Effects of Flavonoids on Prostaglandin E₂Production and on COX-2 and mPGES-1 Expressions in Activated Macrophages

Abstract

Prostaglandin E2 (PGE2) has a central role in inflammation and both cyclooxygenase-2 (COX-2) and prostaglandin E synthases are critical enzymes in its synthesis. In inflammation, bacterial products and cytokines enhance the expression of COX-2 and inducible microsomal prostaglandin E synthase-1 (mPGES-1) which are functionally coupled to result in increased PGE2 formation in macrophages and tissue cells. In the present study, we systematically investigated the effects of 26 naturally occurring flavonoids on PGE2 production and on COX-2 and mPGES-1 expression in activated macrophages. Twelve flavonoids, i.e., flavone, luteolin-7-glucoside, kaempferol, isorhamnetin, morin, quercetin, naringenin, taxifolin, pelargonidin, daidzein, genistein, and genistin effectively inhibited lipopolysaccharide (LPS)-induced PGE2 production. Four flavonoids (flavone, isorhamnetin, daidzein, and genistein) inhibited significantly LPS-induced COX-2 expression, while mPGES-1 expression was downregulated by kaempferol and isorhamnetin. The present study characterizes the effects of flavonoids on PGE2 production and on COX-2 and mPGES-1 expression in activated macrophages. The results add to our knowledge of the anti-inflammatory actions of flavonoids and introduce kaempferol and isorhamnetin as compounds capable of downregulating the expression of mPGES-1.

Anti-inflammatory activity of lupine (Lupinus angustifolius L.) protein hydrolysates in THP-1-derived macrophages

“…There is evidence of the ability of distinct food compounds, including proteins, to modulate inflammation in experimental models involving macrophages (Boesch-Saadatmandi et al, 2011;Hämäläinen et al, 2011;Yu, Correll, & Vanden Heuvel, 2002). Indeed some peptides with anti-inflammatory activity have been purified from plants (Dia, Wang, Oh, de Lumen, & Gonzalez de Mejia, 2009).…”

Effects of Isorhamnetin on Tyrosinase: Inhibition Kinetics and Computational Simulation

“…It has been found to have multiple biological and pharmacological characteristics, including antioxidant activity, 11) cytoprotective capacity, 12) anti-adipogenesis 13) and anti-inflammatory effects. 14,15) Given the above findings, we hypothesized that isorhamnetin can inhibit tyrosinase and can act as an anti-pigmentation agent.…”

Beneficial effects of methanolic extract of Indigofera linnaei Ali. on the inflammatory and nociceptive responses in rodent models

“…Luteolin 7-glucoside, kaempferol and quercetin effectively inhibit lipopolysaccharide (LPS)-induced PGE 2 production. Four flavonoids significantly inhibit LPS-induced COX-2 expression, while mPGES-1 expression was downregulated by kaempferol and isorhamnetin (Hamalainen et al, 2011). The observed beneficial effects of methanol extract of I. linnaei on inflammatory and nociceptive responses in rodents may be due to the presence of these phytochemicals.…”