Paeonol Promotes Reendothelialization After Vascular Injury Through Activation of c-Myc/VEGFR2 Signaling Pathway

Abstract

Purpose Dysfunction of endothelium is associated with multiple pathological vascular diseases. However, how to regulate reendothelialization after vascular injury is not well defined. This study aims to determine whether and how Paeonol controls reendothelialization following artery injury. Methods The endothelium of murine carotid artery was denuded by catheter guide wires injury. H&E staining and IF staining were performed to determine whether Paeonol is critical for reendothelialization. BRDU Incorporation Assay, Boyden Chamber Migration Assay, Tube Formation Assay, and Spheroid Sprouting Assay were used to investigate whether Paeonol is involved in regulating proliferation and migration of endothelial cells. The underlying mechanism of how Paeonol regulates reendothelialization was determined by Molecular docking simulation and CO-IP Assay. Results Paeonol treatment significantly inhibits neointima formation in carotid artery ligation model by promoting proliferation and migration of endothelial cells. Mechanistically, Paeonol enhances c-Myc expression, consequently interacts with VEGFR2 results in activating VEGF signaling pathway, and eventually promotes reendothelialization after vascular injury. Conclusion Our data demonstrated that Paeonol plays a critical role in regulating vascular reendothelialization, which may be therapeutically used for treatment of pathological vascular diseases.

Natural-derived acetophenones: chemistry and pharmacological activities

“…It has been found to effectively inhibit the growth of Aspergillus flavus, a fungus that can damage agricultural products [126]. Paeonol treatment can also promote reendothelialization, the process of regrowing the endothelial layer of blood vessels, which is important for the treatment of vascular diseases [127]. Sancin (1971) identified acetophenone derivative, named acetovanillone (219) in the roots of Apocynum venetum (Apocynaceae) [128].…”

“…Acetophenone glycoside (228) was isolated from Cassia sophera (Fabaceae) [135]. Edayadulla (127) for the first time from the leaves of Dysoxylum lenticellare (Meliaceae) [138]. In addition, Wei-sheng et al isolated the same compound from Saxifraga stolonifera (Saxifragaceae) that was previously unknown in the genus [139].…”

“…There are reports of the presence of acetophenone compounds in Gymnosperms. Osswald et al reported the extraction of p-hydroxyacetophenone (127) in Picea abies (spruce needles) (Pinaceae) and explored the fungitoxic activity of that compound towards Cladosporium cucumerinum and Ospbaera kalkhoffii [145]. Attempts to screen the compounds from the members of gymnosperms perpetuated as Inatomi et al identified seven acetophenone derivatives from Juniperus occidentalis (Cupressaceae).…”