School of Chinese Medicine, The University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong.
Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hum, Kowloon, Hong Kong.
Phytomedicine. 2021 Dec;93:153795. doi: 10.1016/j.phymed.2021.153795. Epub 2021 Oct 8.
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.
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.
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.
BYC could promote neurogenesis and neurological functional recovery in post ischemic brains by regulating the mitochondrial functions and Akt signaling pathway.
保元胶囊（BYC）是一种具有专利的中药方剂，用于促进健康，但它在缺血性中风中的应用尚不清楚。在这项研究中，我们提出了一个假设，即 BYC 通过促进线粒体功能和激活 PI3K/Akt 信号通路来促进神经发生和神经功能恢复。
我们首先使用 QIT-TOF-MS 技术进行化学鉴定研究。然后，我们研究了 BYC（1 g/kg、2 g/kg、4 g/kg/天）对改善短暂性大脑中动脉闭塞（MCAO）缺血小鼠神经功能恢复的影响。
我们从 BYC 提取物中初步鉴定了 36 种化合物。在 4 g/kg 剂量下，BYC 有效改善了运动能力，减轻了焦虑样行为，增强了 MCAO 缺血小鼠的探索行为、学习和记忆能力。BYC 治疗促进了 MCAO 小鼠侧脑室下区（SVZ）和颗粒下区（SGZ）神经干细胞的分化。BYC 还上调了海马中乌头酸酶 2（ACO2）、琥珀酸脱氢酶复合体亚单位 A（SDHA）、磷酸化 AMP 激活蛋白激酶（p-AMPK）、蛋白激酶 B（p-Akt）和糖原合酶激酶 3β（p-GSK3β）的表达。BYC（200 µg/ml）显著改善了培养的小鼠多能神经样 C17.2 细胞中的线粒体功能。在缺氧-葡萄糖剥夺（OGD）条件下，BYC 处理也促进了 C17.2 细胞的神经元分化。用 ATP 合成抑制剂寡霉素和 PI3K/Akt 抑制剂wortmannin 共同处理，神经发生作用被消除。此外，寡霉素显著降低了 Akt 的磷酸化。
BYC 通过调节线粒体功能和 Akt 信号通路，可促进缺血后大脑的神经发生和神经功能恢复。
