cis-Aconitic acid is a constituent from the leaves of Echinodorus grandiflorus, a medicinal plant traditionally used in Brazil to treat inflammatory conditions, including arthritic diseases. The present study aimed to investigate the anti-arthritic effect of cis-aconitic acid in murine models of antigen-induced arthritis and monosodium urate-induced gout. The possible underlying mechanisms of action was evaluated in THP-1 macrophages. Oral treatment with cis-aconitic acid (10, 30, and 90 mg/kg) reduced leukocyte accumulation in the joint cavity and C-X-C motif chemokine ligand 1 and IL-1β levels in periarticular tissue. cis-Aconitic acid treatment reduced joint inflammation in tissue sections of antigen-induced arthritis mice and these effects were associated with decreased mechanical hypernociception. Administration of cis-aconitic acid (30 mg/kg p. o.) also reduced leukocyte accumulation in the joint cavity after the injection of monosodium urate crystals. cis-Aconitic acid reduced in vitro the release of TNF-α and phosphorylation of IκBα in lipopolysaccharide-stimulated THP-1 macrophages, suggesting that inhibition of nuclear factor kappa B activation was an underlying mechanism of cis-aconitic acid-induced anti-inflammatory effects. In conclusion, cis-aconitic acid has significant anti-inflammatory effects in antigen-induced arthritis and monosodium urate-induced arthritis in mice, suggesting its potential for the treatment of inflammatory diseases of the joint in humans. Additionally, our findings suggest that this compound may contribute to the anti-inflammatory effect previously reported for E. grandiflorus extracts.

中文翻译：

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顺乌头酸，一种大花刺槐叶的成分，可抑制小鼠的抗原诱导的关节炎和痛风

顺乌头酸是大花棘豆的叶子中的一种成分，大花棘豆是巴​​西传统上用于治疗包括关节炎在内的炎症性疾病的一种药用植物。本研究旨在研究顺乌头酸在抗原诱导的关节炎和尿酸单钠诱导的痛风小鼠模型中的抗关节炎作用。在 THP-1 巨噬细胞中评估了可能的潜在作用机制。用顺乌头酸（10、30 和 90 mg/kg）口服治疗可减少关节腔中的白细胞积聚和 CXC 基序趋化因子配体 1 和关节周围组织中的 IL-1β 水平。顺乌头酸治疗减少了抗原诱导的关节炎小鼠组织切片中的关节炎症，这些作用与机械性过度伤害感受降低有关。注射尿酸盐晶体后，顺乌头酸（30 mg/kg p.o.）的给药也减少了关节腔内白细胞的积累。顺乌头酸在体外减少脂多糖刺激的 THP-1 巨噬细胞中 TNF-α 的释放和 IκBα 的磷酸化，表明抑制核因子 kappa B 活化是顺乌头酸诱导的抗炎作用的潜在机制. 综上所述，顺乌头酸对小鼠抗原性关节炎和尿酸单钠性关节炎具有显着的抗炎作用，提示其在治疗人类关节炎症性疾病方面的潜力。此外，我们的研究结果表明，这种化合物可能有助于先前报道的大花提取物的抗炎作用。) 也减少了注射尿酸单钠晶体后关节腔内的白细胞积累。顺乌头酸在体外减少脂多糖刺激的 THP-1 巨噬细胞中 TNF-α 的释放和 IκBα 的磷酸化，表明抑制核因子 kappa B 活化是顺乌头酸诱导的抗炎作用的潜在机制. 综上所述，顺乌头酸对小鼠抗原性关节炎和尿酸单钠性关节炎具有显着的抗炎作用，提示其在治疗人类关节炎症性疾病方面的潜力。此外，我们的研究结果表明，这种化合物可能有助于先前报道的大花提取物的抗炎作用。) 也减少了注射尿酸单钠晶体后关节腔内的白细胞积累。顺乌头酸在体外减少脂多糖刺激的 THP-1 巨噬细胞中 TNF-α 的释放和 IκBα 的磷酸化，表明抑制核因子 kappa B 活化是顺乌头酸诱导的抗炎作用的潜在机制. 综上所述，顺乌头酸对小鼠抗原性关节炎和尿酸单钠性关节炎具有显着的抗炎作用，提示其在治疗人类关节炎症性疾病方面的潜力。此外，我们的研究结果表明，这种化合物可能有助于先前报道的大花提取物的抗炎作用。