Transporter-mediated Natural Product-Drug Interactions

Abstract

The increasing use of natural products in the clinical practice has raised great concerns about the potential natural product-drug interactions (NDIs). Drug transporters mediate the transmembrane passage of a broad range of drugs and thus are important determinants for drug pharmacokinetics and pharmacodynamics. Generally, transporters can be divided into ATP binding cassette (ABC) family and solute carrier (SLC) family. Numerous natural products have been identified as inhibitors, substrates, inducers, and/or activators of drug transporters. This review article aims to provide a comprehensive summary of the recent progress on the research of NDIs, focusing on the main drug transporters, such as P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), organic anion transporter 1 and 3 (OAT1/OAT3), organic anion-transporting polypeptide 1B1 and 1B3 (OATP1B1/OATP1B3), organic cation transporter 2 (OCT2), multidrug and toxin extrusion protein 1 and 2-K (MATE1/MATE2-K). Additionally, the challenges and strategies of studying NDIs are also discussed.

Transporter proteins knowledge graph construction and its application in drug development

“…The natural product Luteolin with known transporter information was selected for further validating the effectiveness of the obtained AutoInt_KG predictive frame. The transporters OAT1, OAT3, and OATP1B1 of Luteolin have been reported by Li et al and Xiang et al [36] , [37] . The predicted results of AutoInt_KG was summarized and shown in Table 2 .…”

The Important Role of Transporter Structures in Drug Disposition, Efficacy, and Toxicity

“…Transporters can be generally divided into ABC and SLC superfamilies based on their sequence homology and transport mechanism (Liu, 2019a;Bi et al, 2023) 1), which mediate the efflux of a wide range of lipids, drugs and other molecules (Thomas and Tampe, 2020;Juan-Carlos et al, 2021). As shown in Supplemental Table 1, 10 ABC transporters (ABCA3, ABCB1, ABCB4, ABCB6, ABCB8, ABCB11, ABCC1, ABCC6, ABCC8, and ABCG2) have been reported to mediate the translocation of approved drugs.…”

“…Transporters are critical determinants of drug disposition (absorption, distribution, and excretion), clinical efficacy and toxicity, as they specifically mediate the influx and efflux of various substrates and drugs (DeGorter et al, 2012;Hong, 2017;Liu, 2019a;Liu, 2019b;Yin et al, 2020;Roberts, 2021). Based on the transport mechanism, transporters can be generally divided into ATP-binding cassette (ABC) and solute carrier (SLC) superfamilies (Liu, 2019a;Bi et al, 2023). ABC transporters are closely associated with the pharmacokinetics of many drugs, and SLC transporters are very important therapeutic targets for various diseases (Lusvarghi et al, 2020;Wang et al, 2020;Zhou et al, 2022).…”

Potential, Limitations and Risks of Cannabis-Derived Products in Cancer Treatment

“…Efflux pumps are found in the intestine, liver, kidneys, brain and many tumours. Overexpression in cancer cells contributes to multidrug resistance [ 123 , 124 ]. Altering the efficacy of such transporters may alter the cellular concentration of drug compounds that serve as substrates for them [ 125 ].…”