Expression of the xenobiotic metabolizing enzyme cytochrome P450 1B1 alters anti‐inflammatory activity of quercetin, kaempferol and taxifolin in macrophage and monocyte (830.25)

Abstract

Diet‐derived flavonoids quercetin (Q), kaempferol (K) and taxifolin (T) were studied for their anti‐inflammatory property in J774A.1 mouse macrophage, undifferentiated‐ (u‐) and differentiated‐ (d‐) human THP‐1 cells. Cells were pre‐incubated with respective compound for 48 h followed by stimulation with bacterial lipopolysaccharide (LPS) to induce inflammatory response. All test compounds inhibited LPS induction of the pro‐inflammatory cytokines IL‐6 mRNA expressions in J774A.1 cells with EC50 at 6 µM for Q, 5 µM for K, and 16 µM for T, respectively. Interestingly, all compounds at concentration up to 10 µM exerted no inhibitory effect on LPS induction of IL‐6 mRNA expression in u‐THP‐1 cells. In d‐THP‐1 cells, Q and K significantly inhibited LPS stimulation of IL‐6 mRNA expression, while T showed no inhibitory effect. This differential effect in different cell lines appeared to be associated with differential ability of the compounds to inhibit expression of the xenobiotic metabolizing enzyme, cytochrome p450 1B1 (CYP1B1), with potency of inhibition ranked K>Q>>T. CYP1B1 mRNA was detected in both u‐ and d‐THP‐1, but absent in J774A.1. In summary, among the structurally similar flavonoids, K exhibited most potent anti‐inflammatory effects, and possessed the most potent inhibitory effect on CYP1B1 expression. Hence, the anti‐inflammatory efficacy of a compound is negatively related to CYP1B1 expression.