Ferroptosis‐Inhibitory Effect and Possible Mechanisms of Ellagitannin Geraniin

Chen, Dong Feng; Li, Xican; Liu, Jie; Li, Yuling; Dai, Wanjian; Chen, Yingci; Chen, Dongfeng

doi:10.1002/open.202000255

Cited by 8 publications

(2 citation statements)

References 33 publications

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“…The reaction of 16-DOXYL-stearic acid • with 4.0 mg/mL chebulagic acid proceeded under the conditions described in a previous method [ 70 ]. Briefly, a methanol solution of the sample was mixed with a methanol/6-DOXYL-stearic acid • solution with a molar ratio of 1:2, and the resulting mixture was incubated for 24 h at room temperature in the dark.…”

Section: Methodsmentioning

confidence: 99%

Ferroptosis-Inhibitory Difference between Chebulagic Acid and Chebulinic Acid Indicates Beneficial Role of HHDP

et al. 2021

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The search for a safe and effective inhibitor of ferroptosis, a recently described cell death pathway, has attracted increasing interest from scientists. Two hydrolyzable tannins, chebulagic acid and chebulinic acid, were selected for the study. Their optimized conformations were calculated using computational chemistry at the B3LYP-D3(BJ)/6-31G and B3LYP-D3(BJ)/6-311 + G(d,p) levels. The results suggested that (1) chebulagic acid presented a chair conformation, while chebulinic acid presented a skew-boat conformation; (2) the formation of chebulagic acid requires 762.1729 kcal/mol more molecular energy than chebulinic acid; and (3) the 3,6-HHDP (hexahydroxydiphenoyl) moiety was shown to be in an (R)- absolute stereoconfiguration. Subsequently, the ferroptosis inhibition of both tannins was determined using a erastin-treated bone marrow-derived mesenchymal stem cells (bmMSCs) model and compared to that of ferrostatin-1 (Fer-1). The relative inhibitory levels decreased in the following order: Fer-1 > chebulagic acid > chebulinic acid, as also revealed by the in vitro antioxidant assays. The UHPLC–ESI-Q-TOF-MS analysis suggested that, when treated with 16-(2-(14-carboxytetradecyl)-2-ethyl-4,4-dimethyl-3-oxazolidinyloxy free radicals, Fer-1 generated dimeric products, whereas the two acids did not. In conclusion, two hydrolyzable tannins, chebulagic acid and chebulinic acid, can act as natural ferroptosis inhibitors. Their ferroptosis inhibition is mediated by regular antioxidant pathways (ROS scavenging and iron chelation), rather than the redox-based catalytic recycling pathway exhibited by Fer-1. Through antioxidant pathways, the HHDP moiety in chebulagic acid enables ferroptosis-inhibitory action of hydrolyzable tannins.

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Section: Methodsmentioning

confidence: 99%

Ferroptosis-Inhibitory Difference between Chebulagic Acid and Chebulinic Acid Indicates Beneficial Role of HHDP

et al. 2021

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“…In addition, a large number of studies have shown that PACs activate the Nrf2-HO-1 pathway and ameliorate CIRI, bringing a new direction for CIRI treatment ( Chumboatong et al, 2020 ). In 2022, Yuan et al found downregulation of oxidative stress and neuronal death after injection of the phenolic substance geraniin by the middle cerebral artery occlusion-reperfusion (MCAO/R), and OGD/R models, as well as by neurological scoring assays, CCK8 assessment, TUNEL staining, detection of cells by flow cytometry, and Western blotting assessment ( Chen et al, 2021 ). Meanwhile, they found that the infarcted portion of brain tissue upregulated ex vivo and in vivo Nrf2, HO-1 protein expression in a concentration-dependent manner in the tMCAO model ( Chumboatong et al, 2020 ).…”

Section: Small Molecule Ferroptosis Inhibitorsmentioning

confidence: 99%

Ferroptosis inhibitors: past, present and future

Zhang,

Luo,

Xiang

et al. 2024

Front. Pharmacol.

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Ferroptosis is a non-apoptotic mode of programmed cell death characterized by iron dependence and lipid peroxidation. Since the ferroptosis was proposed, researchers have revealed the mechanisms of its formation and continue to explore effective inhibitors of ferroptosis in disease. Recent studies have shown a correlation between ferroptosis and the pathological mechanisms of neurodegenerative diseases, as well as diseases involving tissue or organ damage. Acting on ferroptosis-related targets may provide new strategies for the treatment of ferroptosis-mediated diseases. This article specifically describes the metabolic pathways of ferroptosis and summarizes the reported mechanisms of action of natural and synthetic small molecule inhibitors of ferroptosis and their efficacy in disease. The paper also describes ferroptosis treatments such as gene therapy, cell therapy, and nanotechnology, and summarises the challenges encountered in the clinical translation of ferroptosis inhibitors. Finally, the relationship between ferroptosis and other modes of cell death is discussed, hopefully paving the way for future drug design and discovery.

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Natural Products in the Prevention of Degenerative Bone and Joint Diseases: Mechanisms Based on the Regulation of Ferroptosis

Gao,

Lv,

et al. 2024

Phytotherapy Research

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Degenerative bone and joint diseases (DBJDs), characterized by osteoporosis, osteoarthritis, and chronic inflammation of surrounding soft tissues, are systemic conditions primarily affecting the skeletal system. Ferroptosis, a programmed cell death pathway distinct from apoptosis, autophagy, and necroptosis. Accumulating evidence suggests that ferroptosis is intricately linked to the pathogenesis of DBJDs, and targeting its regulation could be beneficial in managing these conditions. Natural products, known for their anti‐inflammatory and antioxidant properties, have shown unique advantages in preventing DBJDs, potentially through modulating ferroptosis. This article provides an overview of the latest research on ferroptosis, with a focus on its role in the pathogenesis of DBJDs and the therapeutic potential of natural products targeting this cell death pathway, offering novel insights for the prevention and treatment of DBJDs.

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Ferroptosis‐Inhibitory Effect and Possible Mechanisms of Ellagitannin Geraniin

Cited by 8 publications

References 33 publications

Ferroptosis-Inhibitory Difference between Chebulagic Acid and Chebulinic Acid Indicates Beneficial Role of HHDP

Ferroptosis-Inhibitory Difference between Chebulagic Acid and Chebulinic Acid Indicates Beneficial Role of HHDP

Ferroptosis inhibitors: past, present and future

Natural Products in the Prevention of Degenerative Bone and Joint Diseases: Mechanisms Based on the Regulation of Ferroptosis

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