白芷挥发油抗炎镇痛活性成分的虚拟筛选

Virtual Screening of Anti-Inflammatory and Analgesic Constituents in Volatile Oil of Angelicae Dahuricae Radix

目的:研究白芷挥发油中抗炎镇痛的活性物质和潜在的靶点蛋白,为进一步明确白芷的抗炎镇痛机制提供科学依据。方法:通过检索文献,确定含量较高的脂肪烃(醇)和萜类成分共计17个小分子化合物为分子对接配体;根据抗炎镇痛的相关靶点,确定κ阿片受体(κOR)、Toll样受体2(TLR2)和诱导性一氧化氮合酶(iNOS)等18个蛋白为对接受体。采用AutoDock Vina软件,将配体和受体分别进行分子对接,根据打分值虚拟筛选白芷挥发油中的抗炎镇痛活性成分并初步确定潜在的靶点。结果:发现挥发性成分中36、41、45对受体κOR(PDBID:4DJH)的结合能力较强,而化合物75对受体TLR2(PDB ID:5D3I)的结合力最强,为-8.3 kcal/mol。结论:倍半萜、环十五烷酮等化合物可能是白芷挥发油中的重要抗炎镇痛活性物质基础,而κOR和TLR2是潜在的作用靶点。

Objective:To find the anti-inflammatory and analgesic constituents and the associated potential receptors in volatile oil of Angelicae Dahuricae Radix,thus to provide scientific basis for the mechanism in anti-inflammation and analgesia of the herb.Methods:By reviewing the published articles,17 small molecules containing aliphatic hydrocarbons and terpenes were chosen as ligands;and 18 proteins includingκopioid receptor(κOR),Toll-like receptor 2(TLR2)and inducible nitric oxide synthase(iNOS)were chosen as target receptors for molecular docking.The software AutoDock Vina was used to dock and score the 17 ligands from volatile oil and receptor proteins downloaded from the protein data bank(PDB).The anti-inflammatory and analgesic constituents,as well as the potential targets in volatile oil of Angelicae Dahuricae Radix was virtually screened based on the scores.Results:Compounds 36,41 and 45 were found to possess higher binding affinity to the proteinκOR(PDB ID:4DJH),whereas compound 75 was most active in binding to protein 5D3I,with the score of-8.3 kcal/mol.Conclusion:Sesquiterpenes and cyclopentadecanone might be the chemical basis of the anti-inflammatory and analgesic effects of volatile oil in Angelicae Dahuricae Radix,andκOR and TLR2 were the potential key target proteins for the activities.