Baicalein, the aglycone formed by hydrolysis of baicalin in the intestine, is well absorbed by passive diffusion but subjected to extensive intestinal glucuronidation. Efflux of baicalin, the low passive permeability glucuronide of baicalein from enterocytes, likely depends on a carrier-mediated transport. The present study was designed to explore potential drug-herb interaction by investigating the inhibitory effect of baicalin on the transport of reporter substrates by transporters and to identify the transporters responsible for the efflux of baicalin from enterocytes and hepatocytes. The interaction of baicalin with specific ABC transporters was studied using membranes from cells overexpressing human BCRP, MDR1, MRP2, MRP3 and MRP4. Baicalin was tested for its potential to inhibit vesicular transport by these transporters. The transport of baicalin by the selected transporters was also investigated. Transport by BCRP, MRP3 and MRP4 was inhibited by baicalin with an IC50 of 3.41 ± 1.83 μM, 14.01 ± 2.51 μM and 14.39 ± 5.69 μM respectively. Inhibition of MDR1 (IC50  = 94.84 ± 31.10 μM) and MRP2 (IC50  = 210.13 ± 110.49 μM) was less potent. MRP2 and BCRP are the apical transporters of baicalin that may mediate luminal efflux in enterocytes and biliary efflux in hepatocytes. The basolateral efflux of baicalin is likely mediated by MRP3 and MRP4 both in enterocytes and hepatocytes. Via inhibition of transport by ABC transporters, baicalin could interfere with the absorption and disposition of drugs.

The use and significance of baicalin, the main bioactive component found in Radix Scutellaria, have been on the rise due to its interesting pharmacological properties. Baicalin, a low passive permeability compound, is directly absorbed from the upper intestine and its hepatic elimination is dominant. However, interaction but no transport studies have implicated organic anion‐transporting polypeptides in its cellular uptake. By using mammalian cells stably expressing the uptake transporters of interest, we are showing that baicalin is a potent substrate of Organic anion‐transporting polypeptide 2B1 (OATP2B1) and less potent substrate of OATP1B3. OATP2B1 and OATP1B3 transport baicalin and may play a role in the hepatic uptake of baicalin formed in the intestine.

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