title: Effects of Zuogui Pill () and Yougui Pill () on the expression of brain-derived neurotrophic factor and cyclic adenosine monophosphate/protein kinase A signaling transduction pathways of axonal regeneration in model rats with experimental autoimmune encephalomyelitis.
abstract: OBJECTIVE
  To study the effects of Zuogui Pill (, ZGP) and Yougui Pill (, YGP) on the expressions of brain-derived neurotrophic factor (BDNF) and cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling of axonal regeneration in the Lewis rats with experimental autoimmune encephalomyelitis (EAE), in order to explore the possible mechanism of ZGP and YGP on promoting axonal regeneration.
  
  
  METHODS
  The rats were randomly divided into normal control (NC), model (MO), prednisone acetate (PA), ZGP and YGP groups. The EAE model of rat was established by injecting antigen containing myelin basic protein (MBP)68-86. The brain and spinal cord were harvested on the 14th and 28th day post-immunization (PI), the protein and mRNA expression of BDNF and PKA in the brain and spinal cord of rats were detected by Western blot analysis and real-time quantitative polymerase chain reaction (PCR), and the cAMP levels were detected by using enzyme-immunoassay method.
  
  
  RESULTS
  (1) On the 28th day PI, the mRNA expression of BDNF in brain white matter and spinal cord of rats in ZGP and YGP groups were up-regulated, especially in YGP group (P<0.05 or P<0.01). (2) On the 14th day PI, the cAMP levels in brain white matters significantly increased in PA and YGP groups compared with MO group (P<0.05 or P<0.01), and the cAMP level in YGP group was higher than that in ZGP group (P<0.05). The cAMP level in spinal cord also significantly increased in YGP group compared with MO, PA and ZGP groups, respectively (P<0.01). (3) On the 14th day PI, the PKA expression in spinal cord of rats in ZGP group was significantly decreased compared with MO and YGP groups, respectively (P<0.05). (4) On the 28th day PI, there was a positive correlation between cAMP and PKA expression in the brain white matter of YGP rats.
  
  
  CONCLUSIONS
  The results suggest that ZGP and YGP may promote axonal regeneration by modulating cAMP/PKA signal transduction pathway, but the targets of molecular mechanism of ZGP may be different from those of YGP.
authors.affiliation: School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, China.
authors.forename: Yi-zhou
authors.initials: YZ
authors.lastname: Wang
authors.forename: Shuang
authors.initials: S
authors.lastname: Kou
authors.forename: Ling-yun
authors.initials: LY
authors.lastname: Gu
authors.forename: Qi
authors.initials: Q
authors.lastname: Zheng
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.forename: Fang
authors.initials: F
authors.lastname: Qi
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000473:pathology; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D009416:Nerve Regeneration / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013607:Tablets
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D004365:Drugs, Chinese Herbal; D012333:RNA, Messenger; D013607:Tablets; C552041:yougui; C552040:zuogui; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases