白术活性成分干预糖尿病肾病的网络药理学预测与分子对接验证

Network Pharmacology Prediction and Molecular Docking Validation of Active Components of Atractylodes macrocephala in Intervening Diabetic Nephropathy

摘要: 糖尿病肾病(diabetic kidney disease, DKD)是糖尿病微血管并发症的主要死因，其与晚期糖基化终末产物–受体(AGE-RAGE)通路的异常激活密切相关。本研究基于TCMSP数据库筛选中药白术(Atractylodes macrocephala) 7种活性成分(基于OB ≥ 30%和DL ≥ 0.18原则)，预测得到349个白术-DKD共同靶点，PPI网络分析显示AKT1、TNF、SRC等为核心靶点。KEGG富集分析发现AGE-RAGE信号通路是DKD治疗的关键靶点，分子对接研究证实白术三醇与RAGE蛋白可以稳定结合，结合势能为−7.1 kcal/mol。本研究首次阐明白术通过抑制AGE-RAGE通路减轻DKD中氧化应激与炎症反应的多靶点机制，为中药治疗DKD提供理论依据。

Abstract: Diabetic kidney disease (DKD) is a leading cause of mortality among diabetic microvascular complications, closely associated with the aberrant activation of the advanced glycation end product-receptor (AGE-RAGE) pathway. In this study, seven active components of Atractylodes macrocephala (based on OB ≥ 30% and DL ≥ 0.18 criteria) were screened from the TCMSP database, yielding 349 shared targets of Atractylodes macrocephala-DKD. Protein-protein interaction (PPI) network analysis identified AKT1, TNF, and SRC as core targets. KEGG enrichment analysis revealed the AGE-RAGE signaling pathway as a pivotal therapeutic target for DKD. Molecular docking studies confirmed stable binding between atractylenolide III and the RAGE protein, with a binding energy of −7.1 kcal/mol. This study is the first to elucidate the multi-target mechanism by which Atractylodes macrocephala alleviates oxidative stress and inflammatory responses in DKD through inhibition of the AGE-RAGE pathway, providing a theoretical basis for traditional Chinese medicine in DKD treatment.