The Regulatory Effects and the Signaling Pathways of Natural Bioactive Compounds on Ferroptosis

Natural bioactive compounds abundantly presented in foods and medicinal plants have recently received a remarkable attention because of their various biological activities and minimal toxicity. In recent years, many natural compounds appear to offer significant effects in the regulation of ferroptosis. Ferroptosis is the forefront of international scientific research which has been exponential growth since the term was coined. This type of regulated cell death is driven by iron-dependent phospholipid peroxidation. Recent studies have shown that numerous organ injuries and pathophysiological processes of many diseases are driven by ferroptosis, such as cancer, arteriosclerosis, neurodegenerative disease, diabetes, ischemia-reperfusion injury and acute renal failure. It is reported that the initiation and inhibition of ferroptosis plays a pivotal role in lipid peroxidation, organ damage, neurodegeneration and cancer growth and progression. Recently, many natural phytochemicals extracted from edible plants have been demonstrated to be novel ferroptosis regulators and have the potential to treat ferroptosis-related diseases. This review provides an updated overview on the role of natural bioactive compounds and the potential signaling pathways in the regulation of ferroptosis.

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The Role of 5-Lipoxygenase and Leukotrienes in Shock and Ischemia-Reperfusion Injury

The Scientific World JOURNAL ◽

10.1100/tsw.2007.34 ◽

2007 ◽

Vol 7 ◽

pp. 56-74 ◽

Cited By ~ 5

Author(s):

Antonietta Rossi ◽

Carlo Pergola ◽

Salvatore Cuzzocrea ◽

Lidia Sautebin

Keyword(s):

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Biological Activities ◽

Ischemia Reperfusion ◽

Targeted Disruption ◽

Pathological Conditions ◽

Metabolic Products ◽

Important Regulator ◽

Multicellular Organisms

The leukotrienes (LTs) are metabolic products of arachidonic acid via the 5-lipoxygenase (5-LO) pathway. The biological activities of LTs suggest that they are mediators of acute inflammatory and immediate hypersensitivity responses. In particular, the 5-LO activation has been proposed to be an important regulator for pathogenesis in multicellular organisms. The role of LTs in tissue damage, associated with septic and nonseptic shock and ischemia-reperfusion, has been extensively studied by the use of 5-LO inhibitors, receptor antagonists, and mice with a targeted disruption of the 5-LO gene (5-LOKO). In particular, several data indicate that LTs regulate neutrophil trafficking in damaged tissue in shock and ischemia-reperfusion, mainly through the modulation of adhesion molecule expression. This concept may provide new insights into the interpretation of the protective effect of 5-LO inhibition, which may be useful in the therapy of pathological conditions associated with septic and nonseptic shock and ischemia-reperfusion injury.

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Role of carvacrol in cardioprotection against myocardial ischemia/reperfusion injury in rats through activation of MAPK/ERK and Akt/eNOS signaling pathways

European Journal of Pharmacology ◽

10.1016/j.ejphar.2016.11.053 ◽

2017 ◽

Vol 796 ◽

pp. 90-100 ◽

Cited By ~ 28

Author(s):

Yunping Chen ◽

Lina Ba ◽

Wei Huang ◽

Yan Liu ◽

Hao Pan ◽

...

Keyword(s):

Myocardial Ischemia ◽

Reperfusion Injury ◽

Signaling Pathways ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Myocardial Ischemia Reperfusion Injury ◽

Myocardial Ischemia Reperfusion

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Vitamin C to Improve Organ Dysfunction in Cardiac Surgery Patients—Review and Pragmatic Approach

Nutrients ◽

10.3390/nu10080974 ◽

2018 ◽

Vol 10 (8) ◽

pp. 974 ◽

Cited By ~ 17

Author(s):

Aileen Hill ◽

Sebastian Wendt ◽

Carina Benstoem ◽

Christina Neubauer ◽

Patrick Meybohm ◽

...

Keyword(s):

Cardiac Surgery ◽

Vitamin C ◽

Acute Stress ◽

Ischemia Reperfusion Injury ◽

Current Knowledge ◽

Ischemia Reperfusion ◽

Organ Damage ◽

Current Evidence ◽

Organ Systems

The pleiotropic biochemical and antioxidant functions of vitamin C have sparked recent interest in its application in intensive care. Vitamin C protects important organ systems (cardiovascular, neurologic and renal systems) during inflammation and oxidative stress. It also influences coagulation and inflammation; its application might prevent organ damage. The current evidence of vitamin C’s effect on pathophysiological reactions during various acute stress events (such as sepsis, shock, trauma, burn and ischemia-reperfusion injury) questions whether the application of vitamin C might be especially beneficial for cardiac surgery patients who are routinely exposed to ischemia/reperfusion and subsequent inflammation, systematically affecting different organ systems. This review covers current knowledge about the role of vitamin C in cardiac surgery patients with focus on its influence on organ dysfunctions. The relationships between vitamin C and clinical health outcomes are reviewed with special emphasis on its application in cardiac surgery. Additionally, this review pragmatically discusses evidence on the administration of vitamin C in every day clinical practice, tackling the issues of safety, monitoring, dosage, and appropriate application strategy.

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Emerging Role of Ferroptosis in the Pathogenesis of Ischemic Stroke: A New Therapeutic Target?

