Ginsenoside Rd attenuates redox imbalance and improves stroke outcome after focal cerebral ischemia in aged mice

Abstract

We previously found that ginsenoside Rd (Rd), one of the main active ingredients in Panax ginseng, protects against ischemic brain damage induced by oxygen-glucose deprivation in vitro and middle cerebral artery occlusion (MCAO) in vivo. Considering stroke happens frequently in aged individuals, we herein sought to further define the protective effects of Rd in the aged mice. 16-18-month-old mice administered with Rd (0.1-200 mg/kg) or vehicle were subjected to transient MCAO. Rd at the doses of 10-50 mg/kg significantly reduced both cortical and striatal infarct volume. This protection was associated with an improvement in neurological function and was sustained for at least 2 weeks after the insult. Importantly, Rd was effective even when administered up to 4 h after recirculation. To evaluate the underlying mechanisms, oxidative DNA damage was identified by 8-hydroxy-deoxyguanosine immunostaining, oxidative protein damage was identified by the assessment of protein carbonyl, and lipid peroxidation was estimated by determining the malondialdehyde formation. Rd significantly suppressed the accumulations of DNA, protein and lipid peroxidation products at 24 h post-ischemia. Rd also protected mitochondria at 4 and 24 h after reperfusion as indicated by preserved respiratory chain complex activities and aconitase activity, lowered mitochondrial hydrogen peroxide production, and hyperpolarized mitochondrial membrane potential. Furthermore, Rd partly enhanced endogenous antioxidant activities following MCAO. Collectively, these findings demonstrated that Rd exerts neuroprotection against transient focal ischemia in the aged brain, which may be associated with the attenuation of redox imbalance.