BACKGROUNDRegenerative 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.PURPOSEThis 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.METHODSThe 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.RESULTSSalidroside 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.CONCLUSIONSSalidroside-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.

31 Dec 2025·Science and Technology of Advanced Materials

Poly(ARTEMA), a novel artesunate-based polymer induces ferroptosis in breast cancer cells

Article

Author: Ebara, Mitsuhiro ; Nabil, Ahmed ; Uto, Koichiro ; Ito, Natsumi

Ferroptosis, a form of non-apoptotic cell death, is emerging as a promising strategy for cancer therapy. Artesunate (ART), an extract obtained from the traditional Chinese medicine Qinghaosu, has been shown to exhibit anti-cancer activity by inducing ferroptosis in cancer cells. While previous research has focused on incorporating ART monomer into drug delivery systems for enhanced cancer targeting, this study presents 2-methacryloyloxyethyl ART polymer (poly(ARTEMA)), a novel polymer synthesized from ART for the first time. Our goal was evaluation of poly(ARTEMA) anticancer potential on breast cancer cells. First, we synthesized ARTEMA using esterification followed by its polymerization using the reversible addition-fragmentation chain transfer (RAFT) polymerization method. We evaluated its mechanism of action, focusing on two key pathways: temperature-triggered singlet oxygen generation and ferrous ions (Fe²⁺) release, both of which contribute to ferroptosis. Our results demonstrate that poly(ARTEMA) selectively generates singlet oxygen and Fe²⁺ due to the endoperoxide crosslinks, leading to cell death in breast cancer cells. We also investigated the anti-cancer potential of poly(ARTEMA) on breast cancer cells with and without a ferroptosis inhibitor. The IC₅₀ values were 125 µM for the MCF-7 cancer cell line and 300 µM for the normal MCF-10 cell line, indicating enhanced toxicity toward cancer cell lines. These findings suggested that poly(ARTEMA) induces ferroptosis in cancer cells and may serve as a promising candidate for cancer therapy with minimal cytotoxicity. To the best of our knowledge, this report may be the first that successfully synthesized poly(ARTEMA) using ART, with its anticancer potential evaluation.

01 Jul 2025·Journal of Hazardous Materials

Isobavachalcone confers protection against Cryptococcus neoformans-induced ferroptosis in Caenorhabditis elegans via lifespan extension and GSH-GPX-1 axis modulation

Article

Author: Wang, Ting ; Li, Yongdong ; Liu, Na ; Chen, Si ; Lu, Jiaxing ; Liu, Qiming ; Qian, Weidong

The recent designation of Cryptococcus neoformans as a critical-priority fungal pathogen by the World Health Organization highlights the imperative need for novel antifungal agents with distinct mechanisms of action. This study elucidates the novel ferroptotic pathway underlying C. neoformans-induced cell death in Caenorhabditis elegans and investigates the therapeutic potential of isobavachalcone (IBC) through comprehensive evaluation of core biochemical markers: total glutathione (GSH), malondialdehyde, ferrous iron content, and lipid reactive oxygen species (ROS). Integrated transcriptomic analysis via RNA-seq and subsequent RT-qPCR validation revealed critical gene expression patterns associated with antiferroptotic regulation. Our findings demonstrate that C. neoformans infection initiates ferroptosis in C. elegans through iron-dependent lipid peroxidation cascades. Remarkably, IBC administration conferred significant protection against fungal-induced ferroptosis by restoring redox homeostasis-evidenced by elevated GSH levels, attenuated ROS accumulation, and decreased ferrous iron content. Mechanistic investigations identified IBC-mediated upregulation of SKN-1 and GSH biosynthesis genes, coupled with suppression of GPX-1 activity. These coordinated effects disrupted the iron-ROS amplification loop through modulation of the GSH-GPX-1 axis, ultimately extending host lifespan in C. neoformans-challenged models. Our results position IBC as a ferroptosis inhibitor with dual antioxidant and iron-chelating properties, offering a therapeutic strategy against cryptococcal infections through targeting of evolutionary conserved cell death pathways.

100 Deals associated with Ferroptosis inhibitors (CMD)

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Indication	Highest Phase	Country/Location	Organization	Date
Alzheimer Disease	Preclinical	United States	Collaborative Medicinal Development LLC	01 Dec 2024
Huntington Disease	Preclinical	United States	Collaborative Medicinal Development LLC	01 Dec 2024
Parkinson Disease	Preclinical	United States	Collaborative Medicinal Development LLC	01 Dec 2024

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