Quercetin Inhibits Pyroptosis in Diabetic Cardiomyopathy through the Nrf2 Pathway

Zhang, Wei; Jing, Zhou; Kang, Pan; Chao, Shi; Shaohuan, Qian

doi:10.1155/2022/9723632

Cited by 19 publications

(13 citation statements)

References 30 publications

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“…These results provide strong evidence that IL-37 inhibits macrophage ferroptosis by activating the NRF2 pathway. As a classical transcription factor, a large number of studies have reported that the transfer of NRF2 to the nucleus is the key to the biological function of NRF2 ( 18 , 28 , 44 ). It was reported that lycopene ameliorates DEHP exposure-induced renal pyroptosis through enhancing NRF2 nuclear translocation ( 45 ).…”

Section: Discussionmentioning

confidence: 99%

IL‑37 suppresses macrophage ferroptosis to attenuate diabetic atherosclerosis via the NRF2 pathway

Xia

Zhao

et al. 2023

Exp Ther Med

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IL-37 is a newly discovered inflammatory factor. However, the protective effect and underlying mechanisms of IL-37 on atherosclerosis remain unclear. In the present study, IL-37 was used for intraperitoneal injection in diabetic ApoE -/- mice caused by streptozotocin. High glucose (HG)/ox-LDL was used to stimulate THP-1 original macrophage followed by IL-37 pretreatment in vitro . The atheromatous plaque area, oxidative stress and inflammation levels in ApoE -/- mice were evaluated, and the level of macrophage ferroptosis was detected in vivo and in vitro . It was identified that IL-37 treatment significantly decreased plaque area in diabetic ApoE -/- mice. IL-37 not only improved blood lipid levels in mice, but also reduced serum levels of inflammatory factors including IL-1β and IL-18. Furthermore, IL-37 increased GPX4 and nuclear factor erythroid 2-related factor 2 (NRF2) in the aorta of diabetic mice. In vitro experiment revealed that IL-37 inhibited HG/ox-LDL-induced ferroptosis in macrophages, as evidenced by improved cell membrane oxidation, reduced malondialdehyde production and increased GPX4 expression. Moreover, it was also found that IL-37 enhanced the nuclear translocation of NRF2 in macrophages, while ML385, a specific NRF2 inhibitor, significantly attenuated the protective effect of IL-37 on macrophage ferroptosis caused by HG/ox-LDL. In conclusion, IL-37 suppressed macrophage ferroptosis to attenuate atherosclerosis progression via activating the NRF2 pathway.

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Section: Discussionmentioning

confidence: 99%

IL‑37 suppresses macrophage ferroptosis to attenuate diabetic atherosclerosis via the NRF2 pathway

Xia

Zhao

et al. 2023

Exp Ther Med

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“…Other studies have shown that Gps can improve myocardial injury and control the progression of DCM by inhibiting the activation of ROS‐induced NLRP3 inflammasome. It has been found that quercetin can reduce the levels of inflammatory cytokines in a diabetic rat model, inhibit the expression of pyroptosis proteins, increase the levels of antioxidant factors, reduce ROS accumulation, and effectively inhibit the pyroptosis process, thereby improving DCM (Z. Wei, Jing, et al, 2022). An experiment involving intervention with ginsenoside Rb1 in mice with diabetic cardiomyopathy (DCM) showed significant improvements in oxidative stress and inflammatory response in the hearts of DCM mice after ginsenoside Rb1 intervention.…”

Section: Natural Substances Treat Dcm By Targeting Different Pcdsmentioning

confidence: 99%

Targeting the programmed cell death (PCD) signaling mechanism with natural substances for the treatment of diabetic cardiomyopathy (DCM)

