Journal of Clinical Chemistry and Laboratory Medicine
Open Access
ISSN: 2736-6588
ISSN: 2736-6588
Xuexue Zhu, Xinyao Dua, Xinyu Ma, Xinyu Meng, Chenyang Zhao, Taiyue Li, Xiaoyi Yu, Xuerui Zhu, Yuanyuan Wen, Shijie Zhang, Bao Hou, Weiwei Cai, Fei Xu* and Liying Qiu*
Diabetic Nephropathy (DN), one of the common chronic complications of diabetes, is the leading cause of end-stage renal disease. vaccarin, a highly active chinese medicinal monomer isolated from vaccariae semen, confers protective effects against Type 2 Diabetes Mellitus (T2DM). However, the effects of vaccarin on kidney injury in DN remain unclear. Our study showed that vaccarin ameliorated renal dysfunction and histological damage in diabetic mice through inhibiting renal fibrosis, overproduction of inflammation cytokine and Reactive Oxygen Species (ROS). Additionally, vaccarin treatment significantly suppressed the process of Epithelial-to-Mesenchymal Transition (EMT), a key step for renal fibrosis, in High Glucose (HG)-induced Hexokinase 2 (HK-2) cells. Mechanistically, the network pharmacology analysis and molecular docking revealed that Epidermal Growth Factor Receptor (EGFR) may be the potential target of vaccarin. In support, the phosphorylated levels of EGFR and its downstream mediator Extracellular Signal-Regulated Kinase 1/2 (ERK1/2) were abrogated by vaccarin in diabetic kidneys and HG-treated HK-2 cells. Blockade of either EGFR or ERK1/2 showed similar renal benefits as vaccarin. In conclusion, our results reveal that vaccarin attenuates diabetic renal damage via inactivation of EGFR signaling.
Published Date: 2023-09-01; Received Date: 2023-08-02