Abstract:AbstractBackgroundSpinal cord injury (SCI) causes devastating loss of function and neuronal death without effective treatment. (−)-Epigallocatechin-3-gallate (EGCG) has antioxidant properties and plays an essential role in the nervous system. However, the underlying mechanism by which EGCG promotes neuronal survival and functional recovery in complete spinal cord transection (ST) remains unclear.Method… Show more
“…We believe that EGCG is a candidate phytochemical. A large number of studies have demonstrated that EGCG could affect the expression of specific proteins and signal pathways, such as AMPK and related pathways [ 28 , 30 , [60] , [61] , [62] ], and intervene in a variety of RCD forms, such as autophagy, apoptosis, and ferroptosis [ [34] , [35] , [36] , [63] , [64] , [65] ], all of which confirm its pharmacological characteristics, multiple targets, and underlying mechanisms [ 24 , 25 ]. Our results revealed that in DIC, EGCG pretreatment effectively decreased iron accumulation, inhibited excess ROS generation and oxidative stress, and rectified abnormal lipid metabolism in vitro and in vivo, which was similar to the intervention effects of the ferroptosis inhibitor Fer-1 [ 19 , 20 ], iron chelator Dxz [ 52 , 58 ], and mitochondrial free radical scavenger MitoTEMPO [ 18 , 19 ].…”
Section: Discussionmentioning
confidence: 99%
“…Recent reports revealed that EGCG protected mouse intestinal epithelial cells and alleviated ionizing radiation-induced ferroptosis [ 34 ], iron overload and erastin-induced pancreatic cell ferroptosis [ 35 ]. Furthermore, it was found to promote PKD1 phosphorylation and inhibit ferroptosis after spinal cord injury [ 36 ]. Fig.…”
“…We believe that EGCG is a candidate phytochemical. A large number of studies have demonstrated that EGCG could affect the expression of specific proteins and signal pathways, such as AMPK and related pathways [ 28 , 30 , [60] , [61] , [62] ], and intervene in a variety of RCD forms, such as autophagy, apoptosis, and ferroptosis [ [34] , [35] , [36] , [63] , [64] , [65] ], all of which confirm its pharmacological characteristics, multiple targets, and underlying mechanisms [ 24 , 25 ]. Our results revealed that in DIC, EGCG pretreatment effectively decreased iron accumulation, inhibited excess ROS generation and oxidative stress, and rectified abnormal lipid metabolism in vitro and in vivo, which was similar to the intervention effects of the ferroptosis inhibitor Fer-1 [ 19 , 20 ], iron chelator Dxz [ 52 , 58 ], and mitochondrial free radical scavenger MitoTEMPO [ 18 , 19 ].…”
Section: Discussionmentioning
confidence: 99%
“…Recent reports revealed that EGCG protected mouse intestinal epithelial cells and alleviated ionizing radiation-induced ferroptosis [ 34 ], iron overload and erastin-induced pancreatic cell ferroptosis [ 35 ]. Furthermore, it was found to promote PKD1 phosphorylation and inhibit ferroptosis after spinal cord injury [ 36 ]. Fig.…”
“…Kose et al discovered that EGCG protected pancreatic cells against erastin-induced ferroptosis through chelating iron and preventing GSH depletion and lipid peroxidation [ 101 ]. Inhibition of ferroptosis by EGCG reduced oxidative stress and promoted recovery in spinal cord transection rats [ 108 ]. In addition, Nrf2 and its downstream targets comprising antioxidant proteins SLC7A11, HO-1 and GPX4 are essential for the radioprotective effects of EGCG in HIEC cells [ 109 ].…”
Section: Natural Bioactive Compounds As Ferroptosis Regulatorsmentioning
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.
“…In our previous study, we revealed that EGCG can exert neuroprotective roles in BPRA and SCI [ 8 , 38 ]. In the present study, we revealed that EGCG upregulated miR-137-3p, inhibited neuronal Parthanatos, and reduced oxidative stress to promote the functional recovery and alleviate ICH-induced brain injury in mice following ICH.…”
Section: Discussionmentioning
confidence: 99%
“…The ELISA was performed, as previously described [ 37 , 38 ]. The segment of perihematoma in the ipsilateral cortex was obtained.…”
Intracranial hemorrhage (ICH) causes high mortality and disability without effective treatment in the clinical setting. (−)-Epigallocatechin-3-gallate (EGCG) exerts an essential role in the central nervous system and offers a promising therapeutic agent for the treatment of oxidative damage-related diseases. MiR-137 can inhibit the oxidative stress and apoptosis to attenuate neuronal injury. However, the role of EGCG in regulating miR-137-3p and neuronal Parthanatos remains to be unclear. In the present study, we build the ICH mice model to investigate the antioxidant effects of EGCG via upregulating miR-137-3p and inhibiting neuronal Parthanatos. We revealed that EGCG upregulated miR-137-3p and inhibited neuronal Parthanatos, and promoted the functional recovery, alleviated ICH-induced brain injury, and reduced oxidative stress in mice following ICH. However, following the inhibition of miR-137-3p and activation of Parthanatos, EGCG was unable to exert neuroprotective roles. These combined results suggest that EGCG may upregulate miR-137-3p and inhibit neuronal Parthanatos to accelerate functional recovery in mice after ICH, laying the foundation for EGCG to be a novel strategy for the treatment of neuronal injuries related to Parthanatos.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
