Antistress effects of bacosides of Bacopa monnieri: modulation of Hsp70 expression, superoxide dismutase and cytochrome P450 activity in rat brain.
The antistress effect of bacosides of Brahmi (Bacopa monnieri, BBM), dissolved in distilled water, was -studied in adult male Sprague Dawley rats by administering oral doses of 20 and 40 mg/kg for 7 consecutive days. In half of the animals treated with 20 or 40 mg/kg of BBM, stress was given 2 h after the last dose. Stress was also administered to the animals treated with distilled water alone. BBM, at both doses, did not induce a significant change in the expression of Hsp70 in any brain region studied while stress alone produced a significant increase in the Hsp70 expression in all the brain regions. A significant decrease in the activity of superoxide dismutase (SOD) was evident in the hippocampus with the lower dose of BBM and in animals given stress alone, while an increase in the activity of SOD was observed in the brain regions with the higher dose of BBM. An increase in the activity of cytochrome P450 (P450) dependent 7-pentoxyresorufin-o-dealkylase (PROD) and 7-ethoxyresorufin-o-deethylase (EROD) was observed in all the brain regions after exposure to stress alone and with both doses of BBM although the magnitude of induction of P450 expression was less with a higher dose of BBM. Interestingly, stress when given to the animals pretreated with BBM for 7 days resulted in a decrease in Hsp70 expression in all the brain regions with a significant decrease occurring only in the hippocampus. Likewise the activity of SOD was found to be further reduced in all the brain regions in the animals treated with the lower dose of BBM followed by stress. However, when stress was given to the animals pretreated with the higher dose of BBM, a significant increase in the enzyme activity was observed in the cerebral cortex and in the rest of the brain while the activity of SOD was reduced to a much greater extent in the cerebellum and in the hippocampus. Likewise, the activity of P450 enzymes was found to be restored to almost control levels in the animals given stress and pretreated with the higher dose of BBM, while a lesser degree of induction, compared with animals treated with BBM or stress alone, was observed in the animals pretreated with the lower dose of BBM and given stress. The data indicate that BBM has potential to modulate the activities of Hsp70, P450 and SOD thereby possibly allowing the brain to be prepared to act under adverse conditions such as stress.
Chowdhuri
D Kar
DK
Industrial Toxicology Research Center, PO Box 80, M.G. Marg, Lucknow - 226001, UP, India.
Parmar
D
D
Kakkar
P
P
Shukla
R
R
Seth
P K
PK
Srimal
R C
RC
D000284:Administration, Oral; D000818:Animals; D034681:Bacopa; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D019363:Cytochrome P-450 CYP1A1 / Q000187:drug effects / Q000378:metabolism; D019362:Cytochrome P-450 CYP2B1 / Q000187:drug effects / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D018840:HSP70 Heat-Shock Proteins / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008297:Male; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D012503:Saponins / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D013482:Superoxide Dismutase / Q000187:drug effects* / Q000378:metabolism; D014315:Triterpenes / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D018840:HSP70 Heat-Shock Proteins; D010936:Plant Extracts; D012503:Saponins; D014315:Triterpenes; D003577:Cytochrome P-450 Enzyme System; D019363:Cytochrome P-450 CYP1A1; D019362:Cytochrome P-450 CYP2B1; D013482:Superoxide Dismutase