Abstract
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.
Highlights
The term of ferroptosis was coined in 2012 to describe the type of cell death triggered by anticancer molecule erastin, which inhibited the activity of cystine-glutamate antiporter and resulted in the depletion of glutathione (GSH) and inactivation of the phospholipid peroxidase glutathione peroxidase 4 (GPX4) [4,5]
Activation of Nrf2 pathways confers resistance to GPX4 inhibitor induced ferroptosis in cancer cells [53]. These results indicate that targeting Nrf2 or its downstream targets could be a dependable approach to regulate ferroptosis
Reported that piperlongumine induced human pancreatic cancer cell line death by dramatically increasing the intracellular reactive oxygen species (ROS) level and inhibited GSH activity. This effect was inhibited by ferroptosis inhibitors and iron chelators, but not apoptosis or necrosis inhibitors, which suggested that piperlongumine could induce cell death via ferroptosis [120]
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Ferroptosis is a recently recognized mode of cell death, it plays a crucial role in many human diseases and is identified as a potential therapeutic target [6]. Ferroptosis is closely linked to multiple physiological and pathological processes in humans and animals, including cancer, arteriosclerosis, ischemiareperfusion injury, neurodegenerative diseases, and acute renal failure [7,8,9,10,11]. Based on the intensive study on ferroptosis, many clinical drugs and reagents have been demonstrated to be able to regulate ferroptosis Chemotherapeutic agents such as sulfasalazine and cisplatin, targeted agents such as sorafenib and lapatinib, and antibiotics are proven as ferroptosis-inducers [14,15,16,17]. The aim of this review was to provide the updated information on natural compounds that have promising regulatory effects on ferroptosis and their molecular targets and mechanisms
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