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

IF 5.2 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Redox Report Pub Date : 2025-12-01 Epub Date: 2025-01-28 DOI:10.1080/13510002.2025.2455914

Lixuan Chen, Yingnan Wu, Tiying Lv, Rui Tuo, Yang Xiao

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引用次数: 0

Abstract

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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红萝卜苷增强间充质干细胞通过Keap1/Nrf2/GPX4信号抑制铁凋亡并改善卵巢早衰

背景：再生医学研究表明，间充质干细胞（MSCs）可能是治疗卵巢早衰（POI）的有效方法。然而，MSCs的疗效仍然有限。目的：本研究旨在解释红景天苷与MSCs联合是否为POI的治疗策略，并探索红景天苷增强的MSCs通过Keap1/Nrf2/GPX4信号通路抑制铁ptosis。方法：分析红景天苷和间充质干细胞对卵巢颗粒细胞（GCs）的影响。治疗后，测定大鼠激素水平和生育能力。检测脂质过氧化水平、铁沉积和线粒体形态。检测Keap1/Nrf2/GPX4信号通路的基因和蛋白。结果：红景天苷和间充质干细胞通过减少过氧化作用和细胞内亚铁抑制GCs细胞死亡。红景天苷促进卵巢间充质干细胞增殖，支持细胞存活。红红草苷联合MSCs治疗可恢复卵巢功能，优于MSCs单药治疗。红景天苷增强MSCs抑制铁下垂。结果显示Keap1/Nrf2/GPX4信号被激活，抗铁下垂分子增加。结论：红柳苷增强MSCs可作为铁下垂抑制剂，为POI提供新的治疗策略。MSCs的可能机制与通过Keap1/Nrf2/GPX4信号通路维持氧化还原稳态有关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Redox Report 生物-生化与分子生物学

CiteScore

6.10

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： Redox Report is a multidisciplinary peer-reviewed open access journal focusing on the role of free radicals, oxidative stress, activated oxygen, perioxidative and redox processes, primarily in the human environment and human pathology. Relevant papers on the animal and plant environment, biology and pathology will also be included. While emphasis is placed upon methodological and intellectual advances underpinned by new data, the journal offers scope for review, hypotheses, critiques and other forms of discussion.