跨膜转运作为药物吸收、分布与代谢的核心环节，直接决定中药活性成分的生物利用度及靶组织分布，是其体内暴露水平与药效发挥的关键制约因素。中药成分结构多样、机制复杂，其口服生物利用度普遍较低，严重限制了临床疗效的充分发挥，成为现代中药制剂研发的瓶颈。通过系统综述黄酮类、生物碱类、皂苷类、萜类、多糖及有机酸等主要中药活性成分的跨膜转运机制，重点揭示了其结构-转运关系及多种转运蛋白（如P-糖蛋白、多药耐药相关蛋白、有机阴离子转运多肽等）参与的复杂调控网络。鉴于传统研究长期聚焦于成分的定性定量分析，对跨膜转运机制的解析相对薄弱，制约了基于机制导向的制剂设计与优化。通过进一步深入梳理基于转运机制的新型增效策略，包括新型递送系统、结构修饰、外排蛋白抑制、菌群代谢增效及中药配伍协同，旨在为突破中药有效成分的体内递送屏障，提升中药制剂生物利用度以及实现临床精准用药提供启示。

Transmembrane transport, as a core process in drug absorption, distribution, and metabolism, directly determines the bioavailability and target tissue distribution of active ingredients in traditional Chinese medicine (TCM). It is a key limiting factor for their systemic exposure and exertion of drug efficacy. The structural diversity and complex mechanisms of TCM components generally lead to low oral bioavailability, which severely restricts their full clinical therapeutic effects and has become a bottleneck in the development of modern TCM formulations. This article systematically reviews the transmembrane transport mechanisms of major active ingredients in TCM, such as flavonoids, alkaloids, saponins, terpenoids, polysaccharides, and organic acids, with a focus on elucidating their structure-transport relationships and the complex regulatory networks involving various transport proteins (e.g., P-glycoprotein, multidrug resistance-associated proteins, organic anion transporting polypeptides, etc.). Given that traditional research has long focused on qualitative and quantitative analysis of components while relatively neglecting the exploration of transmembrane transport mechanisms, hindering mechanism-guided formulation design and optimization. This review further delves into novel enhancement strategies based on transport mechanisms. These include advanced delivery systems, structural modification, efflux protein inhibition, gut microbiota-mediated metabolic enhancement, and synergistic compatibility of TCM ingredients. The aim is to overcome the in vivo delivery barriers of active TCM components, improve the bioavailability of TCM formulations, and ultimately provide insights for achieving precise clinical medication.

R285

国家自然科学基金资助项目(82474098)