Diosmin Suppresses the Proinflammatory Mediators in Lipopolysaccharide-Induced Raw264.7 Macrophages Via Nf-Κb and Mapks Signal Pathways

Abstract

Diosmin is an unsaturated flavonoid glycoside, presents in citrus fruits. The aim of this study is to investigate the molecular mechanism of diosmin with respect to the NF-kappa B and MAPKs signaling pathways. Firstly, 10, 20, 30, 40 and 50 mu M diosmin were treated to lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. The anti-inflammatory effects of diosmin was displayed via measuring prostaglandin E-2 (PGE(2)), nitric oxide (NO), interleukines (IL-6, IL-12), tumor necrosis factor alpha (TNF-alpha) production, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), IL-6, IL-12, TNF-alpha mRNA levels, and phosphorylation levels of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor alpha (I kappa B-alpha) and mitogen-activated protein kinases (MAPKs); JNK, ERK, and p38 in LPS induced RAW264.7 macrophages. Our study showed that especially high concentrations of diosmin decreased NO, PGE 2 , IL-6, IL-12, TNF-alpha production and mRNA levels of these mediators (p < 0.05). The expression of phosphorylated-JNK was significantly suppressed by diosmin at 40 and 50 mu M concentrations. Furthermore, diosmin significantly inhibited the expression of phosphorylated-ERK, p38, and p-I kappa B-alpha in a dose-dependent manner. Our results suggest that diosmin is a potent anti-inflammatory agent and has potential for development into a therapeutic agent for inflammation-associated disorders.