Li Mengting, Wang Yanli, Chen Yi, Dong Lijinchuan, Liu Jieyuan, Dong Yu, Yang Qing, Cai Weiyan, Li Qi, Peng Bo, Li Yujie, Weng Xiaogang, Wang Yajie, Zhu Xiaoxin, Gong Zipeng, Chen Ying
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China; State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 550025, China.
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
Pharmacol Ther. 2024 Dec;264:108728. doi: 10.1016/j.pharmthera.2024.108728. Epub 2024 Oct 9.
Oral administration of Chinese Herbal Medicine (CHM) faces various challenges in reaching the target organs including absorption and conversion in the gastrointestinal tract, hepatic metabolism via the portal vein, and eventual systemic circulation. During this process, factors such as gut microbes, physical or chemical barriers, metabolic enzymes, and transporters play crucial roles. Particularly, interactions between different herbs in CHM have been observed both in vitro and in vivo. In vitro, interactions typically manifest as detectable physical or chemical changes, such as facilitating solubilization or producing precipitates when decoctions of multiple herbs are administered. In vivo, such interactions cause alterations in the ADME (absorption, distribution, metabolism, and excretion) profile on metabolic enzymes or transporters in the body, leading to competition, antagonism, inhibition, or activation. These interactions ultimately contribute to differences in the therapeutic and pharmacological effects of multi-herb formulas in CHM. Over the past two thousand years, China has cultivated profound expertise and solid theoretical frameworks over the scientific use of herbs. The combination of multiple herbs in one decoction has been frequently employed to synergistically enhance therapeutic efficacy or mitigate toxic and side effects in clinical settings. Additionally combining herbs with increased toxicity or decreased effect is also regarded as a remedy, a practice that should be approached with caution according to Traditional Chinese Medicine (TCM) physicians. Such historical records and practices serve as a foundation for predicting favorable multi-herb combinations and their potential risks. However, systematic data that are available to support the clinical practice and the exploration of novel herbal formulas remain limited. Therefore, this review aims to summarize the pharmacokinetic interactions and mechanisms of herb-herb or herb-drug combinations from existing works, and to offer guidance as well as evidence for optimizing CHM and developing new medicines with CHM characteristics.
口服中药在抵达靶器官的过程中面临各种挑战，包括在胃肠道的吸收与转化、经门静脉的肝脏代谢以及最终的体循环。在此过程中，肠道微生物、物理或化学屏障、代谢酶和转运体等因素发挥着关键作用。特别值得一提的是，已在体外和体内观察到中药中不同草药之间的相互作用。在体外，相互作用通常表现为可检测到的物理或化学变化，例如当多种草药的煎剂混合时促进溶解或产生沉淀。在体内，这种相互作用会导致体内代谢酶或转运体的ADME（吸收、分布、代谢和排泄）特征发生改变，从而引发竞争、拮抗、抑制或激活。这些相互作用最终导致中药复方在治疗和药理作用上存在差异。在过去的两千年里，中国在草药的科学应用方面积累了深厚的专业知识和坚实的理论框架。在临床环境中，常将多种草药组合在一剂煎剂中，以协同增强治疗效果或减轻毒副作用。此外，将毒性增加或效果降低的草药组合使用也被视为一种治疗方法，但中医医生应谨慎对待这种做法。这些历史记录和实践为预测良好的多草药组合及其潜在风险奠定了基础。然而，可用于支持临床实践和探索新型草药配方的系统数据仍然有限。因此，本综述旨在总结现有研究中草药-草药或草药-药物组合的药代动力学相互作用及机制，为优化中药和开发具有中药特色的新药提供指导和依据。
