Anti-inflammatory Activity of Natural Geranylated Flavonoids: Cyclooxygenase and Lipoxygenase Inhibitory Properties and Proteomic Analysis

0476495 - ÚEB 2018 RIV US eng J - Journal Article
Hanáková, Z. - Hošek, J. - Kutil, Zsófia - Temml, V. - Landa, Přemysl - Vaněk, Tomáš - Schuster, D. - Dall’Acqua, S. - Cvačka, Josef - Polanský, O. - Šmejkal, K.
Anti-inflammatory Activity of Natural Geranylated Flavonoids: Cyclooxygenase and Lipoxygenase Inhibitory Properties and Proteomic Analysis.
Journal of Natural Products. Roč. 80, č. 4 (2017), s. 999-1006. ISSN 0163-3864. E-ISSN 1520-6025
Grant - others:GA MŠk(CZ) ED0006/01/01
Institutional support: RVO:61389030 ; RVO:61388963
Keywords : PAULOWNIA-TOMENTOSA FRUITS * PRENYLATED FLAVONOIDS * FLAVANONES
OECD category: Biochemistry and molecular biology
Impact factor: 3.885, year: 2017

Geranyl flavones have been studied as compounds that potentially can be developed as anti-inflammatory agents. A series of natural geranylated flavanones was isolated from Paulownia tomentosa fruits, and these compounds were studied for their anti-inflammatory activity and possible mechanism of action. Two new compounds were characterized [paulownione C (17) and tomentodiplacone O (20)], and all of the isolated derivatives were assayed for their ability to inhibit cyclooxygenases (COX-1 and COX-2) and 5-lipoxygenase (5-LOX). The compounds tested showed variable degrees of activity, with several of them showing activity comparable to or greater than the standards used in COX-1, COX-2, and 5-LOX assays. However, only the compound tomentodiplacone O (20) showed more selectivity against COX-2 versus COX-1 when compared with ibuprofen. The ability of the test compounds to interact with the above-mentioned enzymes was supported by docking studies, which revealed the possible incorporation of selected test substances into the active sites of these enzymes. Furthermore, one of the COX/LOX dual inhibitors, diplacone (14) (a major geranylated flavanone of P. tomentosa), was studied in vitro to obtain a proteomic overview of its effect on inflammation in LPS-treated THP-1 macrophages, supporting its previously observed anti-inflammatory activity and revealing the mechanism of its anti-inflammatory effect.
Permanent Link: http://hdl.handle.net/11104/0272981