of 50% ethanolic extract of the root bark of Cananga odorata with gossypol. DESIGN: Controlled research laboratory study. SETTING: University research laboratory. ANIMAL(S): Male albino rats (Sprague Dawley, body weight 150 +/- 5 g) bred in university animal house. INTERVENTION(S): A 50% ethanolic extract of the root bark of Cananga odorata and gossypol was administered orally for 60 days. On day 61, one third of the animals in each group were killed for various analyses. One half of the remaining animals were used for the evaluation of fertility index, and other half was maintained for 15 days more on normal diet. MAIN OUTCOME MEASURE(S): The epididymal sperm motility, morphology, and count, the testicular activities of HMG CoA reductase, 3beta-hydroxy steroid dehydrogenase, glucose-6-phosphate dehydrogenase, and testicular cholesterol and serum testosterone were assessed. RESULT(S): Differences were not observed in the sperm count and fertility index of the gossypol group in comparison with the C odorata group. But statistically significant alterations were noted in the sperm morphology as well as in the activity of HMG CoA reductase, 3beta-hydroxy steroid dehydrogenase, glucose-6-phosphate dehydrogenase, cholesterol, and protein of the testis and in serum testosterone. On withdrawal of the drugs, sperms in C odorata group became completely motile but not in the gossypol group. The active component is a 52 kd protein. CONCLUSION(S): The ethanolic extract of Cananga odorata possesses antifertility effects.