Interaction of Compounds Isolated from Boesenbergia rotunda with Human Renal Organic Anion and Cation Transporters

Abstract

Boesenbergia rotunda extract (BPE) is used as a dietary supplement and therapeutic purposes, such as antioxidant activity, antibacterial, anticancer, and antiobesity. Therefore, co-use of this herb and therapeutic drug possibly causes herb-drug interaction and leads to altering drug efficiency and toxicity. Organic anion transporters (OAT1 and OAT3) and organic cation transporters (OCT2) play an important role in renal excretion of anionic and cationic drugs. Inhibition of these transporters influences the plasma level of the drugs. Thus, the study was set up to determine the interaction of the extract and pure compounds isolated from B. rotunda with OAT1, OAT3 and OCT2 in human renal proximal tubular cells (RPTEC/TERT1) by measuring the uptake of ³H-PAH, ³H-ES and ³H-MPP⁺ which is a prototypical substrate of OAT1, OAT3 and OCT2, respectively. The results showed that BPE did not inhibit OAT1-mediated ³H-PAH uptake and OAT3-mediated ³H-ES uptake. BPE inhibited OCT2-mediated ³H-MPP⁺ uptake with a half maximal inhibitory concentration (IC50) of 44.17 ± 0.09 μg/ml. The effect of major compounds isolated from B. rotunda, panduratin A, pinocembrin and pinostrobin, on OCT2 function was determined. Pinocembrin and pinostrobin but not panduratin A inhibited OCT2-mediated ³H-MPP⁺ uptake with an IC₅₀ of 33.50 ± 0.16 μM. These data suggest that the use of B. rotunda as dietary supplement or for therapeutic purposes may cause herb-drug interaction and subsequently alter renal cationic drug clearance.