ArticleFrontiers in pharmacology2025
Typical and atypical metabolic characteristics of three iridaceae isoflavone components:
Article in Frontiers in pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Methods: In this study, human liver microsomes (HLMs) and Cytochrome P450 (CYP) recombinant enzymes were used to study the metabolic stability, identify the metabolic pathways and enzyme kinetics of these three components, and elucidate their possible binding sites through molecular docking. Results: When tectorigenin, irigenin, and irisflorentin were co-incubated with HLMs and CYP recombinant enzymes, hydroxylation metabolite for tectorigenin, demethylated metabolite for irigenin, and 6,7-dihydroxy-5,3',4',5'-tetramethoxy isoflavone originating from irisflorentin were identified. CYP2E1 and CYP3A4 have high metabolic rates for tectorigenin, whereas CYP2C19 and CYP1A2 are the most important metabolic enzymes for irigenin and irisflorentin, respectively. The kinetics showed that the metabolism of tectorigenin and irigenin conformed to the Michaelis-Menten model, while the Eadie-Hofstee plot of irisflorentin yielded a convex curve with a unique "hooked" characteristic, and it conformed to the sigmoidal kinetics characteristic. Furthermore, molecular simulations showed that tectorigenin and irigenin bind to the orthosteric site of CYP isoforms via hydrogen bonds and π-π stacking, whereas irisflorentin is principally bound to CYP1A2 via π-π stacking and hydrophobic interactions. Conclusion: Collectively, these
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