丹参和降香配伍协同改善骨关节炎炎症微环境作用的计算机模拟研究  

Computer simulation study on the synergistic effect of Radix Salviae miltiorrhizae and Lignum Dalbergiae odoriferae on improving the inflammatory microenvironment of osteoarthritis

作　　者：赵金阁 杨燕妮 付长龙 马德尊 叶锦霞 郑春松 ZHAO Jin-ge;YANG Yan-ni;FU Chang-long;MA De-zun;YE Jin-xia;ZHENG Chun-song(Academy of Integrative Medicine,Fujian University of Traditional Chinese Medicine;College of Pharmacy,Fujian University of Traditional Chinese Medicine;Fujian Key Laboratory of Integrative Medicine on Geriatrics,Fuzhou,Fujian 350122)

机构地区：[1]福建中医药大学中西医结合研究院 [2]福建中医药大学药学院 [3]福建省中西医结合老年性疾病重点实验室,福建福州350122

出　　处：《赣南医学院学报》2023年第9期910-917,共8页JOURNAL OF GANNAN MEDICAL UNIVERSITY

基　　金：福建省自然科学基金项目(2019J01354)。

摘　　要：目的:从分子水平可视化探讨丹参和降香配伍在改善骨关节炎炎症微环境中的协同作用。方法:①从北京大学天然产物库中,检索180个丹参化学成分和119个降香化学成分,构建各自的化学成分数据集;从化学结构角度进行聚类分析,并计算两者的全局指纹相似度分值。②依托定量构效关系及主成分分析平台,分析丹参和降香化学成分数据集的化学空间。③以白细胞介素1β(Interleukin-1β,IL-1β)、IL-6、肿瘤坏死因子α(Tumor necrosis factor-α,TNF-α)、基质金属蛋白酶1(Matrix Metallopeptidase 1,MMP-1)、MMP-3、MMP-9和MMP-13为改善骨关节炎炎症微环境的靶点,利用分子对接和生物网络等平台,研究其与丹参、降香中化学成分的相互作用,并构建丹参和降香的化合物-靶点网络,分析丹参和降香配伍在改善骨关节炎炎症微环境中的意义。结果:①对丹参和降香化学成分数据集进行聚类,发现丹参和降香化学成分数据集在第1、2、3、4、5、6、8、9、10类存在交集,但在第7类仅出现丹参化学成分;同时,对两个数据集的全局指纹进行比较,发现其相似度分值为0.6375。②丹参和降香化学成分数据集在化学空间的后底部存在相近的分布。③丹参化合物-靶点网络显示,丹参的潜在活性化合物个数达到32个,其核心化合物为酚酸类成分,核心作用靶点为IL-1β、IL-6、TNF-α、MMP-1和MMP-9;降香化合物-靶点网络显示,降香中的潜在活性化合物个数达到64个,其核心化合物为黄酮类成分,核心作用靶点为IL-1β、IL-6、TNF-α、MMP-1、MMP-3和MMP-9。结论:从化学结构特征及化学空间分布看,丹参和降香存在相似之处,配伍后具有更多的潜在活性成分种类和数量、更广的化学空间分布,可通过对应的特定靶点和共同靶点在改善骨关节炎炎症微环境中相互作用发挥互补协同效应。即计算机模拟实现丹参和降香配伍协同改善骨关节炎�Objective:To explore the visualization of the synergistic effect of compatibility of Radix Salviae miltiorrhizae(Danshen in Chinese)and Lignum Dalbergiae odoriferae(Jiangxiang in Chinese)on improving the inflammation microenvironment of osteoarthritis(OA)from the molecular level.Methods:①180 chemical components in Danshen and 119 chemical components in Jiangxiang were retrieved from the universal natural products database(UNPD)of Peking University.The corresponding chemical composition datasets were built,clustered by chemical structure,and compared by global fingerprint.②Based on the platforms of quantitative structure-activity relationship and principal component analysis,the distributions of the above datasets were analyzed in the chemical space.③Interleukin-1 beta(IL-1β),IL-6,tumor necrosis factor alpha(TNF-α),matrix metalloproteinase-1(MMP-1),MMP-3,MMP-9 and MMP-13,were chosen as study targets related to improving the inflammation microenvironment of OA.The platforms of molecular docking and compound-target network were used to study the interactions between above targets and compounds from Danshen and Jiangxiang,and compound-target networks of Danshen and Jiangxiang were constructed to explore the significance of their compatibility in improving the inflammation microenvironment of OA.Results:①The chemical composition datasets of Danshen and Jiangxiang coexisted in the 1 st,2 nd,3 rd,4 th,5 th,6 th,8 th,9 th,10 th cluster category,while only the former existed in the 7 th category.Meanwhile,the similarity score between the two datasets was 0.6375.②Some of chemical compositions in Danshen and Jiangxiang existed similar distribution at the back and bottom of chemical space.③The Danshen compound-target networks showed that there were 32 potential active compounds improving the inflammation microenvironment.The core active substances of Danshen contained phenolic acids.Their core targets were IL-1β,IL-6,TNF-α,MMP-1 and MMP-9.In addition,the Jiangxiang compound-target networks showed that there w

关 键 词：丹参 降香 中药配伍 骨关节炎 炎症微环境 计算机模拟 数据可视化 

分 类 号：R284[医药卫生—中药学] R684.3[医药卫生—中医学]