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SERCHING FOR DISCOVERY OF RHEUMATOID ARTHRITIS DRUG FROM TRIPTERYGIUM WILFORDII.

寻找从雷公藤中发现类风湿性关节炎药物。

基本信息

批准号：
10557209
负责人：
TAKAISHI Yoshihisa
金额：
$ 7.36万
依托单位：
University of Tokushima
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

项目摘要

In recently years, a refined extract from the root xylem of Tripterygium wilfordii (TII) has been used in the clinical treatment of rheumatoid arthrits, and for other inflammatory and autoimmune diseases, including systermic lupus erythemasus etc. However, the precise mechanism of the therapeutic effect of TII has not been completely delineated. We has started work on the isolation of T.hypoglaucum and T.wildfordii and the TII extract to discover new drug for Rheumatoid Arthrits desease. We isolated five new triterpenes, two new diterpenes, and twelve new sesquiterpene pyridine alkaloids, as well as thirty-three known compounds from the root outer barks of T.hypoglaucum. From the TII extract of T.wilfordii, seven new triterpenes, four new diterpenes, twenty new sesquiterpene pyridine alkaloids, as well as fifty-six known compounds. In the bioactive screening experiment for isolated compoinds, the auther examined inhibitory effect on cytokine production and anti-HIV activity. Three compounds showed extreamely potent inhibitory effect on cytokine production from LPS stimulated human peripheral mononuclea cellscompared with reference compound. and sesquiterpene alkaloid inhibited HIV replication in H9 lymphocytes with therapeutic index value of>1000, this compound is a new class of potent anti-HIV agents from natural source.

近年来，雷公藤（Tripterygium wilfordii）根木质部提取物（TII）已被用于临床治疗类风湿关节炎、系统性红斑狼疮等炎性和自身免疫性疾病，但其确切的治疗机制尚未完全阐明。我们已经开始了对昆明山海棠和昆明山海棠的分离和TII提取物的研究，以发现治疗风湿性关节炎的新药。我们从昆明山海棠的根外树皮中分离出5个新的三萜类化合物、2个新的二萜类化合物和12个新的倍半萜类吡啶生物碱，以及33个已知化合物。从雷公藤的TII提取物中分离得到7个新的三萜类化合物、4个新的二萜类化合物、20个新的倍半萜吡啶类生物碱以及五十六个已知化合物。在生物活性筛选实验中，作者考察了分离的化合物对细胞因子产生的抑制作用和抗HIV活性。与对照化合物相比，三个化合物对LPS刺激的人外周血单核细胞产生细胞因子具有极强的抑制作用。倍半萜类生物碱抑制HIV在H9淋巴细胞中的复制，治疗指数值>1000，该化合物是一类新的天然来源的有效抗HIV药物。