Medhya Rasayana Restores Memory Function against Doxorubicin-induced Cognitive Decline: Possibly by its Neuroprotective Effect

Abstract

Background: Medhya Rasayana (MR) is an ayurvedic formulation used to rejuvenate the intellectual functions. It was shown to improve the cognitive function in rats. Hence, the present study was designed to study the neuroprotective effect of MR against Doxorubicin (DOX)-induced cognitive deficits which usually occurs in long-term breast cancer survivors. Methods: The neuroprotective effect of MR was studied in-vitro using IMR-32 cell lines against DOX-induced toxicity while the protective effect of MR against DOX-induced cognitive dysfunction was evaluated in Novel object recognition task (NORT) assay in rats. Results: In IMR-32 cell line, DOX (100 nM) treatment reduced the cell viability and arrested the cell cycle at G2/M phase. Pre-treatment with MR significantly prevented the DOX-induced cytotoxicity and reduced the G2/M phase arrest indicating that MR exhibits protection against DOX-induced toxicity. In NORT, DOX treatment significantly decreased the Recognition and discriminative indices (RI and DI) indicating DOX impairs episodic memory. Treatment with MR (1.26 and 1.52 g/ kg) significantly protected against DOX-induced cognitive dysfunctions. DOX treatment also increased the brain oxidative stress and produced hepato, cardio, nephrotoxicity and myelosuppression. MR treatment ameliorated the DOX-induced toxicity. Conclusion: These results showed that MR pre-treatment could protect against post chemotherapyinduced cognitive dysfunction along with an overall reduction in chemotherapy-induced toxicity.