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Anti-angiogenic effect of triptolide in rheumatoid arthritis by targeting angiogenic cascade

Anti-angiogenic effect of triptolide in rheumatoid arthritis...

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第十四届全国中药和天然药物学术研讨会

作者： Xiangying KONG Yanqiong ZHANG chunfang lju Wei GUO Xiangbin LI Xiaohui SU Hongye WAN Yanqun SUN Na LIN Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences

Rheumatoid arthritis(RA) is characterized by a pre-vascular seriously inflammatory phase,followed by a vascular phase with high increase in vessel *** angiogenesis has been considered as an essential event in perpetuating inflammatory and immune responses,as well as supporting pannus growth and development of RA,inhibition of angiogenesis has been proposed as a novel therapeutic strategy for ***,a diterpenoid triepoxide from Tripterygium wilfardii Hook F,has been extensively used in treatment of RA *** also acts as a small molecule inhibitor of tumor angiogenesis in several cancer ***,it is unclear whether triptolide possesses an anti-angiogenic effect in *** address this problem,we firstly constructed collagen-induced arthritis(CIA)model using DA rats by the injection of bovine type II ***,CIA rats were treated with triptolide(11-45 ug/kg/day) starting on the day 1 after first *** arthritis scores(P<0.05) and the arthritis incidence(P<0.05) of inflamed joints were both significantly decreased in triptolide-treated CIA rats compared to vehicle-treated CIA *** interestingly,doses of 115ug/kg triptolide could markedly reduce the capillaries,small,medium and large vessel density in synovial membrane tissues of inflamed joints(all P<0.05).Moreover,triptolide inhibited matrigel-induced cell adhesion of HFLS-RA and *** also disrupted tube formation of HUVEC on matrigel and suppressed the VEGF-induced chemotactic migration of HFLS-RA and HUVEC,***,triptolide significantly reduced the expression of angiogenic activators including TNF-α,IL-17,VEGF,VEGFR,Ang-1,Ang-2 and Tie2,as well as suppressed the IL1-β-induced phosphorylated of ERK,p38 and JNK at protein *** conclusion,our data suggest for the first time that triptolide may possess anti-angiogenic effect in RA both in vivo and in vitro assay systems by downregulating angiogenic activators and inhibiting the activation of

关键词： triptolide rheumatoid arthritis angiogenesis angiogenic activator mitogen-activated protein kinase

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