Diosmin Treats Lipopolysaccharide-Induced Inflammatory Pain and Peritonitis by Blocking NF-κB Activation in Mice

• Published in: Journal of natural products (Washington, D.C.) D.C.), 2020-04, Vol.83 (4), p.1018-1026
• Main Authors: Fattori, Victor, Rasquel-Oliveira, Fernanda S, Artero, Nayara A, Ferraz, Camila R, Borghi, Sergio M, Casagrande, Rubia, Verri, Waldiceu A
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - pharmacology; Antioxidants - pharmacology; Diosmin - adverse effects; Hyperalgesia - drug therapy; Inflammation; Interleukin-1beta; Lipopolysaccharides - chemistry; Lipopolysaccharides - pharmacology; Macrophages - chemistry; Macrophages - metabolism; Mice; Molecular Structure; Neutrophil Infiltration - drug effects; NF-kappa B - antagonists & inhibitors; NF-kappa B - chemistry; Oxidative Stress - drug effects; Peritonitis - drug therapy; Signal Transduction - drug effects
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/acs.jnatprod.9b00887

Gram-negative bacterial infections induce inflammation and pain. Lipopolysaccharide (LPS) is a pathogen-associated molecular pattern and the major constituent of Gram-negative bacterial cell walls. Diosmin is a citrus flavonoid with antioxidant and anti-inflammatory activities. Here we investigated the efficacy of diosmin in a nonsterile model of inflammatory pain and peritonitis induced by LPS. Diosmin reduced in a dose-dependent manner LPS-induced inflammatory mechanical hyperalgesia, thermal hyperalgesia, and neutrophil recruitment to the paw (myeloperoxidase activity). Diosmin also normalized changes in paw weight distribution assessed by static weight bearing as a nonreflexive method of pain measurement. Moreover, treatment with diosmin inhibited LPS-induced peritonitis as observed by a reduction of leukocyte recruitment and oxidative stress. Diosmin reduced LPS-induced total ROS production (DCFDA assay) and superoxide anion production (NBT assay and NBT-positive cells). We also observed a reduction of LPS-induced oxidative stress and cytokine production (IL-1β, TNF-α, and IL-6) in the paw. Furthermore, we demonstrated that diosmin inhibited LPS-induced NF-κB activation in peritoneal exudate. Thus, we demonstrated, using a model of nonsterile inflammation induced by LPS, that diosmin is a promising molecule for the treatment of inflammation and pain.