BDNF/PI3K/Akt and Nogo-A/RhoA/ROCK signaling pathways contribute to neurorestorative effect of Houshiheisan against cerebral ischemia injury in rats.
BACKGROUND
Houshiheisan (HSHS), a classic traditional medicine prescription, has notable effects on patients with stroke AIM OF THE STUDY: To investigate the neurorestorative effects of HSHS on ischemic stroke and explore its mode of action.


METHODS
Focal cerebral ischemia models were induced by permanent middle cerebral artery occlusion (pMCAO). Male Sprague-Dawley (SD) rats were randomly divided into 5 experimental groups: sham vehicle, ischemia vehicle, pMCAO+HSHS at 5.1, 10.2g/kg, and pMCAO+Ginaton 0.028g/kg. HSHS or Ginaton was administrated 6h after pMCAO onset. Neurological function was assessed and then rats were sacrificed 7 days after MCAO. Cerebral ischemic injury was evaluated by hematoxylin and eosin (HE) staining and Neuronal nuclear antigen (NeuN) immunofluorescence analysis. The levels of BDNF were detected by enzyme linked immunosorbent assay (ELISA), and the expression levels of PI3K/Akt and Nogo-A/RhoA/ROCK2 signaling pathway were detected by western blot and quantitative real-time PCR (qRT-PCR).


RESULTS
Compared with those results of pMCAO group, HSHS 5.1 and HSHS 10.2 groups markedly improved neurological function, alleviated pathological damage, promoted the neuronal survival, increased the expression of BDNF, PI3K, Akt, in protein and mRNA, decreased the expression of Nogo-A, NgR, RhoA and ROCK2 in protein and mRNA 7 days after pMCAO.


CONCLUSIONS
The findings demonstrate that HSHS had significant therapeutic effects on ischemic stroke and it perhaps worked through the activation of BDNF/PI3K/Akt and down-regulation of Nogo-A/RhoA/ROCK signaling pathways.
School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China; Beijing Key Lab of TCM Collateral Disease Theory Research, Beijing 100069, China.
Jiahui
J
Chang
School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China; Beijing Key Lab of TCM Collateral Disease Theory Research, Beijing 100069, China.
Xiaoquan
X
Yao
School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China; Beijing Key Lab of TCM Collateral Disease Theory Research, Beijing 100069, China.
Haiyan
H
Zou
School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China; Beijing Key Lab of TCM Collateral Disease Theory Research, Beijing 100069, China.
Lei
L
Wang
School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China; Beijing Key Lab of TCM Collateral Disease Theory Research, Beijing 100069, China.
Yue
Y
Lu
School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China; Beijing Key Lab of TCM Collateral Disease Theory Research, Beijing 100069, China. Electronic address: zqx1310@sina.com.
Qiuxia
Q
Zhang
School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China; Beijing Key Lab of TCM Collateral Disease Theory Research, Beijing 100069, China. Electronic address: zhaohuishouyi@sina.com.
Hui
H
Zhao
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D000070798:Nogo Proteins / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D020521:Stroke / Q000188:drug therapy / Q000378:metabolism; D054460:rho-Associated Kinases / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; D004365:Drugs, Chinese Herbal; D018696:Neuroprotective Agents; D000070798:Nogo Proteins; C526713:ginaton; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein
3,5-Di-caffeoylquinic acid (PubChem CID: 6474310); 4,5-Di-caffeoylquinic acid (PubChem CID: 6474309); BDNF/PI3K/Akt signaling pathway; Cerebral ischemia; Cynaroside (PubChem CID: 5280637); Houshiheisan; Neuroregeneration; Nogo-A/RhoA/ROCK2 signaling pathway; apigenin-7-O-glucoside (PubChem CID: 5280704); chlorogenic acid (PubChem CID: 1794427)