The antioxidant effects of decursin inhibit EndMT progression through PI3K/AKT/NF-κB and Smad signaling pathways.

Endothelial cells (ECs) undergo endothelial-to-mesenchymal transition (EndMT) during the pathophysiology of cardiovascular diseases, a complex cellular transdifferentiation process closely associated with increased oxidative stress under adverse conditions such as myocardial infarction (MI). Decursin, a major constituent of Angelica gigas Nakai, displays diverse pharmacological properties. This study aimed to examine the antioxidant impact of decursin on EndMT regulation in both in vitro and in vivo models as a potential therapeutic strategy for MI. In vitro the inhibitory effects of decursin treatment were analyzed by measuring the expression of EndMT-associated genes, assessing endothelial function, intracellular ROS levels, and mitochondrial membrane potential. Furthermore, the study elucidated antioxidation-related signaling mechanisms within EndMT-induced ECs. In vivo, the therapeutic potential of decursin was investigated using a mouse model of MI. Decursin administration attenuated the EndMT process by upregulating CD31 and VE-Cadherin while decreasing fibronectin and α-SMA expression in EndMT-induced ECs. It also lowered ROS levels, preserved mitochondrial membrane potential, and modulated functional properties, resulting in enhanced LDL uptake and diminished endothelial permeability. Endothelial integrity was sustained via regulation of the PI3K/AKT/NF-κB and Smad-dependent signaling pathways, both responsive to oxidative stress during EndMT. In the MI mouse model, decursin reversed EndMT, lessened myocardial fibrosis and apoptosis, and promoted recovery of infarcted regions. The treated hearts demonstrated improved cardiovascular performance. Decursin represents a novel therapeutic strategy targeting intracellular oxidative stress induced by EndMT. By exerting antioxidant activity through the PI3K/AKT/NF-κB and Smaddependent pathways, decursin maintains endothelial function, suppresses myocardial fibrosis, and supports cardiac recovery following MI therapy.