ASN NEURO ◽

10.1177/17590914211037505 ◽

2021 ◽

Vol 13 ◽

pp. 175909142110375

Author(s):

Zhong-Qi Bu ◽

Hai-Yang Yu ◽

Jue Wang ◽

Xin He ◽

Yue-Ran Cui ◽

...

Keyword(s):

Ischemic Stroke ◽

Molecular Mechanisms ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

High Morbidity ◽

Treatment And Prevention ◽

Regulated Cell Death ◽

Programmed Death ◽

Research Findings

Ischemic stroke is one of the main causes of high morbidity, mortality, and disability worldwide; however, the treatment methods are limited and do not always achieve satisfactory results. The pathogenesis of ischemic stroke is complex, defined by multiple mechanisms; among them, programmed death of neuronal cells plays a significant role. Ferroptosis is a novel type of regulated cell death characterized by iron redistribution or accumulation and increased lipid peroxidation in the membrane. Ferroptosis is implicated in many pathological conditions, such as cancer, neurodegenerative diseases, and ischemia-reperfusion injury. In this review, we summarize current research findings on ferroptosis, including possible molecular mechanisms and therapeutic applications of ferroptosis regulators, with a focus on the involvement of ferroptosis in the pathogenesis and treatment of ischemic stroke. Understanding the role of ferroptosis in ischemic stroke will throw some light on the development of methods for diagnosis, treatment, and prevention of this devastating disease.

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Thromboinflammatory Functions of Platelets in Ischemia–Reperfusion Injury and Its Dysregulation in Diabetes

Seminars in Thrombosis and Hemostasis ◽

10.1055/s-0037-1613694 ◽

2018 ◽

Vol 44 (02) ◽

pp. 102-113 ◽

Cited By ~ 11

Author(s):

Sophie Maiocchi ◽

Imala Alwis ◽

Mike Wu ◽

Yuping Yuan ◽

Shaun Jackson

Keyword(s):

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Microvascular Dysfunction ◽

Antiplatelet Agents ◽

Organ Damage ◽

Acute Therapy ◽

Risk Of Death ◽

Increased Risk

AbstractIschemia–reperfusion (IR) injury is a common complication of a variety of cardiovascular diseases, including ischemic stroke and myocardial infarction (MI). While timely re-establishment of blood flow in a thrombosed artery is the primary goal of acute therapy in these diseases, paradoxically, reperfusion of ischemic tissue can cause widespread microvascular dysfunction that significantly exacerbates organ damage. Reperfusion injury is associated with activation of the humoral and cellular components of the hemostatic and innate immune systems and also with excessive reactive oxygen species production, endothelial dysfunction, thrombosis, and inflammation. Platelets are critical mediators of thromboinflammation during reperfusion injury and a hyperactive platelet phenotype may contribute to an exaggerated IR injury response. This is particularly relevant to diabetes which is characteristically associated with hyperactive platelets, significantly worse IR injury, increased organ damage, and increased risk of death. However, the mechanisms underlying vulnerability to IR injury in diabetic individuals is not well defined, nor the role of “diabetic platelets” in this process. This review summarizes recent progress in understanding the role of platelets in promoting microvascular dysfunction and inflammation in the context of IR injury. Furthermore, the authors discuss aspects of the thromboinflammatory function of platelets that are dysregulated in diabetes. They conclude that diabetes likely enhances the capacity of platelets to mediate microvascular thrombosis and inflammation during IR injury, which has potentially important implications for the future design of antiplatelet agents that can reduce microvascular dysfunction and inflammation.

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The Role of the Signaling Pathways Involved in the Protective Effect of Exogenous Hydrogen Sulfide on Myocardial Ischemia-Reperfusion Injury

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.723569 ◽

2021 ◽

Vol 9 ◽

Author(s):

Shuangyu Lv ◽

Xiaotian Li ◽

Shizhen Zhao ◽

Huiyang Liu ◽

Honggang Wang

Keyword(s):

Blood Flow ◽

Hydrogen Sulfide ◽

Signaling Pathways ◽

Structural Changes ◽

Ischemia Reperfusion Injury ◽

Tissue Injury ◽

Ischemia Reperfusion ◽

Cell Swelling ◽

Signal Pathways

Ischemia/reperfusion (I/R) injury refers to the functional and structural changes in the process of blood flow recovery after ischemia. In addition to ischemia, the blood flow recovery can also lead to very harmful damage, such as the obvious cell swelling and the irreversible cell necrosis. I/R injury is related with many diseases, including myocardial I/R injury. Myocardial I/R injury refers to the aggravation of ischemic myocardial tissue injury due to sudden disorder of blood circulation. Although there are many studies on myocardial I/R injury, the exact mechanism is not fully understood. Hydrogen sulfide (H2S), like carbon monoxide and nitric oxide, is an important gas signal molecule. It plays an important role in many physiological and pathological processes. Recent studies indicate that H2S can improve myocardial I/R injury, however, its mechanism is not fully understood, especially the involved signal pathways. In this review, we summarize the related researches about the role of the signaling pathways involved in the protective effects of exogenous H2S on myocardial I/R injury, so as to provide theoretical reference for the future in-depth researches.

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