State‐of‐the‐art Nrf2 Inhibitors: Therapeutic Opportunities in Non‐cancer Diseases DOI

Emil G. Ayala‐Cosme,

Deborah J. Yang,

Kyara Vences

et al.

ChemMedChem, Journal Year: 2024, Volume and Issue: unknown

Published: July 31, 2024

Abstract Nuclear factor erythroid 2‐related (Nrf2) is a cytoprotective transcription that induces the of genes responsible for cell's response to oxidative stress. While Nrf2 activation has led development clinically relevant therapeutics, oncogenic role in proliferation cancer cells underscored complex nature and necessity inhibitors. Although application inhibitors appears limited as anticancer agents, recent studies have begun pinpoint impairment autophagy diseases cellular marker shifts from protective deleterious state. Therefore, cytoplasmic accumulation can lead lipid hydroperoxides and, ultimately, ferroptosis. However, some aimed at elucidating non‐cancer yielded conflicting results, attributed differences approaches used inhibit or activate Nrf2, well variations vitro and/or vivo disease models. Overall, these results highlight deeper evaluation Nrf2′s diseases, especially chronic diseases. In this review, we discuss where inhibition holds potential beneficial therapeutic effects summarize recently reported exploiting medicinal chemistry suitable targeting factors like Nrf2.

Language: Английский

Chronic environmental exposure to polystyrene microplastics increases the risk of nonalcoholic fatty liver disease DOI
Yujie Shi,

Runyang Hong,

Zhencheng Fan

et al.

Toxicology, Journal Year: 2025, Volume and Issue: 511, P. 154067 - 154067

Published: Jan. 25, 2025

Language: Английский

Citations

1

Zearalenone induces liver injury in mice through ferroptosis pathway DOI

Lige Bao,

Yongze Huang,

Fuhua Gu

et al.

The Science of The Total Environment, Journal Year: 2024, Volume and Issue: 952, P. 175875 - 175875

Published: Aug. 30, 2024

Language: Английский

Citations

7

Targeting non-classical autophagy-dependent ferroptosis and the subsequent HMGB1/TfR1 feedback loop accounts for alleviating solar dermatitis by Senkyunolide I DOI
Qi Wei,

Fengchun He,

Jiangyan Rao

et al.

Free Radical Biology and Medicine, Journal Year: 2024, Volume and Issue: 223, P. 263 - 280

Published: Aug. 6, 2024

Language: Английский

Citations

5

Fucoxanthin Induces Ferroptosis in Cancer Cells via Downregulation of the Nrf2/HO−1/GPX4 Pathway DOI Creative Commons

Hao-Fei Du,

Jiawei Wu,

Yu-Shan Zhu

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(12), P. 2832 - 2832

Published: June 14, 2024

This study investigated the mechanism by which fucoxanthin acts as a novel ferroptosis inducer to inhibit tongue cancer. The MTT assay was used detect inhibitory effects of on SCC-25 human squamous carcinoma cells. levels reactive oxygen species (ROS), mitochondrial membrane potential (MMP), glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), and total iron were measured. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) Western blotting assess peroxidase 4 (GPX4), nuclear factor erythroid 2-related 2 (Nrf2), Keap1, solute carrier family 7 member 11 (SLC7A11), transferrin receptor protein 1 (TFR1), p53, heme oxygenase (HO-1) expression. Molecular docking performed validate interactions. Compared with control group, activity fucoxanthin-treated cells significantly decreased in dose- time-dependent manner. MMP, GSH, SOD cells; ROS, MDA, increased. mRNA expression GPX4, Nrf2, HO-1 decreased, whereas TFR1 p53 increased, concentration-dependent analysis revealed that binding free energies SLC7A11, HO-1, below -5 kcal/mol, primarily based active site hydrogen bonding. Our findings suggest can induce cells, highlighting its treatment for

Language: Английский

Citations

4

Z-ligustilide provides a neuroprotective effect by regulating the phenotypic polarization of microglia via activating Nrf2-TrxR axis in the Parkinson's disease mouse model DOI Creative Commons
Shoujiao Peng, Yao Chen, Ran Wang

et al.

Redox Biology, Journal Year: 2024, Volume and Issue: 76, P. 103324 - 103324

Published: Aug. 23, 2024

The polarization phenotype of microglia is critical in the progression Parkinson's disease (PD). Molecules that can polarize toward M2 represent a promising class compounds for anti-PD medications. Z-ligustilide (ZLG) naturally occurring enol ester with diverse pharmacological properties, especially neuroprotection. For first time, we investigated effect ZLG on and elucidated its underlying mechanism. results primarily showed attenuated motor deficits mice prevented loss dopaminergic neurons substantia nigra. Mechanistically, alleviates oxidative stress-induced apoptosis by triggering endogenous antioxidant system. Besides, modulated phenotypic through activation Nrf2-TrxR axis, leading to towards phenotype. Taken together, our research prospective therapy candidate PD altering restoring redox equilibrium axis.

Language: Английский

Citations

4

Nrf2 Signaling Pathway Studies in Drosophila melanogaster : Parallel Roles in Human Health and Insect Environmental Responses DOI
Jing Li, Shixiang Sun, Ying Li

et al.

Xenobiotica, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 30

Published: Feb. 11, 2025

The Nrf2 signaling pathway is crucial for cellular defense against oxidative stress and xenobiotic toxicity, highlighting its importance in both human health environmental responses.

Language: Английский

Citations

0

Regulation of Ferroptosis in Cancer and Immune Cells DOI Open Access

Naeyoon Jang,

Il‐Kyu Kim,

Diana Jung

et al.

Immune Network, Journal Year: 2025, Volume and Issue: 25(1)

Published: Jan. 1, 2025

Ferroptosis, an iron-dependent form of regulated cell death, is driven by lipid peroxidation and shaped metabolic antioxidant pathways. In immune cells, ferroptosis susceptibility varies types, composition, demands, influencing responses in cancer, infections, autoimmune diseases. Therapeutically, targeting holds promise cancer immunotherapy enhancing antitumor immunity or inhibiting immunosuppressive cells. This review highlights the pathways underlying ferroptosis, its regulation dual role tumor progression immunity, context-dependent therapeutic implications for optimizing treatment.

Language: Английский

Citations

0

SR-B1 deficiency suppresses progression in acute myeloid leukemia via ferroptosis and reverses resistance to venetoclax DOI
Junfeng Shi, Yifeng Cheng, Lixue Wang

et al.

Free Radical Biology and Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

0

Therapeutic innovations: targeting ROS production in AML with natural and synthetic compounds DOI
Mohammed H. Mohammed,

Raed Fanoukh Aboqader Al-Aouadi,

Subasini Uthirapathy

et al.

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: March 31, 2025

Language: Английский

Citations

0

Polyphyllin I induces rapid ferroptosis in acute myeloid leukemia through simultaneous targeting PI3K/SREBP-1/SCD1 axis and triggering of lipid peroxidation DOI
Xinyu Zhou,

Duanna Zhang,

Jieting Lei

et al.

Journal of Natural Medicines, Journal Year: 2024, Volume and Issue: 78(3), P. 618 - 632

Published: April 26, 2024

Language: Английский

Citations

3