The Effects of Traditional Chinese Medicine on P-Glycoprotein Mediated Multidrug Resistance and Approaches for Studying the Herb-P-Glycoprotein Interactions.

As a member of anATP-dependent membrane transport proteins, P-Glycoprotein (P-gp) is known to pump substrates out of cells in the ATP-dependent mechanism. The over-expression of P-gp in tumor cells reduces the intracellular drug concentrations, which decreases the efficacy of extensive antitumor drugs and leads to multidrug resistance (MDR) clinically. The combination of anti-cancer drugs with P-gp inhibitor has been an attractive and promising strategy to reverse MDR in cancer treatment. However, non-specific or non-selective distribution of P-gp inhibitors to non-target organs is one of the most fatal shortcomings in clinical application. Thus, there is an urgent need for effective and non‑toxic MDR reversal agents, particularly in P‑gp‑mediated MDR. Traditional Chinese medicine (TCM) natural products may provide less toxic for use in P-gp inhibition to promote MDR reversal. P-gp modulatory effects have been previously demonstrated using selected TCM, including the flavonoids, alkaloids, terpenoids, coumarins, and quinonoids compounds, and some Chinese medicine extracts. Moreover, the approaches for screening active components from TCM are necessary and facing more challenges. At present, the approaches to study the interaction between TCM and P-gp are divided into in vitro, in vivo and in silico methods. This review will provide an overview and update on the role of TCM in overcoming P-gp mediated MDR and the approaches to study the interaction between TCM and P-gp. Significance Statement This review summarized some traditional Chinese medicine identified to have a modulatory effect towards P-gp, including flavonoids, alkaloids, terpenoids, coumarins, quinonoids compounds and some Chinese medicine extracts, and introduced the possible mechanisms. The approaches to study the interaction between TCM and P-gp are divided into in vitro, in vivo, and in silico methods.