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Activation of FXR by ganoderic acid A promotes remyelination in multiple sclerosis via anti-inflammation and regeneration mechanism.
Jia, Yue; Zhang, Dandan; Li, Haoran; Luo, Shaolei; Xiao, Yuhuan; Han, Li; Zhou, Fuchun; Wang, Chuanyue; Feng, Lei; Wang, Gang; Wu, Peng; Xiao, Chunjie; Yu, Haijing; Du, Jing; Bao, Hongkun.
Affiliation
  • Jia Y; Yunnan University, School of Medicine and College of Life Sciences, 2 Cuihu North Road, Kunming, Yunnan 650091, China.
  • Zhang D; Yunnan University, School of Medicine and College of Life Sciences, 2 Cuihu North Road, Kunming, Yunnan 650091, China.
  • Li H; Yunnan University, School of Medicine and College of Life Sciences, 2 Cuihu North Road, Kunming, Yunnan 650091, China.
  • Luo S; Yunnan University, School of Medicine and College of Life Sciences, 2 Cuihu North Road, Kunming, Yunnan 650091, China.
  • Xiao Y; Yunnan University, School of Medicine and College of Life Sciences, 2 Cuihu North Road, Kunming, Yunnan 650091, China.
  • Han L; Yunnan University, School of Medicine and College of Life Sciences, 2 Cuihu North Road, Kunming, Yunnan 650091, China.
  • Zhou F; The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital & Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing 100088, China.
  • Wang C; The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital & Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing 100088, China.
  • Feng L; The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital & Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing 100088, China.
  • Wang G; The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital & Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing 100088, China.
  • Wu P; Yunnan Plateau Characteristic Agricultural Industry Research Institute, Yunnan Agricultural University, Kunming, Yunnan 650201, China.
  • Xiao C; Yunnan University, School of Medicine and College of Life Sciences, 2 Cuihu North Road, Kunming, Yunnan 650091, China.
  • Yu H; Yunnan University, School of Medicine and College of Life Sciences, 2 Cuihu North Road, Kunming, Yunnan 650091, China.
  • Du J; Yunnan University, School of Medicine and College of Life Sciences, 2 Cuihu North Road, Kunming, Yunnan 650091, China; The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital & Advanced Innovation Center for Human Brain
  • Bao H; Yunnan University, School of Medicine and College of Life Sciences, 2 Cuihu North Road, Kunming, Yunnan 650091, China. Electronic address: baohongkun@ynu.edu.cn.
Biochem Pharmacol ; 185: 114422, 2021 03.
Article in En | MEDLINE | ID: mdl-33482151
Multiple sclerosis (MS), as an inflammatory demyelinating disorder of central nervous system, is the leading cause of non-traumatic neurologic disability in young adults. The pathogenesis of MS remains unknown, however, a dysregulation of glia-neuroimmune signaling plays a key role during progressive disease stage. Most of the existing drugs are aimed at the immune system, but there is no approved drug by promoting remyelination after demyelination so far. There is a great interest in identifying novel agents for treating MS bytargeting to switch the immune imbalance from pro-inflammation and apoptosis to anti-inflammation and regeneration during remyelination phase. Here, we reported that ganoderic acid A (GAA) significantly enhanced the remyelination and rescued motor deficiency in two animal models of MS, including cuprizone-induced demyelination and myelin oligodendrocyte glycoprotein (MOG) 35-55-induced experimental autoimmune encephalomyelitis model. In these two independent MS animal models, GAA modulated neuroimmune to enhance the anti-inflammatory and regeneration markers IL-4 and BDNF, inhibited inflammatory markers IL-1ß and IL-6, followed by down-regulation of microglia activation and astrocyte proliferation. Pharmacological and genetic ablation of farnesoid-X-receptor (FXR) abolished GAA-induced remyelination and restoration of motor deficiency in MS mice. Thus, GAA is a novel and potential therapeutic agent that can rescue MS neuroimmune imbalance and remyelination through an FXR receptor-dependent mechanism. Clinical investigation on the therapeutic effect of GAA in improving remyelination of the MS patients to rescue the motor function is warranted.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Regeneration / Receptors, Cytoplasmic and Nuclear / Remyelination / Heptanoic Acids / Lanosterol / Anti-Inflammatory Agents / Multiple Sclerosis Limits: Animals Language: En Journal: Biochem Pharmacol Year: 2021 Document type: Article Affiliation country: China Country of publication: United kingdom

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Regeneration / Receptors, Cytoplasmic and Nuclear / Remyelination / Heptanoic Acids / Lanosterol / Anti-Inflammatory Agents / Multiple Sclerosis Limits: Animals Language: En Journal: Biochem Pharmacol Year: 2021 Document type: Article Affiliation country: China Country of publication: United kingdom