Schisandrin A Attenuates Diabetic Nephropathy via EGFR/AKT/GSK3β Signaling Pathway Based on Network Pharmacology and Experimental Validation
Pengyu Wang,
Qing Lan,
Qi Huang,
Ruyi Zhang,
Shuo Zhang,
Leiming Yang,
Yan Song,
Tong Wang,
Guandi Ma,
Xiufen Liu,
Xiying Guo,
Youzhi Zhang,
Chao Liu
Affiliations
Pengyu Wang
School of Pharmacy, Hubei Engineering Research Center of Traditional Chinese Medicine of South Hubei Province, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China
Qing Lan
School of Pharmacy, Hubei Engineering Research Center of Traditional Chinese Medicine of South Hubei Province, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China
Qi Huang
School of Pharmacy, Hubei Engineering Research Center of Traditional Chinese Medicine of South Hubei Province, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China
Ruyi Zhang
School of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430000, China
Shuo Zhang
School of Pharmacy, Hubei Engineering Research Center of Traditional Chinese Medicine of South Hubei Province, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China
Leiming Yang
School of Pharmacy, Hubei Engineering Research Center of Traditional Chinese Medicine of South Hubei Province, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China
Yan Song
School of Pharmacy, Hubei Engineering Research Center of Traditional Chinese Medicine of South Hubei Province, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China
Tong Wang
School of Pharmacy, Hubei Engineering Research Center of Traditional Chinese Medicine of South Hubei Province, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China
Guandi Ma
School of Pharmacy, Hubei Engineering Research Center of Traditional Chinese Medicine of South Hubei Province, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China
Xiufen Liu
Hubei Key Laboratory of Diabetes and Angiopathy, Medical Research Institute, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China
Xiying Guo
Hubei Key Laboratory of Diabetes and Angiopathy, Medical Research Institute, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China
Youzhi Zhang
School of Pharmacy, Hubei Engineering Research Center of Traditional Chinese Medicine of South Hubei Province, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China
Chao Liu
Hubei Key Laboratory of Diabetes and Angiopathy, Medical Research Institute, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China
Diabetic nephropathy (DN) is one of the common complications of diabetes and the main cause of end-stage renal disease (ESRD) in clinical practice. Schisandrin A (Sch A) has multiple pharmacological activities, including inhibiting fibrosis, reducing apoptosis and oxidative stress, and regulating immunity, but its pharmacological mechanism for the treatment of DN is still unclear. In vivo, streptozotocin (STZ) and a high-fat diet were used to induce type 2 diabetic rats, and Sch A was administered for 4 weeks. At the same time, protein–protein interaction (PPI) networks were established to analyze the overlapping genes of DN and Sch A. Subsequently, the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses were performed to determine the hub pathway. In addition, molecular docking was used to preliminarily verify the affinity of hub proteins and Sch A. Further, H&E staining, Sirius red staining, immunohistochemistry, immunofluorescence, and western blot analysis were used to detect the location and expression of related proteins in DN. This study revealed the multi-target and multi-pathway characteristics of Sch A in the treatment of DN. First, Sch A could effectively improve glucose tolerance, reduce urine microprotein and urine creatinine levels, and alleviate renal pathological damage in DN rats. Second, EGFR was the hub gene screened in overlapping genes (43) of Sch A (100) and DN (2524). Finally, it was revealed that Sch A could inhibit the protein expression levels of EGFR and PTRF and reduced the expression of apoptosis-related proteins, and this effect was related to the modulation of the AKT/GSK-3β signaling pathway. In summary, Sch A has a protective effect in DN rats, EGFR may be a potential therapeutic target, throughout modulating AKT/GSK-3β pathway.
