Biliverdin modulates the Nrf2/A20/eEF1A2 axis to alleviate cerebral ischemia-reperfusion injury by inhibiting pyroptosis

Bai, Wenya; Huo, Siying; Zhou, Guilin; Li, Junjie; Yang, Yuan; Shao, Jianlin

doi:10.1016/j.biopha.2023.115057

Cited by 4 publications

(3 citation statements)

References 69 publications

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“…Moreover, it also inhibits the expression of the pro-inflammatory cytokines interleukin 1β, tumor necrosis factor α, and interleukin 6 to achieve an anti-inflammatory role ( 54 ). Studies have shown that the anti-oxidative stress effect of biliverdin (cofactors and vitamins) can be accomplished by scavenging superoxide ( 55 ); meanwhile, biliverdin protects vascular tissue from vessel damage by reducing c-Jun NH2 terminal kinase activation and preventing endothelial cell apoptosis ( 56 ); additionally, it regulates the Nrf2/A20/eEF1A2 axis to suppress cellular death and thereby attenuates cerebral ischemia–reperfusion injury ( 57 ). However, the main mechanisms involved in the pathogenesis of ICH include damage to the cerebral vascular wall, vitellosis, and lipid deposition ( 4 ); in the latest study, oxidative stress erythrocyte-associated erythrocyte-brain endothelial interactions that can induce microglia activation in vivo also lead to cerebral hemorrhage ( 58 ).…”

Section: Discussionmentioning

confidence: 99%

Exploring the causal association between genetically determined circulating metabolome and hemorrhagic stroke

Wang,

Shen,

et al. 2024

Front. Nutr.

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BackgroundHemorrhagic stroke (HS), a leading cause of death and disability worldwide, has not been clarified in terms of the underlying biomolecular mechanisms of its development. Circulating metabolites have been closely associated with HS in recent years. Therefore, we explored the causal association between circulating metabolomes and HS using Mendelian randomization (MR) analysis and identified the molecular mechanisms of effects.MethodsWe assessed the causal relationship between circulating serum metabolites (CSMs) and HS using a bidirectional two-sample MR method supplemented with five ways: weighted median, MR Egger, simple mode, weighted mode, and MR-PRESSO. The Cochran Q-test, MR-Egger intercept test, and MR-PRESSO served for the sensitivity analyses. The Steiger test and reverse MR were used to estimate reverse causality. Metabolic pathway analyses were performed using MetaboAnalyst 5.0, and genetic effects were assessed by linkage disequilibrium score regression. Significant metabolites were further synthesized using meta-analysis, and we used multivariate MR to correct for common confounders.ResultsWe finally recognized four metabolites, biliverdin (OR 0.62, 95% CI 0.40–0.96, PMVMR = 0.030), linoleate (18. 2n6) (OR 0.20, 95% CI 0.08–0.54, PMVMR = 0.001),1-eicosadienoylglycerophosphocholine* (OR 2.21, 95% CI 1.02–4.76, PMVMR = 0.044),7-alpha-hydroxy-3 -oxo-4-cholestenoate (7-Hoca) (OR 0.27, 95% CI 0.09–0.77, PMVMR = 0.015) with significant causal relation to HS.ConclusionWe demonstrated significant causal associations between circulating serum metabolites and hemorrhagic stroke. Monitoring, diagnosis, and treatment of hemorrhagic stroke by serum metabolites might be a valuable approach.

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Section: Discussionmentioning

confidence: 99%

Exploring the causal association between genetically determined circulating metabolome and hemorrhagic stroke

Wang,

Shen,

et al. 2024

Front. Nutr.

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“…Biliverdin is a product of heme metabolism and has significant anti-inflammatory and antioxidant effects. Research has shown that biliverdin inhibits the NF-κB pathway through the Nrf2/ A20/eEF1A2 axis and suppresses cell apoptosis to alleviate brain ischemia-reperfusion injury (Bai et al, 2023). Additionally, biliverdin reductase, also known as biliverdin, converts biliverdin to bilirubin.…”

Section: Discussionmentioning

confidence: 99%

Causal relationship between human blood metabolites and risk of ischemic stroke: a Mendelian randomization study

He,

Xu,

Yang

et al. 2024

Front. Genet.

