Attenuation of Cisplatin-Induced Emetogenesis by Standardized Bacopa monnieri Extracts in the Pigeon: Behavioral and Neurochemical Correlations

摘要

Nausea and vomiting are the most distressing and common side effects of cancer chemotherapy which often result in patient noncompliance. In the present study, standardized methanolic and n-butanolic fractions of Bacopa monnieri were evaluated against cisplatin-induced emesis in the pigeon in relation to their activity on central and intestinal neurotransmitters levels. Cisplatin (7.0 mg/kg, i.v.) induced reproducible emesis without lethality in healthy pigeons. The methanolic (10-40 mg/kg) and the bacoside-rich n-butanolic fractions of B. monnieri (5-20 mg/kg), as well as the antioxidant N-(2-mercaptopropionyl) glycine (10 mg/kg), attenuated cisplatin-induced emesis by 66.3% (p<0.05), 71.6% (p< 0.001), and 76.5% (p< 0.001), respectively, where the standard antiemetic metoclopramide (30 mg/kg) produced a 48.9% reduction (p<0.01). The methanolic and n-butanolic fractions of B. monnieri at all of the doses tested significantly reduced the serotonin concentration (p< 0.001) in the brain stem and intestine 3 h after cisplatin administration, while at the 18th h, B. monnieri treatments attenuated not only the dopamine upsurge in the area postrema and brain stem (p< 0.05-0.001), but also the intestinal 5-HT concentration (p< 0.01-0.001). B. monnieri treatments alone did not alter the basal neurotransmitters or their metabolites in the brain areas and intestine. The prolonged suppressive effect of B. monnieri treat-ments on the behavioral signs of cisplatin-induced emesis, the subsequent supportive neural evidence, and the safety and tolerability profile suggest that B. monnieri methanolic and bacoside-rich n-butanolic fractions might be a valuable adjunct in the treatment of emetogenic chemotherapy, and this warrants further study in other models of emesis.