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BDNF/PI3K/Akt and Nogo-A/RhoA/ROCK signaling pathways contribute to neurorestorative effect of Houshiheisan against cerebral ischemia injury in rats.
J Ethnopharmacol. 2016 Dec 24; 194:1032-1042.JE

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.

Authors+Show Affiliations

School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China; Beijing Key Lab of TCM Collateral Disease Theory Research, Beijing 100069, China.School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China; Beijing Key Lab of TCM Collateral Disease Theory Research, Beijing 100069, China.School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China; Beijing Key Lab of TCM Collateral Disease Theory Research, Beijing 100069, China.School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China; Beijing Key Lab of TCM Collateral Disease Theory Research, Beijing 100069, China.School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China; Beijing Key Lab of TCM Collateral Disease Theory Research, Beijing 100069, China.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.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.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27833029

Citation

Chang, Jiahui, et al. "BDNF/PI3K/Akt and Nogo-A/RhoA/ROCK Signaling Pathways Contribute to Neurorestorative Effect of Houshiheisan Against Cerebral Ischemia Injury in Rats." Journal of Ethnopharmacology, vol. 194, 2016, pp. 1032-1042.
Chang J, Yao X, Zou H, et al. BDNF/PI3K/Akt and Nogo-A/RhoA/ROCK signaling pathways contribute to neurorestorative effect of Houshiheisan against cerebral ischemia injury in rats. J Ethnopharmacol. 2016;194:1032-1042.
Chang, J., Yao, X., Zou, H., Wang, L., Lu, Y., Zhang, Q., & Zhao, H. (2016). BDNF/PI3K/Akt and Nogo-A/RhoA/ROCK signaling pathways contribute to neurorestorative effect of Houshiheisan against cerebral ischemia injury in rats. Journal of Ethnopharmacology, 194, 1032-1042. https://doi.org/10.1016/j.jep.2016.11.005
Chang J, et al. BDNF/PI3K/Akt and Nogo-A/RhoA/ROCK Signaling Pathways Contribute to Neurorestorative Effect of Houshiheisan Against Cerebral Ischemia Injury in Rats. J Ethnopharmacol. 2016 Dec 24;194:1032-1042. PubMed PMID: 27833029.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - BDNF/PI3K/Akt and Nogo-A/RhoA/ROCK signaling pathways contribute to neurorestorative effect of Houshiheisan against cerebral ischemia injury in rats. AU - Chang,Jiahui, AU - Yao,Xiaoquan, AU - Zou,Haiyan, AU - Wang,Lei, AU - Lu,Yue, AU - Zhang,Qiuxia, AU - Zhao,Hui, Y1 - 2016/11/08/ PY - 2016/04/27/received PY - 2016/10/06/revised PY - 2016/11/04/accepted PY - 2016/11/12/pubmed PY - 2017/4/12/medline PY - 2016/11/12/entrez KW - 3,5-Di-caffeoylquinic acid (PubChem CID: 6474310) KW - 4,5-Di-caffeoylquinic acid (PubChem CID: 6474309) KW - BDNF/PI3K/Akt signaling pathway KW - Cerebral ischemia KW - Cynaroside (PubChem CID: 5280637) KW - Houshiheisan KW - Neuroregeneration KW - Nogo-A/RhoA/ROCK2 signaling pathway KW - apigenin-7-O-glucoside (PubChem CID: 5280704) KW - chlorogenic acid (PubChem CID: 1794427) SP - 1032 EP - 1042 JF - Journal of ethnopharmacology JO - J Ethnopharmacol VL - 194 N2 - 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. SN - 1872-7573 UR - https://www.unboundmedicine.com/medline/citation/27833029/BDNF/PI3K/Akt_and_Nogo_A/RhoA/ROCK_signaling_pathways_contribute_to_neurorestorative_effect_of_Houshiheisan_against_cerebral_ischemia_injury_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-8741(16)31739-1 DB - PRIME DP - Unbound Medicine ER -