基于网络药理学、分子对接和动物实验探究壮药金缕半枫荷对抑郁症炎症的作用机制

Mechanism of effect of Zhuang medicine Semiliquidambar cathayen.sis Chang on depression inflammation based on network pharmacology,molecular docking and animal experiments

目的 通过网络药理学及分子对接预测金缕半枫荷的关键靶点及信号通路等,并通过利血平诱导的抑郁大鼠模型验证金缕半枫荷对抑郁症炎症反应的作用机制。方法 通过网络药理学数据库预测药物及疾病的靶点,构建蛋白互作网络图,分析生物功能富集和通路,使用AGFR软件进行分子对接。基于利血平诱导的大鼠抑郁模型,通过行为学、分子生物学、病理学等手段验证金缕半枫荷对抑郁症炎症的作用。结果 共筛选得到活性成分13个,金缕半枫荷调控抑郁症的关键靶点11个,生物富集结果主要与认知、突触可塑性调节等有关,通路主要与Rap1信号通路、Toll样受体信号通路等有关。验证实验结果表明,金缕半枫荷提取物高、低剂量能明显缩短小鼠强迫游泳不动时间;明显减少大鼠圈内保留时间,升高血清中5-HT、DA的水平,降低血清中IL-6的水平,改善前额皮层炎性浸润情况,降低脑组织中IL-6、IL-1β、TNF-α mRNA的表达,升高脑组织中AKT1 mRNA的表达。结论 该研究揭示了金缕半枫荷可通过多成分、多靶点、多通路发挥抗抑郁作用,实验验证结果表明,金缕半枫荷可通过TOLL样信号通路改善抑郁症炎症反应,从而改善抑郁样症状。

Aim To predict the key targets and signaling pathways of Semiliquidambar cathayen.sis Chang(JLBFH)by network pharmacology and molecular docking,etc,then to explore the mechanism of JLBFH′s effect on inflammatory response to depression through reserpine-induced depression rat model.Methods The target of drug and disease was predicted by network pharmacological database,protein interaction network diagram was constructed,biofunctional enrichment and pathways were analyzed,and molecular docking prediction was performed by AGFR software.Based on reserpine-induced depression,the role of JLBFH in depression inflammation was verified by behavior,molecular biology and pathological examination,and so on.Results A total of 13 active ingredients were screened,11 key targets of JLBFH modulation of depression were selected,and the bioenrichment results were mainly related to cognition,prominent plasticity regulation,etc.The pathways were mainly related to Rap1 signaling pathway,Toll-like receptor signaling pathways.The results of validation experiments showed that high and low doses of JLBFH extract significantly shortened the forced swimming immobility time in mice,markedly reduced the retention time in the circle of rats,increased serum levels of 5-HT and DA,decreased serum levels of IL-6,improved inflammatory infiltration in the prefrontal cortex,decreased brain tissue levels of IL-6,IL-1β,TNF-αmRNA expression,and increased AKT1 mRNA expression in brain tissue.Conclusions The present study reveals that JLBFH can exert antidepressant effects through multi-component,multi-target and multi-pathway,and the experimental validation results show that JLBFH can improve the depression-like symptoms by improving the inflammatory response of depression through TOLL-like signaling pathway.