Anti-inflammatory Activity of Natural Geranylated Flavonoids: Cyclooxygenase and Lipoxygenase Inhibitory Properties and Proteomic Analysis.
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.
Zuzana
Z
Hanáková
Jan
0000-0003-0975-1671
J
Hošek
Laboratory of Plant Biotechnologies, Institute of Experimental Botany, The Czech Academy of Sciences , 16502 Prague, Czech Republic.
Zsófia
Z
Kutil
Veronika
V
Temml
Laboratory of Plant Biotechnologies, Institute of Experimental Botany, The Czech Academy of Sciences , 16502 Prague, Czech Republic.
Přemysl
P
Landa
Laboratory of Plant Biotechnologies, Institute of Experimental Botany, The Czech Academy of Sciences , 16502 Prague, Czech Republic.
Tomáš
T
Vaněk
Daniela
0000-0002-9933-8938
D
Schuster
Department of Pharmaceutical and Pharmacological Sciences, University of Padua , 35131 Padua, Italy.
Stefano
0000-0001-8264-6953
S
Dall'Acqua
Mass Spectrometry Group, Institute of Organic Chemistry and Biochemistry, The Czech Academy of Sciences , CZ-16610 Prague, Czech Republic.
Josef
0000-0002-3590-9009
J
Cvačka
Veterinary Research Institute , CZ-62100 Brno, Czech Republic.
Ondřej
O
Polanský
Karel
0000-0002-4336-7924
K
Šmejkal
D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D005419:Flavonoids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D005638:Fruit / Q000737:chemistry; D016859:Lipoxygenase Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D019684:Magnoliopsida / Q000737:chemistry*; D015394:Molecular Structure; D040901:Proteomics
D000893:Anti-Inflammatory Agents; D052246:Cyclooxygenase 2 Inhibitors; D005419:Flavonoids; D016859:Lipoxygenase Inhibitors; D001094:Arachidonate 5-Lipoxygenase; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2