Mesenchymal stem cells enchanced by salidroside to inhibit ferroptosis and improve premature ovarian insufficiency via Keap1/Nrf2/GPX4 signaling

Background Regenerative medicine researches have shown that mesenchymal stem cells (MSCs) may be an effective treatment method for premature ovarian insufficiency (POI). However, the efficacy of MSCs is still limited.Purpose This study aims to explain whether salidroside and MSCs combination is a th...

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Main Authors: Lixuan Chen, Yingnan Wu, Tiying Lv, Rui Tuo, Yang Xiao
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Redox Report
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Online Access:https://www.tandfonline.com/doi/10.1080/13510002.2025.2455914
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author Lixuan Chen
Yingnan Wu
Tiying Lv
Rui Tuo
Yang Xiao
author_facet Lixuan Chen
Yingnan Wu
Tiying Lv
Rui Tuo
Yang Xiao
author_sort Lixuan Chen
collection DOAJ
description Background Regenerative medicine researches have shown that mesenchymal stem cells (MSCs) may be an effective treatment method for premature ovarian insufficiency (POI). However, the efficacy of MSCs is still limited.Purpose This study aims to explain whether salidroside and MSCs combination is a therapeutic strategy to POI and to explore salidroside-enhanced MSCs inhibiting ferroptosis via Keap1/Nrf2/GPX4 signaling.Methods The effect of salidroside and MSCs on ovarian granular cells (GCs) was analyzed. After treatment, hormone levels and -fertility of rats were measured. Lipid peroxidation levels, iron deposition and mitochondrial morphology were detected. The genes and proteins of Keap1/Nrf2/GPX4 signaling were examined.Results Salidroside and MSCs were found to inhibit cell death of GCs by reducing peroxidation and intracellular ferrous. Salidroside promotes the proliferation of MSCs and supports cell survival in ovary. Salidroside combined with MSCs therapy restored ovarian function, which was better than MSCs monotherapy. Salidroside-enhanced MSCs to inhibit ferroptosis. The results showed activation of the Keap1/Nrf2/GPX4 signaling and an increase in anti-ferroptosis molecule.Conclusions Salidroside-enhanced MSCs as a ferroptosis inhibitor and provide new therapeutic strategies for POI. The possible mechanisms of MSCs were related to maintaining redox homeostasis via a Keap1/Nrf2/GPX4 signaling.
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issn 1351-0002
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publishDate 2025-12-01
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spelling doaj-art-7f8e10796f934b2ea9320d86fc31599f2025-01-28T17:04:27ZengTaylor & Francis GroupRedox Report1351-00021743-29282025-12-0130110.1080/13510002.2025.2455914Mesenchymal stem cells enchanced by salidroside to inhibit ferroptosis and improve premature ovarian insufficiency via Keap1/Nrf2/GPX4 signalingLixuan Chen0Yingnan Wu1Tiying Lv2Rui Tuo3Yang Xiao4Department of Hematology, Shenzhen Qianhai Shekou Pilot Free Trade Zone Hospital, Shenzhen, People’s Republic of ChinaTranslational Medicine Center, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of ChinaGuangzhou University of Chinese Medicine, Guangzhou, People’s Republic of ChinaGuangzhou University of Chinese Medicine, Guangzhou, People’s Republic of ChinaDepartment of Hematology, Shenzhen Qianhai Shekou Pilot Free Trade Zone Hospital, Shenzhen, People’s Republic of ChinaBackground Regenerative medicine researches have shown that mesenchymal stem cells (MSCs) may be an effective treatment method for premature ovarian insufficiency (POI). However, the efficacy of MSCs is still limited.Purpose This study aims to explain whether salidroside and MSCs combination is a therapeutic strategy to POI and to explore salidroside-enhanced MSCs inhibiting ferroptosis via Keap1/Nrf2/GPX4 signaling.Methods The effect of salidroside and MSCs on ovarian granular cells (GCs) was analyzed. After treatment, hormone levels and -fertility of rats were measured. Lipid peroxidation levels, iron deposition and mitochondrial morphology were detected. The genes and proteins of Keap1/Nrf2/GPX4 signaling were examined.Results Salidroside and MSCs were found to inhibit cell death of GCs by reducing peroxidation and intracellular ferrous. Salidroside promotes the proliferation of MSCs and supports cell survival in ovary. Salidroside combined with MSCs therapy restored ovarian function, which was better than MSCs monotherapy. Salidroside-enhanced MSCs to inhibit ferroptosis. The results showed activation of the Keap1/Nrf2/GPX4 signaling and an increase in anti-ferroptosis molecule.Conclusions Salidroside-enhanced MSCs as a ferroptosis inhibitor and provide new therapeutic strategies for POI. The possible mechanisms of MSCs were related to maintaining redox homeostasis via a Keap1/Nrf2/GPX4 signaling.https://www.tandfonline.com/doi/10.1080/13510002.2025.2455914Salidrosidemesenchymal stem cellspremature ovarian insufficiencyferroptosisKeap1/Nrf2/GPX4 signaling‌redox homeostasis
spellingShingle Lixuan Chen
Yingnan Wu
Tiying Lv
Rui Tuo
Yang Xiao
Mesenchymal stem cells enchanced by salidroside to inhibit ferroptosis and improve premature ovarian insufficiency via Keap1/Nrf2/GPX4 signaling
Redox Report
Salidroside
mesenchymal stem cells
premature ovarian insufficiency
ferroptosis
Keap1/Nrf2/GPX4 signaling
‌redox homeostasis
title Mesenchymal stem cells enchanced by salidroside to inhibit ferroptosis and improve premature ovarian insufficiency via Keap1/Nrf2/GPX4 signaling
title_full Mesenchymal stem cells enchanced by salidroside to inhibit ferroptosis and improve premature ovarian insufficiency via Keap1/Nrf2/GPX4 signaling
title_fullStr Mesenchymal stem cells enchanced by salidroside to inhibit ferroptosis and improve premature ovarian insufficiency via Keap1/Nrf2/GPX4 signaling
title_full_unstemmed Mesenchymal stem cells enchanced by salidroside to inhibit ferroptosis and improve premature ovarian insufficiency via Keap1/Nrf2/GPX4 signaling
title_short Mesenchymal stem cells enchanced by salidroside to inhibit ferroptosis and improve premature ovarian insufficiency via Keap1/Nrf2/GPX4 signaling
title_sort mesenchymal stem cells enchanced by salidroside to inhibit ferroptosis and improve premature ovarian insufficiency via keap1 nrf2 gpx4 signaling
topic Salidroside
mesenchymal stem cells
premature ovarian insufficiency
ferroptosis
Keap1/Nrf2/GPX4 signaling
‌redox homeostasis
url https://www.tandfonline.com/doi/10.1080/13510002.2025.2455914
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