Inhibition of the tobacco-specific nitrosamine metabolizing cytochrome p450 2a13 by herbal p;ants from eastern part of Thailand

Name: Athitaya Insee

ThaSH: Burapha University -- Biological Science Faculy Of Science

Classification :.DDC: 615.321

ThaSH: Herbs -- Therapeutic use -- Testing

ThaSH: Tobacco -- Toxicology

ThaSH: อุตสาหกรรมการเกษตรและเทคโนโลยีชีวภาพ

Abstract: The lung-specific cytochrome P450 2A13 (CYP2A13) is an enzyme that plays an important role in metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1- butanone nitrosamine (NNK) which is associated with the development of NNKinduced lung cancer in various smokers. The 8-methoxypsoralen (8-MOP) had been reported to specifically inhibit the CYP2A13 mediated NNK-metabolism and resulting in decreased lung cancer formation in mice. As administration of 8-MOP can cause various side effects in smokers, the CYP2A13 inhibitors from naturalderived compounds could be proper candidates for lung cancer prevention. This research aims to investigate the inhibitory activity of some medicinal plants from Eastern part of Thailand on CYP2A13 enzyme in vitro. The CYP2A13 and NADPHcytochrome P450 reductase (CPR) enzymes had successfully expressed in Escherichia coli and purified by Ni2+-affinity chromatography. Among selected medicinal plant extracts, the ethanolic extract of Pluchea indica Less showed the highest inhibitory activity and was subsequently characterized. The results herein indicated that the isolated quercetin from ethyl acetate fraction can inhibit the CYP2A13 enzyme with a competitive reversible inhibition. The inhibition constant (Ki) value was determined as 4.32 M. The bio-assay guided isolation in the hexane fraction yielded six hexane sub-fractions that could potently inhibit the CYP2A13 enzyme. Furthermore, the isolated quercetin and all six sub-fractions showed less inhibitory activity on CYP3A4 mediated-testoterone 6-hydroxylation compared to the CYP2A13 mediated coumarin 7-hydroxylation suggesting the specific inhibition. This finding will be applied towards CYP2A13. For medicinal plant in lung cancer.

Address: CHONBURI

Email: buulibrary@buu.ac.th

Name: Songklod Sarapusit

Role: Principal advisor

Created: 2015

Modified: 2025-02-24

Issued: 2559-02-01

วิทยานิพนธ์/Thesis

application/pdf

eng

DegreeName: Master of Science

Level: Master's Degree

Descipline: Biological Science

Grantor: Burapha University

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