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. 2025 Jun;105(6):e70104.
doi: 10.1111/cbdd.70104.

Erianin Protects Human Umbilical Vein Endothelial Cells From Oxidized Low-Density Lipoprotein-Induced Apoptosis and Oxidative Stress Through Activation of Nuclear Factor E2-Related Factor 2 Signaling

Zhaowei Wang  1 , Linru Wang  1 , Yuanyuan Wang  1 , Juanzi Zhang  1
Affiliations

Erianin Protects Human Umbilical Vein Endothelial Cells From Oxidized Low-Density Lipoprotein-Induced Apoptosis and Oxidative Stress Through Activation of Nuclear Factor E2-Related Factor 2 Signaling

Zhaowei Wang et al. Chem Biol Drug Des. 2025 Jun.

Abstract

Oxidized low-density lipoprotein (ox-LDL)-induced endothelial cell damage plays an important role in the pathogenesis of atherosclerosis (AS). This study aimed to investigate the ability of Erianin to protect human umbilical vein endothelial cells (HUVECs) against ox-LDL-induced oxidative stress and its underlying mechanisms. HUVECs were treated with Erianin (0, 5, 10, and 20 μM) for 2 h and then stimulated with ox-LDL (100 μg/mL) for 24 h. Flow cytometry and MTT assay determined cell apoptosis and viability, respectively. The protein levels of caspase-9, caspase-3, cleaved poly (ADP-ribose) polymerase-1 (PARP-1), nuclear factor E2-related factor 2 (Nrf2), histone H3, NAD(P)H: quinone oxidoreductase-1 (NQO-1), heme oxygenase-1 (HO-1), cytochrome c, and cytochrome c oxidase subunit IV (COX IV) were evaluated by Western blot. Matrix metalloproteinase (MMP) membrane potential was measured. The impact of Erianin on ox-LDL-induced injury in HUVECs was confirmed by using small interfering RNA si-Nrf-2. Erianin pretreatment notably rescued the impaired ox-LDL-treated HUVEC viability and apoptosis and inhibited ox-LDL-induced mitochondrial dysfunction in HUVECs. Furthermore, Erianin reduced ox-LDL-induced oxidative stress by enhancing Nrf2 signaling activation, and Nrf2 knockdown by siRNAs diminished the anti-oxidative role of Erianin in HUVECs. These suggest that Erianin suppresses ox-LDL-induced apoptosis and oxidative stress by regulating Nrf2 signaling in HUVECs.

Keywords: HUVECs; Nrf2; atherosclerosis; erianin; oxidative stress; ox‐LDL.

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