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Updated: Mar 17, 2026
Author Spotlight: Illuminating New Avenues for Adipose Tissue Metabolism and Disease Prevention
Published on: October 6, 2023
Metabolism of Flavone-8-acetic Acid in Mice
Minh Hien Pham1, Nicolas Auzeil2, Anne Regazzetti2
1Chemical, Genetic and Imaging Pharmacology Laboratory, Faculty of Pharmacy, Chimie ParisTech, Paris Descartes University, Sorbonne Paris Cité, INSERM U1022, CNRS UMR8151, Paris, France Medical Oncology and Cellular Therapy Department, Tenon Hospital, Public Assistance Hospitals of Paris, Alliance for Cancer Research, Paris, France Laboratory of Therapeutic Drug Monitoring, Platform for Peptidomic, Metabolomic and Drug Measurements, Saint Antoine Hospital, Paris, France minh-hien.pham@aphp.fr.
Abstract:
Flavone-8-acetic acid (FAA) is a potent antivascular agent in mice but not in humans. Assuming that FAA was bioactivated in mice, we previously demonstrated that 6-OH-FAA was formed from FAA by mouse microsomes but not by human microsomes; its antivascular activity was 2.1- to 15.9-fold stronger than that of FAA, and its antivascular activity was mediated through the Ras homolog gene family (Rho) protein kinase A (RhoA) pathway. The present work aimed to study FAA metabolism in order to verify if 6-OH-FAA is formed in mice. Using synthesized standards and high-performance liquid chromatography (HPLC) coupled with ultraviolet (UV) detection and mass spectrometry (MS) analysis, we herein demonstrated, for the first time, that in vitro FAA and its monohydroxylated derivatives could directly undergo phase II metabolism forming glucuronides, and two FAA epoxides were mostly scavenged by NAC and GSH forming corresponding adducts. FAA was metabolized in mice. Several metabolites were formed, in particular 6-OHFAA. The antitumor activity of 6-OH-FAA in vivo is worthy of investigation.
Insights
Flavone-8-acetic acid (FAA) is metabolized in mice, forming 6-OH-FAA. This metabolite shows stronger antivascular activity, suggesting potential for cancer treatment investigation.
Area of Science:
- Pharmacology
- Drug Metabolism
- Biochemistry
Background:
- Flavone-8-acetic acid (FAA) exhibits potent antivascular effects in mice, but not humans.
- Previous research indicated 6-OH-FAA formation from FAA by mouse microsomes, with enhanced antivascular activity via the RhoA pathway.
Purpose of the Study:
- To investigate Flavone-8-acetic acid (FAA) metabolism in mice.
- To confirm the in vivo formation of 6-OH-FAA from FAA.
Main Methods:
- High-performance liquid chromatography (HPLC) with UV detection.
- Mass spectrometry (MS) analysis.
- In vitro studies with synthesized standards, microsomes, N-acetylcysteine (NAC), and glutathione (GSH).
Main Results:
- FAA undergoes phase II metabolism, forming glucuronides with monohydroxylated derivatives.
- Two FAA epoxides were primarily scavenged by NAC and GSH, forming adducts.
- FAA is metabolized in mice, with 6-OH-FAA identified as a key metabolite.
Conclusions:
- This study confirms FAA metabolism in mice, yielding 6-OH-FAA.
- The formation of 6-OH-FAA in mice warrants further investigation into its in vivo antitumor activity.
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