Mechanism of Bao Gan Ning decoction in attenuating hepatic fibrosis via modulation of the gut microbiome and PPAR/CYP7A1-mediated bile acid metabolismShow others and affiliations
2025 (English)In: Journal of Ethnopharmacology, ISSN 0378-8741, E-ISSN 1872-7573, Vol. 353, article id 120488Article in journal (Refereed) Published
Abstract [en]
Ethnopharmacological relevance: Timely intervention in hepatic fibrosis (HF) is imperative to reduce mortality associated with cirrhosis and prevent progression to hepatocellular carcinoma. Bao Gan Ning Decoction (BGN), a Traditional Chinese Medicine formula, demonstrates therapeutic efficacy against HF. However, its mechanism of action remains incompletely defined. Aim of the study: To elucidate the mechanistic role of BGN in attenuating HF through modulation of specific gut microbiota taxa and bile acid (BA) metabolism. Materials and methods: HF was induced in mice using CCl<inf>4</inf>. Gut microbiota composition was analyzed using 16S rRNA gene sequencing. Hepatic BA profiles were quantified using LC-MS/MS, targeting 53 specific BA in negative ion mode through multiple reaction monitoring. Complementary histopathological, molecular, and functional analyses were performed. Results: The findings indicate that BGN mediates remodelling of the gut microbiota by enriching probiotic taxa (Lactobacillus, Bifidobacterium) and depleting pathobionts. Furthermore, BGN attenuates fibrosis by increasing anti-fibrotic BA levels (e.g., ursodeoxycholic acid) while reducing hepatotoxic BA; it activates the PPARα/CYP7A1 signalling axis to upregulate hepatointestinal BA transporters (Slc10a1/NTCP, ABCB11/BSEP, OSTα/β, Slc10a2/ASBT). Conclusions: BGN alleviates HF through gut microbiota-dependent restoration of BA homeostasis and activation of the PPARα/CYP7A1 pathway. This study provides novel mechanistic insights into BGN's anti-fibrotic activities, positioning it as a microbiota-modulating therapeutic candidate for HF management.
Place, publisher, year, edition, pages
Elsevier BV , 2025. Vol. 353, article id 120488
Keywords [en]
Bao Gan Ning decoction (BGN), Bile acid (BA), Gut microbiota, Hepatic fibrosis (HF), Traditional Chinese medicine (TCM)
National Category
Gastroenterology and Hepatology Cell and Molecular Biology Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:kth:diva-369604DOI: 10.1016/j.jep.2025.120488ISI: 001566260300001PubMedID: 40865652Scopus ID: 2-s2.0-105014649720OAI: oai:DiVA.org:kth-369604DiVA, id: diva2:1997419
Note
QC 20250912
2025-09-122025-09-122025-12-08Bibliographically approved