Journal
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
Volume 66, Issue 25, Pages 6269-6280Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jafc.8b00959
Keywords
gout arthritis; cytokines; NLRP3 inflammasome; NF-kappa B; oxidative stress
Funding
- Coordenadoria de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
- Financiadora de Estudo e Projetos Apoio a Infraestrutura (CT-INFRA) [01.13.0049.00]
- Central Multiusuaria de Laboratorios de Pesquisa da UEL (CMLP-UEL)
- Sao Paulo Research Foundation (FAPESP)
- Center for Research on Inflammatory Diseases (CRID)
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
- Pesquisa para o Sistema Unico de Saiide (PPSUS)
- Ministerio da Ciencia, Tecnologia e Inovacao (MCTI)
- Secretaria da Ciencia, Tecnologia e Ensino Superior (SETI)
- Decit/SCTIE/MS through CNPq
- Fundacao Araucaria and Secretaria da Saucle do Estado do Parana (SESAPR)
- Parana State Government (Brazil)
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Gout arthritis is a painful inflammatory disease induced by monosodium urate (MSU) crystals. We evaluate the therapeutic potential of the flavonoid hesperidin methylchalcone (HMC) in a mouse model of gout arthritis induced by intra-articular injection of MSU (100 mu g/10 mu L). Orally given HMC (3-30 mg/kg, 100 mu L) reduced in a dose-dependent manner the MSU-induced hyperalgesia (44%, p < 0.05), edema (54%, p < 0.05), and leukocyte infiltration (70%, p < 0.05). HMC (30 mg/ kg) inhibited MSU-induced infiltration of LysM-eGFP(+) cells (81%, p < 0.05), synovitis (76%, p < 0.05), and oxidative stress (increased GSH, FRAP, and ABTS by 62, 78, and 73%, respectively; reduced O-2(-) and NO by 89 and 48%, p < 0.05) and modulated cytokine production (reduced IL-1 beta, TNF-alpha, IL-6, and IL-10 by 35, 72, 37, and 46%, respectively, and increased TGF-beta by 90%, p < 0.05). HMC also inhibited MSU-induced NF-kappa B activation (41%, p < 0.05), gp91(phox) (66%, p < 0.05) and NLRP3 inflammasome components mRNA expression in vivo (72, 77, 71, and 73% for NLRP3, ASC, pro-caspase-1, and pro-II-1 beta respectively, p < 0.05), and induced Nrf2/HO-1 mRNA expression (3.9- and 5.1-fold increase, respectively, p < 0.05). HMC (30, 100, and 300 mu M) did not inhibit IL-1 beta secretion by macrophages primed by LPS and challenged with MSU (450 mu g/mL), demonstrating that the anti-inflammatory effect of HMC in gout arthritis depends on inhibiting NF-kappa B but not on direct inhibition of inflammasome. The pharmacological effects of HMC indicate its therapeutic potential for the treatment of gout.
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