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.

transmembrane transport  /  bioavailability  /  membrane barrier penetration  /  transporter regulation  /  passive diffusion  /  active transport  /  bioavailability-enhancing strategies