Zhi-Zi-chi decoction: A promising remedy for liver inflammation via gut microbiota modulation.

Background: The microbiota-gut-liver axis is increasingly recognized for its critical role in liver diseases, particularly liver injury. Zhi Zi Chi decoction (ZZCD), composed of Gardenia jasminoides J. Ellis and Glycine max (L.) Merr, is a TCM formula extensively used in the treatment of liver diseases. However, the mechanisms by which ZZCD modulates the microbiota-gut-liver axis to ameliorate liver injury remain poorly understood.

Methods: In this project, we employed liquid chromatography-mass spectrometry to analyze the chemical constituents of ZZCD. A liver injury model was established using lipopolysaccharide (LPS). Following ZZCD treatment, a comprehensive analysis involving paraffin section and H&E staining, ELISA, qPCR, western blotting, 16S rDNA sequencing, and metabolomic analyses was conducted to elucidate the interactions between intestinal flora and metabolites in LPS-induced mice, thereby clarifying the mechanism of ZZCD in liver injury treatment.

Results: ZZCD primarily contains geniposide, bruceine D, soyasaponin I, crocin, and rabdosiin. ZZCD was found to mitigate liver and intestinal injury induced by LPS, suppress the production of inflammatory factors, and modulate the PI3K/Akt signaling pathway. Meanwhile, ZZCD treatment resulted in an increased abundance of Rikenellaceae, Bacillaceae, Lachnospiraceae and Lactobacillaceae, while reducing the abundance of Prevotellaceae. Additionally, there was a significant increase in the fecal content of tyrosocholic acid, glaucarubin, camphoric acid, and alprazolam following ZZCD administration.

Conclusions: These findings suggest that ZZCD alleviates liver inflammation and damage through pleiotropic mechanisms by modulating the microbiota-gut-liver axis.