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You-Gui pills promote nerve regeneration by regulating netrin1, DCC and Rho family GTPases RhoA, Racl, Cdc42 in C57BL/6 mice with experimental autoimmune encephalomyelitis.
J Ethnopharmacol 2016; 187:123-33JE

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

You-Gui pills (YGPs) are an effective traditional Chinese formula being used clinically for the treatment of multiple sclerosis (MS). Previous studies demonstrated that YGPs exerted the potent neuroprotective effects in murine models of experimental autoimmune encephalomyelitis (EAE), which is an equivalent animal model for multiple sclerosis (MS). However, the mechanism of YGPs functions remained unclear.

AIM OF THIS STUDY

The aim of this study was to evaluate the therapeutic effect of YGPs in MOG35-55-induced EAE mice and to further elucidate the underlying molecular mechanism.

METHODS

Female C57BL/6 mice were divided into six groups, including the non-treated EAE model, prednisone acetate- and 1.2, 2.4 or 4.8g/kg YGPs-treated EAE groups, and a normal control group. The EAE model was established by injecting the mice subcutaneously with MOG35-55 antigen. The body weights were measured and the neurological functions were scored in each group. The pathology and morphology of the brain and spinal cord was examined. The expression of MAP-2 was detected by immunofluorescent staining. The levels of netrin1, DCC, RhoA, Rac1, and Cdc42 were assayed by immunohistochemistry, qRT-PCR and Western blot on day 40 post-immunization (PI).

RESULTS

YGPs treatments significantly reduced neurological function scores in EAE mice, where the inflammatory infiltration was reduced and the axon and myelin damage in both brain and spinal cord was alleviated. In the brain and spinal cord tissues, YGPs increased the expression of neuronal factors MAP-2, netrin1 and DCC. The expression of Rac1 and Cdc42 were increased, while RhoA was reduced following YGPs treatments.

CONCLUSION

Our results demonstrated that YGPs exhibited a neuroprotective effect on promoting nerve regeneration at the brain and spinal cord in EAE mice induced by MOG35-55. Netrin1, DCC and the Rho family GTPases of RhoA, Racl, Cdc42 were involved in mediating the effects of YGPs on nerve regeneration.

Authors+Show Affiliations

School of Traditional Chinese Medicine, Beijing Key Lab of TCM Collateral Disease Theory Research, Capital Medical University, Beijing 100069, PR China.School of Traditional Chinese Medicine, Beijing Key Lab of TCM Collateral Disease Theory Research, Capital Medical University, Beijing 100069, PR China.School of Traditional Chinese Medicine, Beijing Key Lab of TCM Collateral Disease Theory Research, Capital Medical University, Beijing 100069, PR China.School of Traditional Chinese Medicine, Beijing Key Lab of TCM Collateral Disease Theory Research, Capital Medical University, Beijing 100069, PR China.School of Traditional Chinese Medicine, Beijing Key Lab of TCM Collateral Disease Theory Research, Capital Medical University, Beijing 100069, PR China.School of Traditional Chinese Medicine, Beijing Key Lab of TCM Collateral Disease Theory Research, Capital Medical University, Beijing 100069, PR China.School of Traditional Chinese Medicine, Beijing Key Lab of TCM Collateral Disease Theory Research, Capital Medical University, Beijing 100069, PR China.School of Traditional Chinese Medicine, Beijing Key Lab of TCM Collateral Disease Theory Research, Capital Medical University, Beijing 100069, PR China.School of Traditional Chinese Medicine, Beijing Key Lab of TCM Collateral Disease Theory Research, Capital Medical University, Beijing 100069, PR China.School of Traditional Chinese Medicine, Beijing Key Lab of TCM Collateral Disease Theory Research, Capital Medical University, Beijing 100069, PR China. Electronic address: wxj0517@sina.com.School of Traditional Chinese Medicine, Beijing Key Lab of TCM Collateral Disease Theory Research, Capital Medical University, Beijing 100069, PR China. Electronic address: tmwangl@ccmu.edu.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27106785

