Biotransformace sekundárních rostlinných metabolitů a jejich modulační účinky na enzymy metabolizující léčiva

Šadibolová, Michaela

Charles University, Faculty of Pharmacy in Hradec Králové Training Workplace Department of Biochemical Sciences Doctoral Degree Program Xenobiochemistry and Pathobiochemistry Candidate Mgr. Michaela Šadibolová Supervisor Assoc. Prof. PharmDr. Iva Boušová, Ph.D. Advisor Title of Doctoral Thesis Biotransformation of plant secondary metabolites and their modulatory effects on drug-metabolizing enzymes Sesquiterpenes and prenylflavonoids represent two classes of plant secondary metabolites that form an inherent part of human diet. They exert many beneficial biological activities, and accordingly, they are used as active constituents of herbal products. However, as xenobiotics, they also interact with a battery of drug-metabolizing enzymes and can in turn modulate their activity and/or expression, which may lead to herb-drug interactions. Sesquiterpenes and prenylflavonoids mentioned in this dissertation have been under-researched in this aspect. Three acyclic sesquiterpenes (farnesol, cis-nerolidol, trans-nerolidol) and three cyclic sesquiterpenes (α-humulene, β-caryophyllene, β-caryophyllene oxide) activated gene transcription mediated by pregnane X receptor; however, they did not alter the mRNA or protein expression of their downstream targets, namely cytochrome P450 (CYP) 3A4 and CYP2C, neither did...

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