Inhibition of UDP-glucuronosyltransferase by Aglycons of Natural Glucuronides inKampoMedicines Using SN-38 as a Substrate
| Autor: | Tsuyoshi Yokoi, Eiichi Nagai, Hisao Hagiwara, Mikako Narita, Tetsuya Kamataki, Masaki Aburada |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Male
Cancer Research Glucuronosyltransferase Metabolite Glucuronates Baicalein —Glycyrrhetic acid Pharmacology Irinotecan Article Nitrophenols chemistry.chemical_compound In vivo Animals Enzyme Inhibitors Rats Wistar Luteolin Enterohepatic circulation SN‐38‐glucuronide biology Biological activity Rats Baicalein Kinetics Aglycone Oncology chemistry Biochemistry Microsomes Liver biology.protein Camptothecin 1‐Naphthol Drugs Chinese Herbal |
| Zdroj: | Japanese Journal of Cancer Research : Gann |
| ISSN: | 0910-5050 |
| DOI: | 10.1111/j.1349-7006.1995.tb03011.x |
| Popis: | 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-ethyl-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 beta-glucuronidase in gut flora, we propose that materials in Kampo (Japanese herbal) medicines containing these aglycons of natural glucuronides could be used in vivo to decrease the enterohepatic circulation of SN-38 and other drugs. |
| Databáze: | OpenAIRE |
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