基于网络药理学探讨陈皮对糖尿病肾病作用机制

Exploration on the Mechanism of Chenpi in Treating Diabetic Nephropathy Based on Network Pharmacology

摘要: 目的：探讨陈皮治疗糖尿病肾病(DN)的潜在作用机制，为其临床应用提供理论依据。方法：采用网络药理学方法筛选陈皮的有效成分及其作用靶点，结合GeneCards和OMIM数据库获取糖尿病肾病相关靶点，获得交集靶点。构建“药物–成分–靶点”网络和PPI互作网络，筛选核心靶点。通过GO富集分析和KEGG通路分析揭示潜在生物学过程及信号通路。结果：筛选出陈皮的5种有效成分(β-谷甾醇、柚皮素、香叶木素、橙皮苷、川陈皮素)及61个与糖尿病肾病的交集靶点。PPI互作网络结果提示PPARG、PTGS2、BCL2、ESR1、SRC和MMP9等靶点在网络图中作用占比较高。GO和KEGG分析表明，陈皮可能通过调控AGE-RAGE信号通路、平滑肌细胞增殖等途径发挥治疗作用。结论：陈皮通过多成分、多靶点、多通路的作用机制治疗糖尿病肾病，预测中药潜在作用机制，为进一步临床验证及药理实验提供理论支持。

Abstract: Objective: This study aimed to investigate the potential mechanism of action of Chenpi (dried tangerine peel) in treating diabetic nephropathy (DN) using network pharmacology, thereby providing a theoretical foundation for its clinical application. Methods: The active components of Chenpi and their corresponding targets were identified through network pharmacology. Disease-related targets for DN were retrieved from the GeneCards and OMIM databases, followed by intersection analysis to identify shared targets. A “drug-component-target” network and a protein-protein interaction (PPI) network were constructed to elucidate core targets. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to explore potential biological processes and signaling pathways. Results: Five bioactive components of Chenpi (β-sitosterol, naringenin, geranitin, hesperidin, and nobiletin) were identified, along with 61 overlapping targets associated with DN. The PPI network highlighted key targets such as PPARG, PTGS2, BCL2, ESR1, SRC, and MMP9, suggesting their central roles in the therapeutic mechanism. GO and KEGG analyses revealed that Chenpi may exert its therapeutic effects by modulating pathways such as the AGE-RAGE signaling pathway and smooth muscle cell proliferation. Conclusion: Chenpi likely treats DN through a multi-component, multi-target, and multi-pathway mechanism. These findings provide insights into the pharmacological actions of Chenpi and support further clinical and experimental validation.