Phytomedicine : international journal of phytotherapy and phytopharmacology · 2025
Bupleuri Radix polysaccharides enhance the efficacy and intestinal absorption of baicalin via regulating intestinal β-glucuronidase activity in MASH mice.
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Zhang Anna, Gao Siqi, Shen Conghua, Wu Sijia, Wang Xingxing, Shen Qin, Hua Jiekai, Wang Jingjing, Shi Jiewen, Chen Senjie, Qin Luping, Liu Wei, Wu Jianjun
Аннотация
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.
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.