Effects and mechanisms of Paeoniflorin, a bioactive glucoside from paeony root, on adjuvant arthritis in rats
Effects and mechanisms of Paeoniflorin, a bioactive glucoside from paeony root, on adjuvant arthritis in rats
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DOI：
10.1007/s00011-006-6002-5
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发表时间：
2007-05-01
影响因子：
6.7
通讯作者：
Liu, J.-X.
中科院分区：
文献类型：
--
作者：
Zheng, Y.-Q.;Wei, W.;Liu, J.-X.
目的与设计：白芍是中医公认的治疗类风湿性关节炎(RA)的有价值的中药。目的：探讨白芍中活性糖苷(PF)对佐剂性关节炎(AA)大鼠的治疗作用及其机制。材料：以10 mg/ml完全弗氏佐剂(10 mg/ml)后爪注射的方法诱导大鼠佐剂性关节炎。治疗：在大鼠注射完全弗氏佐剂后14~20天灌胃给药(5，10，20 mg/kg/d)。方法：通过后足肿胀、关节炎多项指数、免疫器官重量和组织学检查评价佐剂性关节炎。用3-(4，5-2-二甲基噻唑-2基)-2，5-二苯基四氮唑(四甲基偶氮唑蓝)比色法测定胸腺细胞增殖活性。放射免疫法测定前列腺素E-2(PGE(2))含量。采用酶联免疫吸附试验检测滑膜匀浆中IL-6、粒细胞-巨噬细胞集落刺激因子(GM-CSF)和血管内皮生长因子(VEGF)水平。免疫印迹法检测G蛋白抑制亚单位(GI)和环氧合酶-2(COX-2)的表达。结果：AA大鼠存在明显的继发性炎症反应，并伴有免疫器官重量减轻。PF(10，20 mg/kg/d，i.g，第14~20天)可抑制AA大鼠的炎症反应，恢复免疫器官的重量。AA大鼠滑膜细胞增殖明显增强，滑膜匀浆中IL-1、PGE2、IL-6、VEGF、GM-CSF水平较正常组明显升高。给予PF(10，20 mg/kg/d，i.g，第14-20天)可显著减轻上述变化。AA大鼠滑膜匀浆中Gi1、GI2、Gi3和COX-2的表达也升高。结论：PF通过抑制滑膜细胞的异常增殖，抑制滑膜细胞产生IL-1、PGE2、IL-6、VEGF和GM-CSF，减少滑膜中GI和COX-2的表达，从而抑制AA大鼠的再生障碍性关节炎。
Objective and design: Paeoniae alba Radix has been recognized as a valuable herb in the treatment of rheumatoid arthritis (RA) in traditional Chinese medicine. The purpose of this study was to investigate the effects of Paeoniflorin (PF), a bioactive glucoside from paeony root, on the rats with adjuvants arthritis (AA) and underlying mechanisms.Materials: AA was induced by injecting Complete Freund's adjuvant (10mg/ml) into hind paw in male Sprague-Dawley rats.Treatment: PF (5, 10, 20mg/kg/d) was orally administered to the rats 14 to 20 days after injection of complete Freund's adjuvant.Methods: Arthritis was evaluated by hind paw swelling, polyarthritis index, immune organ weights, and histological examination. Interleukin-1 (IL-1) activity was assessed by thymocyte proliferation as quantified by the 3-(4, 5-2-dimethylthiazal-2yl) 2,5-diphenyltetrazoliumbromide (MTT) assay. The content of prostaglandin E-2 (PGE(2)) was measured by radioimmunoassay. The levels of IL-6, granulocyte macrophage colony stimulating factor (GM-CSF) and vascular epidermal growth factor (VEGF) in synovium homogenates were measured by enzyme-linked immuno-absorbent assay (ELISA) respectively. Expression of inhibitory subunits of G protein (Gi) and cyclo-oxygenase-2 (COX-2) were detected by Western blotting technique.Results: There were significant secondary inflammatory reactions in AA rats, which were accompanied by a decrease in immune organ weights. The administration of PF (10, 20 mg/kg/day, i.g., days 14-20) inhibited the inflammatory response and restored the weight of immune organs of AA rats. Synoviocyte proliferation of AA rats increased significantly, and the levels of IL-1, PGE2, IL-6, VEGF and GM-CSF in synovial homogenates of AA rats were also elevated compared with the normal group. The administration of PF (10, 20 mg/kg/day, i.g., days 14-20) reduced the above changes significantly. Finally, the expression of Gi1, Gi2, Gi3 and COX-2 in synovial homogenates of AA rats were also elevated. The administration of PF reduced Gi expression at doses of 10 and 20mg/kg and decreased COX-2 expression at a dose of 20mg/kg.Conclusion: PF suppresses rat AA at least partly by inhibiting abnormal proliferation of synoviocytes and the production of IL-1, PGE2, IL-6, VEGF and GM-CSF by synoviocytes and reducing Gi and COX-2 expression in synovium.