In silico prediction of phytoconstituents from Ehretia laevis targeting TNF-αin arthritis  

毛萼厚壳树植物成分对关节炎TNF-α靶点的预测

作　　者：Subhash R.Yende Sapan K.Shah Sumit K.Arora Keshav S.Moharir Govind K.Lohiya 

机构地区：[1]Department of Pharmacology,Gurunanak College of Pharmacy,Nagpur,Maharashtra 440026,India [2]Department of Pharmaceutical Chemistry,Priyadarshini J.L.College of Pharmacy,Nagpur,Maharashtra 440016,India [3]Department of Pharmacognosy and Phytochemistry,Gurunanak College of Pharmacy,Nagpur,Maharashtra 440026,India [4]Department of Pharmaceutics,Gurunanak College of Pharmacy,Nagpur,Maharashtra 440026,India

出　　处：《Digital Chinese Medicine》2021年第3期180-190,共11页数字中医药（英文）

摘　　要：Objective Rheumatoid arthritis(RA)is an autoimmune disease involving the synovial lining of the major joints.Current therapies have noteworthy side effects.Our study involved in silico evaluation of Ehretia laevis(E.laevis)phytoconstituents targeting tumor necrosis factor-α(TNF-α).Methods Molecular docking studies performed to investigate the binding pattern of the plant E.laevis phytoconstituents along with the crystal structure of TNF-α(PDB ID:2 AZ5)using AutoDock Vina followed by a study of interacting amino acid residues and their influence on the inhibitory potentials of the active constituents.Further the pharmacokinetic profile and toxicity screening carried out using Swiss ADME and pk CSM.Results The docked results suggest that lupeol(-9.4 kcal/mol)andα-amyrin(-9.4 kcal/mol)has best affinity towards TNF-αcompared to standard drug thalidomide(-7.4 kcal/mol).The active chemical constituents represents better interaction with the conserved catalytic residues,leading to the inhibition/blockade of the TNF-α-associated signaling pathway in RA.Furthermore,pharmacokinetics and toxicity parameters of these phytochemicals were within acceptable limits according to ADMET studies.Conclusion The binding potential of phytoconstituents targeting TNF-αshowed promising results.Nonetheless,it encourages the traditional use of E.laevis and provides vital information on drug development and clinical treatment.目的类风湿性关节炎(RA)是一种涉及主要关节滑膜衬里的自身免疫性疾病。目前的治疗方法有明显的副作用。我们的研究通过计算机模拟来评估毛萼厚壳树植物成分对肿瘤坏死因子-α(TNF-α)的靶向作用。方法利用AutoDock Vina进行分子对接实验,以研究毛萼厚壳树植物成分与TNF-α(PDB ID:2AZ5)晶体结构的结合模式;随后,研究相互作用的氨基酸残基及其对活性成分抑制潜力的影响;进一步使用SwissADME和pkCSM进行药代动力学分析和毒性筛选。结果对接实验结果表明,与标准药物沙利度胺(−7.4 kcal/mol)相比,羽扇豆醇(−9.4 kcal/mol)和α-香树脂醇(−9.4 kcal/mol)对TNF-α的亲和力最强。其活性化学成分与保守的催化残基具有更好的相互作用,从而抑制或阻断RA中的TNF-α相关信号通路。此外,根据ADMET研究,这些植物化学物质的药代动力学和毒性参数均在可接受的范围内。结论植物成分靶向TNF-α的结合潜力显示出良好的结果。尽管如此,本研究鼓励毛萼厚壳树的传统应用,并为药物开发和临床治疗提供了重要的信息。

关 键 词：Rheumatoid arthritis Ehretia laevis In silico Molecular docking Pharmacokinetics Tumor necrosis factor-α(TNF-α) LUPEOL α-Amyrin 

分 类 号：R285[医药卫生—中药学]