Scientia Sinica Vitae, Journal Year: 2024, Volume and Issue: unknown
Published: Oct. 6, 2024
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
Citations
0
International Immunopharmacology, Journal Year: 2024, Volume and Issue: 131, P. 111849 - 111849
Published: March 18, 2024
Language: Английский
Citations
3
Chinese Medical Journal, Journal Year: 2024, Volume and Issue: 137(10), P. 1237 - 1239
Published: April 9, 2024
To the Editor: Chronic obstructive pulmonary disease (COPD) is a global public health challenge without effective treatment currently available, affecting >300 million individuals worldwide. Comprehensively understanding pathogenesis of this required. Recently, ferroptosis, form cell death driven by iron-dependent lipid peroxidation, has been associated with COPD.[1] Multiple signaling pathways, such as glutathione peroxidase 4 (GPX4), ferroptosis suppressor protein 1 (FSP1), and tetrahydrobiopterin-dependent well iron metabolism, are involved in regulating ferroptosis[2,3] [Figure 1A]. Here, we provide comprehensive overview recent advances role COPD, highlighting potential therapeutic strategies targeting for treating disease.Figure 1: (A) Signaling pathways ferroptosis. (B–D) Ferroptosis BECs (B), macrophages (C), ECs (D) contributes to COPD. (E) Targeting various cells mitigate ACSL4: Acyl-CoA synthetase long-chain family member 4; ALOX15: Arachidonate 15-lipoxygenase; ALOX5: 5-lipoxygenase; BECs: Bronchial epithelial cells; COPD: disease; circSAV1: Circular RNA SAV1; DHFR: Dihydrofolate reductase; ECs: Endothelial FSP1: 1; FTH: Ferritin heavy chain; FTL: light GPX4: Glutathione GSH: Glutathione; GSS: synthetase; GSSG: Oxidized glutathione; GSR: Glutathione-disulfide HMOX-1: Heme oxygenase-1; iNOS: Inducible nitric oxide synthase; IREB2: Iron-responsive element binding 2; LOX: Lipoxygenase; LTB4: Leukotriene B4; MFG-E8: Milk fat globule-EGF factor 8; MMP9: Matrix metalloproteinase 9; MMP12: 12; NCOA4: Nuclear receptor coactivator Nrf2: erythroid 2-related PGE2: Prostaglandin E PLOO•: Lipid peroxyl radicals; PLOOH: Phospholipid hydroperoxides; PRMT7: Arginine methyltransferase 7; PTGS2: synthase PUFAs: Polyunsaturated fatty acids; PUFA-PLs: PUFA containing phospholipids; RAP1A: Ras-related 1A; SIRT3: Sirtuin 3; SLC40A1: Solute carrier 40A1; STEAP3: Six-transmembrane antigen prostate TF: Transferrin; TFRC: Transferrin receptor; TXNRD1: Thioredoxin reductase USP14: Ubiquitin-dpecific protease 14; YTHDF1: YTH N6-methyladenosine 1.Ferroptosis bronchial (BECs) Excessive deposition cigarette smoke (CS)-exposed leads increased ferritin expression. This process activates ferritinophagy mediated nuclear (NCOA4). Notably, knockdown NCOA4 mice reduces CS-induced ferroptosis.[4] In downregulated 2 (Nrf2) expression Nrf2 promoter hypermethylation. Conversely, enhances GPX4 levels, inhibits BECs, mitigates COPD.[5] Moreover, CS extract (CSE)-induced peroxidation sirtuin3 inactivation promoting inducible (iNOS) levels potentially triggering COPD.[6] globule epidermal growth 8 (MFG-E8) identified mitigator CSE-induced ubiquitin specific peptidase 14 (USP14) stabilizes MFG-E8 protein, suppressing ferroptosis.[7] m6A-modified circular SAV1 (circSAV1) forms an RNA–protein complex that promotes translation iron-responsive (IREB2) mRNA. Increased IREB2 disrupt homeostasis, resulting accumulation labile pool contributing cells. circSAV1 reversed suggesting its crucial regulatory process.[8] Overall, COPD 1B]. ferroptosis-sensitive M2-like macrophages.[9] Protein arginine 7 (PRMT7) regulated kappa B (NF-κB)/RelA activation also lung injury severity Pro-inflammatory PRMT7 stimulate arachidonate 5-lipoxygenase leukotriene B4 release, inducing acetyl coenzyme A (acyl-CoA) (ACSL4) rendering them more susceptible COPD.[1,10] M2 matrix (MMP) 9 MMP12 were observed CS-exposed co-cultured CSE-treated BECs.[11] exposure led elevated overload peroxidation-induced may contribute macrophage polarization 1C]. endothelial (ECs) interaction between exacerbating Wang Xia[12] exposed CSE homocysteine, characterized reduced FSP1 ACSL4 suggests disruption microvascular barrier Yu et al[13] discovered normal release exosomes micro (miR)-26a-5p, which can be transported into BECs. Within miR-26a-5p targets prostaglandin-endoperoxide (PTGS2) mRNA, inhibiting These findings suggest beneficial 1D]. Dihydroquercetin Nrf2-mediated inhibit COPD.[14] Curcumin attenuates inflammation BECs.[15] Scutellarein potent inhibitor through chelating Fe2+ reducing intracellular but antiferroptotic effects hindered 15-lipoxygenase overexpression.[16] addition these natural compounds, deferoxamine, ferrostatin-1, liproxstatin-1 BECs.[4,8] Sodium pyruvate GPX4/Nrf2 pathway BECs.[17] Hydrogen sulfide (H2S) peroxisome proliferator-activated receptor-γ NCOA4-mediated autophagy.[18] hydrosulfide (NaHS), H2S donor, Furthermore, gene therapy using lentiviral system (si_ACSL4) showing promise strategy COPD.[12] 1E]. study induce found M1 resistant whereas susceptible.[9] exhibited higher heme oxygenase-1 (HMOX1) than macrophages. Inhibiting HMOX1 zinc protoporphyrin (ZnPP) effectively prevented induced CSE. ZnPP, deferoxamine bronchoalveolar lavage fluid from treatments protected against COPD.[9] exacerbates dyslipidemia, atherosclerotic plaque formation, induces function decline, causes pathological damage, disrupts function, triggers fed high-fat diet. By mitigating preserving Tongxinluo prevent complicated atherosclerosis.[19] highlight approach summary, comprehensively analyze macrophages, treatment. However, several important questions remain addressed. First, future studies should use integrative omics approaches elucidate underlying mechanisms Second, further investigation required understand inhibitors on other types Finally, it determine whether occurs during entire development or mainly manifests advanced stages. Funding work was supported National Natural Science Foundation China (No. 82200084), Sichuan Province 2023NSFSC1456), Postdoctoral funded project TB2023047), Fundamental Research Funds Central Universities, University Interdisciplinary Innovation Fund 0020404153020). Conflicts interest None.
