Bupleuri Radix polysaccharides enhance the efficacy and intestinal absorption of baicalin via regulating intestinal β-glucuronidase activity in MASH mice.

BACKGROUND

Bupleuri Radix polysaccharides (BRP) and baicalin (BAI) are key coexisting constituents in the traditional Chinese medicine (TCM) pair Bupleuri Radix-Scutellariae Radix, a classical herbal pair widely used in TCM formulations for treating liver diseases. However, the influence of BRP on BAI's intestinal metabolism, absorption, and therapeutic efficacy remains insufficiently explored.

PURPOSE: This study investigated BRP's effects on the oral pharmacokinetics and therapeutic efficacy of BAI in mice with metabolic dysfunction-associated steatohepatitis (MASH) to elucidate underlying mechanisms.

METHODS

Mice with MASH, induced by a methionine- and choline-deficient (MCD) diet, received oral BAI with or without BRP. BAI and its metabolite, baicalein (BE), were quantified using LC-MS/MS. 16S rRNA gene sequencing profiled gut microbiota composition, and intestinal β-glucuronidase (β-GUS) activity was measured via ELISA. Bile acid (BA) and polyunsaturated fatty acid (PUFA) profiles were evaluated LC-MS/MS.

RESULTS

BRP enhanced BAI's efficacy against liver injury and lipid accumulation. Co-administration elevated serum BAI concentrations and increased BE levels in serum and liver. Intestinal β-GUS activity significantly increased following co-administration. BRP regulated gut microbiota, such as Blautia, RF39, Desulfovibrio, Muribaculaceae and f_Clostridium_methylpentosum_group, which were correlated with β-GUS activity. Moreover, BRP potentiated BAI's regulatory effects on BA and PUFA profiles.

CONCLUSION

BRP improved BAI's intestinal absorption and therapeutic efficacy in MASH mice, potentially by modulating gut microbiota and enhancing β-GUS activity, thereby facilitating the deglycosylation of BAI. These findings reveal the potential synergistic mechanism of Bupleuri Radix-Scutellariae Radix pair and propose a feasible approach to improve the bioavailability and therapeutic effect of BAI.