Shuang Kou1, Qi Zheng2, Yizhou Wang2, Hui Zhao2, Qiuxia Zhang2, Ming Li2, Fang Qi2, Ling Fang2, Lei Liu2, Junyao Ouyang2, Haiyu Zhao3, Lei Wang4. 1. School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, PR China; Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, PR China. 2. School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, PR China. 3. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, PR China. 4. School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, PR China. Electronic address: tmwangl@ccmu.edu.cn.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Zuo-Gui pills (ZGPs) and You-Gui pills (YGPs) are 2 traditional Chinese herbal formulas used for treating multiple sclerosis (MS) in the clinical setting and have been shown to have neuroprotective effects in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. The aim of this study was to explore the mechanisms underlying the neuroprotective functions of ZGPs and YGPs. MATERIALS AND METHODS: Female Lewis rats were randomly divided into normal control, EAE model, 2g/kg ZGP-treated EAE, 3g/kg YGP-treated EAE, and prednisone acetate-treated groups. EAE model was induced by subcutaneous injection of MBP68-86 antigen. The neurological function scores were estimated. Histological structures of the brains and spinal cords were observed, and myelinated and axons imaged. NogoA, Nogo receptor (NgR), and RhoA transcript and protein levels were measured by real-time quantitative RT-PCR and western blotting on postimmunization (PI) days 14 (acute stage) and 28 (remission stage). RESULTS: ZGPs and YGPs significantly reduced neurological functions scores and abrogated inflammatory infiltrates, demyelination, and axonal damage. Furthermore, treatment with ZGPs and YGPs inhibited NogoA, NgR, and RhoA mRNA and protein expression in rats at both the acute and remission stages. ZGPs exhibited stronger effects on NogoA and RhoA expressions, as well as neurological function, during the acute stage of EAE, while YGPs caused greater reductions in NogoA expression during the remission stage. CONCLUSIONS: Our findings suggested that ZGPs and YGPs exerted neuroprotective effects by downregulation of NogoA, NgR, and RhoA pathways, with differences in response times and targets observed between ZGPs and YGPs.
ETHNOPHARMACOLOGICAL RELEVANCE: Zuo-Gui pills (ZGPs) and You-Gui pills (YGPs) are 2 traditional Chinese herbal formulas used for treating multiple sclerosis (MS) in the clinical setting and have been shown to have neuroprotective effects in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. The aim of this study was to explore the mechanisms underlying the neuroprotective functions of ZGPs and YGPs. MATERIALS AND METHODS: Female Lewis rats were randomly divided into normal control, EAE model, 2g/kg ZGP-treated EAE, 3g/kg YGP-treated EAE, and prednisone acetate-treated groups. EAE model was induced by subcutaneous injection of MBP68-86 antigen. The neurological function scores were estimated. Histological structures of the brains and spinal cords were observed, and myelinated and axons imaged. NogoA, Nogo receptor (NgR), and RhoA transcript and protein levels were measured by real-time quantitative RT-PCR and western blotting on postimmunization (PI) days 14 (acute stage) and 28 (remission stage). RESULTS: ZGPs and YGPs significantly reduced neurological functions scores and abrogated inflammatory infiltrates, demyelination, and axonal damage. Furthermore, treatment with ZGPs and YGPs inhibited NogoA, NgR, and RhoA mRNA and protein expression in rats at both the acute and remission stages. ZGPs exhibited stronger effects on NogoA and RhoA expressions, as well as neurological function, during the acute stage of EAE, while YGPs caused greater reductions in NogoA expression during the remission stage. CONCLUSIONS: Our findings suggested that ZGPs and YGPs exerted neuroprotective effects by downregulation of NogoA, NgR, and RhoA pathways, with differences in response times and targets observed between ZGPs and YGPs.
Authors: Tao Yang; Qi Zheng; Su Wang; Ling Fang; Lei Liu; Hui Zhao; Lei Wang; Yongping Fan Journal: BMC Complement Altern Med Date: 2017-05-02 Impact factor: 3.659
Authors: Jong Hee Choi; Min Jung Lee; Minhee Jang; Eun-Jeong Kim; Insop Shim; Hak-Jae Kim; Sanghyun Lee; Sang Won Lee; Young Ock Kim; Ik-Hyun Cho Journal: PLoS One Date: 2015-10-07 Impact factor: 3.240