Interactions Of 172 Plant Extracts With Human Organic Anion Transporter 1(SCL22A6) And 3(SCL22A8):A Study On Herb-drug Interactions

Herb-drug interactions?HDIs?resulting from concomitant use of herbal products with clinical drugs may cause adverse reactions.Organic anion transporter 1?OAT1?and 3?OAT3?are highly expressed in the kidney and play a key role in the renal elimination of substrate drugs.So far,little is known about the herbal extracts that could modulate OAT1 and OAT3 activities.Objective:A range of natural plants are used as folk medicine and food,however there is little information about their function on transporters which are important for drug absorption,distribution,metabolism and excretion.This study aims to evaluate the inhibitory effects of hexane,dichloromethane,butanol,and aqueous extracts from37 species containing above 172 samples on h OAT1 and hOAT3,proteins known to transport drugs from the blood into the tubular epithelium.Methods:HEK293 cells stably expressing human OAT1?HEK293-hOAT1?and OAT3?HEK293-hOAT3?were established and characterized.A total of 172 extracts from 37 medicinal and economic plants were prepared.An initial concentration of 5?g/ml for each extract was used to evaluate their effects on 6-carboxylfluorescein?6-CF?uptake in HEK293-hOAT1 and HEK293-hOAT3 cells.Concentration-dependent inhibition studies were conducted for those extracts with more than 50%inhibition to OAT1 and OAT3.The extract of Juncus effusus,a well-known traditional Chinese medicine,was assessed for its effect on the in vivo pharmacokinetic parameters of furosemide,a diuretic drug which is a known substrate of both OAT1 and OAT3.Results:More than 30%of the plant extracts at the concentration of 5?g/ml showed strong inhibitory effect on the 6-CF uptake mediated by OAT1?61 extracts?and OAT3?55 extracts?.Among them,three extracts for OAT1 and fourteen extracts for OAT3 were identified as strong inhibitors with IC₅₀ values being<5?g/ml.Juncus effusus,a well-known traditional Chinese medicine,showed a strong inhibition to OAT3 in vitro,and markedly altered the in vivo pharmacokinetic parameters of furosemide in rats.Conclusion:The present study identified the potential interactions of medicinal and economic plants with OAT1 and OAT3,which is helpful to predict and to avoid potential OAT1-and OAT3-mediated HDIs.