A network pharmacology-based study on the mechanism of astragaloside IV alleviating renal fibrosis through the AKT1/GSK-3ß pathway.
J Ethnopharmacol
; 297: 115535, 2022 Oct 28.
Article
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| MEDLINE
| ID: mdl-35840059
ABSTRACT
ETHNOPHARMACOLOGICAL REVELVANCE Astragaloside IV, a glycoside derived from Astragalus membranaceus, has anti-renal fibrosis effects. However, its mechanism of action has not yet been fully elucidated. AIM OF THE STUDY The purpose of this study was to investigate the anti-fibrotic effect of AS-IV and to clarify its underlying mechanism. MATERIALS AND METHODS:
The network pharmacology method, molecular docking and surface plasmon resonance (SPR) was used to identify potential targets and pathways of AS-IV. A unilateral ischemia-reperfusion injury (UIRI) animal model, as well as TGF-ß1-induced rat renal tubular epithelial cells (NRK-52E) and renal fibroblasts (NRK-49F) were used to investigate and validate the anti-fibrotic activity and pharmacological mechanism of AS-IV. Network pharmacology was performed to construct a drug-target-pathway network. The anti-fibrosis effect of AS-IV was determined using hematoxylin-eosin (H&E) and MASSON staining, as well as immunostaining methods. qRT-PCR and western blotting were used to elucidate and validate the mechanism of AS-IV.RESULTS:
Network pharmacology revealed that the PI3K/AKT pathway is an important pathway in AS-IV. AS-IV inhibited the expression of α-SMA, collagen I, and fibronectin in NRK-52E, NRK-49F, and UIRI rats, and reduced serum creatinine and blood urea nitrogen levels in UIRI rats. AS-IV inhibited AKT phosphorylation, blocked GSK-3ß phosphorylation, and restored GSK-3ß activity, which contributed to the degradation of ß-catenin, thereby preventing epithelial-mesenchymal transition (EMT).CONCLUSION:
Astragaloside IV alleviated renal fibrosis through the AKT1/GSK-3ß pathway. In addition, our findings indicate that the network pharmacology method is a powerful tool for exploring the pharmacological mechanisms of drugs.Palabras clave
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Bases de datos:
MEDLINE
Asunto principal:
Fosfatidilinositol 3-Quinasas
/
Enfermedades Renales
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
J Ethnopharmacol
Año:
2022
Tipo del documento:
Article
País de afiliación:
China