人参化学成分的药物代谢动力学研究

Pharmacokinetic Studies of Chemical Constituents of Ginseng

人参广泛的治疗和保健作用已有许多研究,其主要有效成分人参皂苷调节多种生理活动。生物和环境因素可能影响人参皂苷的功效。人参皂苷的药代动力学和代谢研究结果证明:1人参皂苷在胃肠道的吸收性随分子结构中糖基化程度不同而不同;2在人源肠Caco-2细胞单层模型,多糖基化原形人参皂苷的膜渗透性差是限制其口服吸收不良的主要原因;3人参皂苷在被吸收进入循环系统之前,主要被代谢为相应的次皂苷和/或皂苷元;4某些人参皂苷在肠道内由肠内细菌所致生物转化产生的生物活性中间体和/或终末产物,能够反映它们的生物活化作用,提示人参皂苷很可能是前药;5原形人参皂苷及其脱糖基代谢产物从体内清除。本文概述了人参皂苷生物转化和/或代谢以及药代动力学的最新研究进展,为明确人参的药效物质基础提供了循证科学依据。

The wide range of therapeutic and health care potential of ginseng has been studied extensively, and ginsenosides, the principal active ingredients of ginseng, are shown to be involved in modulating multiple physiological activities. Biological and environmental factors may affect the efficacy of ginsenosides. Evidence from pharmacokinetic and metabolic studies of ginsenosides demonstrated that （1） the absorption of many ginsenosides from gastrointestinal tract is different along with their different degrees of glycosylation in the molecular structure; （2） the poor membrane permeability of polyglycosylated prototypic ginsenoside predicted from the human Caco-2 cell monolayer model restricted their oral absorption badly; （3） ginsenoside may be metabolized mainly to their prosaponins and/or aglycones by intestinal microflora before absorption into circulatory system; （4） the intestinal microflora-dependent hiotransformation of some ginsenosides in the gastrointestinal tract could reflect a pathway of bioactivation resulting in the formation of bioactive intermediates and/or end- products, suggesting that ginsenoside is likely to be a prodrug; and （5） intact and some deglycosylated products are cleared from the body. This review provides an overview of the recent advances in biotransformation and/or metabolism as well as pharmacokinetics of ginsenosides, which might greatly contribute to supply the scientific basis for Evidence-Based Medicine in clarifying the effective substance basis of ginseng.