Effect of Dietary Doses of Quercetin on Hepatic Drug Metabolizing Enzymes in Spontaneously Hypertensive Rats
- 41 Downloads
Administration of quercetin (QR) has shown several health benefits in clinical and pre-clinical studies.
This study investigates the effect of dietary doses of QR on hepatic drug metabolizing enzymes in spontaneously hypertensive rats in order to investigate the potential for herb–drug interactions.
The activity and/or protein expression of selected cytochrome P450 (CYP) enzymes and microsomal epoxide hydrolase were measured in hepatic microsomes using specific probe substrates and/or polyclonal antibodies. Cytosolic fraction was utilized to measure protein level and activity of major antioxidant systems.
The doses employed in our study did not cause any significant alterations in the activity and/or protein level of CYP1A1, CYP2A6, CYP2E, and glutathione (GSH). While the activity and apoprotein levels of CYP1A2 and CYP2B1/2 were significantly reduced by the medium and high doses of QR, the activity and/or protein level of microsomal CYP3A and cytosolic GSH-S-transferase, GSH reductase, and GSH peroxidase were significantly enhanced. Activity and protein level of CYP2C9 were significantly inhibited by all doses. Only the high-dose QR resulted in significant inhibition of both microsomal and soluble epoxide hydrolase as well as induction of the antioxidant enzymes, catalase and superoxide dismutase.
This study demonstrates that dietary doses of QR may offer chemoprevention through stimulation of the endogenous antioxidant systems and inhibition of CYP enzymes involved in bioactivation of procarcinogens. However, modulation of drug metabolizing enzymes by QR could have potential for herb–drug interactions with the possibility of serious complications.
Compliance with Ethical Standards
This work was supported in part by the Medical Research Foundation of Oregon (MRF), Collins Medical Trust, Faculty Development Grant from Pacific University, Oregon and Dean’s Incentive Grant from Pacific University School of Pharmacy, Oregon (F.E.).
Conflict of interest
The authors declare no conflict of interest.
All procedures were approved by the Institutional Animal Care and Use Committee of Pacific University (protocol # 1003001). All institutional and national guidelines for the care of the laboratory animals were followed.
- 4.Wattenberg LW. Effects of dietary constituents on the metabolism of chemical carcinogens. Cancer Res. 1975;35 Part 2(11):3326.Google Scholar
- 16.Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970;227(5259):680–5.Google Scholar
- 18.Bioanalytical method validation; guidance for industry. 2018. https://www.fda.gov/media/70858/download. Accessed 20 Feb 2019.
- 23.Abdelkawy KS, Balyshev ME, Elbarbry F. A new validated HPLC method for the determination of quercetin: application to study pharmacokinetics in rats. Biomed Chromatogr. 2017;31(3):e3819.Google Scholar
- 27.Gibellini L, Pinti M, Nasi M, Montagna JP, De BS, Roat E, et al. Quercetin and cancer chemoprevention. Evid Based Complement Altern Med. 2011;2011:591356.Google Scholar
- 48.Imig JD. Epoxide hydrolase and epoxygenase metabolites as therapeutic targets for renal diseases. Am J Physiol Ren Physiol. 2005;289(3):F496–503.Google Scholar