首页|基于网络药理学和体外实验探究天麻抗抑郁的作用机制

基于网络药理学和体外实验探究天麻抗抑郁的作用机制

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目的 基于网络药理学、分子对接技术及体外实验,预测及验证天麻抗抑郁的作用机制.方法 首先采用网络药理学方法预测天麻抗抑郁的关键成分及潜在靶点,然后采用分子对接技术进行初步验证,最后采用经典的抑郁症体外模型验证关键成分天麻素的药效及作用靶点.结果 网络药理学分析显示,共收集到101个天麻活性成分和549个关键靶点,整合后进一步得到10个核心靶点,包括丝氨酸/苏氨酸蛋白激酶1(AKT1)、肿瘤坏死因子(TNF)、白细胞介素6(IL6)、脑源性神经营养因子(BDNF)等,并且天麻关键成分(天麻素、4-羟基苄醇、香草醛)与这些核心靶点均有较好结合力.天麻抗抑郁的关键通路主要富集在磷脂酰肌醇3-激酶/蛋白激酶B(PI3K-AKT)、环磷酸腺苷(cAMP)、低氧诱导因子-1(HIF-1)等通路.体外实验结果显示,与模型组相比,天麻素能显著促进PC12细胞存活,增加BDNF和p-AKT/AKT蛋白的表达水平,并显著抑制促炎细胞因子IL-6和TNF-α的表达.结论 天麻可通过多成分、多靶点、多途径干预抑郁症.
Mechanism of antidepressant effect of Gastrodia elata Bl.based on network pharmacology and in vitro experiments
Objective To predict and verify the anti-depression mechanism of Gastrodia elata Bl.based on network pharmacology,molecular docking and in vitro experiments.Methods The key components and potential targets of Gastrodia elata Bl.were predicted by network pharmacology,and then molecular docking was used for the preliminary verification.The efficacy and targets of gastrodia(GAS)were verified by classical in vitro depression models.Results Network pharmacological analysis showed that 101 active ingredients and 549 key targets were collected,and 10 core targets were further obtained after the integration,including serine/thronine protein kinase 1(AKT1),tumor necrosis factor(TNF),interleukin 6(IL6),brain-derived neurotrophic factor(BDNF),etc.The key components of Gastrodia elata Bl.(GAS,4-hydroxybenzyl alcohol,and vanillin)had good binding force with these core targets.In addition,the key pathways of the antidepression effect of Gastrodia elata Bl.mainly concentrated in phosphoinositol 3-kinase/protein kinase B(PI3K-AKT),cyclic adenosine phosphate(cAMP),and hypoxic-inducing-factor-1(HIF-1).The in vitro experiments showed that GAS significantly promoted the survival of PC 12 cells and increased the expression level of BDNF and p-AKT/AKT protein,but inhibited the expression of pro-inflammation cytokines IL-6 and TNF-a.Conclusion Gastrodia elata Bl.can intervene depression via multi-components,multi-targets and multi-pathways.

Gastrodia elata Bl.depressionnetwork pharmacologymolecular dockinggastrodiamolecular mechanism

杨淑贤、刘树森、韩雯、李草、赵志刚

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首都医科大学附属北京天坛医院药学部,北京 100070

哈尔滨商业大学药学院,哈尔滨 150076

中国医学科学院北京协和医学院药用植物研究所,北京 100193

天麻 抑郁症 网络药理学 分子对接 天麻素 分子机制

北京市医院管理局临床医学发展专项扬帆计划

ZYLX201827

2024

中南药学
湖南省药学会

中南药学

CSTPCD
影响因子:0.736
ISSN:1672-2981
年,卷(期):2024.22(3)
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