Xuan,

Zhang

2023

Phytotherapy Research

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Diabetic cardiomyopathy (DCM) is one of the severe complications of diabetes, characterized by structural and functional abnormalities in the hearts of diabetic patients without hypertension, coronary heart disease, or valvular heart disease. DCM can progress to heart failure, which is a significant cause of death in diabetic patients, but currently, there is no effective treatment available. Programmed cell death (PCD) is a genetically regulated form of cell death that includes apoptosis, autophagy, necroptosis, ferroptosis, and pyroptosis. PCD is essential for tissue homeostasis and normal development of the body. DCM is a complex condition, and abnormalities in the cascade of PCD signaling have been observed in its pathological process, suggesting that targeting PCD could be a potential therapeutic strategy. Studies have shown that natural substances can effectively modulate PCD to intervene in the treatment of DCM, and their use is safe. This review explores the role of different forms of PCD in the pathogenesis of DCM and summarizes the research progress in targeting PCD with natural substances to treat DCM. It can serve as a basis for further research and drug development to provide new treatment strategies for DCM patients.

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“…22 Additionally, ML385 (5 mg/mL) dissolved in DMSO was administered weekly by ip injection (20 mg/kg body weight) for 6 weeks. 23 Animals that served as controls were injected with the same volume of DMSO or normal saline alone. each of the other groups, with each group housed in separate cages.…”

Section: Establishment Of Rat Modelmentioning

confidence: 99%

“…The concentration of nigericin (an activator of NLRP3) used in the experiments was 10 μM, which has been confirmed in previous studies. 23…”

Section: Cell Line Model Of Doxorubicin-induced Cardiotoxicitymentioning

confidence: 99%

Bardoxolone methyl attenuates doxorubicin‐induced cardiotoxicity by inhibiting the TXNIP–NLRP3 pathway through Nrf2 activation

Zhang,

Shi,

Yao

et al. 2023

Environmental Toxicology

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Bardoxolone methyl, which triggers nuclear factor erythroid 2‐related factor (Nrf2), has therapeutic effects against myocardial infarction, heart failure, and other diseases. Nrf2 can inhibit the activation of the thioredoxin‐interacting protein (TXNIP)/NLR family pyrin domain‐containing protein 3 (NLRP3) pathway. Doxorubicin is an anthracycline chemotherapeutic drug associated with cardiotoxicity, limiting its clinical use. In this study, we explored the specific mechanism of the Nrf2–TXNIP–NLRP3 pathway in doxorubicin‐induced cardiotoxicity using bardoxolone methyl in animal and cell models. Using in vivo and in vitro experiments, we show that doxorubicin can induce oxidative stress and pyroptosis in the heart. Western blot and co‐immunoprecipitation experimental results found that doxorubicin can reduce the interaction between TXNIP and TRX, increase the interaction between TXNIP and NLRP3, and activate the pyroptosis process. Bardoxolone methyl reduces the accumulation of reactive oxygen species in cardiomyocytes through the Nrf2 pathway, inhibits the interaction between TXNIP and NLRP3, and alleviates the progression of myocardial damage and cardiac fibrosis. Bardoxolone methyl lost its therapeutic effect when the expression of Nrf2 was decreased. Additionally, repressing the expression of TXNIP can inhibit the activation of NLRP3 and alleviate myocardial damage caused by doxorubicin. Collectively, our findings confirm that bardoxolone methyl alleviates doxorubicin‐induced cardiotoxicity by activating Nrf2 and inhibiting the TXNIP–NLRP3 pathway.

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Quercetin Inhibits Pyroptosis in Diabetic Cardiomyopathy through the Nrf2 Pathway

Cited by 19 publications

References 30 publications

IL‑37 suppresses macrophage ferroptosis to attenuate diabetic atherosclerosis via the NRF2 pathway

IL‑37 suppresses macrophage ferroptosis to attenuate diabetic atherosclerosis via the NRF2 pathway

Targeting the programmed cell death (PCD) signaling mechanism with natural substances for the treatment of diabetic cardiomyopathy (DCM)

Bardoxolone methyl attenuates doxorubicin‐induced cardiotoxicity by inhibiting the TXNIP–NLRP3 pathway through Nrf2 activation

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