Inhibition of UDP‐glucuronosyltransferase by Aglycons of Natural Glucuronides in Kampo Medicines Using SN‐38 as a Substrate

7‐Ethyl‐10‐[4‐(piperidino)‐1‐piperidino]carbonyloxycamptothecin (CPT‐11), a potent anticancer agent for lung and gynecological cancers, is metabolized in vivo to the active compound, 7‐ethyI‐10‐hydroxycamptothecin (SN‐38), which is subsequently conjugated to SN‐38‐glucuronide by UDP‐glucuronosyltransferase (UDP‐GT). Three purified aglycons of natural glucuronides, baicalein, luteolin and glycyrrhetic acid, inhibited UDP‐GT activity towards SN‐38 as a substrate. The inhibitory potencies of these aglycons toward UDP‐GT were similar to that of 1‐naphthol. Based on these results, together with our previous finding that the corresponding glucuronides used in the present study strongly inhibited β‐glucuronidase in gut flora, we propose that materials in Kampo (Japanese herbal) medicines containing these aglycons of natural glucuronides could he used in vivo to decrease the enterohepatic circulation of SN‐38 and other drugs.