柴胡总皂苷的大鼠体内代谢特征谱研究

Study on metabolic profiling of total saponins of Bupleurum chinense DC in rats

目的研究柴胡总皂苷在大鼠体内的代谢情况,分析其发挥药效的关键成分。方法首先基于UPLC-MS/MS技术,建立柴胡总皂苷提取物化学成分特征谱,对其总体皂苷类成分进行鉴定分析;进一步采用离体外翻肠囊、肝门静脉取血和腹主动脉取血的方法,比较大鼠肠吸收成分、肠代谢的入血成分和肝代谢的血中成分的化学成分特征谱,筛选柴胡皂苷类成分体内发挥药效的关键成分。结果本研究共鉴定出柴胡总皂苷提取物中52种柴胡皂苷类成分,其中只能通过肠道直接吸收入血的成分有16种,只能通过肠道菌群和肝脏代谢的成分有3种,既能直接通过肠道吸收入血又能通过肠道菌群代谢和肝代谢而吸收的成分有3种;通过比较3个代谢特征谱发现,乙酰柴胡皂苷E、柴胡皂苷元A、柴胡皂苷元G、柴胡皂苷A、柴胡皂苷B_(2)、柴胡皂苷元C可能是柴胡皂苷类成分体内发挥药效的关键成分。结论通过柴胡总皂苷提取物在离体外翻肠囊法、肝门静脉取血和腹主动脉取血的化学成分特征谱分析,初步探讨了柴胡皂苷发挥药效的关键成分,为深入研究柴胡皂苷类成分药效物质提供新的依据。

Objective To study the metabolism of the total saponin extract of Bupleurum chinense DC in rats and analyze the key components for its efficacy.Methods Based on the UPLC-MS/MS technique,the chemical composition profile of the total saponin extract of Bupleurum chinense DC was established,and the chemical composition profile of intestine-absorbed components,intestine-metabolized blood components and hepatic metabolized blood components in adult male SD rats were compared by using the everted rat gut sac method,hepatic portal vein blood sampling and abdominal aorta blood sampling,respectively.The key components of saikosaponins to exert their medicinal effects were analyzed.Results A total of 52 saikosaponins were identified in the total saponin extract of Bupleurum chinense DC.,including 16 saikosaponins that could be absorbed directly into the blood by the intestinal tract,3 saikosaponins that could be metabolized by the intestinal flora and liver and failed to be absorbed directly into the blood through the intestinal tract,and 3 saikosaponins that could be absorbed into the blood both directly through the intestinal tract and through the metabolism of the intestinal flora and liver metabolism.By comparing the three metabolic profiles,it was found that acetyl-saikosaponin E,saikogenin A,saikogenin G,saikosaponin A,saikosaponin B_(2) and saikogenin C may be the key components of saikosaponins to exert their pharmacological effects in vivo.Conclusion The chemical composition profiling of the total saponin extracts of Bupleurum chinense DC.identified 52 saikodaponins,and their metabolism characteristics were compared by the everted rat gut sac method,blood sampling from the hepatic portal vein,and blood sampling from the abdominal aorta,respectively.The key components of saikosaponins to exert their pharmacological effects were compared,providing a new basis for the in-depth study of the pharmacological substances of saikosaponins.