title: The inhibitory effects of nor-oleanane triterpenoid saponins from Stauntonia brachyanthera towards UDP-glucuronosyltransferases.
abstract: The inhibition of UDP-glucuronosyltransferases (UGTs) by herbal components might be an important reason for clinical herb-drug interaction (HDI). The inhibitory effects on UGTs via nor-oleanane triterpenoid saponins, which were the bioactive ingredients from Stauntonia brachyanthera, a traditional Chinese folk medicines with highly biological values, were evaluated comprehensively with recombinant UGT isoforms as enzyme source and a nonspecific substrate 4-methylumbelliferone (4-MU) as substrate. The results showed that there are seven compounds, 2, 3, 4, 8, 9, 13 and 14, respectively, exhibited potential inhibitions towards UGT1A1, UGT1A3 and UGT1A10 among all 23 compounds isolated from the plants. The IC50 values were 17.1μM, 13.5μM, 9.5μM, 15.7μM, 16.3μM, 1.1μM, and 0.3μM, respectively. Data fitting using Dixon and Lineweaver-Burk plots demonstrated that the inhibition of UGT1A10, UGT1A1 and UGT1A3 was best fit to noncompetitive type and competitive, respectively. The inhibition kinetic parameter (Ki) was calculated to be 39μM, 17μM, 3.3μM, 10μM, 9.3μM, 0.19μM, and 0.016μM, respectively. All these experimental data suggested that HDI might occur when compounds containing herbs were co-administered with drugs which mainly undergo UGTs-mediated metabolism.
authors.affiliation: Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.affiliation: Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Li
authors.affiliation: Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Jia-Qi
authors.initials: JQ
authors.lastname: Qi
authors.affiliation: Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: mengdl@163.com.
authors.forename: Da-Li
authors.initials: DL
authors.lastname: Meng
authors.affiliation: Key Laboratory of Contraceptives and Devices Research (NPFPC), Shanghai Engineer and Technology Research Center of Reproductive Health Drug and Devices, 200000, China; Translational Medicine Center, The First Affiliated Hospital of Liaoning Medical University, Jing Zhou, China.
authors.forename: Yun-Feng
authors.initials: YF
authors.lastname: Cao
mesh_terms: D004365:Drugs, Chinese Herbal; D014453:Glucuronosyltransferase / Q000037:antagonists & inhibitors*; D041743:Herb-Drug Interactions; D019684:Magnoliopsida / Q000737:chemistry*; D015394:Molecular Structure; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D012503:Saponins / Q000737:chemistry*; D000099148:UGT1A1 Enzyme
chemical_list: D004365:Drugs, Chinese Herbal; D014453:Glucuronosyltransferase; D009828:Oleanolic Acid; D012503:Saponins; D000099148:UGT1A1 Enzyme; C413246:oleanane; C476725:bilirubin uridine-diphosphoglucuronosyl transferase 1A10
keywords: Herb-drug interaction; Nor-oleanane triterpenoid saponins; UDP-glucuronosyltransferases