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Diosmin Treats Lipopolysaccharide-Induced Inflammatory Pain and Peritonitis by Blocking NF-κB Activation in Mice
Victor Fattori1, Fernanda S Rasquel-Oliveira1, Nayara A Artero1
1Departament of Pathology, Center of Biological Sciences, Londrina State University, Londrina 86057-970, Paraná, Brazil.
Abstract:
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.
Insights
Diosmin effectively reduces inflammation and pain caused by Gram-negative bacterial infections. This citrus flavonoid alleviates LPS-induced hyperalgesia, neutrophil recruitment, and oxidative stress, showing promise for treating inflammatory conditions.
Area of Science:
- Pharmacology
- Immunology
- Microbiology
Background:
- Gram-negative bacterial infections trigger inflammation and pain.
- Lipopolysaccharide (LPS) is a key component of Gram-negative bacteria, inducing these responses.
- Diosmin, a citrus flavonoid, possesses known antioxidant and anti-inflammatory properties.
Purpose of the Study:
- To investigate the efficacy of diosmin in mitigating nonsterile inflammation and pain induced by LPS.
- To evaluate diosmin's impact on LPS-induced hyperalgesia, peritonitis, and associated molecular pathways.
Main Methods:
- Utilized a nonsterile mouse model of inflammation and peritonitis induced by LPS.
- Assessed pain using mechanical and thermal hyperalgesia tests, and static weight bearing.
- Quantified neutrophil recruitment via myeloperoxidase activity and leukocyte counts.
- Measured oxidative stress markers, including ROS and superoxide anion production.
- Analyzed cytokine levels (IL-1β, TNF-α, IL-6) and NF-κB activation.
Main Results:
- Diosmin dose-dependently reduced LPS-induced mechanical and thermal hyperalgesia.
- Diosmin significantly decreased neutrophil and leukocyte recruitment in paws and peritoneal exudates.
- Treatment with diosmin attenuated LPS-induced oxidative stress and pro-inflammatory cytokine production.
- Diosmin inhibited NF-κB activation in response to LPS.
Conclusions:
- Diosmin demonstrates significant efficacy in reducing LPS-induced inflammation and pain in a nonsterile model.
- The anti-inflammatory and analgesic effects of diosmin are linked to its ability to reduce oxidative stress and inhibit NF-κB signaling.
- Diosmin represents a promising therapeutic candidate for managing inflammation and pain associated with Gram-negative bacterial infections.
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