Xu Chunmei, Miao Huikai, Chen Xiaoxuan, Zhang Haiqing
Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
Shandong Key Laboratory of Endocrinology and Lipid Metabolism, Shandong Provincial Hospital, Jinan, China.
Front Pharmacol. 2023 Jan 13;13:1096536. doi: 10.3389/fphar.2022.1096536. eCollection 2022.
Diabetic kidney disease (DKD) becomes the leading cause of death for end-stage renal disease, whereas the potential mechanism is unclear and effective therapy is still rare. Our study was designed to investigate the cellular mechanism of Forsythiaside against DKD. The targets of Forsythiaside and the DKD-related targets were obtained from databases. The overlapping targets in these two sets were regarded as potential targets for alleviation of DKD by Forsythiaside. The targets of diabetic podocytopathy and tubulopathy were also detected to clarify the mechanism of Forsythiaside ameliorating DKD from the cellular level. Our results explored that PRKCA and RHOA were regarded as key therapeutic targets of Forsythiaside with excellent binding affinity for treating DKD podocytopathy. Enrichment analysis suggested the underlying mechanism was mainly focused on the oxidative stress and mTOR signaling pathway. The alleviated effects of Forsythiaside on the reactive oxidative species accumulation and PRKCA and RHOA proteins upregulation in podocytes were also confirmed. The present study elucidates that Forsythiaside exerts potential treatment against DKD which may act directly RHOA and PRKCA target by suppressing the oxidative stress pathway in podocytes. And Forsythiaside could be regarded as one of the candidate drugs dealing with DKD in future experimental or clinical researches.
糖尿病肾病（DKD）成为终末期肾病的主要死因，而其潜在机制尚不清楚，有效的治疗方法仍然很少。我们的研究旨在探讨连翘苷抗DKD的细胞机制。从数据库中获取连翘苷的靶点和与DKD相关的靶点。这两组中的重叠靶点被视为连翘苷缓解DKD的潜在靶点。还检测了糖尿病足细胞病和肾小管病的靶点，以从细胞水平阐明连翘苷改善DKD的机制。我们的研究结果表明，蛋白激酶Cα（PRKCA）和RhoA小G蛋白（RHOA）被视为连翘苷治疗DKD足细胞病具有优异结合亲和力的关键治疗靶点。富集分析表明其潜在机制主要集中在氧化应激和雷帕霉素靶蛋白（mTOR）信号通路。连翘苷对足细胞中活性氧积累以及PRKCA和RHOA蛋白上调的缓解作用也得到了证实。本研究阐明，连翘苷对DKD具有潜在治疗作用，可能通过抑制足细胞中的氧化应激途径直接作用于RHOA和PRKCA靶点。连翘苷可被视为未来实验或临床研究中治疗DKD的候选药物之一。
