Dendrobium nobile Lindl. alleviates acute alcoholic liver injury in mice by modulating bile acid metabolism via the enterohepatic circulation.

ETHNOPHARMACOLOGICAL RELEVANCE Dendrobium nobile Lindl. (DNL), a traditional Chinese medicine used for over two millennia, is attached for nourishing Yin, clearing heat, and promote fluid production. Despite its hepatoprotective potential, the underlying mechanisms need to be further explored.

Aim

OF THE STUDY This study aimed to investigate the protective effects and further elucidate the mechanisms of Dendrobium nobile Lindl. aqueous extract (DNAE) from two different geographical origins (Chishui and Haikou) against acute alcoholic liver injury (AALI) using an integrated approach, with a particular focus on the modulation of bile acid metabolism via the enterohepatic FXR signaling pathway.

Materials And Methods

In this study, an acute alcoholic liver injury (AALI) mouse model was established by a single intragastric administration of 53% alcohol, following 14 consecutive days of pretreatment with DNAE from Chishui or Haikou. Physiological and pathological changes were evaluated, and the hepatic BA profiles were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Chemical compositional differences between DNL from Chishui and Haikou were characterized by UPLC-Q/TOF-MS and GC. The expression levels of genes involved in BA synthesis and metabolism were measured in both liver and intestine by quantitative real-time PCR (qRT-PCR). Additionally, Fxr-knockout mice were employed to verify the role of FXR in the observed effects.

Results

DNAE from both Chishui and Haikou origins significantly ameliorated alcohol-induced physiological and pathological alterations. The chemical composition of DNL, particularly the profile of secondary metabolites and the content of dendrobine, remains largely consistent between Chishui and Haikou origins. DNAE restored the metabolic balance of hepatic BAs by reducing primary BAs (CA, CDCA, βMCA, αMCA) and secondary BAs (DCA, LCA). Notably, DNAE derived from Chishui exhibited a more pronounced regulatory effect, specifically in enhancing the abundance of taurine-conjugated BAs. Consistently, DNAE pretreatment upregulated the hepatic BA synthase genes Cyp8b1 and Cyp7a1, downregulated the BA metabolism-associated genes Fxr and Shp. In Fxr-knockout mice, DNAE treatment did not attenuate alcohol-induced liver injury. Interestingly, DNAE increased the expression of intestinal BA metabolism genes Fxr and Fgf15, triggered extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK) signaling to downregulate Cyp7a1 expression and inhibits BA synthesis.

Conclusion

DNAE from both Chishui and Haikou origins alleviates acute alcoholic liver injury in mice by modulating bile acid metabolism via the enterohepatic FXR signal pathway, with the Chishui origin showing a more potent regulatory effect on taurine-conjugated BA abundance.