1. Integrating network pharmacology and experimental validation to decipher the mechanism of the Chinese herbal prescription modified Shen-Yan-Fang-Shuai formula in treating diabetic nephropathy
- Author
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Borui Yu, Mengqi Zhou, Zhaocheng Dong, Huijuan Zheng, Yuxue Zhao, Jingwei Zhou, Chao Zhang, Fudong Wei, Guoyong Yu, Wei Jing Liu, Hongfang Liu, and Yaoxian Wang
- Subjects
Traditional Chinese medicine formula ,protein-protein interaction network ,MAPK signaling pathway ,inflammation ,Therapeutics. Pharmacology ,RM1-950 - Abstract
AbstractContext Diabetic nephropathy (DN) is the main cause of end-stage renal disease. Modified Shen-Yan-Fang-Shuai formula (M-SYFSF) has excellent clinical efficacy in treating diabetic kidney disease. However, the potential mechanism of M-SYFSF remains unknown.Objective To investigate the mechanism of M-SYFSF against DN by network pharmacological analysis and biological experiments.Materials and methods Utilizing a web-based pharmacology database, the potential mechanisms of M-SYFSF against DN were identified. In vivo experiments, male SD rats were injected with streptozotocin (50 mg/kg) and got uninephrectomy to construct a model of DN. M-SYFSF (11.34 g/kg/d) was gavaged once per day for 12 weeks after model establishment. In vitro experiments, human proximal tubular cells (HK-2) were performed with advanced glycation end-products (AGEs) (100 μg/mL), then intervened with M-SYFSF freeze-dried powder. Pathological staining, WB, IHC, ELISA were conducted to explore the mechanism of M-SYFSF against DN.Results Network pharmacological analysis showed that MAPK pathway was the potential pathway. Results showed that compared with the Model group, M-SYFSF significantly reduced 24h urine albumin, UACR, and serum creatinine levels (54.90 ± 26.67 vs. 111.78 ± 4.28, 8.87 ± 1.69 vs. 53.94 ± 16.01, 11.56 ± 1.70 vs. 118.70 ± 49.57, respectively), and improved renal pathological changes. Furthermore, the intervention of M-SYFSF reduced the expression of pro-inflammatory cytokines and inhibited the activation of MAPK pathway in AGEs-treated HK-2 cells.Discussion and conclusion M-SYFSF is likely to reduce inflammation in DN by inhibiting the MAPK pathway. It provides a theoretical basis for the clinical application of M-SYFSF in the treatment of DN.
- Published
- 2023
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