Hesperidin Methylchalcone Suppresses Experimental Gout Arthritis in Mice by Inhibiting NF-kappa B Activation

作者：Ruiz Miyazawa Kenji W; Pinho Ribeiro Felipe A; Borghi Sergio M; Staurengo Ferrari Larissa; Fattori Victor; Amaral Flavio A; Teixeira Mauro M; Alves Filho Jose C; Cunha Thiago M; Cunha Fernando Q; Casagrande Rubia; Verri Waldiceu A Jr^*

来源：Journal of Agricultural and Food Chemistry, 2018, 66(25): 6269-6280.

DOI：10.1021/acs.jafc.8b00959

• gout arthritis
• cytokines
• NLRP3 inflammasome
• NF-kappa B
• oxidative stress

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.

• 出版日期2018-6-27