Ris multifida. Food Chem Toxicol. 2017;108(B): 524?1.70 Structure nhibition relationship of flavonoids against UDPglucuronosyltransferase 1A1 XinYu Liu1,two, Xia Lv2, Ping Wang2, LiWei Zou2, GuangBo Ge2, Hui Tang1, Ling Yang2 1 Essential Laboratory of Xinjiang Phytomedicine Resource and Utilization, Clonixin Purity & Documentation Ministry of Education, Pharmacy College of ShiHezi University, Xinjiang 832000, China; 2 Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China Correspondence: Hui Tang [email protected]; GuangBo Ge [email protected] Journal of Chinese Medicine 2018, 13(Suppl 1):70 Background: Uridine-disphosphate glucuronosyltransferase 1A1 (UGT1A1), one of the most important phase II conjugative enzymes, plays important role in the elimination and detoxification of a host of potentially dangerous compounds (for example bilirubin) and clinical drugs (which include etoposide and diethylstilbestrol). Consequently, it is actually of good significance to systematically evaluate the BzATP (triethylammonium salt) Formula inhibitory effects of natural merchandise in dietary supplements (for example flavonoids) against human UGT1A1 [1,2]. A previous study by us has created a specific fluorescent probe (NCHN) for UGT1A1, This study aimed to discover the structure nhibition relationships of flavonoids against human UDP-glucuronosyltransferase UGT1A1 applying a high-throughput screening approach. Solutions: More than thirty natural flavonoids happen to be collected and assayed using the probe NCHN which is often utilized for high-throughput screening (HTS) and characterization of UGT1A1 inhibitors by utilizing human liver microsomes (HLM) and UGT1A1 because the enzyme source within this paper [3]. To research the effect of inhibition against UGT1A1 mediated NCHN-O-glucuronidation in HLM, and pick the suitable concentration of inhibitor (flavonoids) to ascertain the IC50 value; According to the IC50 worth, the compounds which has the strongest inhibitory impact (IC50 5 mol L-1) could be the selected to proceed the subsequent study; The single enzymes and HLM have been utilized as enzyme sources, respectively. Using the IC50 value as well as the appropriate concentration of substrate which determined by enzyme kinetics, the compound inhibited glucuronyl transferase enzyme inhibition kinetics experiment was studied to determine the inhibition constants Ki of the compound and its inhibit competitive kind, respectively. Benefits: The results demonstrated that kaempferol which with multiple phenolic groups displayed powerful inhibition against UGT1A1 mediated NCHN-O-glucuronidation in HLM and UGT1A1(IC505 M) in these flavoids, the IC50 values of kaempferol was determined as 3.34 and two.44 M, respectively. Further investigation around the inhibitory behaviors of kaempferol demonstrated that tested nature flavonoids are non-competitive inhibitors against UGT1A1 mediated NCHNO-glucuronidation, at the similar time, that is definitely competitive inhibitors against HLM, UGT1A1 mediated NCHN-O-glucuronidation, with theKi values are 1.74 and 0.90 M, respectively. Although, the glycosyl flavonoids are hardly to inhibit UGT1A1 (IC50 100 M) within this study. What’s a lot more, the saturated flavonoids displayed weaker inhibition against UGT1A1 mediated NCHN-O-glucuronidation in HLM than that of unsaturated flavonoids. Conclusion: Unique sorts of flavonoids and flavonoids with various structure expressed diverse levels inhibition against UGT1A1 mediated NCHN-O-glucuronidation in HLM. At the same time it appears to become extra inclined to create flavonone as novel fl.
