Effect of Hippophae Rhamnoides Fruit Extract on Doxorubicin-Induced Oxidative Brain Damage and Behavioral Impairment in Rats

Background and Objective: Doxorubicin (DOX) use can promote neurobehavioral changes and neurodegeneration, which have been attributed to oxidative stress. Thus, this study aimed to examine the effect of Hippophae rhamnoides L., fruit extract (HRe), against possible oxidative brain damage and behavioral disorders in rats caused by DOX.Materials and Methods: A total of 24 male Sprague-Dawley rats were utilized in this study and were divided randomly into four groups (n = 6 in each groups): CG, healthy control; HRe, 50 mg/kg HRe; DOX, 5 mg/kg i.p., in a single intraperitoneal dose of DOX; Hre + DOX, 50 mg/kg HRe + 5 mg/kg DOX. HRe was administered orally once a day for two weeks, while DOX was administered intraperitoneally twice a week for two weeks. Subsequently, behavioral tests were performed-the sucrose preference test (SPT) and pole test-to assess depression-like behaviors and motor function, respectively. Then, the level of oxidative stress was biochemically evaluated in the brain tissues of the rats. One-way analysis of variance (ANOVA) was conducted, followed by a post hoc Tukey's test for the statistical analysis. A p-value < 0.05 was considered statistically significant.Results: The HRe treatment markedly reduced DOX-induced depression-like behaviors and improved motor dysfunction. The HRe treatment also restored the impaired antioxidant response by inhibiting the DOX-related malondialdehyde increase and reducing the decrease in total glutathione levels, as well as superoxide dismutase and catalase activities.Conclusion: The present study indicates that HRe treatment has beneficial effects on motor dysfunction as well as depression-like behavior associated with neurodegeneration following DOX-induced brain damage. Possible mechanisms underlying these beneficial effects include lipid peroxidation inhibition and restoration of antioxidant defense mechanisms by HRe.