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

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:61

Enthalten in:

Pharmaceutical biology - 61(2023), 1 vom: 11. Dez., Seite 1222-1233

Sprache:

Englisch

Beteiligte Personen:

Yu, Borui [VerfasserIn]
Zhou, Mengqi [VerfasserIn]
Dong, Zhaocheng [VerfasserIn]
Zheng, Huijuan [VerfasserIn]
Zhao, Yuxue [VerfasserIn]
Zhou, Jingwei [VerfasserIn]
Zhang, Chao [VerfasserIn]
Wei, Fudong [VerfasserIn]
Yu, Guoyong [VerfasserIn]
Liu, Wei Jing [VerfasserIn]
Liu, Hongfang [VerfasserIn]
Wang, Yaoxian [VerfasserIn]

Links:

Volltext

Themen:

Drugs, Chinese Herbal
Glycation End Products, Advanced
Inflammation
Journal Article
MAPK signaling pathway
Protein-protein interaction network
Traditional Chinese medicine formula

Anmerkungen:

Date Completed 14.08.2023

Date Revised 16.08.2023

published: Print

Citation Status MEDLINE

doi:

10.1080/13880209.2023.2241521

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM360651976