| 郑春松,杨燕妮,段辛威,黄蕾,叶蕻芝,朱晓勤,曾建伟.基于化学空间和分子对接探讨人参在治疗骨关节炎中发挥抗炎镇痛的可行性[J].实用中西医结合临床,2022,22(2): |
| 基于化学空间和分子对接探讨人参在治疗骨关节炎中发挥抗炎镇痛的可行性 |
| Anti - inflammatory and analgesic feasibility of Panax ginseng for osteoarthritisbased on chemical space and molecular docking |
| 投稿时间：2021-10-19 修订日期：2021-11-03 |
| DOI： |
| 中文关键词: 人参 健脾法 骨关节炎 化学空间 分子对接 活性化合物 |
| 英文关键词: Panax ginseng Replenishing spleen method Osteoarthritis Chemical space Molecular docking ActiveScompounds |
| 基金项目:福建省自然科学(2019J01354) |
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| 中文摘要: |
| 目的 探讨人参在治疗骨关节炎（Osteoarthritis,OA）中发挥抗炎镇痛的可行性。方法 从中药系统药理数据库及分析平台（traditional Chinese medicine
systems pharmacology database and analysis platform,TCMSP）中筛选人参中口服生物利用度≥30%和类药性≥0.18的成分，从活性化合物专家（https://www.
selleck.cn/）中检索OA疼痛密切相关白细胞介素-1β（interleukin-1β,IL-1β）、白细胞介素-6（interleukin-6,IL-6）和肿瘤坏死因子-α（tumor necrosis factor-α,TNF-α）的抑制剂，在Discovery studio（DS）模拟平台，分别建立人参和抑制剂分子数据集；在定量构效关系（DS QSAR）模块下，计算和分析两分子数据集的化学空间，两数据集中的化合物在空间上距离越近，代表具有相似作用的可能性越大；以IL-1β、IL-6、TNF-α为OA抗炎镇痛的治疗靶点，从蛋白质数据库（RCSB PDB）中下载其与配体的复合物结构，代码分别为6Y8M、1ALU和2AZ5，在DS LigandFit中，研究人参分子数据集中化合物与抗炎镇痛靶点IL-1β、IL-6、TNF-α之间的相互作用，从中筛选出比蛋白与各自原配体作用的DOCK-SCORE高的化合物，视为人参抗炎镇痛的活性成分。结果 人参分子数据集含有化学成分22个，抑制剂分子数据集含有化学成分26个；在三维的化学空间中，人参和抑制剂分子数据集中化合物均聚集在后背部，且距离较近，具有相似的化学空间，意味着可能具有相似的作用；以IL-1β、IL-6和TNF-α与各自原配体的DOCK-SCORE为阈值，从人参中发现抗炎镇痛的潜在活性化合物有11个，分别为脱氧三尖杉酯碱（Deoxyharringtonine）、石竹胺（Dianthramine）、苏齐内酯（Suchilactone）、花生四烯酸（Arachidonate）、山柰酚（Kaempferol）、人参皂苷Rg5（Ginsenoside Rg5）、人参皂苷Rh2（Ginsenoside Rh2）、五味子酯乙（Gomisin B）、苯代南蛇碱（Celabenzine）、菊黄质（Chrysanthemaxanthin）和5-苯甲酰基-4-乙酰基锥序南蛇藤呋喃四醇（Malkangunin）。结论 综合分析人参的化学空间及其存在抗炎镇痛的活性成分，认为人参在治疗OA方面具有抗炎镇痛的作用，本研究可为健脾法在OA临床中的应用提供新依据。 |
| 英文摘要: |
| Objective: To explore anti-inflammatory and analgesic feasibility of Panax ginseng for osteoarthritis(OA).Method: The chemical compositions of Panax ginseng with oral bioavailability ≥30% and drug- like index ≥0.18 were screened from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP).The inhibitors of interleukin-1β(IL-1β), interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) related to OA pain were searched from active compound experts(https://www.selleck.cn/). Based on the Discovery Studio (DS) simulation platform,they were constructed into molecular data sets of ginseng and inhibitor, respectively.Their chemical spaces were calculated and analyzed by quantitative structure-activity relationship (QSAR) of DS.The closer the spatial distance between the compounds in the two data sets is, the more likely they are to have similar effects.The complex structures of IL-1β, IL-6 and TNF-α with ligand were downloaded from RCSB protein data bank,their codes of 6Y8M, 1ALU and 2AZ5 respectively.In the module of DS LigandFit,the interactions between ginseng molecular data set compounds and anti-inflammatory and analgesic targets IL-1β, IL-6, TNF-α were studied, and the compounds with higher dock-scores than the dock-score of proteins and their respective primary ligands, were regarded as the active ingredient of ginseng with anti-inflammatory and analgesic effect.Results: The ginseng molecular dataset contained 22 chemical components, while the inhibitor molecular dataset contained 26 chemical components. In the three-dimensional chemical space, the compounds in ginseng and inhibitor molecular data sets were all clustered in the back and close to each other, which have similar chemical spaces, indicating that they may have similar effects.Using the dock-scores of IL-1β, IL-6, TNF-α and their respective primary ligands as thresholds, 11 potential anti-inflammatory and analgesic compounds including deoxyharringtonine, dianthramine, suchilactone, arachidonate, kaempferol, ginsenoside Rg5, ginsenoside Rh2, gomisinB, celabenzine, chrysanthemaxanthin and 5-benzoyl-4-acetyl malkangunin were screened.Conclusion:Through comprehensive analysis of the chemical space of ginseng and its anti-inflammatory and analgesic active components, it,s believed that ginseng may have anti-inflammatory and analgesic effects in the treatment of OA. This study can provide a new basis for the clinical application of spleen tonifying method in OA. |
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