Biotransformation of aesculin by human gut bacteria and identification of its metabolites in rat urine

AIM： To observe the biotransformation process of a Chinese compound, aesculin, by human gut bacteria, and to identify its metabolites in rat urine.METHODS： Representative human gut bacteria were collected from 20 healthy volunteers, and then utilized in vitro to biotransform aesculin under anaerobic conditions. At 0, 2, 4, 8, 12, 16, 24, 48 and 72 h postincubation, 10 mL of culture medium was collected. Metabolites of aesculin were extracted 3 × from rat urine with methanol and analyzed by HPLC. For in vivo metabolite analysis, aesculetin （100 mg/kg） was administered to rats via stomach gavage, rat urine was collected from 6 to 48 h post-administration, and metabolite analysis was performed by LC/ESI-MS and MS/MS in the positive and negative modes.RESULTS： Human gut bacteria could completely convert aesculin into aesculetin in vitro. The biotransformation process occurred from 8 to 24 h post-incubation, with its highest activity was seen from 8 to 12 h. The in vitro process was much slower than the in vivo process. In contrast to the in vitro model, six aesculetin metabolites were identified in rat urine, including 6-hydroxy-7-glucocoumarin（M1）, 6-hydroxy-7-sulf-coumarin （M2）, 6, 7-digluco-coumarin （M3）, 6-glc-7-gluco-coumarin （M4）, 6-O-methyl-7-gluco-coumarin （MS） and 6-O-methyl-7- sulf-coumarin （M6）. Of which, M2 and M6 were novel metabolites.CONCLUSION： Aesculin can be transferred into aesculetin by human gut bacteria and is further modified by the host in vivo. The diverse metabolites of aesculin may explain its pleiotropic pharmaceutical effects.

中药皂苷类成分的体内代谢研究进展

皂苷是中药中的一类重要活性成分,根据苷元结构的不同又可分为三萜皂苷和甾体皂苷两种结构类型。本文对多种代表性中药皂苷如人参皂苷、甘草皂苷、柴胡皂苷、知母皂苷和薯蓣皂苷等的体内代谢途径进行了综述,并对其代谢规律进行了总结。皂苷原形成分口服给药后往往吸收较差,其体内代谢通常经由胃肠道的水解和吸收入血后肝脏的代谢两步完成。其中,胃肠道水解后产生的次级苷或苷元往往具有更高的生物利用度,而肝脏对入血成分的进一步代谢则以Ⅰ相代谢为主。明确中药皂苷的体内代谢特征,有助于正确理解该类成分发挥药效的体内物质基础,并为基于活性天然产物的新药开发提供科学依据。