Diosmetin-7-O- β-D-glucopyranoside suppresses endothelial-mesenchymal transformation through endoplasmic reticulum stress in cardiac fibrosis

In this study, molecular docking results showed that diosmetin-7-O-glucoside bound well to ER stress and Src pathway markers. Diosmetin-7-O-glucoside suppressed cardiac fibrosis induced by isoprenaline (ISO) and reduced the levels of EndMT, ER stress in mice heart. Primary cardiac microvascular endothelial cells (CMECs) were induced by transforming growth factor-β1 (TGF-β1) to perform EndMT. Diosmetin-7-O-glucoside could effectively regulate EndMT and diminish the accumulation of collagen I and collagen III. We also showed that the tube formation in CMECs was restored, and the capacity of migration was partially inhibited. Diosmetin-7-O-glucoside also ameliorated ER stress through the three unfolded protein response branches, as evidenced by organelle structure in transmission electron microscopy images and the expression of protein biomarkers like the glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP). Further analysis showed that diosmetin-7-O-glucoside could suppress the expression level of Src phosphorylation, then block EndMT with the maintenance of endothelial appearance and endothelial marker expression. These results suggested that the diosmetin-7-O-glucoside can regulate EndMT through ER stress, at least in part via Src-dependent pathways.PMID:37430476 | DOI:10.1111/1440-1681.13802
Source: Clinical and Experimental Pharmacology and Physiology - Category: Drugs & Pharmacology Authors: Source Type: research