Departamento de Ciências Patológicas , Universidade Estadual de Londrina-UEL , Rod. Celso Garcia Cid, Km 380, PR445, Cx. Postal 10.011 , 86057-970 Londrina , Paraná , Brazil.
Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Laboratório de Imunofarmacologia , Universidade Federal de Minas Gerais , 31270-567 Belo Horizonte , Minas Gerais , Brazil.
J Agric Food Chem. 2018 Jun 27;66(25):6269-6280. doi: 10.1021/acs.jafc.8b00959. Epub 2018 Jun 13.
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 μg/10 μL). Orally given HMC (3-30 mg/kg, 100 μL) 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 and NO by 89 and 48%, p < 0.05) and modulated cytokine production (reduced IL-1β, TNF-α, IL-6, and IL-10 by 35, 72, 37, and 46%, respectively, and increased TGF-β by 90%, p < 0.05). HMC also inhibited MSU-induced NF-κB activation (41%, p < 0.05), gp91 (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-IL-1 β, 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 μM) did not inhibit IL-1β secretion by macrophages primed by LPS and challenged with MSU (450 μg/mL), demonstrating that the anti-inflammatory effect of HMC in gout arthritis depends on inhibiting NF-κB but not on direct inhibition of inflammasome. The pharmacological effects of HMC indicate its therapeutic potential for the treatment of gout.
痛风性关节炎是一种由单钠尿酸盐（MSU）晶体引起的疼痛性炎症性疾病。我们评估了黄酮类化合物橙皮苷甲基查尔酮（HMC）在 MSU 关节内注射（100 μg/10 μL）诱导的痛风性关节炎小鼠模型中的治疗潜力。HMC（3-30 mg/kg，100 μL）以剂量依赖性方式降低 MSU 诱导的痛觉过敏（44%，p<0.05）、水肿（54%，p<0.05）和白细胞浸润（70%，p<0.05）。HMC（30 mg/kg）抑制 MSU 诱导的 LysM-eGFP 细胞浸润（81%，p<0.05）、滑膜炎（76%，p<0.05）和氧化应激（增加 GSH、FRAP 和 ABTS 分别为 62%、78%和 73%；减少 O 和 NO 分别为 89%和 48%，p<0.05）并调节细胞因子产生（减少 IL-1β、TNF-α、IL-6 和 IL-10 分别为 35%、72%、37%和 46%，增加 TGF-β 为 90%，p<0.05）。HMC 还抑制 MSU 诱导的 NF-κB 激活（41%，p<0.05）、gp91（66%，p<0.05）和 NLRP3 炎症小体成分的体内 mRNA 表达（NLRP3、ASC、pro-caspase-1 和 pro-IL-1β 分别为 72%、77%、71%和 73%，p<0.05），并诱导 Nrf2/HO-1 mRNA 表达（分别增加 3.9 倍和 5.1 倍，p<0.05）。HMC（30、100 和 300 μM）不抑制 LPS 预激活并用 MSU 挑战的巨噬细胞中 IL-1β 的分泌（450 μg/mL），表明 HMC 在痛风性关节炎中的抗炎作用取决于抑制 NF-κB 而不是直接抑制炎症小体。HMC 的药理学作用表明其具有治疗痛风的潜力。
