Structural determination of two new sesquiterpenes biotransformed from germacrone by Mucor alternata

Eight transformed sesquiterpenes of germacrone by Mucor alternata were obtained. Their structures were characterized on the basis of spectral methods including 2D NMR. Among them, (1S, 4S, 5S, 10R)-isozedoarondiol (2) and (1R, 4S, 5S, 10R)-diepoxy-12-hydroxygermacrone (3) are new compounds.     

Simultaneous quantification of curdione,furanodiene and germacrone in rabbit plasma using liquid chromatography–tandem mass spectrometry and its application to a pharmacokinetic study

A simple, rapid and sensitive method was developed for the simultaneous quantification of curdione, furanodiene and germacrone in rabbit plasma using a LC‐MS/MS analysis. The plasma sample preparation was a simple deproteinization by the addition of 3 vols of acetonitrile followed by centrifugation. The analytes and internal standard (IS) costunolide were separated on a Zorbax SB‐C₁₈ column (3.5 µm, 2.1 × 100 mm) with mobile phase of methanol–water (90:10, v/v) containing 0.1% formic acid at a flow rate of 0.3 mL/min with an operating temperature of 25°C. Detection was carried out by atmospheric pressure chemical ionization in positive ion selected reaction monitoring mode. Linear detection responses were obtained for the three test compounds ranging from 5 to 5000 ng/mL and the lower limits of quantitation were 5‐10ng/mL. The intra‐ and inter‐day precisions (relative standard deviations) were within 9.4% for all analytes, while the deviation of assay accuracies was within ±10.0%. The average recoveries of analytes were >80.0%. All analytes were proved to be stable during all sample storage, preparation and analytical procedures. The method was successfully applied to the pharmacokinetic study of the three compounds after vaginal drug delivery of Baofukang suppository to rabbit. Copyright © 2015 John Wiley & Sons, Ltd.     

Kinetic Characteristics of Curcumin and Germacrone in Rat and Human Liver Microsomes: Involvement of CYP Enzymes

Curcumin and germacrone, natural products present in the Zingiberaceae family of plants, have several biological properties. Among these properties, the anti-NSCLC cancer action is noteworthy. In this paper, kinetics of the two compounds in rat liver microsomes (RLMs), human liver microsomes (HLMs), and cytochrome P450 (CYP) enzymes (CYP3A4, 1A2, 2E1, and 2C19) in an NADPH-generating system in vitro were evaluated by UP-HPLC–MS/MS (ultrahigh-pressure liquid chromatography–tandem mass spectrometry). The contents of four cytochrome P450 (CYP) enzymes, adjusting by the compounds were detected using Western blotting in vitro and in vivo. The t_1/2 of curcumin was 22.35 min in RLMs and 173.28 min in HLMs, while 18.02 and 16.37 min were gained for germacrone. The V_max of curcumin in RLMs was about 4-fold in HLMs, meanwhile, the V_max of germacrone in RLMs was similar to that of HLMs. The single enzyme t1/2 of curcumin was 38.51 min in CYP3A4, 301.4 min in 1A2, 69.31 min in 2E1, 63.01 min in 2C19; besides, as to the same enzymes, t1/2 of germacrone was 36.48 min, 86.64 min, 69.31 min, and 57.76 min. The dynamic curves were obtained by reasonable experimental design and the metabolism of curcumin and germacrone were selected in RLMs/HLMs. The selectivities in the two liver microsomes differed in degradation performance. These results meant that we should pay more attention to drugs in clinical medication–drug and drug–enzyme interactions.