Regulation of ferroptosis by bioactive phytochemicals: Implications for medical nutritional therapy

Zheng, Kai; Dong, Yun; Yang, Rong; Liang, Youfang; Wu, Haiqiang; He, Zhendan

doi:10.1016/j.phrs.2021.105580

Cited by 44 publications

(43 citation statements)

References 191 publications

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“…Increasing evidence demonstrates that natural compounds, such as saponins, flavonoids and isothiocyanates, can either induce or inhibit ferroptosis [ 159 ]. In particular, flavonoids, polyphenols and phenylpropanoids have been shown to regulate Fe 2+ metabolism, inhibit LOXs and ROS, as well as activate NRF2/GPX4 signaling to antagonize ferroptosis [ 159 ]. With the rapid growth of works on ferroptosis, the interaction between ferroptosis and natural products has been gradually established.…”

Section: Potential Therapeutic Interventionsmentioning

confidence: 99%

“…With the rapid growth of works on ferroptosis, the interaction between ferroptosis and natural products has been gradually established. The results from the studies available so far [ 159 ] clearly indicate the need to also test bioactive phytochemicals in randomized clinical trials to combat ferroptosis and, therefore, reduce multiorgan damage.…”

Section: Potential Therapeutic Interventionsmentioning

confidence: 99%

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Is Ferroptosis a Key Component of the Process Leading to Multiorgan Damage in COVID-19?

et al. 2021

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Even though COVID-19 is mostly well-known for affecting respiratory pathology, it can also result in several extrapulmonary manifestations, leading to multiorgan damage. A recent reported case of SARS-CoV-2 myocarditis with cardiogenic shock showed a signature of myocardial and kidney ferroptosis, a novel, iron-dependent programmed cell death. The term ferroptosis was coined in the last decade to describe the form of cell death induced by the small molecule erastin. As a specific inducer of ferroptosis, erastin inhibits cystine-glutamate antiporter system Xc-, blocking transportation into the cytoplasm of cystine, a precursor of glutathione (GSH) in exchange with glutamate and the consequent malfunction of GPX4. Ferroptosis is also promoted by intracellular iron overload and by the iron-dependent accumulation of polyunsaturated fatty acids (PUFA)-derived lipid peroxides. Since depletion of GSH, inactivation of GPX4, altered iron metabolism, and upregulation of PUFA peroxidation by reactive oxygen species are peculiar signs of COVID-19, there is the possibility that SARS-CoV-2 may trigger ferroptosis in the cells of multiple organs, thus contributing to multiorgan damage. Here, we review the molecular mechanisms of ferroptosis and its possible relationship with SARS-CoV-2 infection and multiorgan damage. Finally, we analyze the potential interventions that may combat ferroptosis and, therefore, reduce multiorgan damage.

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Section: Potential Therapeutic Interventionsmentioning

confidence: 99%

Section: Potential Therapeutic Interventionsmentioning

confidence: 99%

Is Ferroptosis a Key Component of the Process Leading to Multiorgan Damage in COVID-19?

et al. 2021

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“…Lipid peroxidation is a characteristic attribute of ferroptosis. ,, The levels of lipid and cytosolic ROS were measured using flow cytometry with the fluorescent probes BODIPY 581/591C11 (BODIPY-C11) and 2′,7′-dichlorodihydrofluorescein diacetate (H 2 DCFDA), respectively. As shown in Figure A and B, compound 4 dose-dependently attenuated RSL3-induced lipid and cytosolic ROS accumulation.…”

Section: Resultsmentioning

confidence: 99%

Ferroptosis Inhibitory Aromatic Abietane Diterpenoids from Ajuga decumbens and Structural Revision of Two 3,4-Epoxy Group-Containing Abietanes

Peng

Tan

et al. 2022

J. Nat. Prod.

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Two new 3,4-epoxy group-containing abietane diterpenoids (1 and 2), together with five known diterpenoids (3−7), were isolated from Ajuga decumbens. Their structures were elucidated by spectroscopic data analysis, NMR calculations, and X-ray diffraction experiments. The structures of two known abietane diterpenoids were revised based on NMR calculations and X-ray diffraction data. Notably, compound 4 specifically inhibited RSL3-induced ferroptosis with an EC 50 of 56 nM by antioxidation. Moreover, 4 significantly decreased RSL3-induced lipid and cytosolic ROS accumulation and ferroptosis marker gene PTGS2 mRNA expression. This work reports the most potent natural inhibitor against ferroptosis found so far.

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“…Moreover, medical nutritional therapy with healthy foods and their bioactive ingredients has been considered an alternative strategy for the treatment of certain chronic diseases [ 102 ]. With the rapid development of studies on ferroptosis, increasing evidence has revealed that natural products can regulate ferroptosis, and are related to cancers, Parkinson’s disease, intracerebral hemorrhage, and other diseases [ 103 , 104 , 105 , 106 ]. In terms of ferroptosis in ECs, the potential role of natural products in regulating ferroptosis-mediated diseases requires further study and may be a hot area for future research.…”

Section: Potential Ferroptosis Inhibitorsmentioning

confidence: 99%

Ferroptosis of Endothelial Cells in Vascular Diseases

et al. 2022

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Endothelial cells (ECs) line the inner surface of blood vessels and play a substantial role in vascular biology. Endothelial dysfunction (ED) is strongly correlated with the initiation and progression of many vascular diseases. Regulated cell death, such as ferroptosis, is one of the multiple mechanisms that lead to ED. Ferroptosis is an iron-dependent programmed cell death associated with various vascular diseases, such as cardiovascular, cerebrovascular, and pulmonary vascular diseases. This review summarized ferroptosis of ECs in vascular diseases and discussed potential therapeutic strategies for treating ferroptosis of ECs. In addition to lipid peroxidation inhibitors and iron chelators, a growing body of evidence showed that clinical drugs, natural products, and intervention of noncoding RNAs may also inhibit ferroptosis of ECs.

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Regulation of ferroptosis by bioactive phytochemicals: Implications for medical nutritional therapy

Cited by 44 publications

References 191 publications

Is Ferroptosis a Key Component of the Process Leading to Multiorgan Damage in COVID-19?

Is Ferroptosis a Key Component of the Process Leading to Multiorgan Damage in COVID-19?

Ferroptosis Inhibitory Aromatic Abietane Diterpenoids from Ajuga decumbens and Structural Revision of Two 3,4-Epoxy Group-Containing Abietanes

Ferroptosis of Endothelial Cells in Vascular Diseases

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