| 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作用的可行性[J].实用中西医结合临床,2022,22(2):7-11 |
| 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作用的可行性 |
| To Explore the Feasibility of Ginseng in the Treatment of Osteoarthritis Anti-inflammatory and Analgesic Effect Based on Chemical Space and Molecular Docking |
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| DOI： |
| 中文关键词: 骨关节炎 人参 健脾法 化学空间 分子对接 活性化合物 |
| 英文关键词: Osteoarthritis Ginseng Spleen strengthening method Chemical space Molecular docking Active compounds |
| 基金项目:福建省自然科学基金项目（编号：2019J01354） |
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| 摘要点击次数: 331 |
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| 中文摘要: |
| 目的：探讨人参在治疗骨关节炎（OA）中发挥抗炎镇痛作用的可行性。方法：从中药系统药理数据库及分析平台（TCMSP）中筛选人参中口服生物利用度≥30%和类药性≥0.18的成分，从活性化合物专家网站中检索OA疼痛密切相关白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）和肿瘤坏死因子-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，从人参中筛选出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临床治疗中的应用提供新依据。 |
| 英文摘要: |
| Objective: To explore the feasibility of ginseng in the treatment of osteoarthritis (OA) anti-inflammatory and analgesic effect. Method: The components with oral bioavailability≥30% and drug-likeness≥0.18 in ginseng were screened from the pharmacological database and analysis platform of traditional Chinese medicine system (TCMSP), and the Interleukin-1β(IL-1β), Interleukin-6 (IL-6) and tumor necrosis factor-α (TNF- α) which were closely related to OA pain was retrieved from the active compound expert website. The molecular data sets of ginseng and inhibitors were established on the discovery studio (DS) simulation platform; under the quantitative structure-activity relationship (DS QSAR) module,the chemical space of the two molecular data sets was calculated and analyzed. The closer the compounds in the two data sets were in space, the greater the possibility of representing similar effects. Taking IL-1β, IL-6, TNF-α as the therapeutic target of anti-inflammatory and analgesic in OA, the complex structure with ligand was downloaded from the protein database (RCSB PDB), with codes of 6Y8M, 1ALU and 2AZ5 respectively. In DS Ligandfit, the interaction between compounds in ginseng molecular data set and anti-inflammatory and analgesic targets IL-1β, IL-6、TNF-α was studied. 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 had similar chemical spaces, indicating that they may have similar effects. Using the DOCK-SCORE of IL-1β, IL-6, TNF-α and their respective primary ligands as thresholds, 11 potential anti-inflammatory and analgesic active compounds including Deoxyharringtonine, Dianthramine, Suchilactone, Arachidonate, Kaempferol, Ginsenoside Rg5, Ginsenoside Rh2, GomisinB, Celabenzine, Chrysanthemaxanthin and 5-benzoyl-4-acetyl malkangunin were screened from Panax ginseng. Conclusion: By comprehensively analyzing the chemical space of ginseng and its active components of anti-inflammatory and analgesic, it is considered that ginseng has the effect of anti-inflammatory and analgesic in the treatment of OA. This study can provide a new basis for the application of spleen strengthening method in the clinical treatment of OA. |
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