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整合生物信息学分析、分子对接和动物实验研究小檗碱治疗过敏性鼻炎的作用机制。

Integration of bioinformatics analysis, molecular docking and animal experiments to study the therapeutic mechanisms of berberine against allergic rhinitis.

机构信息

Department of Otolaryngology, Fujian Provincial Governmental Hospital, Fuzhou, 350003, China.

Department of Otolaryngology, People's Hospital of Changji Hui Autonomous Prefecture, Changji, 831100, China.

出版信息

Sci Rep. 2024 May 25;14(1):11999. doi: 10.1038/s41598-024-60871-4.

Abstract

Allergic rhinitis is a prevalent inflammatory condition that impacts individuals of all age groups. Despite reports indicating the potential of berberine in alleviating allergic rhinitis symptoms, the specific molecular mechanisms and therapeutic targets of berberine remain unclear. This research aims to explore the pharmacological mechanism of berberine in the treatment of allergic rhinitis through bioinformatic analyses and experimental validation. The research utilized public databases to identify potential targets of berberine. Furthermore, differentially expressed genes (DEGs) related to allergic rhinitis were pinpointed from the GSE52804 dataset. Through bioinformatics techniques, the primary targets were discovered and key KEGG and GO-BP pathways were established. To confirm the therapeutic mechanisms of berberine on allergic rhinitis, an OVA-induced allergic rhinitis model was developed using guinea pigs. We identified 32 key genes responsible for the effectiveness of berberine in treating allergic rhinitis. In addition, five central genes (Alb, Il6, Tlr4, Ptas2, and Il1b) were pinpointed. Further examination using KEGG and GO-BP pathways revealed that the main targets were primarily involved in pathways such as NF-kappa B, IL-17, TNF, and inflammatory response. Molecular docking analysis demonstrated that berberine exhibited strong affinity towards these five key targets. Furthermore, the expression levels of IL-6, TLR4, PTGS2, and IL-1β were significantly upregulated in the model group but downregulated following berberine treatment. This research has revealed the mechanism through which berberine combats allergic rhinitis and has identified its potential to regulate pathways linked to inflammation. These discoveries provide valuable insights for the development of novel medications for the treatment of allergic rhinitis.

摘要

变应性鼻炎是一种普遍的炎症性疾病,影响所有年龄段的个体。尽管有报道称小檗碱具有缓解变应性鼻炎症状的潜力,但小檗碱的确切分子机制和治疗靶点尚不清楚。本研究旨在通过生物信息学分析和实验验证探索小檗碱治疗变应性鼻炎的药理机制。该研究利用公共数据库来识别小檗碱的潜在靶点。此外,从 GSE52804 数据集确定与变应性鼻炎相关的差异表达基因 (DEGs)。通过生物信息学技术,发现了主要靶点,并建立了关键的 KEGG 和 GO-BP 途径。为了验证小檗碱治疗变应性鼻炎的治疗机制,我们使用豚鼠建立了 OVA 诱导的变应性鼻炎模型。我们确定了 32 个关键基因,这些基因负责小檗碱治疗变应性鼻炎的有效性。此外,还确定了 5 个中心基因 (Alb、Il6、Tlr4、Ptas2 和 Il1b)。进一步通过 KEGG 和 GO-BP 途径的检查发现,主要靶点主要参与 NF-kappa B、IL-17、TNF 和炎症反应等途径。分子对接分析表明,小檗碱对这五个关键靶点具有很强的亲和力。此外,模型组中 IL-6、TLR4、PTGS2 和 IL-1β 的表达水平显著上调,但经小檗碱治疗后下调。这项研究揭示了小檗碱对抗变应性鼻炎的机制,并确定了其调节与炎症相关途径的潜力。这些发现为开发治疗变应性鼻炎的新型药物提供了有价值的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b41a/11127925/867141084d5e/41598_2024_60871_Fig1_HTML.jpg

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