TY - JOUR
T1 - Baoyuan Capsule promotes neurogenesis and neurological functional recovery through improving mitochondrial function and modulating PI3K/Akt signaling pathway
AU - Du, Qiaohui
AU - Deng, Ruixia
AU - Li, Wenting
AU - Zhang, Dong
AU - Tsoi, Bun
AU - Shen, Jiangang
N1 - Funding Information:
This work was supported by Guangxi Innovation Derived Development Specific Development Scheme, Guangxi Science and Technology Bureau, Guangxi Province, China (No. AA18118049-5 ) and Areas of Excellence Scheme, Research Grant Council, Hong Kong SAR, China (No. AoE/P-705/16 ). We thank Faculty Core Facility, Li Ka Shing Faculty of Medicine, the University of Hong Kong to supply Carl Zeiss LSM 800 for capturing confocal fluorescent images and BD LSR Fortessa for flow cytometry assay.
Publisher Copyright:
© 2021 Elsevier GmbH
PY - 2021/12
Y1 - 2021/12
N2 - 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 effectively 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), phosphorylation of AMP-activated protein kinase (p-AMPK), protein kinase B (p-Akt) and glycogen synthase kinase 3β (p-GSK3β) in the hippocampus of the MCAO mice. BYC (200 µg/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.
AB - 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 effectively 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), phosphorylation of AMP-activated protein kinase (p-AMPK), protein kinase B (p-Akt) and glycogen synthase kinase 3β (p-GSK3β) in the hippocampus of the MCAO mice. BYC (200 µg/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.
KW - BaoYuan Capsule
KW - Mitochondrial function
KW - Neurogenesis
KW - PI3K/Akt pathway
KW - Post-stroke recovery
UR - http://www.scopus.com/inward/record.url?scp=85118505983&partnerID=8YFLogxK
U2 - 10.1016/j.phymed.2021.153795
DO - 10.1016/j.phymed.2021.153795
M3 - Journal article
C2 - 34735905
AN - SCOPUS:85118505983
SN - 0944-7113
VL - 93
JO - Phytomedicine
JF - Phytomedicine
M1 - 153795
ER -