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 he...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.展开更多
Increasing attention is being paid to the scientific evaluation of traditional Chinese medicine （TCM）. As many TCMs are capable of biotransformation in the gastrointestinal tract, attention to biotransforrnation of ...Increasing attention is being paid to the scientific evaluation of traditional Chinese medicine （TCM）. As many TCMs are capable of biotransformation in the gastrointestinal tract, attention to biotransforrnation of TCM in the gastrointestinal tract may lead to discovery of the active components and active mechanisms. In this article, we review reports that host metabolic enzymes and intestinal bacteria may be responsible for the metabolism of TCM. Good understanding of the in vivo course of TCM will help us to know how to conduct metabolism evaluation of TCM by using in vitro human-derived system. This evaluation system will create new views on TCM as effective and safe therapeutic agents.展开更多
基金Supported by Department of Traditional Chinese Medicine,Sichuan Province,No.03JY-002
文摘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.
文摘Increasing attention is being paid to the scientific evaluation of traditional Chinese medicine （TCM）. As many TCMs are capable of biotransformation in the gastrointestinal tract, attention to biotransforrnation of TCM in the gastrointestinal tract may lead to discovery of the active components and active mechanisms. In this article, we review reports that host metabolic enzymes and intestinal bacteria may be responsible for the metabolism of TCM. Good understanding of the in vivo course of TCM will help us to know how to conduct metabolism evaluation of TCM by using in vitro human-derived system. This evaluation system will create new views on TCM as effective and safe therapeutic agents.
