a Yijishan Hospital of Wannan Medical College , Wuhu , China.
b The Second Affiliated Hospital of Wannan Medical College , Wuhu , China.
Pharm Biol. 2018 Dec;56(1):455-464. doi: 10.1080/13880209.2018.1506939.
Garcinia mangostana Linn. (Guttiferae) pericarp is used as a traditional medicine in South Asia to treat inflammatory diseases.
This study investigates therapeutic effects of G. mangostana pericarp ethanol extract (MAN) on collagen-induced arthritis (CIA) and interactions with methotrexate in vivo.
Male Sprague-Dawley rats with CIA were treated with MAN (0.5 g/kg/day), methotrexate (0.5 mg/kg, bw) or combination of both for 36 days, respectively (n = 8/group). Another eight healthy and CIA rats served as normal and model control, respectively. Therapeutic effects were evaluated based on paw edema and arthritis score during the experiment and serological markers at the end of the study period. Histological and radiological examinations were used to assess joint destructions. The immune status was investigated by immunohistochemistry and flow cytometry.
All treatments decreased the arthritis score and paw inflammation in CIA rats. Combination regimen significantly reduced anti-cyclic citrullinated peptide antibody in CIA rats to 85.83% (p < 0.05) and notably alleviated synovial hyperplasia and cartilage degradation in joints. Different from methotrexate, MAN significantly augmented CD25 cells distribution (from 2.72 to 3.35%) and IL-10 secretion (from 202.4 to 241.2 pg/mL) in CIA rat blood. Meanwhile, MAN induced a greater IL-17 decrease and a FOXP3 increase in immune organs than MTX. Reduced TLR4 and IL-17 expression and elevated FOXP3 expression in joints also occurred under MAN treatment.
MAN protected joints from destruction in CIA rats and exerted synergistic effects with methotrexate by improving immune microenvironment. The combination regimen could bring additional benefits to rheumatoid arthritis patients.
藤黄科藤黄属植物的果皮被用作南亚的传统药物，用于治疗炎症性疾病。
本研究旨在探讨藤黄果皮乙醇提取物（MAN）对胶原诱导性关节炎（CIA）的治疗作用，并研究其与甲氨蝶呤在体内的相互作用。
雄性 Sprague-Dawley 大鼠建立 CIA 模型后，分别给予 MAN（0.5g/kg/d）、甲氨蝶呤（0.5mg/kg，bw）或两者联合治疗 36 天（每组 8 只）。另 8 只健康大鼠和 CIA 大鼠分别作为正常对照组和模型对照组。实验过程中根据爪肿胀和关节炎评分评估治疗效果，研究结束时检测血清学标志物。采用组织学和影像学检查评估关节破坏情况。通过免疫组化和流式细胞术检测免疫状态。
所有治疗均降低 CIA 大鼠的关节炎评分和爪肿胀。联合治疗可将 CIA 大鼠的抗环瓜氨酸肽抗体降低至 85.83%（p<0.05），明显减轻关节滑膜增生和软骨降解。与甲氨蝶呤不同，MAN 可显著增加 CIA 大鼠血液中 CD25 细胞分布（从 2.72%增加至 3.35%）和 IL-10 分泌（从 202.4pg/mL 增加至 241.2pg/mL）。同时，与 MTX 相比，MAN 可使免疫器官中的 IL-17 降低和 FOXP3 增加更为显著。在 MAN 治疗下，关节中 TLR4 和 IL-17 表达降低，FOXP3 表达升高。
MAN 可保护 CIA 大鼠关节免受破坏，并通过改善免疫微环境与甲氨蝶呤发挥协同作用。联合治疗方案可能为类风湿关节炎患者带来额外获益。
