Apigenin and its octoic acid diester attenuated glycidol-induced autophagic-dependent apoptosis via inhibiting the ERK/JNK/p38 signaling pathways in human umbilical vein endothelial cells (HUVECs)

Yue Zhao; Qingqing Jiang; Limin Guo; Daming Fan; Mingfu Wang; Yueliang Zhao

doi:10.1016/j.crfs.2023.100447

Apigenin and its octoic acid diester attenuated glycidol-induced autophagic-dependent apoptosis via inhibiting the ERK/JNK/p38 signaling pathways in human umbilical vein endothelial cells (HUVECs)

Curr Res Food Sci. 2023 Jan 16:6:100447. doi: 10.1016/j.crfs.2023.100447. eCollection 2023.

Authors

Yue Zhao^{1

2}, Qingqing Jiang^{1

2}, Limin Guo³, Daming Fan⁴, Mingfu Wang⁵, Yueliang Zhao^{1

2}

Affiliations

¹ College of Food Science and Technology, Shanghai Ocean University, Shanghai, 201306, China.
² Laboratory of Quality and Safety Risk Assessment for Aquatic Products on Storage and Preservation (Shanghai), Ministry of Agriculture, Shanghai, 201306, China.
³ Institute of Agro-Products Storage and Processing, Xinjiang Academy of Agricultural Sciences, Urumqi, 830091, China.
⁴ School of Food Science and Technology, Jiangnan University, Wuxi, China.
⁵ Institute for Advanced Study, Shenzhen University, Shenzhen, China.

Abstract

Glycidol is a well-known food contaminant mainly formed in refined edible oils and various thermally processed foods. Here, we studied the toxicity effects and related mechanism of glycidol on Human umbilical vein endothelial cells (HUVECs). Glycidol was found to induce Gap period 2 (G2)/Mitosis (M) phase cell cycle arrest, apoptosis, and autophagy in HUVECs. Inhibition of autophagy by 3-methyladenine (3-MA) attenuated glycidol-induced cell death, suggesting that glycidol-induced apoptosis was autophagy-dependent. Moreover, glycidol treatment induced phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal protein kinase (JNK), and p38. Inhibition of ERK, JNK, and p38 phosphorylation by the inhibitors U0126, SP600125, and SB203580 attenuated glycidol-induced autophagy and prevented glycidol-mediated reduction in cell viability, demonstrating that glycidol inhibited HUVECs growth by inducing autophagic-dependent apoptosis through activation of the ERK, JNK and p38 signaling pathways. In addition, apigenin (API) and its octoic acid diester apigenin-7 (API-C8), 4'-O-dioctanoate were found to significantly attenuate glycidol-induced cell growth inhibition by inhibiting the above signaling pathways. Collectively, glycidol induces autophagic-dependent apoptosis via activating the ERK/JNK/p38 signaling pathways in HUVECs and API-C8 could attenuate the toxicity effects.

Keywords: Apigenin; Apoptosis; Autophagy; Glycidol; MAPK signaling Pathway; Mitogen-activated protein kinase (MAPK).