Huangkui capsule combined with finerenone attenuates diabetic nephropathy by regulating the JAK2/STAT3 signaling pathway based on network pharmacology, molecular docking, and experimental verification

作者：Xingyu Liu, Chunjiang Zhang, Yang Fu, Jingjing Dai, James Lu, Gang Liu, Xiaoping Yang · 发表于：Frontiers in Pharmacology · 年份：2025 · DOI：10.3389/fphar.2025.1625286 · 被引用次数：3 · 研究领域：Cytokine Signaling Pathways and Interactions、Inflammasome and immune disorders、Chronic Kidney Disease and Diabetes

Introduction Diabetic nephropathy (DN) is a serious complication of diabetes with limited therapeutic options. Although Huangkui capsule (HKC) and finerenone individually show potential in DN management, their combined mechanism remains unclear. This study aimed to explore the therapeutic effects and underlying mechanisms of HKC and finerenone combination for DN. Methods An integrative approach combining network pharmacology, molecular docking, kinetic simulations, and experimental validation was employed in this study. Active components of HKC and finerenone, along with their potential targets, were identified through database mining. A “drug-component-target-disease” network was constructed, and interactions with the JAK2/STAT3 pathway were validated. In vivo , DN mice were treated with HKC, finerenone, and their combination (CDI group), while in vitro , HK-2 cells were treated with quercetin (a core HKC component) and finerenone. The binding index between quercetin and finerenone was analyzed by using the Chou–Talalay method. Results Network pharmacology identified three core HKC components (quercetin, myricetin, and gossypetin) and 11 key targets (e.g., JAK2, STAT3, and AKT1). Molecular docking revealed strong binding affinity between quercetin–finerenone and JAK2/STAT3 (ΔG = −65.465 kcal/mol for STAT3-quercetin). In DN mice, combined therapy significantly reduced 24-h urinary protein (358.54 ± 21.21 mg/L vs. 1046.48 ± 72.84 mg/L in the model group, p < 0.001), imp...