Unique mechanisms of sheng yu decoction ( shèng yù tang) on ischemic stroke mice revealed by an integrated neurofunctional and transcriptome analysis.
Sheng Yu Decoction ( Shèng Yù Tang; SYD) is a popular traditional Chinese medicine (TCM) remedy used in treating cardiovascular and brain-related dysfunction clinically; yet, its neuroprotective mechanisms are still unclear. Here, mice were subjected to an acute ischemic stroke to examine the efficacy and mechanisms of action of SYD by an integrated neurofunctional and transcriptome analysis. More than 80% of the mice died within 2 days after ischemic stroke with vehicle treatment. Treatments with SYD (1.0 g/kg, twice daily, orally or p.o.) and recombinant thrombolytic tissue plasminogen activator (rt-PA; 10 mg/kg, once daily, intravenously or i.v.) both significantly extended the lifespan as compared to that of the vehicle-treated stroke group. SYD successfully restored brain function, ameliorated cerebral infarction and oxidative stress, and significantly improved neurological deficits in mice with stroke. Molecular impact of SYD by a genome-wide transcriptome analysis using brains from stroke mice showed a total of 162 out of 2081 ischemia-induced probe sets were significantly influenced by SYD. Mining the functional modules and genetic networks of these 162 genes revealed a significant upregulation of neuroprotective genes in Wnt receptor signaling pathway (3 genes) and regulation of cell communication (7 genes) and downregulation of destructive genes in response to stress (13 genes) and in the induction of inflammation (5 genes), cytokine production (4 genes), angiogenesis (3 genes), vasculature (6 genes) and blood vessel (5 genes) development, wound healing (7 genes), defense response (7 genes), chemotaxis (4 genes), immune response (7 genes), antigen processing and presenting (3 genes), and leukocyte-mediated cytotoxicity (2 genes) by SYD. Our results suggest that SYD could protect mice against ischemic stroke primarily through significantly downregulating the damaging genes involved in stress, inflammation, angiogenesis, blood vessel formation, immune responses, and wound healing, as well as upregulating the genes mediating neurogenesis and cell communication, which make SYD beneficial for treating ischemic stroke.
Department of Traditional Medicine, Tao-yuan General Hospital, Department of Health, Tao-yuan, Taiwan. ; Department of Bioscience Technology, Chuan-yuan Christian University, Taoyuan, Taiwan.
Yu-Chang
YC
Hou
Division of Clinical Chinese Medicine, National Research Institute of Chinese Medicine, Taipei, Taiwan.
Chung-Kuang
CK
Lu
National Taipei University of Nursing and Health Science, Taipei, Taiwan.
Yea-Hwey
YH
Wang
Division of Neurovascular Disease, Neurological Institute, Taipei Veterans General Hospital and School of Medicine, National Yang-Ming University, Taipei, Taiwan.
Chang-Ming
CM
Chern
Department of Chinese Martial Arts and Graduate Institute of Sport Coaching Science, Chinese Culture University, Taipei, Taiwan.
Kuo-Tong
KT
Liou
Institute of Microbiology and Immunology, and Cancer Research Center and Genome Research Center, National Yang-Ming University, Taipei, Taiwan.
Hsei-Wei
HW
Wang
Division of Clinical Chinese Medicine, National Research Institute of Chinese Medicine, Taipei, Taiwan. ; National Taipei University of Nursing and Health Science, Taipei, Taiwan. ; Institute of Biomedical Sciences, National Chung-Hsing University, Taichung, Taiwan.
Yuh-Chiang
YC
Shen
Genome-wide transcriptome analysis; Ischemic stroke; Microarray; Positron emission tomography; Sheng Yu Decoction