title: Common and unique mechanisms of Chinese herbal remedies on ischemic stroke mice revealed by transcriptome analyses.
abstract: BACKGROUND
  Four traditional Chinese herbal remedies (CHR) including Buyang Huanwu decoction (BHD), Xuefu Zhuyu decoction (XZD), Tianma Gouteng decoction (TGD) and Shengyu decoction (SYD) are popular used in treating brain-related dysfunction clinically with different syndrome/pattern based on traditional Chinese medicine (TCM) principles, yet their neuroprotective mechanisms are still unclear.
  
  
  METHODS
  Mice were subjected to an acute ischemic stroke to examine the efficacy and molecular mechanisms of action underlying these CHR.
  
  
  RESULTS
  CHR treatment significantly enhanced the survival rate of stroke mice, with BHD being the most effective CHR. All CHR were superior to recombinant tissue-type plasminogen activator (rt-PA) treatment in successfully ameliorating brain function, infarction, and neurological deficits in stroke mice that also paralleled to improvements in blood-brain barrier damage, inflammation, apoptosis, and neurogenesis. Transcriptome analyses reveals that a total of 774 ischemia-induced probe sets were significantly modulated by four CHR, including 52 commonly upregulated genes and 54 commonly downregulated ones. Among them, activation of neurogenesis-associated signaling pathways and down-regulating inflammation and apoptosis pathways are key common mechanisms in ischemic stroke protection by all CHR. Besides, levels of plasma CX3CL1 and S100a9 in patients could be used as biomarkers for therapeutic evaluation before functional recovery could be observed.
  
  
  CONCLUSIONS
  Our results suggest that using CHR, a combinatory cocktail therapy, is a better way than rt-PA for treating cerebral ischemic-associated diseases through modulating a common as well as a specific group of genes/pathways that may partially explain the syndrome differentiation and treatment principle in TCM.
authors.affiliation: National Research Institute of Chinese Medicine, Taipei, Taiwan; Institute of Biomedical Sciences, National Chung-Hsing University, Taichung, Taiwan; National Taipei University of Nursing and Health Science, , Taipei,Taiwan. Electronic address: yuhcs@nricm.edu.tw.
authors.forename: Yuh-Chiang
authors.initials: YC
authors.lastname: Shen
authors.affiliation: National Research Institute of Chinese Medicine, Taipei, Taiwan.
authors.forename: Chung-Kuang
authors.initials: CK
authors.lastname: Lu
authors.affiliation: Department of Chinese Martial Arts and Graduate Institute of Sport Coaching Science, Chinese Culture University, Taipei, Taiwan.
authors.forename: Kuo-Tong
authors.initials: KT
authors.lastname: Liou
authors.affiliation: Department of Traditional Medicine, Tao-yuan General Hospital, Department of Health, Tao-yuan, Taiwan; Department of Bioscience Technology, Chuan‑yuan Christian University, Taoyuan, Taiwan.
authors.forename: Yu-Chang
authors.initials: YC
authors.lastname: Hou
authors.affiliation: National Research Institute of Chinese Medicine, Taipei, Taiwan; School of Pharmacy, National Taiwan University, Taipei, Taiwan.
authors.forename: Yun-Lan
authors.initials: YL
authors.lastname: Lin
authors.affiliation: Division of Neurovascular Disease, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan; National Taipei University of Nursing and Health Science, , Taipei,Taiwan.
authors.forename: Yea-Hwey
authors.initials: YH
authors.lastname: Wang
authors.affiliation: Institute of Biomedical Informatics, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Hsing-Jen
authors.initials: HJ
authors.lastname: Sun
authors.affiliation: Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Ko-Hsun
authors.initials: KH
authors.lastname: Liao
authors.affiliation: Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan; Cancer Research Center and Genome Research Center, National Yang-Ming University, Taipei, Taiwan; Institute of Biomedical Informatics, National Yang-Ming University, Taipei, Taiwan; Departments of Education and Research, Taipei City Hospital, Taipei, Taiwan.
authors.forename: Hsei-Wei
authors.initials: HW
authors.lastname: Wang
mesh_terms: D000818:Animals; D040502:Calgranulin B / Q000235:genetics; D054360:Chemokine CXCL1 / Q000235:genetics; D004359:Drug Therapy, Combination; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D020869:Gene Expression Profiling; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008516:Medicine, Chinese Traditional; D008813:Mice, Inbred ICR; D055495:Neurogenesis / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D008517:Phytotherapy
chemical_list: D040502:Calgranulin B; D054360:Chemokine CXCL1; C475895:Cxcl1 protein, mouse; D004365:Drugs, Chinese Herbal; D018696:Neuroprotective Agents; C576329:S100A9 protein, mouse; C513826:Xue-Fu-Zhu-Yu decoction; C460102:buyang huanwu; C000609562:shengyu; C000589486:tianma gouteng
keywords: Acute ischemic stroke (AIS); Buyang Huanwu decoction (BHD); Shengyu decoction (SYD); Tianma Gouteng decoction (TGD); Xuefu Zhuyu decoction (XZD); functional modules and genetic networks; genome-wide transcriptome analysis; micro-positron emission tomography (µPET); neurogenesis; syndrome differentiation.