title: Zuo-Gui and You-Gui pills, two traditional Chinese herbal formulas, downregulated the expression of NogoA, NgR, and RhoA in rats with experimental autoimmune encephalomyelitis.
abstract: BACKGROUND
  Zuo-Gui pills (ZGPs) and You-Gui pills (YGPs) are 2 traditional Chinese herbal formulas used for treating multiple sclerosis (MS) in the clinical setting and have been shown to have neuroprotective effects in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. The aim of this study was to explore the mechanisms underlying the neuroprotective functions of ZGPs and YGPs.
  
  
  METHODS
  Female Lewis rats were randomly divided into normal control, EAE model, 2g/kg ZGP-treated EAE, 3g/kg YGP-treated EAE, and prednisone acetate-treated groups. EAE model was induced by subcutaneous injection of MBP68-86 antigen. The neurological function scores were estimated. Histological structures of the brains and spinal cords were observed, and myelinated and axons imaged. NogoA, Nogo receptor (NgR), and RhoA transcript and protein levels were measured by real-time quantitative RT-PCR and western blotting on postimmunization (PI) days 14 (acute stage) and 28 (remission stage).
  
  
  RESULTS
  ZGPs and YGPs significantly reduced neurological functions scores and abrogated inflammatory infiltrates, demyelination, and axonal damage. Furthermore, treatment with ZGPs and YGPs inhibited NogoA, NgR, and RhoA mRNA and protein expression in rats at both the acute and remission stages. ZGPs exhibited stronger effects on NogoA and RhoA expressions, as well as neurological function, during the acute stage of EAE, while YGPs caused greater reductions in NogoA expression during the remission stage.
  
  
  CONCLUSIONS
  Our findings suggested that ZGPs and YGPs exerted neuroprotective effects by downregulation of NogoA, NgR, and RhoA pathways, with differences in response times and targets observed between ZGPs and YGPs.
authors.affiliation: School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, PR China; Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, PR China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Kou
authors.affiliation: School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, PR China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zheng
authors.affiliation: School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, PR China.
authors.forename: Yizhou
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
authors.affiliation: School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, PR China.
authors.forename: Qiuxia
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, PR China.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, PR China.
authors.forename: Fang
authors.initials: F
authors.lastname: Qi
authors.affiliation: School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, PR China.
authors.forename: Ling
authors.initials: L
authors.lastname: Fang
authors.affiliation: School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, PR China.
authors.forename: Junyao
authors.initials: J
authors.lastname: Ouyang
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, PR China.
authors.forename: Haiyu
authors.initials: H
authors.lastname: Zhao
authors.affiliation: School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, PR China. Electronic address: tmwangl@ccmu.edu.cn.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000503:physiopathology; D009185:Myelin Proteins / Q000235:genetics; D018696:Neuroprotective Agents / Q000494:pharmacology*; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D051381:Rats; D011917:Rats, Inbred Lew; D060888:Real-Time Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D020742:rhoA GTP-Binding Protein / Q000235:genetics
chemical_list: D004365:Drugs, Chinese Herbal; D058851:GPI-Linked Proteins; D009185:Myelin Proteins; D018696:Neuroprotective Agents; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D011956:Receptors, Cell Surface; C000603197:Rtn4 protein, rat; C486581:Rtn4r protein, rat; C552041:yougui; C552040:zuogui; D020742:rhoA GTP-Binding Protein
keywords: Experimental autoimmune encephalomyelitis; Nogo receptor; NogoA; RhoA; You-Gui pills; Zuo-Gui pills