Baoyuan Capsule promotes neurogenesis and neurological functional recovery through improving mitochondrial function and modulating PI3K/Akt signaling pathway

Background: Bao Yuan Capsule (BYC) is a patented Chinese medicinal formula for health promotion but its application for ischemic stroke remains unknown. In this study, we proposed the hypothesis that BYC could promote neurogenesis and neurological functional recovery through promoting mitochondrial function and activating PI3K/Akt signaling pathway. Methods: We firstly performed chemical identification studies by using QIT-TOF-MS technology. Then, we investigated the effects of BYC (1 g/kg, 2 g/kg, 4 g/kg per day) on improving the recovery of the neurological functions in transient middle cerebral artery occlusion (MCAO) ischemic mice. Results: We tentatively characterized 36 compounds from the BYC extractions. At dosage of 4 g/kg, BYC effec-tively improved locomotor ability, attenuated anxiety-like behaviors, and enhanced the exploring behaviors, learning and memory capability in the transient MCAO ischemic mice. BYC treatment promoted neural stem cell differentiations in the subventricular zone (SVZ) and subgranular zone (SGZ) of the MCAO mice. BYC also up-regulated the expression of Aconitase 2 (ACO2), Succinate dehydrogenase complex, subunit A (SDHA), phos-phorylation of AMP-activated protein kinase (p-AMPK), protein kinase B (p-Akt) and glycogen synthase kinase 38 (p-GSK38) in the hippocampus of the MCAO mice. BYC (200 mu g/ml) significantly improved the mitochondrial functions in cultured mouse multipotent neural stem like C17.2 cells. BYC treatment also promoted neuronal differentiations in the C17.2 cells under oxygen-glucose deprivation (OGD) condition. The neurogenetic effects were abolished by co-treatments of ATP synthesis inhibitor oligomycin and PI3K/Akt inhibitor wortmannin. Moreover, Akt phosphorylation was dramatically reduced by oligomycin. Conclusion: BYC could promote neurogenesis and neurological functional recovery in post ischemic brains by regulating the mitochondrial functions and Akt signaling pathway.