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基于网络药理学和分子对接技术探讨益气健脾通窍方治疗变应性鼻炎小鼠模型的潜在靶点及分子机制

Exploration of Potential Targets and Molecular Mechanisms of the Yiqi Jianpi Tongqiao Formula in Treating Allergic Rhinitis Mouse Model based on Network Pharmacology and Molecular Docking.

作者信息

Huang Sihong, Huang Yue

机构信息

Department of Pediatric, Baoshan Branch, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Department of Otolaryngology-Head and Neck Surgery, Children's Hospital of Fudan University, Shanghai, China.

出版信息

Curr Comput Aided Drug Des. 2024 May 24. doi: 10.2174/0115734099299714240516160158.

Abstract

OBJECTIVE

To investigate the therapeutic effect of Yiqi Jianpi Tongqiao (YJT) formula (Hedysarum Multijugum Maxim, Magnoliae Flos, Xanthii Fructus, Notopterygii Rhizoma Et Radix, Kaempferiae Rhizoma, Acoritataninowii Rhizoma, Saposhnikoviae Radix) on an allergic rhinitis mouse model, and to explore the active ingredients, key targets, and molecular mechanisms of this formula using network pharmacology and molecular docking methods.

METHODS

An allergic rhinitis mouse model was established to observe changes in rhinitis symptoms, nasal mucosal morphology, and serum indicators after administering the YJT formula. The TCMSP, GeneCards, OMIM, and DisGeNET databases were used to screen for the active ingredients, action targets, and disease targets of the YJT formula. The Cytoscape software was used to construct a network of the active ingredients and action targets. The protein-protein interaction (PPI) network was used to predict hub genes. The corresponding active compounds with the hub genes' highest oral bioavailability (OB) values were identified, followed by molecular docking analysis.

RESULTS

Animal experiments demonstrated that the YJT formula reduced rhinitis symptoms (nasal itching, runny nose, and face scratching) in allergic rhinitis mice, as well as decreased nasal mucosal inflammatory reactions and serum inflammatory indicators (histamine, OVAspecific IgE, IL-1β levels). Furthermore, 63 active components and 101 potential indicator targets of the YJT formula were identified, along with 5 hub genes (IL6, AKT1, IL1B, VEGFA, and PTGS2), and the corresponding active compounds with the highest OB values were quercetin, aloe-emodin, and denudanolide b. Molecular docking results revealed the binding energy between quercetin, aloe-emodin, denudanolide b and 5 hub genes (IL6, AKT1, IL1B, VEGFA, and PTGS2) were -5.78 to -10.22 kcal/mol, the binding energy between dexamethasone and 5 hub genes were -6.3 to -9.7 kcal/mol. In addition, GO and KEGG analysis suggested significant enrichment of these genes in biological processes such as response to lipopolysaccharide, response to molecule of bacterial origin, and response to reactive oxygen species, as well as signaling pathways like AGE-RAGE signaling pathway in diabetic complications, Lipid and atherosclerosis, and IL-17 signaling pathway.

CONCLUSION

The YJT formula has therapeutic effects in an allergic rhinitis mouse model, with the main active components being quercetin, aloe-emodin, and denudanolide b, and the key targets being IL6, AKT1, IL1B, VEGFA, and PTGS2, involving multiple signaling pathways.

摘要

目的

探讨益气健脾通窍方(多序岩黄芪、辛夷、苍耳子、羌活、山柰、石菖蒲、防风)对变应性鼻炎小鼠模型的治疗作用,并运用网络药理学和分子对接方法探索该方的活性成分、关键靶点及分子机制。

方法

建立变应性鼻炎小鼠模型,观察给予益气健脾通窍方后鼻炎症状、鼻黏膜形态及血清指标的变化。利用中药系统药理学数据库与分析平台(TCMSP)、基因卡片(GeneCards)、在线人类孟德尔遗传数据库(OMIM)和疾病基因数据库(DisGeNET)筛选益气健脾通窍方的活性成分、作用靶点及疾病靶点。采用Cytoscape软件构建活性成分与作用靶点网络。利用蛋白质-蛋白质相互作用(PPI)网络预测枢纽基因。鉴定与枢纽基因口服生物利用度(OB)值最高相对应的活性化合物,随后进行分子对接分析。

结果

动物实验表明,益气健脾通窍方减轻了变应性鼻炎小鼠的鼻炎症状(鼻痒、流涕和抓面),降低了鼻黏膜炎症反应及血清炎症指标(组胺、卵清蛋白特异性IgE、IL-1β水平)。此外,确定了益气健脾通窍方的63种活性成分和101个潜在指示靶点,以及5个枢纽基因(IL6、AKT1、IL1B、VEGFA和PTGS2),OB值最高的相应活性化合物为槲皮素、芦荟大黄素和去甲丹叶大黄素B。分子对接结果显示,槲皮素、芦荟大黄素、去甲丹叶大黄素B与5个枢纽基因(IL6、AKT1、IL1B、VEGFA和PTGS2)之间的结合能为-5.78至-10.22 kcal/mol,地塞米松与5个枢纽基因之间的结合能为-6.3至-9.7 kcal/mol。此外,基因本体(GO)和京都基因与基因组百科全书(KEGG)分析表明,这些基因在对脂多糖的反应、对细菌来源分子的反应和对活性氧的反应等生物学过程以及糖尿病并发症中的晚期糖基化终末产物受体(AGE-RAGE)信号通路、脂质与动脉粥样硬化和IL-17信号通路等信号通路中显著富集。

结论

益气健脾通窍方对变应性鼻炎小鼠模型具有治疗作用,主要活性成分为槲皮素、芦荟大黄素和去甲丹叶大黄素B,关键靶点为IL6、AKT1、IL1B、VEGFA和PTGS2,涉及多条信号通路。

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