Danggui-Shaoyao-San ameliorates cognition deficits and attenuates oxidative stress-related neuronal apoptosis in d-galactose-induced senescent mice

Danggui-Shaoyao-San (DSS), a famous traditional Chinese medicine formula consisting of six herbal medicines, has been used to treat gynecological disorders and neural dysfunctions.The present study was carried out to investigate the effects of DSS on cognitive ability and oxidative stress-related neuronal apoptosis in the hippocampus of aging mice induced by d-galactose (d-gal) to elucidate the underlying molecular mechanisms.Ethanol extract of DSS (DE) were orally administered to d-gal-induced senescent mice for six weeks. The cognitive ability was determined by the methods of step-down type passive avoidance test and Morris water maze test. The activities of superoxide dismutase (SOD) and nitric oxide synthase (NOS), and levels of carbonyl protein (CP), glutathione (GSH), malondialdehyde (MDA) and nitric oxide (NO) were also examined. Furthermore, the expression of apoptotic related proteins in hippocampus of d-gal-treated mice, such as Bcl-2, Bax and caspase-3 proteins, were determined by immunohistochemistry.DE at the doses of 1.8, 3.6 and 7.2g/kg significantly enhanced the cognitive performances and restored the abnormal activities of SOD and NOS and levels of CP, MDA, GSH and NO induced by d-gal. Moreover, the neural apoptosis in the hippocampus of d-gal-treated mice was improved by DE through regulating the expression of Bcl-2, Bax and caspase-3.These results demonstrate that DE has neuroprotective effects in d-gal-induced senescent mice by ameliorating oxidative stress induced neuronal apoptosis in the brain.