Liu L, Buchner E, Beitze D, Schmidt-Weber C B, Kaever V, Emmrich F, Kinne R W
Department of Medicine III, University of Erlangen-Nuremberg, Germany.
Int J Immunopharmacol. 1996 Oct;18(10):529-43. doi: 10.1016/s0192-0561(96)00025-2.
The effects of treatment with sinomenine, a pure alkaloid extracted from the chinese medical plant Sinomenium acutum, were investigated in rat adjuvant arthritis (AA) and antigen-induced arthritis (AIA). In AA, long-term, intraperitoneal (i.p.) treatment induced significant improvement of arthritic score, hind paw swelling, body weight and erythrocyte sedimentation rate (ESR) beginning past the clinical peak of the disease. In-acute AIA, short and middle-term treatment with sinomenine around and following induction of arthritis induced a dose-dependent decrease of both joint swelling and ESR, starting after the peak of arthritis, and a significant reduction of joint destruction on day 3. There was no rebound of the arthritic signs following suspension of treatment. Long-term treatment of chronic AIA partially ameliorated clinical parameters and significantly counteracted joint destruction. Maximal plasma concentrations of 22.5 micrograms/ml, fast wash out (half-life 4.24 +/- 0.99 h; mean +/- S.E.M.) and no evidence of accumulation of sinomenine were observed following single or repeated i.p. injection of 150 mg/kg. In vitro, sinomenine markedly inhibited proliferation of synovial fibroblasts from AIA or normal rats, both at rest and following activation with either transforming growth factor beta 2 (TGF-beta 2) or interleukin-1 beta (IL-1 beta). The effect was dose-dependent and half-maximal inhibition of proliferation occurred at 20.6 micrograms/ml, that is, within the in vivo therapeutic range of the drug. Late therapeutic effects of sinomenine in rat arthritic models despite early start of treatment may be related to its antiproliferative effects on synovial fibroblasts in addition to its previously reported anti-inflammatory properties.
研究了从中药植物青风藤中提取的纯生物碱青藤碱的治疗效果，该研究在大鼠佐剂性关节炎（AA）和抗原诱导性关节炎（AIA）模型中进行。在AA模型中，长期腹腔注射治疗可使关节炎评分、后爪肿胀、体重和红细胞沉降率（ESR）显著改善，且在疾病临床高峰期过后开始起效。在急性AIA模型中，在诱导关节炎前后及之后用青藤碱进行短期和中期治疗，可使关节肿胀和ESR呈剂量依赖性降低，且在关节炎高峰期后开始起效，并在第3天显著减轻关节破坏。停药后未出现关节炎症状的反弹。慢性AIA的长期治疗可部分改善临床参数，并显著对抗关节破坏。单次或重复腹腔注射150mg/kg后，观察到最大血浆浓度为22.5μg/ml，药物清除快（半衰期4.24±0.99h；平均值±标准误），且无青藤碱蓄积的证据。在体外，青藤碱显著抑制AIA大鼠或正常大鼠滑膜成纤维细胞的增殖，无论是在静止状态还是在用转化生长因子β2（TGF-β2）或白细胞介素-1β（IL-1β）激活后。该作用呈剂量依赖性，增殖的半数最大抑制浓度为20.6μg/ml，即在该药物的体内治疗范围内。尽管治疗开始较早，但青藤碱在大鼠关节炎模型中的后期治疗效果可能与其对滑膜成纤维细胞的抗增殖作用有关，此外还与其先前报道的抗炎特性有关。
