Hesperetin Alleviated Experimental Colitis via Regulating Ferroptosis and Gut Microbiota

Nutrients, Journal Year: 2024, Volume and Issue: 16(14), P. 2343 - 2343

Published: July 19, 2024

Hesperetin (HT) is a type of citrus flavonoid with various pharmacological activities, including anti-tumor, anti-inflammation, antioxidant, and neuroprotective properties. However, the role mechanism HT in ulcerative colitis (UC) have been rarely studied. Our study aimed to uncover beneficial effects its detailed UC. Experimental was induced by 2.5% dextran sodium sulfate (DSS) for seven days. ameliorated DSS-induced mice, showing marked improvement weight loss, colon length, colonic pathological severity, levels TNFα IL6 serum. A combination informatics, network pharmacology, molecular docking identified eight key targets multi-pathways influenced As highlight, experimental validation demonstrated that PTGS2, marker ferroptosis, along other indicators ferroptosis (such as ACSL4, Gpx4, lipid peroxidation), were regulated vivo vitro. Additionally, supplement increased diversity gut microbiota, decreased relative abundance Proteobacteria Gammaproteobacteria, restored bacteria (Lachnospiraceae_NK4A136_group Prevotellaceae_UCG-001). In conclusion, an effective nutritional against suppressing modulating microbiota.

Language: Английский

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Ferroptosis-related signaling pathways in cancer drug resistance

Cancer Drug Resistance, Journal Year: 2025, Volume and Issue: 8(1)

Published: Jan. 6, 2025

Ferroptosis is an iron-dependent form of programmed cell death induced by lipid peroxidation. This process regulated signaling pathways associated with redox balance, iron metabolism, and metabolism. Cancer cells' increased demand makes them especially susceptible to ferroptosis, significantly influencing cancer development, therapeutic response, metastasis. Recent findings indicate that cells can evade ferroptosis downregulating key related this process, contributing drug resistance. underscores the possibility modulating as approach counteract resistance enhance efficacy. review outlines involved in their interactions cancer-related pathways. We also highlight current understanding resistance, offering insights into how targeting provide novel approaches for drug-resistant cancers. Finally, we explore potential ferroptosis-inducing compounds examine challenges opportunities development evolving field.

Language: Английский

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Natural flavonoids from herbs and nutraceuticals as ferroptosis inhibitors in central nervous system diseases: current preclinical evidence and future perspectives

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: March 24, 2025

Flavonoids are a class of important polyphenolic compounds, renowned for their antioxidant properties. However, recent studies have uncovered an additional function these natural flavonoids: ability to inhibit ferroptosis. Ferroptosis is key mechanism driving cell death in central nervous system (CNS) diseases, including both acute injuries and chronic neurodegenerative disorders, characterized by iron overload-induced lipid peroxidation dysfunction the defense system. This review discusses therapeutic potential flavonoids from herbs nutraceuticals as ferroptosis inhibitors CNS focusing on molecular mechanisms, summarizing findings preclinical animal models, providing insights clinical translation. We specifically highlight such Baicalin, Baicalein, Chrysin, Vitexin, Galangin, Quercetin, Isoquercetin, Eriodictyol, Proanthocyanidin, (−)-epigallocatechin-3-gallate, Dihydromyricetin, Soybean Isoflavones, Calycosin, Icariside II, Safflower Yellow, which shown promising results models injuries, ischemic stroke, cerebral ischemia-reperfusion injury, intracerebral hemorrhage, subarachnoid traumatic brain spinal cord injury. Among these, Baicalin its precursor Baicalein stand out due extensive research favorable outcomes injury models. Mechanistically, not only regulate Nrf2/ARE pathway activate GPX4/GSH-related pathways but also modulate metabolism proteins, thereby alleviating overload inhibiting While show promise especially settings, further needed evaluate efficacy, safety, pharmacokinetics, blood-brain barrier penetration application.

Language: Английский

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Shikonin promotes ferroptosis though NSUN2-mediated m ⁵ C methylation modification of TFRC in acute myelocytic leukemia

Hematology, Journal Year: 2025, Volume and Issue: 30(1)

Published: April 24, 2025

Shikonin (SHK), extracted from the traditional Chinese herb Lithospermum erythrorhizon, demonstrates a wide range of pharmacological activities. This study aimed to explore role and underlying mechanisms 5-methylcytosine (m5C) RNA methyltransferase NOL1/NOP2/SUN domain (NSUN)2 in acute myelocytic leukemia (AML). To assess cell viability death, we employed Cell Counting Kit-8 propidium iodide staining. Ferroptosis-related markers were evaluated using commercial kits Western blot analysis. The m5C levels ferroptosis-associated mRNAs quantified by methylated immunoprecipitation (MeRIP)-qPCR. specific sites on transferrin receptor (TFRC) mRNA identified through dual-luciferase reporter assay, while interaction between NSUN2 TFRC was investigated (RIP). SHK vivo explored xenografted tumor model. Our findings revealed that significantly reduced induced death ferroptosis HL-60 NB4 cells. Notably, treatment led an upregulation expression. Inhibition reversed effects SHK, restoring reducing ferroptosis. Mechanistically, enhanced expression via m5C-dependent methylation. Overexpression similarly decreased increased ferroptosis, mitigated upon silencing TFRC. In vivo, effectively suppressed growth mice. summary, our demonstrated promoted AML modulating NSUN2-mediated methylation These provided novel insights into potential therapeutic strategies for AML.

Language: Английский

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Resveratrol alleviates depression-like behaviors by inhibiting ferroptosis via AKT/NRF2 pathway

Brain Research Bulletin, Journal Year: 2024, Volume and Issue: 220, P. 111136 - 111136

Published: Nov. 20, 2024

Language: Английский

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Photodynamic metabolite-powered zero-waste “ferroptosis amplifier” for enhanced hypertrophic scar therapy

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: June 13, 2024

Hypertrophic scar (HS) is a somatopsychic disease that significantly affects quality of life. 5-aminolevulinic acid (5-ALA)-mediated photodynamic therapy (PDT) shows promise for HS treatment, while challenges like poor transdermal delivery and the accumulation by-products restrict its effectiveness. Inspired by natural phenomenon whale fall brings life to thousands, this study proposes zero-waste strategy leveraging metabolite heme establish “ferroptosis amplifier”, which allows these metabolic wastes be transformed into new sources energy, thereby amplifying ferroptosis response following PDT. This achieved encapsulating 5-ALA baicalin within human H-ferritin (HFn), subsequently incorporated polyvinylpyrrolidone (PVP) microneedles (FAB@MN). The FAB@MN exhibits excellent targeting towards hypertrophic fibroblasts (HSFs) pH-responsive programmed drug release. treatment begins with release 5-ALA, converted PpIX activate Baicalin then released, directly triggers also facilitating breakdown waste Fe²⁺ CO, ferroptosis. Unlike conventional PDT only focuses on immediate effects, approach uses fuel sustained after PDT, offering path treatment.

Language: Английский

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