Proteomics-Guided Study on Buyang Huanwu Decoction for Its Neuroprotective and Neurogenic Mechanisms for Transient Ische
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ORIGINAL ARTICLE
Proteomics-Guided Study on Buyang Huanwu Decoction for Its Neuroprotective and Neurogenic Mechanisms for Transient Ischemic Stroke: Involvements of EGFR/PI3K/Akt/Bad/14-3-3 and Jak2/Stat3/Cyclin D1 Signaling Cascades Xi Chen 1,2,3 & Hansen Chen 3 & Yachong He 3 & Shuping Fu 3,4 & Haosheng Liu 1,2 & Qi Wang 5 & Jiangang Shen 1,2,3 Received: 26 March 2020 / Accepted: 8 July 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract 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.
Keywords Buyang Huanwu Decoction . Stroke . Neurogenesis . Neuroprotection
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12035-020-02016-y) contains supplementary material, which is available to authorized users. * Jiangang Shen [email protected] 1
Department of Core Facility, The People’s Hospital of Bao-an Shenzhen, Shenzhen, China
2
The 8th people’s Hospital of Shenzhen, The Affiliated Bao-an Hospital of Southern Medical University, Shenzhen 518000, China
3
School of Chinese Medicine, The University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong, Hong Kong SAR, China
4
Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing, China
5
Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou, China
Abbreviations BHD Buyang Huanwu Decoction CAV-1 Caveolin-1 DCX Doublecortin D
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