Xiaoyan Lidan formula ameliorates cholecystitis by regulating cholesterol transportation and water permeability of the gall bladder through the activation of LXRβ

Ethnopharmacological relevance: Xiaoyan Lidan Formula (XYLDF), a traditional Chinese Medicine prescription originating from the Lingnan region of China, is primarily used to treat cholecystitis with significant clinical efficacy. However, the mechanism of XYLDF in the treatment of cholecystitis has not been explored.

Aim of the study: This study aims to explore the mechanism by which XYLDF alleviates cholecystitis based on the comprehensive approach of network pharmacology and metabolomics in guinea pigs.

Materials and methods: The therapeutic effect of XYLDF in cholecystitis was evaluated based on a lincomycin-induced cholecystitis guinea pig model. The pharmacological mechanisms of XYLDF intervening cholecystitis were explored by network pharmacology and metabolomics. Finally, the verification was conducted using Molecular Biology techniques both in vivo and in vitro.

Results: XYLDF ameliorated lincomycin-induced mucosa inflammatory injury of the gallbladder and liver. The integration analysis of network pharmacology and metabolomics revealed a therapeutic effect closely related to anti-inflammation, as well as the regulation of Cholesterol efflux and water permeation in the gallbladder. Furthermore, the experimental results indicated that XYLDF significantly promoted the expression of cholecystic LXRβ to regulate Cholesterol transporters and water/ion transport membrane channels, namely ATP-binding cassette transporter A1 (ABCA1), ATP-binding cassette subfamily C member 5/8 (ABCG5/8), aquaporins-1 (AQP-1), and cystic fibrosis transmembrane conductance regulator (CFTR). Meanwhile, XYLDF inhibited the NF-κB signaling pathway to reduce inflammatory response. Noticeably, the suppression of LXRβ attenuated the above efficacy of XYLDF.

Conclusion: XYLDF alleviated lincomycin-induced cholecystitis in guinea pigs by regulating Cholesterol metabolism, water permeation, and inflammatory response through the activation of LXRβ and inhibition of the NF-κB signaling pathway.

Cholecystitis; Cholesterol transporter; LXRβ; Metabolomics; Xiaoyan Lidan formula.