Citation

Ji, Xiaomin, et al. "You-Gui Pills Promote Nerve Regeneration By Regulating Netrin1, DCC and Rho Family GTPases RhoA, Racl, Cdc42 in C57BL/6 Mice With Experimental Autoimmune Encephalomyelitis." Journal of Ethnopharmacology, vol. 187, 2016, pp. 123-33.
Ji X, Liu H, An C, et al. You-Gui pills promote nerve regeneration by regulating netrin1, DCC and Rho family GTPases RhoA, Racl, Cdc42 in C57BL/6 mice with experimental autoimmune encephalomyelitis. J Ethnopharmacol. 2016;187:123-33.
Ji, X., Liu, H., An, C., Wang, Y., Zhao, H., Zhang, Q., ... Wang, L. (2016). You-Gui pills promote nerve regeneration by regulating netrin1, DCC and Rho family GTPases RhoA, Racl, Cdc42 in C57BL/6 mice with experimental autoimmune encephalomyelitis. Journal of Ethnopharmacology, 187, pp. 123-33. doi:10.1016/j.jep.2016.04.025.
Ji X, et al. You-Gui Pills Promote Nerve Regeneration By Regulating Netrin1, DCC and Rho Family GTPases RhoA, Racl, Cdc42 in C57BL/6 Mice With Experimental Autoimmune Encephalomyelitis. J Ethnopharmacol. 2016 Jul 1;187:123-33. PubMed PMID: 27106785.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - You-Gui pills promote nerve regeneration by regulating netrin1, DCC and Rho family GTPases RhoA, Racl, Cdc42 in C57BL/6 mice with experimental autoimmune encephalomyelitis. AU - Ji,Xiaomin, AU - Liu,Haolong, AU - An,Chen, AU - Wang,Yongqiang, AU - Zhao,Hui, AU - Zhang,Qiuxia, AU - Li,Ming, AU - Qi,Fang, AU - Chen,Zhenzhen, AU - Wang,Xiujuan, AU - Wang,Lei, Y1 - 2016/04/20/ PY - 2015/11/30/received PY - 2016/03/14/revised PY - 2016/04/19/accepted PY - 2016/4/24/entrez PY - 2016/4/24/pubmed PY - 2017/3/3/medline KW - Betaine (PubChem CID: 247) KW - Chlorogenic acid (PubChem CID 1794427) KW - Cinnamaldehyde (PubChem CID: 637511) KW - Experimental autoimmune encephalomyelitis KW - Fuziline (PubChem CID 14163819) KW - Hyperin (PubChem CID: 5281643) KW - Loganin (PubChem CID: 87691) KW - Neoline (PubChem CID: 120682) KW - Nerve regeneration KW - Netrin1/DCC KW - Quercitrin (PubChem CID: 5280459) KW - Rho family GTPases RhoA, Rac1 and Cdc42 KW - Songorine (PubChem CID 71456946) KW - Sweroside (PubChem CID: 161036) KW - You-Gui Pills SP - 123 EP - 33 JF - Journal of ethnopharmacology JO - J Ethnopharmacol VL - 187 N2 - ETHNOPHARMACOLOGICAL RELEVANCE: You-Gui pills (YGPs) are an effective traditional Chinese formula being used clinically for the treatment of multiple sclerosis (MS). Previous studies demonstrated that YGPs exerted the potent neuroprotective effects in murine models of experimental autoimmune encephalomyelitis (EAE), which is an equivalent animal model for multiple sclerosis (MS). However, the mechanism of YGPs functions remained unclear. AIM OF THIS STUDY: The aim of this study was to evaluate the therapeutic effect of YGPs in MOG35-55-induced EAE mice and to further elucidate the underlying molecular mechanism. METHODS: Female C57BL/6 mice were divided into six groups, including the non-treated EAE model, prednisone acetate- and 1.2, 2.4 or 4.8g/kg YGPs-treated EAE groups, and a normal control group. The EAE model was established by injecting the mice subcutaneously with MOG35-55 antigen. The body weights were measured and the neurological functions were scored in each group. The pathology and morphology of the brain and spinal cord was examined. The expression of MAP-2 was detected by immunofluorescent staining. The levels of netrin1, DCC, RhoA, Rac1, and Cdc42 were assayed by immunohistochemistry, qRT-PCR and Western blot on day 40 post-immunization (PI). RESULTS: YGPs treatments significantly reduced neurological function scores in EAE mice, where the inflammatory infiltration was reduced and the axon and myelin damage in both brain and spinal cord was alleviated. In the brain and spinal cord tissues, YGPs increased the expression of neuronal factors MAP-2, netrin1 and DCC. The expression of Rac1 and Cdc42 were increased, while RhoA was reduced following YGPs treatments. CONCLUSION: Our results demonstrated that YGPs exhibited a neuroprotective effect on promoting nerve regeneration at the brain and spinal cord in EAE mice induced by MOG35-55. Netrin1, DCC and the Rho family GTPases of RhoA, Racl, Cdc42 were involved in mediating the effects of YGPs on nerve regeneration. SN - 1872-7573 UR - https://www.unboundmedicine.com/medline/citation/27106785/You_Gui_pills_promote_nerve_regeneration_by_regulating_netrin1_DCC_and_Rho_family_GTPases_RhoA_Racl_Cdc42_in_C57BL/6_mice_with_experimental_autoimmune_encephalomyelitis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-8741(16)30215-X DB - PRIME DP - Unbound Medicine ER -