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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

Authors :
Borui Yu
Mengqi Zhou
Zhaocheng Dong
Huijuan Zheng
Yuxue Zhao
Jingwei Zhou
Chao Zhang
Fudong Wei
Guoyong Yu
Wei Jing Liu
Hongfang Liu
Yaoxian Wang
Source :
Pharmaceutical Biology, Vol 61, Iss 1, Pp 1222-1233 (2023)
Publication Year :
2023
Publisher :
Taylor & Francis Group, 2023.

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.

Details

Language :
English
ISSN :
13880209 and 17445116
Volume :
61
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Pharmaceutical Biology
Publication Type :
Academic Journal
Accession number :
edsdoj.3407f4e844cd425abc154a78f57932bd
Document Type :
article
Full Text :
https://doi.org/10.1080/13880209.2023.2241521