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-κB and MAPKs signaling pathways. Firstly, 10, 20, 30, 40 and 50 µM 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 α (TNF-α) production, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), IL-6, IL-12, TNF-α mRNA levels, and phosphorylation levels of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor alpha (IκB-α) 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-α production and mRNA levels of these mediators (p < 0.05). The expression of phosphorylated-JNK was significantly suppressed by diosmin at 40 and 50 µM concentrations. Furthermore, diosmin significantly inhibited the expression of phosphorylated-ERK, p38, and p-IκB-α 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.

Therapeutic Potential of Flavonoids in Pain and Inflammation: Mechanisms of Action, Pre-Clinical and Clinical Data, and Pharmaceutical Development

“…This flavonoid presents anti-inflammatory and anti-hyperalgesic mechanisms described in different models. Some of these effects have been attributed to the reduction of NF-κB activation [47], TNF-α in PC12 cell induced by LPS [117], Il-1β, Tnf-α, and Il-33/St2 mRNA expression in the spinal cord induced by CCI [118], TNF-α, IL-1β and IL-6 in the spinal cord and sciatic nerve tissues [119], NO, PGE 2 , IL-6, IL-12, TNF-α production by macrophages [120], COX-2 and MPO activity [121,122]. In addition, diosmin inhibited LTB 4 synthesis [121].…”

Correction of Morphofunctional Disorders in Experimental Preeclampsy by Combined Use of Trimetazidine and Purified Micronized Flavonoid Fraction as Well as Their Combinations With Methylampsy

“…Кроме этого, диосмин способен снижать индуцированную выработку NO путем ингибирования еNOS [48,53]. К антиоксидантной активности можно отнести способность исследуемого препарата повышать активность глутатионпероксидазы, супероксиддисмутазы, каталазы [53,55,56] и предотвращать перекисное окисление липидов с повышением активности антиоксидантной системы [56,57]. Снижение образования провоспалительных цитокинов и маркеров оксидативного стресса приводит не только к уменьшению повреждения непосредственно тканей плаценты, но и улучшению функции эндотелия.…”

Prophylactic effect of myricetin and apigenin against lipopolysaccharide-induced acute liver injury

“…Relative inducible nitric-oxide synthase (iNOS), and COX-2 mRNA levels were quantified using Real-Time Polymerase Chain Reaction (RT-PCR) with a Roche Light-Cycler 480 II device (Basel, Switzerland) using Invitrogen Universal EXPRESS SYBR GreenER quantitative PCR SuperMixes and Two-Step quantitative RT-PCR kit. RT-PCR protocol was performed according to Berkoz [31], and the PCR primers used for amplification was presented in Table S1 [32]. All sample mRNA levels were normalized to the values of β-actin and the results expressed as fold changes of threshold cycle (C t ) value relative to controls using the 2 −ΔΔCt method [31,32].…”

“…RT-PCR protocol was performed according to Berkoz [31], and the PCR primers used for amplification was presented in Table S1 [32]. All sample mRNA levels were normalized to the values of β-actin and the results expressed as fold changes of threshold cycle (C t ) value relative to controls using the 2 −ΔΔCt method [31,32].…”