Identification and characterization of polysaccharide from Paeoniae Radix Rubra, and its mechanism in alleviating anti-tuberculosis drug-induced liver injury based on integrating gut microbiota and non-targeted metabolomics.

A novel polysaccharide, designated PRRP2, was extracted from the dried root of Paeoniae Radix Rubra. Structural analysis suggested that the PRRP2 backbone was predominantly composed of →4)-Glcp-(1→ and →6)-Glcp-(1→ glycosidic linkages, with a trace amount of →2)-Xylp-(1→ embedded within the backbone. Supplementary PRRP2 effectively ameliorated rifampicin (RFP) + isoniazid (INH)-induced hepatic functional injury. PRRP2 also alleviated intestinal inflammation and enhanced intestinal barrier integrity in RFP + INH-induced liver injury mice. 16S rRNA sequencing results revealed that PRRP2 administration restored gut microbiota homeostasis by promoting the growth of beneficial bacteria, including Lachnospiraceae_NK4A136_group, Bacteroides, norank_f_Prevotellaceae, and Ligilactobacillus. Furthermore, PRRP2 prominently regulated bile acid (BA)-related metabolites in RFP + INH-induced liver injury mice. Supplementary PRRP2 reshaped the BA biosynthesis and excretion process possibly via the modulation of the farnesoid X receptor (FXR)-mediated signaling pathway. Collectively, PRRP2 shows promising prospects as a functional supplement for alleviating anti-tuberculosis drug-induced liver injury.