Gu Peiyuan, Chen Juan, Xin Jingxin, Chen Huiqi, Zhang Ran, Chen Dan, Zhang Yuhan, Shao Shanshan
Key Laboratory of Endocrine Glucose and Lipids Metabolism and Brain Aging, Ministry of Education; Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
Shandong Key Laboratory of Endocrine Metabolism and Aging, Jinan, Shandong, China.
Sci Rep. 2025 Mar 26;15(1):10351. doi: 10.1038/s41598-025-95154-z.
The prevalence of nonalcoholic steatohepatitis (NASH) is rising annually, posing health and economic challenges, with limited treatments available. Diosgenin, a natural steroidal compound found in various plants, holds potential as a therapeutic candidate. Recent studies have confirmed diosgenin's anti-inflammatory and metabolism-modulating properties. However, its therapeutic effects on NASH and the underlying mechanisms are still unclear. This study aims to explore diosgenin's protective effects and pharmacological mechanisms against NASH using network pharmacology, molecular docking, and experimental validation. We gathered potential targets of diosgenin and NASH from various databases to generate protein-protein interaction (PPI) networks. GO and KEGG pathway enrichment analyses identified key targets and mechanisms. Molecular docking confirmed the binding capacity between diosgenin and core target proteins. Additionally, a NASH cell model was developed to validate the pharmacological effects of diosgenin. Our investigation identified nine key targets (ALB, AKT1, TP53, VEGFA, MAPK3, EGFR, STAT3, CASP3, IGF1) that interact with diosgenin. Molecular docking indicated potential bindings interactions, while enrichment analyses revealed that diosgenin may enhance fatty acid metabolism via the PI3K-Akt pathway. Cellular experiments confirmed that diosgenin activates this pathway, reduces SCD1 expression, and decreases triglyceride and IL-6 levels. Our study elucidates that diosgenin may ameliorate triglyceride deposition and inflammation through the PI3K-Akt pathway.
非酒精性脂肪性肝炎（NASH）的患病率逐年上升，带来了健康和经济挑战，且可用治疗方法有限。薯蓣皂苷元是一种存在于多种植物中的天然甾体化合物，具有作为治疗候选物的潜力。最近的研究证实了薯蓣皂苷元的抗炎和调节代谢特性。然而，其对NASH的治疗作用及潜在机制仍不清楚。本研究旨在利用网络药理学、分子对接和实验验证来探索薯蓣皂苷元对NASH的保护作用和药理机制。我们从各种数据库收集了薯蓣皂苷元和NASH的潜在靶点，以生成蛋白质-蛋白质相互作用（PPI）网络。基因本体（GO）和京都基因与基因组百科全书（KEGG）通路富集分析确定了关键靶点和机制。分子对接证实了薯蓣皂苷元与核心靶蛋白之间的结合能力。此外，建立了NASH细胞模型以验证薯蓣皂苷元的药理作用。我们的研究确定了与薯蓣皂苷元相互作用的9个关键靶点（ALB、AKT1、TP53、VEGFA、MAPK3、EGFR、STAT3、CASP3、IGF1）。分子对接表明存在潜在的结合相互作用，而富集分析显示薯蓣皂苷元可能通过PI3K-Akt通路增强脂肪酸代谢。细胞实验证实薯蓣皂苷元激活该通路，降低硬脂酰辅酶A去饱和酶1（SCD1）表达，并降低甘油三酯和白细胞介素-6水平。我们的研究阐明，薯蓣皂苷元可能通过PI3K-Akt通路改善甘油三酯沉积和炎症。
