A Mechanistic Exploratory Study on the Therapeutic Efficacy of Astragaloside IV Against Diabetic Retinopathy Revealed by Network Pharmacology

• DOI: 10.3389/fphar.2022.903485
• Publication Date: 2022-06-22T06:06:07Z
• Authors: Zhi-Hao Zhao; Min Xu; Cong Fu; Ying Huang; Ting-Hua Wang; Zhong-Fu Zuo; Xue-Zheng Liu
• Keywords: KEGG

Purpose: Diabetic retinopathy (DR) is a serious complication of diabetes mellitus, which nearly happens to all the diabetic sufferers. This study aims identify preliminary molecular regulation involved in therapeutic efficacy astragaloside IV (AS- IV) for DR. Methods: rat models were established and treated with AS-IV. Optical coherence tomography (OCT) Hematoxylin-eosin (HE) staining was employed demonstrate histopathological changes. The main targets AS-IV identified by searching from public databases traditional Chinese medicine (GeneCards, PharmMapper Swiss Target Prediction). Besides, disease DR also obtained integrated data GEO datasets predicted databases. Protein-protein interaction (PPI) network constructed Cytoscape overlapping genes 10 core selected, on Gene Ontology (GO) along Kyoto Encyclopedia Genes Genomes (KEGG) enrichment analysis conducted. between these crucial analyzed using docking. RT-qPCR western blot used verify expression variation targets. Results: OCT imaging HE demonstrated that administration significantly increased retinal thickness rats, obviously alleviating induced changes as well elevated blood glucose levels. 107 common determined after intersection. PPI filtered hub potentially targeted AS-IV, including VEGFA, CASP3, HIF1α, STAT3, CTNNB1, SRC, AKT1, EGFR, IL1β IL6. Enrichment indicated mainly enriched biological processes like T cell activation, epithelial proliferation protein kinase B signaling, oxidative stress, apoptosis inflammation-related pathways. docking prediction suggested exhibited stable binding In addition, mRNA levels rats differentially expressed before treatment. Western further revealed treatment DR-depressed PI3K AKT. Conclusion: Our elucidated effect attenuating preliminarily unveiled might be attributed activation PI3K-AKT signaling pathway.