| 引用本文: | 马天宇,平洋,沈梦婷,李楷,王丽红,苏瑾.基于网络药理学和实验验证探讨肉桂抗抑郁的作用机制[J].中国现代应用药学,2023,40(13):1775-1784. |
| MA Tianyu,PING Yang,SHEN Mengting,LI Kai,WANG Lihong,SU Jin.Investigation on the Mechanism of Antidepressant Effect of Cinnamomi Cortex Based on Network Pharmacology and Experimental Verification[J].Chin J Mod Appl Pharm(中国现代应用药学),2023,40(13):1775-1784. |
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| 基于网络药理学和实验验证探讨肉桂抗抑郁的作用机制 |
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马天宇, 平洋, 沈梦婷, 李楷, 王丽红, 苏瑾
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佳木斯大学药学院, 黑龙江省新药创制与药效毒理评价重点实验室, 黑龙江 佳木斯, 154007
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| 摘要: |
| 目的 基于网络药理学方法探讨肉桂治疗抑郁症的作用机制,并根据结果进行实验验证。方法 利用中药系统药理学数据库分析平台(TCMSP)及肉桂活性成分相关文献对肉桂的潜在活性成分进行筛选,并对筛选所得活性成分进行作用靶点预测;通过DisGeNet数据库获得抑郁症的疾病靶点;通过STRING数据库构建蛋白相互作用网络;通过DAVID数据库对关键靶点进行基因本体(GO)富集分析、京都基因与基因组百科全书(KEGG)通路富集分析。基于网络药理学结果,将肉桂油制成固体自微乳作为试药,建立慢性不可预知温和应激(chronic unpredictable mild stress,CUMS)抑郁小鼠模型,通过测定小鼠神经递质和炎症因子的表达水平进行实验验证。结果 通过筛选共得到22种有效成分和186个潜在作用靶点,GO富集分析共得到GO条目275条,其中生物过程222条,细胞组成18条,分子功能35条。KEGG富集共得到96条信号通路。网络药理学结果表明,肉桂抗抑郁的作用机制与神经递质及炎症反应有关。动物实验结果表明,肉桂油固体自微乳可改善由CUMS造成的海马损伤,使海马内神经元排列整齐、细胞结构完整,同时肉桂油中剂量组有效提高了CUMS小鼠脑内5-羟色胺(5-hydroxytryptamine,5-HT)、NE、DA表达水平(P<0.05),降低了血清中IL-6、IL-1β、TNF-α的表达(P<0.05)。动物实验结果与网络药理学结果一致。结论 肉桂的抗抑郁活性具有多成分、多靶点及多途径的特点,调节神经递质及炎症因子表达水平是其发挥作用的重要途径,为肉桂抗抑郁作用机制的深入研究提供了依据。 |
| 关键词: 肉桂 抑郁 网络药理学 信号通路 作用机制 |
| DOI：10.13748/j.cnki.issn1007-7693.20221515 |
| 分类号:R285.5 |
| 基金项目:黑龙江省北药与功能食品特色学科建设项目(黑教联[2018]4号)；佳木斯大学优秀学科团队项目(JDXKTD-2019005)；黑龙江省卫生计生委项目(2018-482)；佳木斯大学科技创新团队校级创新团队(cxtd202103) |
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| Investigation on the Mechanism of Antidepressant Effect of Cinnamomi Cortex Based on Network Pharmacology and Experimental Verification |
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MA Tianyu, PING Yang, SHEN Mengting, LI Kai, WANG Lihong, SU Jin
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Department of Pharmacy, Jamusi University, Heilongjiang Provincial Key Laboratory of New Drug Development and Pharmacotoxicological Evaluation, Jamusi 154007, China
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| Abstract: |
| OBJECTIVE To explore the mechanism of Cinnamomi Cortex in the treatment of depression based on the network pharmacology method, and to verify the experimental results according to the results. METHODS The potential active components of Cinnamomi Cortex were screened by using the Chinese Medicine System Pharmacology Database Analysis Platform(TCMSP) and literatures related to the active components of Cinnamomi Cortex. The target of action of the active ingredients obtained by screening was predicted; the disease targets of depression were obtained from the DisGeNet database; the STRING database protein-protein interaction was used to construct PPI network; Gene Ontology(GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis for key targets through DAVID database. Based on the results of network pharmacology, the solid self-microemulsion of Cinnamomi Cortex oil was used as a reagent to establish a chronic unpredictable mild stress(CUMS) depression mice model, and the experimental verification was carried out by measuring the expression levels of neurotransmitters and inflammatory factors in mice. RESULTS A total of 22 active ingredients and 186 potential targets were obtained through screening. A total of 275 GO items were obtained by GO enrichment analysis, including 222 for biological processes, 18 for cellular composition, and 35 for molecular functions. A total of 96 signaling pathways were obtained from KEGG enrichment. The results of network pharmacology indicated that the antidepressant mechanism of Cinnamomi Cortex was related to neurotransmitter components and inflammatory response. The results of animal experiments indicated that Cinnamomi Cortex oil solid self-microemulsion could improve hippocampal damage caused by CUMS, and make neurons in the hippocampus neatly arranged and cell structure intact. At the same time, it could effectively increase the expression levels of 5-hydroxytryptamine(5-HT), NE and DA in the brain of CUMS mice(P<0.05), and reduce the expression levels of serum IL-6, IL-1β and TNF-α(P<0.05). The results of animal experiments were consistent with the results of network pharmacology. CONCLUSION The antidepressant activity of Cinnamomi Cortex has the characteristics of multi-component, multi-target and multi-pathway. Regulating the expression levels of neurotransmitters and inflammatory factors is an important way of its action, which provides a basis for the in-depth study of the antidepressant mechanism of Cinnamomi Cortex. |
| Key words: Cinnamomi Cortex depression network pharmacology signaling pathway action mechanism |
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