Department of Core Facility, The People's Hospital of Bao-an Shenzhen, Shenzhen, China.
The 8th people's Hospital of Shenzhen, The Affiliated Bao-an Hospital of Southern Medical University, Shenzhen, 518000, China.
Mol Neurobiol. 2020 Oct;57(10):4305-4321. doi: 10.1007/s12035-020-02016-y. Epub 2020 Jul 23.
Buyang Huanwu Decoction (BHD), a classic traditional Chinese medicine (TCM) formula, has been used for recovering neurological dysfunctions and treating post-stroke disability in China for 200 years. In the present study, we investigated the effects of BHD on inhibiting neuronal apoptosis, promoting proliferation and differentiation of neural stem cells (NSCs) and neurite formation and enhancing learning and memory functional recovery in an experimental rat ischemic stroke model. BHD significantly reduced infarct volume and decreased cell apoptosis in the ischemic brain. BHD enhanced neuronal cell viability in vitro. BHD dose-dependently promoted the proliferation of NSCs in ischemic rat brains in vivo. Moreover, BHD promoted neuronal and astrocyte differentiation in primary cultured NSCs in vitro. Water maze test revealed that BHD promoted the recovery of learning function but not memory functions in the transient ischemic rats. We then investigated the changes of the cellular signaling molecules by using two-dimension (2D) gel electrophoresis and focused on the PI3K/Akt/Bad and Jak2/Stat3/cyclin D1signaling pathway to uncover its underlying mechanisms for its neuroprotective and neurogenetic effects. BHD significantly upregulated the expression of p-PI3K, p-Akt, and p-Bad as well as the expression of p-Jak, p-Stat3, and cyclin D1 in vitro and in vivo. In addition, BHD upregulated Hes1 and downregulated cav-1 in vitro and in vivo. Taken together, these results suggest that BHD has neuroprotective effects and neurogenesis-promoting effects via activating PI3K/Akt/Bad and Jak2/Stat3/Cyclin D1 signaling pathways. Graphical Abstract Buyang Huanwu Decoction (BHD) activates the PI3K-AKT-BAD pathway in the ischemic brain for neuroprotection. BHD also activates JAK2/STAT3/Cyclin D1 signaling cascades for promoting neurogenesis in the hippocampus of post-ischemic brains. Moreover, BHD inhibits the expression of caveolin-1 and increases the expression of HES1 for promoting neuronal differentiation. The neuroprotective and neurogenesis-promoting effects in the hippocampus of post-ischemic brains promote learning ability.
补阳还五汤（BHD）是一种经典的中药方剂，在中国已有 200 年的历史，用于恢复神经功能障碍和治疗中风后残疾。本研究旨在探讨 BHD 对实验性大鼠缺血性中风模型抑制神经元凋亡、促进神经干细胞（NSCs）增殖和分化以及增强学习和记忆功能恢复的作用。BHD 显著减少脑梗死体积和缺血性脑内细胞凋亡。BHD 体外增强神经元细胞活力。BHD 体内剂量依赖性促进缺血性大鼠脑内 NSCs 的增殖。此外，BHD 促进原代培养 NSCs 的神经元和星形胶质细胞分化。水迷宫测试表明，BHD 促进短暂性缺血大鼠学习功能的恢复，但不影响记忆功能。然后，我们通过二维（2D）凝胶电泳研究细胞信号分子的变化，并重点关注 PI3K/Akt/Bad 和 Jak2/Stat3/cyclin D1 信号通路，以揭示其神经保护和神经发生作用的潜在机制。BHD 显著上调 p-PI3K、p-Akt 和 p-Bad 以及 p-Jak、p-Stat3 和 cyclin D1 的表达，无论是在体外还是体内。此外，BHD 上调 Hes1 并下调体外和体内的 cav-1。总之，这些结果表明 BHD 通过激活 PI3K/Akt/Bad 和 Jak2/Stat3/Cyclin D1 信号通路具有神经保护和促进神经发生的作用。
