L-(+)-Ergothioneine ameliorates preeclampsia-associated vascular endothelial dysfunction by modulating the Nrf2-PPARγ-sFlt-1 axis
- 1Obstetrics Department, Affiliated Hospital Group of Guangdong Medical University Panyu He Xian Memorial Hospital/Panyu Women and Children’s Medical Center, Guangdong Medical University (Guangzhou Panyu District Maternal and Child Health Hospital), Guangzhou, Guangdong, China
- 2Department of Biochemistry and Molecular Biology, School of Basic Medicine, Guangdong Medical University, Zhanjiang, Guangdong, China
Abstract
Background: Preeclampsia (PE) is a serious complication of pregnancy, with vascular endothelial dysfunction being a core pathological feature. This study aimed to investigate whether L-(+)-ergothioneine (LET) ameliorates PE-associated endothelial dysfunction by regulating the Nrf2-PPARγ-sFlt-1 axis. Methods: A LPS-induced trophoblast dysfunction model was established using lipopolysaccharide (LPS)-induced human trophoblast cells (HTR8/SVneo). Techniques including CCK-8 assay, flow cytometry, wound healing assay, ELISA, qPCR, Western blot, and immunofluorescence were employed to assess the effects of LET on cell viability, apoptosis, invasion, inflammatory cytokine levels, and the expression of key molecules in the signaling pathway. Results: LET significantly increased the viability of LPS-induced trophoblasts, promoted migration, inhibited apoptosis, and downregulated pro-inflammatory cytokines (IL-6, TNF-α, IFN-γ) and endothelial dysfunction markers (sFlt-1, ET-1, PAI-1), while upregulating the anti-inflammatory cytokine IL-4 and plasminogen activators (tPA, uPA). Mechanistically, LET inhibited Nrf2 nuclear translocation and promoted PPARγ expression, consequently reducing sFlt-1 levels. The protective effects of LET were mimicked by the PPARγ activator pioglitazone and reversed by the inhibitor FX-909. Furthermore, the supernatant from LET-treated trophoblasts promoted the viability and invasion of human umbilical vein endothelial cells (HUVECs). Conclusions: L-(+)-Ergothioneine improves trophoblast function and indirectly promotes endothelial recovery by modulating the Nrf2-PPARγ-sFlt-1 axis, suggesting a potential therapeutic target for preeclampsia.
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BibTeX
@article{gong2026lergothioneine,
title = {{L-(+)-Ergothioneine ameliorates preeclampsia-associated vascular endothelial dysfunction by modulating the Nrf2-PPARγ-sFlt-1 axis}},
author = {Jingjin Gong and Yan Liu and Qingju Meng and Junwei Wu and Fang Chen and Yanwen Xu and Yanqiu Li and Qiwei Luo},
journal = {PLOS One},
year = {2026},
month = sep,
doi = {10.1371/journal.pone.0358574},
url = {https://doi.org/10.1371/journal.pone.0358574},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - L-(+)-Ergothioneine ameliorates preeclampsia-associated vascular endothelial dysfunction by modulating the Nrf2-PPARγ-sFlt-1 axis
AU - Jingjin Gong
AU - Yan Liu
AU - Qingju Meng
AU - Junwei Wu
AU - Fang Chen
AU - Yanwen Xu
AU - Yanqiu Li
AU - Qiwei Luo
PY - 2026
DA - 2026/09/18
JO - PLOS One
DO - 10.1371/journal.pone.0358574
UR - https://doi.org/10.1371/journal.pone.0358574
AB - Background: Preeclampsia (PE) is a serious complication of pregnancy, with vascular endothelial dysfunction being a core pathological feature. This study aimed to investigate whether L-(+)-ergothioneine (LET) ameliorates PE-associated endothelial dysfunction by regulating the Nrf2-PPARγ-sFlt-1 axis. Methods: A LPS-induced trophoblast dysfunction model was established using lipopolysaccharide (LPS)-induced human trophoblast cells (HTR8/SVneo). Techniques including CCK-8 assay, flow cytometry, wound healing assay, ELISA, qPCR, Western blot, and immunofluorescence were employed to assess the effects of LET on cell viability, apoptosis, invasion, inflammatory cytokine levels, and the expression of key molecules in the signaling pathway. Results: LET significantly increased the viability of LPS-induced trophoblasts, promoted migration, inhibited apoptosis, and downregulated pro-inflammatory cytokines (IL-6, TNF-α, IFN-γ) and endothelial dysfunction markers (sFlt-1, ET-1, PAI-1), while upregulating the anti-inflammatory cytokine IL-4 and plasminogen activators (tPA, uPA). Mechanistically, LET inhibited Nrf2 nuclear translocation and promoted PPARγ expression, consequently reducing sFlt-1 levels. The protective effects of LET were mimicked by the PPARγ activator pioglitazone and reversed by the inhibitor FX-909. Furthermore, the supernatant from LET-treated trophoblasts promoted the viability and invasion of human umbilical vein endothelial cells (HUVECs). Conclusions: L-(+)-Ergothioneine improves trophoblast function and indirectly promotes endothelial recovery by modulating the Nrf2-PPARγ-sFlt-1 axis, suggesting a potential therapeutic target for preeclampsia.
SN - 1932-6203
ER -