摘要
目的:探讨独活治疗骨关节炎(osteoarthritis,OA)疼痛的药效物质基础和作用靶点。方法:分别从北京大学天然产物库和Drug Bank数据库检索独活的化学成分68个和OA疼痛相关抗炎镇痛药物28个,建立独活化学成分分子数据集和OA疼痛相关药物分子数据集,依托定量构效关系平台,分析2个分子集的化学空间。以白细胞介素(interleukin,IL)-1β、IL-6和肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)作为OA疼痛治疗靶点,利用分子对接和生物网络技术,构建独活活性成分-OA疼痛靶点作用网络,分析独活活性成分与OA疼痛靶点的作用情况。结果:相对于OA疼痛相关药物分子数据集,独活化学成分分子数据集在化学空间上具有很好的分散性,且在后下方与OA疼痛相关药物分子数据集有相似或相近的化学空间。独活治疗OA疼痛的药效物质基础为香豆素类化合物(UNPD80777、UNPD49810、UNPD40977、UNPD35503、UNPD189982、UNPD134852和UNPD126813)和酚类化合物(UNPD24695),其中5个化合物(UNPD49810、UNPD40977、UNPD35503、UNPD189982、UNPD134852)只能作用1个靶点,3个化合物(UNPD80777、UNPD126813、UNPD24695)可以作用2个靶点,而且IL-1β、IL-6、UNPD80777、UNPD126813和UNPD24695具有较高的度和介数值。结论:独活治疗OA疼痛的主要药效物质基础为香豆素类化合物(UNPD80777、UNPD126813)和酚类化合物(UNPD24695),关键作用靶点为IL-1β和IL-6。
Objective：To explore the pharmacodynamic material basis and action targets of heracleum for treatment of osteoarthritis（OA） pain.Methods：Sixty-eight chemical components of heracleum and twenty-eight OA pain-related anti-inflammatory analgesic drugs were retrieved from Peking University Natural Product Library and Drug Bank database respectively to build the molecular dataset of chemical components of heracleum and the molecular dataset of OA pain-related drugs.The chemical space of the 2 molecular datasets were analysed relying on the quantitative structure-activity relationship platform.Interleukin（IL）-1β,IL-6 and tumor necrosis factor-α（TNF-α） were used as therapeutic targets of OA pain.The network of interaction between active ingredients of heracleum and targets of OA pain were constructed by using molecular docking technology and biological network technology,and the interaction between active ingredients of heracleum and targets of OA pain were analyzed.Results：The molecular dataset of chemical components of heracleum had better dispersity in the chemical space compared to the molecular dataset of OA pain-related drugs,and its posterior-inferior part was similar to the molecular dataset of OA pain-related drugs in chemical space.The pharmacodynamic material basis of heracleum for treatment of OA pain included coumarin compounds（UNPD80777,UNPD49810,UNPD40977,UNPD35503,UNPD189982,UNPD134852 and UNPD126813） and phenolic compounds（UNPD24695）.UNPD49810,UNPD40977,UNPD35503,UNPD189982 and UNPD134852 could act on one target;and UNPD80777,UNPD126813 and UNPD24695 could act on two targets.Furthermore,IL-1β,IL-6,UNPD80777,UNPD126813 and UNPD24695 had high degrees and betweenness values.Conclusion：The main pharmacodynamic material basis of heracleum for treatment of OA pain are coumarin compounds（UNPD80777 and UNPD126813） and phenolic compounds（UNPD24695）,and their key action targets include IL-1β and IL-6.
作者
郑春松
付长龙
叶锦霞
吴广文
李西海
叶蕻芝
刘献祥
ZHENG Chunsong FU Changlong YE Jinxia WU Guangwen LI Xihai YE Hongzhi LIU Xianxiang(Fujian University of Traditional Chinese Medicine, Fuzhou 350122, Fujian, China Fujian Key Laboratory of Integrated Medicine on Geriatrics, Fuzhou 350122, Fujian, China)
出处
《中医正骨》
2017年第7期1-4,11,共5页
The Journal of Traditional Chinese Orthopedics and Traumatology
基金
国家自然科学基金项目(81573801)
福建省自然科学基金项目(2015J01338)
关键词
骨关节炎
独活
计算机模拟
疼痛
痹证
osteoarthritis
heracleum
computer simulation
pain
arthralgia syndrome
