Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, Ciudad Universitaria s/n, Ciudad de México, 04650, Mexico.
Facultad de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria s/n, Ciudad de México, 04650, Mexico.
Food Chem Toxicol. 2019 Feb;124:300-315. doi: 10.1016/j.fct.2018.12.018. Epub 2018 Dec 14.
Rheumatoid arthritis (RA) is an autoimmune disease that causes physical disability in people worldwide. Despite progress made in RA treatment in the past decade, new drugs with high efficacy but few long-term adverse effects are still needed. This study focused on evaluating the therapeutic potential of α-mangostin on established collagen-induced arthritis (CIA) in DBA/1J mice. Arthritic DBA/1J mice were orally administered with two doses of α-mangostin (10 and 40 mg/kg) daily, for 33 days. Alpha-mangostin significantly decreased the clinical score in the short term at both doses and decreased the histopathological score at the higher dose. This improvement was accompanied by a reduction on serum levels of anti-collagen IgG2a autoantibodies and of the production of LIX/CXCL5, IP-10/CXCL10, MIG/CXCL9, RANTES/CCL5, IL-6 and IL-33 in the joints of CIA mice. Alpha-mangostin also exhibited an anti-oxidant effect decreasing the NADPH oxidase activity and lipid peroxidation and preserving the levels of reduced glutathione in the arthritic joints. In vitro this xanthone demonstrated modulatory properties on LPS-activated dendritic cells, although in Th1 and Th17-polarized lymphocytes promotes a pro-apoptotic phenotype. Altogether this study illustrates the capacity of α-mangostin to ameliorate the early clinical and histological signs of established CIA by reducing the inflammatory and oxidative responses.
类风湿关节炎（RA）是一种自身免疫性疾病，在全球范围内导致人们身体残疾。尽管在过去十年中 RA 治疗取得了进展，但仍需要具有高效但很少有长期不良反应的新药。本研究集中评估了α-倒捻子素对 DBA/1J 小鼠已建立的胶原诱导性关节炎（CIA）的治疗潜力。关节炎 DBA/1J 小鼠每天口服给予两种剂量的 α-倒捻子素（10 和 40mg/kg），共 33 天。α-倒捻子素在两个剂量下均能在短期内显著降低临床评分，并在高剂量下降低组织病理学评分。这种改善伴随着血清抗胶原 IgG2a 自身抗体水平和关节中 LIX/CXCL5、IP-10/CXCL10、MIG/CXCL9、RANTES/CCL5、IL-6 和 IL-33 的产生减少。α-倒捻子素还表现出抗氧化作用，降低 NADPH 氧化酶活性和脂质过氧化作用，并保持关节炎关节中还原型谷胱甘肽的水平。在体外，这种黄烷酮对 LPS 激活的树突状细胞表现出调节特性，尽管在 Th1 和 Th17 极化的淋巴细胞中促进促凋亡表型。总的来说，这项研究说明了 α-倒捻子素通过降低炎症和氧化反应来改善已建立的 CIA 的早期临床和组织学迹象的能力。