Language: Английский
Citations
3
Phytotherapy Research, Journal Year: 2024, Volume and Issue: 38(7), P. 3509 - 3524
Published: May 2, 2024
Abstract Osteoarthritis (OA), a joint disease that is associated with inflammatory processes involved in destruction. Scutellarein (Scu), component of the medicinal herbs Scutellaria barbata D. Don and Erigeron breviscapus (vant) Hand Mass , has anti‐inflammatory effects. We explored role Scu development OA underlying mechanisms. CCK‐8 assays, Calcein‐AM/PI EdU staining were used to determine chondrocyte viability after exposure. Western blot, qPCR, as well ELISA utilized measure extracellular matrix (ECM) degradation inflammation. Immunofluorescence (IF), western blot luciferase assays examine NF‐kappaB (NF‐κB) pathway. interacting proteins predicted using network pharmacology analysis molecular docking. X‐ray, H&E, Safranin O‐Fast Green(S‐O), toluidine blue, immunohistochemistry therapeutic effects destabilization medial meniscus (DMM) models. demonstrated inhibitory on ECM pro‐inflammatory factor levels chondrocytes treated IL‐1β. Mechanistically, inhibited IL‐1β‐induced activation PI3K/Akt/ NF‐κB signaling pathway cascades. Furthermore, been shown have significant binding capacities PI3K. Additionally, ameliorated progression DMM Our findings suggest may contribute amelioration by targeting PI3K/Akt/NF‐κB pathway, implying possesses promising potential for treatment OA.
Language: Английский
Citations
3
Biochemical Pharmacology, Journal Year: 2025, Volume and Issue: 237, P. 116932 - 116932
Published: April 6, 2025
Language: Английский
Citations
0
Chinese Medicine, Journal Year: 2024, Volume and Issue: 19(1)
Published: March 22, 2024
Abstract Respiratory diseases, marked by structural changes in the airways and lung tissues, can lead to reduced respiratory function and, severe cases, failure. The side effects of current treatments, such as hormone therapy, drugs, radiotherapy, highlight need for new therapeutic strategies. Traditional Chinese Medicine (TCM) offers a promising alternative, leveraging its ability target multiple pathways mechanisms. Active compounds from herbs other natural sources exhibit anti-inflammatory, antioxidant, antitumor, immunomodulatory effects, making them valuable preventing treating conditions. Ferroptosis, unique form programmed cell death (PCD) distinct apoptosis, necrosis, others, has emerged key area interest. However, comprehensive reviews on how products influence ferroptosis diseases are lacking. This review will explore potential mechanisms TCM modulating like acute injury (ALI), asthma, pulmonary fibrosis (PF), chronic obstructive disease (COPD), ischemia–reperfusion (LIRI), hypertension (PH), cancer, aiming provide insights research clinical application health.
Language: Английский
Citations
2
Journal of Ethnopharmacology, Journal Year: 2024, Volume and Issue: 336, P. 118726 - 118726
Published: Aug. 23, 2024
Language: Английский
Citations
2
Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 180, P. 117513 - 117513
Published: Sept. 27, 2024
Language: Английский
Citations
2
The Science of The Total Environment, Journal Year: 2024, Volume and Issue: 957, P. 177534 - 177534
Published: Nov. 15, 2024
Language: Английский
Citations
2
Journal of Pharmaceutical Analysis, Journal Year: 2024, Volume and Issue: 15(1), P. 101050 - 101050
Published: July 24, 2024
Ferroptosis is a form of cell death that occurs when there an excess reactive oxygen species (ROS), lipid peroxidation, and iron accumulation. The precise regulation metabolic pathways, including iron, lipid, amino acid metabolism, crucial for survival. This type death, which associated with oxidative stress, controlled by complex network signaling molecules pathways. It also implicated in various respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), Acute lung injury (ALI), cancer, fibrosis, the coronavirus 2019 (COVID-19). To combat drug resistance, it important to identify appropriate biological markers treatment targets, well intervene disorders either induce or prevent ferroptosis. focus on role ferroptosis development potential targeting prevention treatment. review explores interaction between immune inflammatory mediators diseases, aiming provide more effective strategies managing cellular disorders.
Language: Английский
Citations
1