Diosmin suppresses the proinflammatory mediators in lipopolysaccharide-induced RAW264.7 macrophages via NF-kappa B and MAPKs signal pathways

Berköz M.

GENERAL PHYSIOLOGY AND BIOPHYSICS, vol.38, no.4, pp.315-324, 2019 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 38 Issue: 4
  • Publication Date: 2019
  • Doi Number: 10.4149/gpb_2019010
  • Journal Name: GENERAL PHYSIOLOGY AND BIOPHYSICS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.315-324
  • Keywords: Diosmin, Inflammation, Raw264.7, Lipopolysaccharide, MAPKs, NF-kappa B, NITRIC-OXIDE SYNTHASE, RAW 264.7 MACROPHAGES, TNF-ALPHA, INDUCED INFLAMMATION, DOWN-REGULATION, LUNG INJURY, ACTIVATION, INHIBITION, INDUCTION, CYTOKINES
  • Van Yüzüncü Yıl University Affiliated: Yes

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.