| 翁小建,谈毅,陈明苍,等.百合抗焦虑抗抑郁有效成分与作用机制研究[J].浙江中医药大学学报,2023,47(11):1243-1254, 1269. |
| 百合抗焦虑抗抑郁有效成分与作用机制研究 |
| Study on the Active Components and Mechanism of Lilii Bulbus in Anti-anxiety and Anti-depression |
| DOI：10.16466/j.issn1005-5509.2023.11.002 |
| 中文关键词: 百合 抗焦虑 抗抑郁 生物信息分析 网络药理学 神经递质 |
| 英文关键词: Lilii Bulbus anti-anxiety anti-depression bioinformatics analysis network pharmacology neurotransmitters |
| 基金项目:国家自然科学基金面上项目(82074438)；浙江省中医药计划项目(2016ZQ015) |
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| 中文摘要: |
| [目的] 采用网络药理学与生物信息预测分析并结合体内与分子实验验证百合抗焦虑抗抑郁的作用机制。[方法] 采用中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform，TCMSP)检索百合抗焦虑抗抑郁的潜在活性成分；通过治疗靶点数据库(Therapeutic Target Database，TTD)检索活性成分抗焦虑抗抑郁的潜在作用靶标，构建成分与靶标网络；采用REACTOME与g:Profiler软件进行基因本体(gene ontology，GO)分析，京都基因和基因组数据库(Kyoto Encyclopedia of Genes and Genomes，KEGG)、REAC和WikiPathways代谢通路(WikiPathways，WP)富集分析。以行为绝望抑郁悬尾和强迫游泳实验评价百合水提液抗抑郁活性，以酶联免疫吸附试验(enzyme linked immunosorbent assay，ELISA)检测ICR小鼠海马内神经递质含量，以实时荧光定量聚合酶链式反应(Real-time polymerase chain reaction，Real-time PCR)分析抑郁小鼠脑内抑郁相关基因表达水平。[结果] 百合通过β-谷甾醇、3-去甲基秋水仙碱与26-O-β-D-吡喃葡萄糖基-3β，26-二羟基胆甾烷-16，22-二氧基-3-O-α-L-鼠李糖基-(1→2)-β-D-吡喃葡萄糖苷等5个潜在活性成分，可通过调控hsa-miR-203和hsa-miR-206等miRNAs与特异性蛋白1(specificity protein 1，SP1)、RE1沉默转录因子(RE1 silencing transcription factor，REST)和CCCTC结合因子(CCCTC-binding factor，CTCF)等转录因子的表达，进而共同调控蛋白激酶C epsilon型(protein kinase C epsilon，PRKCE)、γ-氨基丁酸B型受体亚基2(gamma-aminobutyric acid type B receptor subunit 2，GABBR2)、γ-氨基丁酸A型受体亚基β2(gamma-aminobutyric acid type A receptor subunit beta 2，GABRB2)和溶质载体家族6成员4(solute carrier family 6 member 4，SLC6A4)等基因的表达，可能最终影响了γ-氨基丁酸通路、5-羟色胺通路、G蛋白偶联受体通路和单胺氧化酶通路等，增加抑郁小鼠脑内神经递质含量，发挥抗焦虑抗抑郁作用。[结论] 采用网络药理学、生物信息预测以及实验验证百合抗焦虑抗抑郁的活性成分、潜在靶标和信号通路，为百合抗焦虑抗抑郁研究提供参考。 |
| 英文摘要: |
| [Objective] To analyze the anti-anxiety and anti-depression mechanism of Lilii Bulbus by using network pharmacology， bioinformatics analysis， in vivo and molecular experiments. [Methods] Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) was used to obtain the potential anti-anxiety and anti-depressant active ingredients of Lilii Bulbus. Therapeutic Target Database(TTD) was used to analyze the potential targets of anti-anxiety and anti-depressant effects of these poetical active ingredients. A network of components and targets was constructed with TCMSP and TTD. Gene ontology(GO)， Kyoto Encyclopedia of Genes and Genomes(KEGG)， REAC and WikiPathways(WP) enrichment analyses were carried out by REACTOME and g:Profiler. The antidepressant activity of Lilii Bulbus water extract was evaluated by tail suspension and forced swimming experiments. The content of neurotransmitters in hippocampus was determined by enzyme linked immunosorbent assay(ELISA). Real-time polymerase chain reaction(Real-time PCR) was used to analyze the expression level of depression related genes in the brains of depressed mice. [Results] Five potential active components of Lilii Bulbus， such as 26-O-β-D-glucopyranosyl-3β，26-dihydroxy-cholestan-16，22-dioxo-3-O-α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranoside_qt，3-Demethylcolchicine and β-sitosterol， could regulate the gene expression of protein kinase C epsilon(PRKCE)， gamma-aminobutyric acid type B receptor subunit 2(GABBR2)， gamma-aminobutyric acid type A receptor subunit beta 2(GABRB2) and solute carrier family 6 member 4 (SLC6A4)， etc. through coregulation of hsa-miR-203 and hsa-miR-206， etc. and the transcription factors(TFs)， such as specificity protein 1(SP1)， RE1 silencing transcription factor(REST) and CCCTC-binding factor(CTCF). Signaling pathways of gamma-aminobutyric acid(GABA)， serotonin， G protein-coupled receptor(GPCR) and monoamine oxidase(MAO) may play key roles in the anti-anxiety and anti-depression of Lilii Bulbus. [Conclusion] The potential anti-anxiety and anti-depressant active ingredients， targets and signaling pathways of Lilii Bulbus were obtained by using network pharmacology and bioinformatics prediction analyses， which can provide important basis for understanding of the anti-anxiety and anti-depressant effects of Lilii Bulbus. |
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