计算方法解析姜黄素类化合物治疗神经性疼痛的作用机制。
Computational approach to decode the mechanism of curcuminoids against neuropathic pain.
机构信息
School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, China.
Department of Physiology and Pathophysiology, Institute of Neuroscience, Translational Medicine Institute, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shanxi, China.
出版信息
Comput Biol Med. 2022 Aug;147:105739. doi: 10.1016/j.compbiomed.2022.105739. Epub 2022 Jun 23.
BACKGROUND
Curcumin (CUR), demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC) are the main components of turmeric that commonly used to treat neuropathic pain (NP). However, the mechanism of the therapy is not sufficiently clarified. Herein, network pharmacology, molecular docking and molecular dynamics (MD) approaches were used to investigate the mechanism of curcuminoids for NP treatment.
METHODS
Active targets of curcuminoids were obtained from the Swiss Target database, and NP-related targets were retrieved from GeneCards, OMIM, Drugbank and TTD databases. A protein-protein interaction (PPI) network was built to screen the core targets. Furthermore, DAVID was used for GO and KEGG pathway enrichment analyses. Interactions between potential targets and curcuminoids were assessed by molecular docking and the MD simulations were run for 100ns to validate the docking results on the top six complexes.
RESULTS
CUR, DMC, and BDMC had 100, 99 and 100 targets respectively. After overlapping with NP there were 33, 33 and 31 targets respectively. PPI network analysis of TOP 10 core targets, TNF, GSK3β were common targets of curcuminoids. Molecular docking and MD results indicated that curcuminoids bind strongly with the core targets. The GO and KEGG showed that curcuminoids regulated nitrogen metabolism, the serotonergic synapse and ErbB signaling pathway to alleviate NP. Furthermore, specific targets in these three compounds were also analysed at the same time.
CONCLUSIONS
This study systematically explored and compared the anti-NP mechanism of curcuminoids, providing a novel perspective for their utilization.
背景
姜黄素（CUR）、脱甲氧基姜黄素（DMC）和双脱甲氧基姜黄素（BDMC）是常用治疗神经性疼痛（NP）的姜黄的主要成分。然而，其治疗机制尚不完全清楚。本研究采用网络药理学、分子对接和分子动力学（MD）方法，探讨姜黄素类化合物治疗 NP 的作用机制。
方法
从瑞士靶点数据库中获取姜黄素类化合物的活性靶点，从 GeneCards、OMIM、Drugbank 和 TTD 数据库中检索与 NP 相关的靶点。构建蛋白质-蛋白质相互作用（PPI）网络，筛选核心靶点。此外，采用 DAVID 进行 GO 和 KEGG 通路富集分析。采用分子对接评估潜在靶点与姜黄素类化合物的相互作用，并对前六个复合物进行 MD 模拟 100ns，验证对接结果。
结果
CUR、DMC 和 BDMC 分别有 100、99 和 100 个靶点，与 NP 重叠后分别有 33、33 和 31 个靶点。TOP10 核心靶点的 PPI 网络分析显示，TNF、GSK3β 是姜黄素类化合物的共同靶点。分子对接和 MD 结果表明，姜黄素类化合物与核心靶点结合牢固。GO 和 KEGG 分析表明，姜黄素类化合物通过调节氮代谢、5-羟色胺能突触和 ErbB 信号通路来缓解 NP。此外，还同时分析了这三种化合物中特定的靶点。
结论
本研究系统地探讨和比较了姜黄素类化合物抗 NP 的作用机制，为其应用提供了新的视角。
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