[关键词]
[摘要]
目的 挖掘中国古今含酸枣仁-人参药对的复方,并进一步分析药对常治疾病及机制。方法 应用数据挖掘收集含有酸枣仁-人参药对的复方并统计药对常治疾病及药理作用,运用网络药理学预测酸枣仁-人参药对常治疾病机制,并且使用分子对接技术验证候选化合物与潜在靶标的结合能力,最后运用酶联免疫吸附法和免疫组织化学技术验证所发现的酸枣仁-人参药对失眠与神经系统功能的调节机制。结果 检索得到含酸枣仁-人参药对复方596首,经复方药理作用挖掘统计发现酸枣仁-人参药对主要发挥镇静催眠作用,常用于治疗失眠症等疾病。网络药理学分析结果显示,酸枣仁-人参药对可能通过调控神经活性配体-受体相互作用、γ-氨基丁酸(gamma-aminobutyric acid,GABA)能突触及炎症相关通路发挥镇静催眠作用。分子对接结果表明,多种核心活性成分与关键靶点具有较好的结合活性。体内外实验结果显示,酸枣仁-人参药对可改善谷氨酸诱导的SH-SY5Y细胞损伤,提高失眠模型大鼠相关神经递质水平,降低炎症因子水平,并促进海马及下丘脑中γ-氨基丁酸A型受体亚基α1(gamma-aminobutyric acid type A receptor subunit alpha1,GABRA1)和γ-氨基丁酸A型受体亚基γ2(gamma-aminobutyric acid type A receptor subunit gamma 2,GABRG2)的表达。结论 通过对酸枣仁-人参药对常治疾病的挖掘和发挥镇静催眠机制的探索,揭示了酸枣仁-人参药对的主要用药方向及作用机制,为该药对后续的深入研究及临床应用提供了一定的参考。
[Key word]
[Abstract]
Objective Discovering the ancient and modern Chinese compound prescriptions containing Suanzaoren (Ziziphi Spinosae Semen)-(Renshen) Ginseng Radix et Rhizoma herb pair (ZSS-GRR) and further analyzing the diseases commonly treated by the pairs and their therapeutic mechanisms. Methods Data mining method was applied to collect the compound formulas containing ZSS-GRR and count the commonly treated diseases and pharmacological effects, network pharmacology was applied to predict the mechanism of ZSS-GRR herb pair, and molecular docking technique was used to verify the binding ability of candidate compounds to potential targets, and finally enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry were used to validate the discovered mechanisms of ZSS-GRR for insomnia and nervous system function. Results A total of 596 compound formulations containing the ZSS-GRR were searched. Statistical analysis of the pharmacological effects of these formulations revealed that the ZSS-GRR primarily exerts sedative and hypnotic effects and is commonly used to treat conditions such as insomnia. Network pharmacology analysis indicates that the ZSS-GRR may exert its sedative and hypnotic effects by regulating neuroactive ligand-receptor interactions, gamma-aminobutyric acid (GABA) ergic synapses, and inflammation-related pathways. Molecular docking results suggest that multiple core active components exhibit strong binding affinity with key targets. Experimental results demonstrate that the ZSS-GRR combination can alleviate glutamate-induced damage in SH-SY5Y cells, increase levels of relevant neurotransmitters in rats with an insomnia model, reduce levels of inflammatory factors, and promote the expression of gamma-aminobutyric acid type A receptor subunit alpha 1 (GABRA1) and gamma-aminobutyric acid type A receptor subunit gamma 2 (GABRG2) in the hippocampus and hypothalamus. Conclusion Through the exploration of the commonly treated diseases and the sedative-hypnotic mechanism of ZSS-GRR, the main direction and mechanism of action of ZSS-GRR have been revealed, which provides certain valuable references for the subsequent in-depth research and clinical application of the pair.
[中图分类号]
R285
[基金项目]
国家自然科学基金项目(82304774);吉林省科技发展计划项目(YDZJ202301ZYTS114)