The anti-angiogenic effect of sinomenine
The anti-angiogenic effect of sinomenine
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DOI：
10.1007/s10456-005-2892-z
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发表时间：
2005-01-01
期刊：
影响因子：
9.8
通讯作者：
Wong, Ricky N. S.
中科院分区：
文献类型：
--
作者：
Kok, T. W.;Yue, Patrick Y. K.;Wong, Ricky N. S.
青藤碱是从中国药用植物青风藤中提取的一种生物碱，在中国用于治疗类风湿性关节炎（RA）已有2000多年的历史。青藤碱已被证明介导广泛的药理作用，包括抗炎和抗风湿作用。类风湿关节炎是一种慢性免疫介导的疾病，其表现为炎症、异常细胞和激素免疫反应与滑膜增生的重叠表现。由于血管生成被认为在RA的发展中起着关键作用，并且抗血管生成治疗已被提出作为治疗RA的新治疗策略，我们希望看到青藤碱是否具有抗血管生成特性。青藤碱抑制bFGF诱导的人脐静脉内皮细胞（HUVEC）增殖，并使其细胞周期阻滞于G1期。青藤碱可阻断HUVEC在Matrigel上的小管形成，抑制HUVEC的趋化性。此外，青藤碱减少基质胶塞试验中的新生血管以及大鼠主动脉环发芽试验中的微血管生长。这些结果表明，青藤碱抑制bFGF诱导的血管生成在体外和体内。由于白细胞-内皮细胞粘附相互作用在炎症中也起重要作用，我们发现青藤碱减少粒细胞分化的HL 60细胞穿过IL-1 β激活的HUVEC单层的迁移。因此，青藤碱抑制白细胞跨血管壁迁移和抗血管生成作用可能是其减轻RA发病的治疗机制。
Sinomenine is an alkaloid extracted from the Chinese medicinal plant, Sinomenium acutum, which has been utilized to treat rheumatoid arthritis (RA) in China for over 2000 years. Sinomenine has been shown to mediate a wide range of pharmacological actions which includes anti-inflammatory and anti-rheumatic effects. RA has been classified as a chronic immune-mediated disease that exhibits overlapping manifestation of inflammatory, abnormal cellular and hormonal immune responses with synovial hyperplasia. Since, angiogenesis is recognized to play a critical role in the development of RA and anti-angiogenic therapy has been proposed as a new therapeutic strategy for treatment of RA, we would like to see if sinomenine possesses anti-angiogenic property. In this study, sinomenine inhibited bFGF-induced proliferation of human umbilical vein endothelial cells (HUVEC) and arrested its cell cycle in G1 phase. Sinomenine disrupted tube formation of HUVEC on Matrigel and suppressed the chemotaxis of HUVEC. In addition, sinomenine reduced neovascularization in Matrigel plug assay as well as microvascular outgrowth in rat aorta ring sprouting assay. These results suggest that sinomenine inhibited bFGF-induced angiogenesis in vitro and in vivo. As the leukocytes-endothelial adhesive interactions also play an important role in inflammation, we found that sinomenine reduced the transmigration of granulocytic differentiated HL60 cells across IL-1 beta activated HUVEC monolayer. Therefore, the inhibition of leukocytes migration across blood vessel walls and the anti-angiogenic effect of sinomenine may contribute towards its therapeutic mechanisms in alleviating the pathogenesis of RA.