Combined Taraxacum mongolicum and Astragalus polysaccharides attenuate CCl4-induced hepatic fibrosis through modulation of the TLR4/MyD88/NF-κB signaling pathway and gut microbiota composition
TL;DR
TMP combined with APS exerts enhanced anti-hepatic fibrosis effects compared with either monotherapy, and is associated with changes in gut microbiota composition, elevated fecal short-chain fatty acid levels, and reduced expression of hepatic TLR4/MyD88/NF-κB pathway-related molecules.
Abstract
Background Hepatic fibrosis represents a critical pathological stage in the progression of chronic liver diseases, yet clinically effective and low-toxicity therapeutic options remain limited. Taraxacum mongolicum and Astragalus form a classic hepatoprotective herbal pair, and their derived polysaccharides-Taraxacum mongolicum polysaccharides (TMP) and Astragalus polysaccharides (APS)-both exhibit hepatoprotective activities. This study aimed to investigate the ameliorative effects of TMP combined with APS on CCl4-induced hepatic fibrosis in mice and the gut-liver axis-associated changes. Methods Mice were randomly assigned to the blank control, model, silybin, Lizhu Changle (live Bifidobacterium adolescentis capsules), TMP monotherapy, APS monotherapy, and combination groups. Following the establishment of fibrosis by CCl4, a 4-week intervention was administered. Serum liver function parameters and fibrosis markers were measured, and hepatic histopathological changes were observed. Intestinal function was comprehensively evaluated. Gut microbiota composition was analyzed using 16S rRNA gene sequencing, and fecal short-chain fatty acid (SCFA) levels were quantified by high-performance liquid chromatography (HPLC). The protein expression of the hepatic TLR4/MyD88/NF-κB pathway was further assessed. Results Compared with TMP or APS alone, the combination significantly improved multiple fibrosis-related, inflammatory, intestinal barrier, microbial diversity, and SCFA-related indices, although significant superiority was not observed for PC III and TNF-α. The combination also more strongly suppressed hepatic TLR4/MyD88/NF-κB pathway expression. Conclusion TMP combined with APS exerts enhanced anti-hepatic fibrosis effects compared with either monotherapy. These effects are associated with changes in gut microbiota composition, elevated fecal short-chain fatty acid levels, reduced expression of hepatic TLR4/MyD88/NF-κB pathway-related molecules. These findings provide an experimental basis for further investigation of this herbal pair.