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

Abstract

Context

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.

Keywords:

• Traditional Chinese medicine formula
• protein-protein interaction network
• MAPK signaling pathway
• inflammation

Authors contributions

Borui Yu, Mengqi Zhou, Wei Jing Liu, Hongfang Liu, and Yaoxian Wang contributed to the study design, practical work, manuscript writing and revision. Huijuan Zheng, Jingwei Zhou, and Guoyong Yu participated in the research design and manuscript writing. Zhaocheng Dong, Yuxue Zhao, Chao Zhang, and Fudong Wei participated in the experiments and data analysis. All authors read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This study was supported by grants from the National Natural Science Foundation of China (82174342; 82004272; 81874443), Chinese Medicine Inheritance and Innovation Talent Project-Leading Talent Support Program of National Traditional Chinese Medicine (Grant No. 2018, No. 12) .