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Lactucin reverses liver fibrosis by inhibiting TGF-ß1/STAT3 signaling pathway and regulating short-chain fatty acids metabolism.
Qin, Dongmei; Han, Chang; Gao, Yuefeng; Li, Hong; Zhu, Liping.
Afiliación
  • Qin D; Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, School of Pharmacy, Shihezi University, No. 59, North Second Road, Shihezi, 832002, Xinjiang Uygur Autonomous Region, People's Republic of China. qdm_pha@shzu.edu.cn.
  • Han C; Department of Pharmacy, The Seventh Affiliated Hospital of Xinjiang Medical University, Urumqi, People's Republic of China.
  • Gao Y; College of Applied Engineering, Henan University of Science and Technology, Sanmenxia, People's Republic of China.
  • Li H; Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, School of Pharmacy, Shihezi University, No. 59, North Second Road, Shihezi, 832002, Xinjiang Uygur Autonomous Region, People's Republic of China.
  • Zhu L; Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, School of Pharmacy, Shihezi University, No. 59, North Second Road, Shihezi, 832002, Xinjiang Uygur Autonomous Region, People's Republic of China.
Sci Rep ; 14(1): 19323, 2024 08 20.
Article en En | MEDLINE | ID: mdl-39164375
ABSTRACT
TGF-ß1 activation of hepatic stellate cells (HSCs), transcriptional activator 3 (Stat3) activation and short chain fatty acids (SCFAs), metabolite of intestinal bacteria, is closely associated with hepatic fibrosis. Previous studies have shown that Lactucin has significant anti-inflammatory and hepatoprotective effects; however, the mechanism of Lactucin's role in liver fibrosis associated with SCFAs remains unknown. This study was intended to investigate whether effect of Lactucin on liver fibrosis was mediated by TGF-ß1/Stat3 and SCFAs. We found that Lactucin induced apoptosis in HSC-T6 cells, and inhibition of nuclear translocation of Stat3 and p-Stat3. And Smad3 and TGF-ß1 protein expression was significantly inhibited, while TLR4 and Smad7 protein expression was significantly enhanced. For in vivo experiments, we demonstrated that Lactucin alleviated liver fibrosis in mice, as evidenced by a reduction in inflammatory factors, collagen deposition, liver injury and fibrosis-related factors expression, especially the expression of Smad3 and TGF-ß1 proteins was significantly suppressed and Smad7 protein expression was significantly increased in the liver. In addition, the levels of acetic acid, butyric acid and valeric acid in the intestine of Lactucin-treated mice were significantly higher than those in the intestine of liver fibrosis mice. In conclusion, based on the results of in vivo and in vitro experiments, preventive mechanism of Lactucin against liver fibrosis in mice may be to improve the enterohepatic circulation by regulating the metabolites of intestinal microorganisms, acetic acid and butyric acid, and to further regulate the Stat3 and TGF-ß1 signaling pathway through the "gut-liver axis" to combat liver fibrosis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Factor de Transcripción STAT3 / Factor de Crecimiento Transformador beta1 / Células Estrelladas Hepáticas / Ácidos Grasos Volátiles / Cirrosis Hepática Límite: Animals Idioma: En Revista: Sci Rep Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Factor de Transcripción STAT3 / Factor de Crecimiento Transformador beta1 / Células Estrelladas Hepáticas / Ácidos Grasos Volátiles / Cirrosis Hepática Límite: Animals Idioma: En Revista: Sci Rep Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido