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Article Publish Status: FREE
Abstract Title:

Antifibrotic effect of methylated quercetin derivatives on TGFβ-induced hepatic stellate cells.

Abstract Source:

Biochem Biophys Rep. 2019 Dec ;20:100678. Epub 2019 Aug 16. PMID: 31467991

Abstract Author(s):

Munkhzul Ganbold, Yasuhiro Shimamoto, Farhana Ferdousi, Kenichi Tominaga, Hiroko Isoda

Article Affiliation:

Munkhzul Ganbold

Abstract:

Quercetin (QCT) and isorhamnetin (ISO), natural flavonoids, were both shown to possess antifibrotic activity inandmodels of hepatic fibrosis. Although ISO is a direct metabolite of QCT differing by a methyl group, it has been reported to be absorbed more adequately and eliminated slower than QCT after oral administration. Our aim of the study was to investigate biological effect of mono-methylated QCT derivatives against fibrosis using rat hepatic stellate cells (HSC-T6). All test derivatives were synthesized from QCT. HSC-T6 cells were induced by TGFβ and treated with derivatives followed by cell proliferation assay, immunofluorescence staining of αSMA, and gene expression analysis of fibrosis markers. All compounds showed a dose- and time-dependent antiproliferation effect. ISO, 3-O-methylquercetin (3MQ), and rhamnetin (RHA) reduced αSMA mRNA; 3MQ prevented the augmentation of collagen I mRNA; and compounds, except azaleatin and 3MQ, reduced Timp1 mRNA expression in TGFβ-induced HSCs. In conclusion, each compound had singular effect against different features of fibrosis depending on the position of methyl group although the furthermechanism of action of compounds during fibrosis development remains to be investigated. These findings suggest that antifibrotic effect of quercetin can be enhanced by adding methyl group on functionally important position.

Study Type : Human In Vitro
Additional Links
Pharmacological Actions : Anti-Fibrotic : CK(46) : AC(29)

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