Effect of arctigenin on hypoxia-induced apoptosis of preeclampsia trophoblast cells by regulating the ERK/MAPK signaling pathway

WANG Dan; GAO Yuxia; LIU Hongqiao

doi:10.3969/j.issn.1002-7386.2025.11.005

Abstract：Objective To investigate the effect of arctigenin(ARC)on hypoxia-induced apoptosis of preeclampsia(PE)trophoblast cells by regulating the extracellular regulated protein kinase(ERK)/mitogen-activated protein kinase(MAPK)signaling pathway.Methods Hypoxia-induced HTR8/Svneo cells were treated with arctigenin(5.0-20.0mg/L).MTT assay was applied to detect cell proliferation and screen for the optimal ARC concentration.HTR8/Svneo cells without hypoxia induction were served as negative controls.Hypoxia-induced HTR8/Svneo cells were induced with blank control,low-dose,medium-dose and high-dose ARC,and high-dose ARC plus ERK inhibitor U0126.Cell apoptosis,invasion,and cell cycle were measured.Protein expressions of Bcl-2 associated X-protein(Bax),matrix metalloproteinase-9(MMP-9),E-Cadherin,N-Cadherin,and proteins in the ERK/MAPK pathway were detected.Results Treatment of ARC at the concentration of 5.0-20mg/L was able to promote hypoxia-induced proliferation of HTR8/Svneo cells.The concentrations of ARC at 5.0mg/L,10.0mg/L,and 20.0mg/L were selected as the subsequent experimental concentrations.Compared with the negative control,hypoxia-induced HTR8/Svneo cells had significantly lower invasive cell number,number of cells arrested in the S phase,protein levels of MMP-9 and N-Cadherin,p-ERK/ERK and p-MAPK/MAPK,but higher apoptotic rate,number of cells arrested in the G1 phase and protein levels of Bax and E-Cadherin(P＜0.05).Low-dose,medium-dose and high-dose ARC significantly increased invasive cell number,number of cells arrested in the S phase,protein levels of MMP-9 and N-Cadherin,p-ERK/ERK and p-MAPK/MAPK,but decreased apoptotic rate,number of cells arrested in the G1 phase and protein levels of Bax and E-Cadherin in hypoxia-induced HTR8/Svneo cells(P＜0.05).Compared with hypoxia-induced HTR8/Svneo cells treated with high-dose ARC,those treated with high-dose ARC plus U0126 had significantly lower invasive cell number,number of cells arrested in the S phase,protein levels of MMP-9 and N-Cadherin,p-ERK/ERK and p-MAPK/MAPK,but higher apoptotic rate,number of cells arrested in the G1 phase and protein levels of Bax and E-Cadherin(P＜0.05).Conclusion Arctigenin inhibits hypoxia-induced apoptosis of preeclampsia trophoblast cells,and promotes invasion by activating the ERK/MAPK signaling pathway.