Bacoside A downregulates matrix metalloproteinases 2 and 9 in DEN-induced hepatocellular carcinoma.

Cancer metastasis is a complex multi-step process, responsible for a majority of cancer-related deaths by affecting the critical organs and causing complications in therapies. Hepatocellular carcinoma is a multi-factorial disease and is the third most common cause of cancer related mortality worldwide. Clinical and experimental studies have shown that MMP-2 and MMP-9 are involved in tumor invasion and metastases and their elevated expression has been associated with poor prognosis. Our recent studies showed a strong anti-oxidant and hepatoprotective effects of bacoside A (BA) against carcinogen. Nevertheless the effect of BA on the activities and expression of MMP-2 and MMP-9 during hepatocellular carcinoma is not yet recognized. Therefore, the present study was designed to assess the same. Results of gelatin zymography study showed that BA co-treatment significantly decreased the activities of MMP-2 and MMP-9, which is increased during hepatocellular carcinoma. Further immunoblot analysis showed decreased expression of MMP-2 and MMP-9 in rats co-treated with BA compared to DEN-induced hepatocellular carcinoma. Our results reveal that BA exerts its anti-metastatic effect against DEN-induced hepatocellular carcinoma by inhibiting the activities and expressions of MMP-2 and MMP-9.

Chemopreventive effect of bacoside A on N-nitrosodiethylamine-induced hepatocarcinogenesis in rats.

PURPOSE: Chemoprevention is an effective approach to control hepatocarcinogenesis. Bacoside A, the active constituent of Bacopa monniera Linn., is anticipated to play a role in chemoprevention of liver cancer. METHODS: In the present study, we investigated the chemopreventive effect of bacoside A against N-nitrosodiethylamine-induced hepatocarcinogenesis in an animal model. RESULTS: Administration of carcinogen showed a significant elevation in the levels of lipid peroxidation, serum tumor marker enzymes and liver injury marker enzymes with subsequent decrease in the levels of both hemolysate and liver antioxidant status. Bacoside A co-treatment maintained the N-nitrosodiethylamine-induced alterations at near normal level. Histopathological and electron microscopic study of the liver tissue also supports the above biochemical observations. CONCLUSIONS: From our findings we conclude that bacoside A is effective to prevent DEN-induced hepatocellular carcinoma by quenching lipid peroxidation and enhancing antioxidant status through free radical scavenging mechanism and having potential of protecting endogenous enzymatic and non-enzymatic antioxidant activity.

Differential response of Leydig cells in expressing 11beta-HSD type I and cytochrome P450 aromatase in male rats subjected to corticosterone deficiency.

Emerging evidence suggests that the glucocorticoid and estradiol are important for Leydig cell steroidogenesis and are regulated via aromatase for estradiol production and 11beta-HSD for oxidatively inactivating glucocorticoid. Although it is known that corticosterone deficiency impaired Leydig cell steroidogenesis, its effect on the expression of Leydig cell 11beta-HSD type I and aromatase are yet to be recognized. Following metyrapone-induced corticosterone deficiency, serum corticosterone and testosterone levels decrease, whereas serum estradiol remains unaltered. 11beta-HSD type I mRNA and its activity was decreased by corticosterone deficiency, whereas the activity and mRNA of aromatase remains unaltered. Simultaneous administration of corticosterone prevented its deficiency-induced changes of 11beta-HSD type I in Leydig cells. Our results show that metyrapone-induced corticosterone deficiency impairs Leydig cell 11beta-HSD enzyme activity and 11beta-HSD type I mRNA expression, and the Leydig cells need to maintain their intracellular concentration of corticosterone for a normal function.

Hepatoprotective activity of bacoside A against N-nitrosodiethylamine-induced liver toxicity in adult rats.

N-Nitrosodiethylamine (DEN) is a notorious carcinogen, present in many environmental factors. DEN induces oxidative stress and cellular injury due to enhanced generation of reactive oxygen species; free radical scavengers protect the membranes from DEN-induced damage. The present study was designed to evaluate the protective effect of bacoside A (the active principle isolated from Bacopa monniera Linn.) on carcinogen-induced damage in rat liver. Adult male albino rats were pretreated with 15 mg/kg body weight/day of bacoside A orally (for 14 days) and then intoxicated with single necrogenic dose of N-nitrosodiethylamine (200 mg/kg bodyweight, intraperitonially) and maintained for 7 days. The liver weight, lipid peroxidation (LPO), and activity of serum marker enzymes (aspartate transaminases, alanine transaminases, lactate dehydrogenase, alkaline phosphatase, and gamma-glutamyl transpeptidase) were markedly increased in carcinogen-administered rats, whereas the activities of marker enzymes were near normal in bacoside A-pretreated rats. Activities of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutatione-S-transferase, and reduced glutathione) in liver also decreased in carcinogen-administered rats, which were significantly elevated in bacoside A-pretreated rats. It is concluded that pretreatment of bacoside A prevents the elevation of LPO and activity of serum marker enzymes and maintains the antioxidant system and thus protects the rats from DEN-induced hepatotoxicity.