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Sinomenine ameliorates rheumatoid arthritis by modulating tryptophan metabolism and activating aryl hydrocarbon receptor via gut microbiota regulation.
Jiang, Zheng-Meng; Zeng, Su-Ling; Huang, Tian-Qing; Lin, Yang; Wang, Fang-Fang; Gao, Xing-Jiao; Li, Jing; Li, Ping; Liu, E-Hu.
Afiliación
  • Jiang ZM; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210003, China.
  • Zeng SL; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210003, China.
  • Huang TQ; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210003, China.
  • Lin Y; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210003, China.
  • Wang FF; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210003, China.
  • Gao XJ; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210003, China.
  • Li J; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210003, China. Electronic address: lj_cpu@126.com.
  • Li P; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210003, China. Electronic address: liping2004@126.com.
  • Liu EH; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210003, China. Electronic address: liuehu2011@163.com.
Sci Bull (Beijing) ; 68(14): 1540-1555, 2023 Jul 30.
Article en En | MEDLINE | ID: mdl-37422372
Gut microbiota dysbiosis is associated with the development of rheumatoid arthritis (RA). Sinomenine (SIN) is an effective immunosuppressive and anti-inflammatory drug used for treating RA, but how SIN regulates gut microbiota to alleviate RA remains underexplored. To identify the critical gut microbial species and microbial metabolites associated with the RA-protective effects of SIN, the microbiota-dependent anti-RA effects of SIN were assessed by 16S rRNA gene sequencing, antibiotic treatment, and fecal microbiota transplantation. Metabolomics analysis, transcriptional analysis, and targeted bacteria/metabolites gavage were conducted to explore how SIN regulates gut microbiota to reduce the severity of RA. SIN could restore intestinal microbial balance by mainly modulating the abundance of Lactobacillus, and significantly relieve collagen-induced arthritis (CIA) symptoms in a gut microbiota-dependent manner. SIN significantly elevated microbial tryptophan metabolites indole-3-acrylic acid (IA), indole-3-propionic acid (IPA), and indole-3-acetic acid (IAA). Tryptophan metabolites supplementation could activate aryl hydrocarbon receptor (AhR) and regulate Th17/Treg balance in CIA rats. Intriguingly, SIN relieved the arthritis symptoms involving the enrichment of two beneficial anti-CIA Lactobacillus species, L. paracasei and L. casei by mono-colonization. The promising therapeutic function of SIN was mostly attributed to the activation of AhR by explicitly targeting the Lactobacillus and microbial tryptophan metabolites. The intestinal bacterium L. paracasei and L. casei may be used to reduce the severity of CIA.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Sci Bull (Beijing) Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Sci Bull (Beijing) Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos