Study on the attenuated effect of Ginkgolide B on ferroptosis in high fat diet induced nonalcoholic fatty liver disease

Yang, Yuwei; Chen, Jing; Gao, Qin; Shan, Xin; Wang, Jie; Lv, Zhiyang

doi:10.1016/j.tox.2020.152599

Cited by 75 publications

(52 citation statements)

References 37 publications

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“…Consistently, other investigations also discovered that some drugs like Ginkgolide B and dehydroabietic acid have beneficial effects on alleviating NASH severity through inhibiting ferroptosis. In these contexts, Nrf2 and GPx4 stand out as the major protective mechanisms [ 70 , 71 ]. Overall, these results implied that the regulation of ferroptosis in the context of NAFLD is an intriguing notion that deserves further investigation.…”

Section: The Involvement Of Ferroptosis In Typical Liver Diseasesmentioning

confidence: 99%

Ferroptosis in liver disease: new insights into disease mechanisms

et al. 2021

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Characterized by excessive iron accumulation and lipid peroxidation, ferroptosis is a novel form of iron-dependent cell death, which is morphologically, genetically, and biochemically distinct from other well-known cell death. In recent years, ferroptosis has been quickly gaining attention in the field of liver diseases, as the liver is predisposed to oxidative injury and generally, excessive iron accumulation is a primary characteristic of most major liver diseases. In the current review, we first delineate three cellular defense mechanisms against ferroptosis (GPx4 in the mitochondria and cytosol, FSP1 on plasma membrane, and DHODH in mitochondria), along with four canonical modulators of ferroptosis (system Xc−, nuclear factor erythroid 2-related factor 2, p53, and GTP cyclohydrolase-1). Next, we review recent progress of ferroptosis studies delineating molecular mechanisms underlying the pathophysiology of several common liver diseases including ischemia/reperfusion-related injury (IRI), nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), hemochromatosis (HH), drug-induced liver injury (DILI), and hepatocellular carcinoma (HCC). Furthermore, we also highlight both challenges and promises that emerged from recent studies that should be addressed and pursued in future investigations before ferroptosis regulation could be adopted as an effective therapeutic target in clinical practice.

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Section: The Involvement Of Ferroptosis In Typical Liver Diseasesmentioning

confidence: 99%

Ferroptosis in liver disease: new insights into disease mechanisms

et al. 2021

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“…Studies indicate that nuclear factor E2 (NRF2) is one of the most critical factors in regulating the antioxidant response. The GPX4 gene is among the genes regulated by NRF2 10,18–21 . Therefore, GPX4 is also crucial to the regulation of ferroptosis 22 .…”

Section: Introductionmentioning

confidence: 99%

“…The GPX4 gene is among the genes regulated by NRF2. 10 , 18 , 19 , 20 , 21 Therefore, GPX4 is also crucial to the regulation of ferroptosis. 22 Regarding the regulation of GPX4 to reduce the accumulation of lipid peroxidation products, this kind of programmed death has not been demonstrated in the mechanism of spinal cord injury, so we chose a commonly used antioxidant, zinc, to inhibit ferroptosis after spinal cord injury.…”

Section: Introductionmentioning

confidence: 99%

Zinc attenuates ferroptosis and promotes functional recovery in contusion spinal cord injury by activating Nrf2/GPX4 defense pathway

Ge¹,

Tian

Mao³

et al. 2021

CNS Neurosci Ther

136

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Aim Spinal cord injury (SCI) involves multiple pathological processes. Ferroptosis has been shown to play a critical role in the injury process. We wanted to explore whether zinc can inhibit ferroptosis, reduce inflammation, and then exert a neuroprotective effect. Methods The Alice method was used to establish a spinal cord injury model. The Basso Mouse Scale (BMS), Nissl staining, hematoxylin‐eosin staining, and immunofluorescence analysis were used to investigate the protective effect of zinc on neurons on spinal cord neurons and the recovery of motor function. The regulation of the nuclear factor E2/heme oxygenase‐1 (NRF2/HO‐1) pathway was assessed, the levels of essential ferroptosis proteins were measured, and the changes in mitochondria were confirmed by transmission electron microscopy and 5,5′,6,6′‐tetrachloro‐1,1′,3,3′‐tetraethyl‐imidacarbocyanine iodide (JC‐1) staining. In vitro experiments using VSC4.1 (spinal cord anterior horn motor neuroma cell line), 4‐hydroxynonenal (4HNE), reactive oxygen species (ROS), superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), lipid peroxides, and finally the levels of inflammatory factors were detected to assess the effect of zinc. Results Zinc reversed behavioral and structural changes after SCI. Zinc increased the expression of NRF2/HO‐1, thereby increasing the content of glutathione peroxidase 4 (GPX4), SOD, and GHS and reducing the levels of lipid peroxides, MDA, and ROS. Zinc also rescued injured mitochondria and effectively reduced spinal cord injury and the levels of inflammatory factors, and the NRF2 inhibitor Brusatol reversed the effects of zinc. Conclusion Zinc promoted the degradation of oxidative stress products and lipid peroxides through the NRF2/HO‐1 and GPX4 signaling pathways to inhibit ferroptosis in neurons.

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“…Nrf2 can promote the expression of downstream HO-1, GSH, and GPX4, thereby eliminating the accumulation of ROS in the liver and reducing the level of malondialdehyde (MDA) [ 79 ]. In addition, activation of the Nrf2 pathway in the obese mouse model can reduce liver lipid accumulation and significantly improve the NAFLD of the mice [ 80 ].…”

Section: Mechanism Of Ferroptosis In Nafldmentioning

confidence: 99%

Role of Ferroptosis in Non-Alcoholic Fatty Liver Disease and Its Implications for Therapeutic Strategies

Zhang

2021

Biomedicines

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Non-alcoholic fatty liver disease (NAFLD) has become the chronic liver disease with the highest incidence throughout the world, but its pathogenesis has not been fully elucidated. Ferroptosis is a novel form of programmed cell death caused by iron-dependent lipid peroxidation. Abnormal iron metabolism, lipid peroxidation, and accumulation of polyunsaturated fatty acid phospholipids (PUFA-PLs) can all trigger ferroptosis. Emerging evidence indicates that ferroptosis plays a critical role in the pathological progression of NAFLD. Because the liver is the main organ for iron storage and lipid metabolism, ferroptosis is an ideal target for liver diseases. Inhibiting ferroptosis may become a new therapeutic strategy for the treatment of NAFLD. In this article, we describe the role of ferroptosis in the progression of NAFLD and its related mechanisms. This review will highlight further directions for the treatment of NAFLD and the selection of corresponding drugs that target ferroptosis.

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Study on the attenuated effect of Ginkgolide B on ferroptosis in high fat diet induced nonalcoholic fatty liver disease

Cited by 75 publications

References 37 publications

Ferroptosis in liver disease: new insights into disease mechanisms

Ferroptosis in liver disease: new insights into disease mechanisms

Zinc attenuates ferroptosis and promotes functional recovery in contusion spinal cord injury by activating Nrf2/GPX4 defense pathway

Role of Ferroptosis in Non-Alcoholic Fatty Liver Disease and Its Implications for Therapeutic Strategies

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