Camellia nitidissima Chi flower extract ameliorates alcoholic liver disease by reshaping bile acid homeostasis and intestinal barrier function.
Abstract
Background
Bile acid (BA) dyshomeostasis and intestinal barrier dysfunction are critical drivers of alcoholic liver disease (ALD), for which effective pharmacotherapies remain limited. Although Camellia nitidissima Chi flower possesses anti-inflammatory, hepatoprotective, and microbiota-modulatory properties, its role in ALD remains unclear.
Purpose
This study aimed to evaluate the therapeutic efficacy of C. nitidissima Chi flower extract (CNFE) against ALD and elucidate its effects on BA homeostasis and intestinal barrier integrity.
Methods
Bioactive constituents were identified using serum pharmacochemistry. CNFE efficacy was evaluated in an ethanol-escalated ALD mouse model. 16S rRNA sequencing, metabolomics, and molecular biology assays were used to investigate the effects of CNFE on the enterohepatic circulation of BAs and intestinal barrier integrity. Farnesoid X receptor (FXR) involvement was validated through molecular docking, molecular dynamics simulations, microscale thermophoresis, and in vivo FXR-specific interventions.
Results
CNFE effectively ameliorated hepatic injury, systemic inflammation, and intestinal barrier damage in ALD mice. Mechanistically, CNFE reshaped BA homeostasis by suppressing hepatic synthesis, enhancing biliary efflux, reducing ileal reabsorption, and promoting fecal BA excretion, partly through FXR activation. Concurrently, CNFE-driven gut microbiota remodeling increased short-chain fatty acid production and reinforced intestinal barrier integrity. Furthermore, these microbiota alterations were associated with increased bile salt hydrolase activity, which enhanced BA deconjugation, thereby elevating endogenous FXR ligands (cholic acid and chenodeoxycholic acid) and strengthening FXR-mediated feedback regulation of BA homeostasis.
Conclusion
CNFE attenuates ALD by coordinately modulating BA homeostasis and intestinal barrier function via FXR activation and gut microbiota remodeling, supporting its potential as a natural intervention for ALD.