Jiahui Chang1, Xiaoquan Yao1, Haiyan Zou1, Lei Wang1, Yue Lu1, Qiuxia Zhang2, Hui Zhao3. 1. School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China; Beijing Key Lab of TCM Collateral Disease Theory Research, Beijing 100069, China. 2. 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. 3. 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.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: 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. MATERIALS AND 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.
ETHNOPHARMACOLOGICAL RELEVANCE: 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. MATERIALS AND 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.