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

Abstract

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.

A tiered approach to investigate the mechanism of anti-inflammatory activity of an herbal medicinal product containing a fixed combination of thyme herb and primula root extracts

“…Similarly, several single compounds of herbal origin such as flavonoids, quinones, sesquiterpenes, etc. have been shown to reduce eicosanoid production [13,14]. Thyme extracts contain multiple components that act against a broad range of biological targets [15,16].…”

Chemical Constituents from the Flower of Hosta plantaginea with Cyclooxygenases Inhibition and Antioxidant Activities and Their Chemotaxonomic Significance

“…However, only incomplete 1D-NMR data of 1 was given in the literature 10, which was also differ greatly from our data ( Table 1 ). The electronic circular dichroism (CD) spectrum of 1 ( Figure 3 ) showed a negative Cotton effect at 282 nm (π→π * electronic transition) and a positive Cotton effect at 338 nm (n→π * electronic transition), suggesting that the absolute configuration at C-2 was S [ 9 , 11 ]. Thus, the structure of 1 was fully elucidated, and it was named hostaflavanone A.…”

Paulownia C-geranylated flavonoids: their structural variety, biological activity and application prospects

“…Hydroxylation at C-3 in ring C and 4′-methoxy substitution of ring B might cause a loss of bioactive potency (Šmejkal et al 2008a;Wang et al 2019). In addition, the unmodified geranyl group at the C-6 position seemed to be crucial for these various biological effects in vitro and in vivo (Vochyánová et al 2015) of C-geranylated flavonoids, however, hydroxylation on the distal end of the geranyl substituent decreased the biological activities revealed by different research (Alcaráz et al 2000;Š mejkal et al 2010;Hanáková et al 2017;Ryu et al 2017). The presence of a β-carbon (proximal) OH group on the geranyl chain did not affect the cytotoxicity (Hanáková et al 2015).…”