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Lycium barbarum L. Balanced intestinal flora with YAP1/FXR activation in drug-induced liver injury.
Lu, Junlan; Gao, Yuting; Gong, Yi; Yue, Yuan; Yang, Yanguang; Xiong, Yajun; Zhang, Yuman; Xiao, Yan; Wang, Haodong; Fan, Haibo; Shi, Xinli.
Afiliación
  • Lu J; Laboratory of Integrated Medicine Tumor Immunology, Shanxi University of Chinese Medicine, Taiyuan 030000, China; Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, Shijiazhuang, China.
  • Gao Y; Laboratory of Integrated Medicine Tumor Immunology, Shanxi University of Chinese Medicine, Taiyuan 030000, China; Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, Shijiazhuang, China.
  • Gong Y; Laboratory of Integrated Medicine Tumor Immunology, Shanxi University of Chinese Medicine, Taiyuan 030000, China; Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, Shijiazhuang, China.
  • Yue Y; Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, Shijiazhuang, China.
  • Yang Y; Laboratory of Integrated Medicine Tumor Immunology, Shanxi University of Chinese Medicine, Taiyuan 030000, China; Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, Shijiazhuang, China.
  • Xiong Y; Laboratory of Integrated Medicine Tumor Immunology, Shanxi University of Chinese Medicine, Taiyuan 030000, China.
  • Zhang Y; Laboratory of Integrated Medicine Tumor Immunology, Shanxi University of Chinese Medicine, Taiyuan 030000, China; Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, Shijiazhuang, China.
  • Xiao Y; Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, Shijiazhuang, China.
  • Wang H; Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, Shijiazhuang, China.
  • Fan H; Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, Shijiazhuang, China.
  • Shi X; Laboratory of Integrated Medicine Tumor Immunology, Shanxi University of Chinese Medicine, Taiyuan 030000, China; Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, Shijiazhuang, China. Electronic address: sxlsunshine@sina.com.
Int Immunopharmacol ; 130: 111762, 2024 Mar 30.
Article en En | MEDLINE | ID: mdl-38428146
ABSTRACT
Drug-induced liver injury (DILI) is a common and severe adverse drug reaction that can result in acute liver failure. Previously, we have shown that Lycium barbarum L. (wolfberry) ameliorated liver damage in acetaminophen (APAP)-induced DILI. Nevertheless, the mechanism needs further clarification. Herein, we utilized APAP-induced DILI mice to investigate how wolfberry impacts the gut-liver axis to mitigate liver damage. We showed that the abundance of Akkermansia muciniphila (A. muciniphila) was decreased, and intestinal microbiota was disrupted, while the expression levels of YAP1 and FXR-mediated CYP7A1 were reduced in the liver of DILI mice. Furthermore, wolfberry increased the abundance of A. muciniphila and the number of goblet cells in the intestines, while decreasing AST, ALT, and total bile acids (TBA) levels in the serum. Interestingly, A. muciniphila promoted YAP1 and FXR expression in hepatocytes, leading to the inhibition of CYP7A1 expression and a decrease in TBA content. Notably, wolfberry did not exert the beneficial effects mentioned above after the removal of intestinal bacteria by antibiotics (ATB)-containing water. Additionally, Yap1 knockout downregulated FXR expression and enhanced CYP7A1 expression in the liver of hepatocyte-specific Yap1 knockout mice. Therefore, wolfberry stimulated YAP1/FXR activation and reduced CYP7A1 expression by promoting the balance of intestinal microbiota, thereby suppressing the overproduction of bile acids.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ácidos y Sales Biliares / Proteínas de Unión al ARN / Lycium / Enfermedad Hepática Inducida por Sustancias y Drogas / Microbioma Gastrointestinal / Akkermansia / Proteínas Señalizadoras YAP / Acetaminofén Límite: Animals Idioma: En Revista: Int Immunopharmacol Asunto de la revista: ALERGIA E IMUNOLOGIA / FARMACOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ácidos y Sales Biliares / Proteínas de Unión al ARN / Lycium / Enfermedad Hepática Inducida por Sustancias y Drogas / Microbioma Gastrointestinal / Akkermansia / Proteínas Señalizadoras YAP / Acetaminofén Límite: Animals Idioma: En Revista: Int Immunopharmacol Asunto de la revista: ALERGIA E IMUNOLOGIA / FARMACOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos