The antioxidant effects of decursin inhibit EndMT progression through PI3K/AKT/NF-κB and Smad signaling pathways
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Endothelial cells (ECs) undergo endothelial-to-mesenchymaltransition (EndMT) during the pathophysiology of cardiovasculardiseases, a complex cellular transdifferentiation processclosely associated with increased oxidative stress under adverseconditions such as myocardial infarction (MI). Decursin, a majorconstituent of Angelica gigas Nakai, displays diverse pharmacologicalproperties. This study aimed to examine the antioxidantimpact of decursin on EndMT regulation in both in vitroand in vivo models as a potential therapeutic strategy for MI. In vitro the inhibitory effects of decursin treatment were analyzedby measuring the expression of EndMT-associated genes,assessing endothelial function, intracellular ROS levels, andmitochondrial membrane potential. Furthermore, the studyelucidated antioxidation-related signaling mechanisms withinEndMT-induced ECs. In vivo, the therapeutic potential ofdecursin was investigated using a mouse model of MI. Decursinadministration attenuated the EndMT process by upregulatingCD31 and VE-Cadherin while decreasing fibronectinand α-SMA expression in EndMT-induced ECs. It also loweredROS levels, preserved mitochondrial membrane potential, andmodulated functional properties, resulting in enhanced LDLuptake and diminished endothelial permeability. Endothelialintegrity was sustained via regulation of the PI3K/AKT/NF-κBand Smad-dependent signaling pathways, both responsive tooxidative stress during EndMT. In the MI mouse model,decursin reversed EndMT, lessened myocardial fibrosis and apoptosis, and promoted recovery of infarcted regions. Thetreated hearts demonstrated improved cardiovascular performance. Decursin represents a novel therapeutic strategy targetingintracellular oxidative stress induced by EndMT. By exertingantioxidant activity through the PI3K/AKT/NF-κB and Smaddependentpathways, decursin maintains endothelial function,suppresses myocardial fibrosis, and supports cardiac recoveryfollowing MI therapy.
Abstract
Endothelial cells (ECs) undergo endothelial-to-mesenchymaltransition (EndMT) during the pathophysiology of cardiovasculardiseases, a complex cellular transdifferentiation processclosely associated with increased oxidative stress under adverseconditions such as myocardial infarction (MI). Decursin, a majorconstituent of Angelica gigas Nakai, displays diverse pharmacologicalproperties. This study aimed to examine the antioxidantimpact of decursin on EndMT regulation in both in vitroand in vivo models as a potential therapeutic strategy for MI. In vitro the inhibitory effects of decursin treatment were analyzedby measuring the expression of EndMT-associated genes,assessing endothelial function, intracellular ROS levels, andmitochondrial membrane potential. Furthermore, the studyelucidated antioxidation-related signaling mechanisms withinEndMT-induced ECs. In vivo, the therapeutic potential ofdecursin was investigated using a mouse model of MI. Decursinadministration attenuated the EndMT process by upregulatingCD31 and VE-Cadherin while decreasing fibronectinand α-SMA expression in EndMT-induced ECs. It also loweredROS levels, preserved mitochondrial membrane potential, andmodulated functional properties, resulting in enhanced LDLuptake and diminished endothelial permeability. Endothelialintegrity was sustained via regulation of the PI3K/AKT/NF-κBand Smad-dependent signaling pathways, both responsive tooxidative stress during EndMT. In the MI mouse model,decursin reversed EndMT, lessened myocardial fibrosis and apoptosis, and promoted recovery of infarcted regions. Thetreated hearts demonstrated improved cardiovascular performance. Decursin represents a novel therapeutic strategy targetingintracellular oxidative stress induced by EndMT. By exertingantioxidant activity through the PI3K/AKT/NF-κB and Smaddependentpathways, decursin maintains endothelial function,suppresses myocardial fibrosis, and supports cardiac recoveryfollowing MI therapy.