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Background: Ischemic stroke (IS) is a major cause of death and disability worldwide. Previous studies have reported associations between metabolic disorders and IS. However, evidence regarding the causal relationship between blood metabolites and IS lacking.Methods: A two-sample Mendelian randomization analysis (MR) was used to assess the causal relationship between 1,400 serum metabolites and IS. The inverse variance-weighted (IVW) method was employed to estimate the causal effect between exposure and outcome. Additionally, MR-Egger regression, weighted median, simple mode, and weighted mode approaches were employed as supplementary comprehensive evaluations of the causal effects between blood metabolites and IS. Tests for pleiotropy and heterogeneity were conducted.Results: After rigorous selection, 23 known and 5 unknown metabolites were identified to be associated with IS. Among the 23 known metabolites, 13 showed significant causal effects with IS based on 2 MR methods, including 5-acetylamino-6-formylamino-3-methyluracil, 1-ribosyl-imidazoleacetate, Behenoylcarnitine (C22), N-acetyltyrosine, and N-acetylputrescine to (N (1) + N (8))-acetate,these five metabolites were positively associated with increased IS risk. Xanthurenate, Glycosyl-N-tricosanoyl-sphingadienine, Orotate, Bilirubin (E,E), Bilirubin degradation product, C17H18N2O, Bilirubin (Z,Z) to androsterone glucuronide, Bilirubin (Z,Z) to etiocholanolone glucuronide, Biliverdin, and Uridine to pseudouridine ratio were associated with decreased IS risk.Conclusion: Among 1,400 blood metabolites, this study identified 23 known metabolites that are significantly associated with IS risk, with 13 being more prominent. The integration of genomics and metabolomics provides important insights for the screening and prevention of IS.

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“…We determined infarct volume using 2,3,5‐triphenyltetrazolium chloride (TTC) staining at 24 and 72 h after ischemia ( n = 10 per group per time point). The brain tissue was sectioned off into five slices of 2 mm thickness and stained with a 2% solution of TTC at 37°C for 20 min, 16 followed by fixation with 4% paraformaldehyde. We photographed the brain sections stained by TTC and analyzed the digital images using an image analysis software (Image‐Pro Plus 5.1; Media Cybernetics, Inc.).…”

Section: Methodsmentioning

confidence: 99%

Neuroprotective mechanism of salvianolic acid B against cerebral ischemia–reperfusion injury in mice through downregulation of TLR4, p‐p38MAPK, p‐JNK, NF‐κB, and IL‐1β

Zheng,

Zhang,

Dong

et al. 2023

Immunity Inflam & Disease

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ObjectiveTissue injury and inflammation are two potential outcomes of cerebral ischemia–reperfusion (I/R) injury. Salvianolic acid B (Sal B), isolated from the roots of Salvia miltiorrhiza, is one of the major water‐soluble compounds with a wide range of pharmacological effects including antioxidant, anti‐inflammatory, antiproliferative, and neuroprotective effects. In the present study, we explored the neuroprotective effects and potential mechanisms of Sal B after I/R injury.MethodsWe induced cerebral ischemia in male CD‐1 mice through transient (60 min) middle cerebral artery occlusion (tMCAO), and then injected Sal B (30 mg/kg) intraperitoneally. Neurological deficits, infarct volumes, and brain edema were assessed at 24 and 72 h after tMCAO. We detected the expression of Toll‐like receptor 4 (TLR4), phosphorylated‐p38 mitogen‐activated protein kinase (P‐p38 MAPK), phosphorylated c‐Jun amino (N)‐terminal kinases (p‐JNK), nuclear factor‐κB (NF‐κB), and interleukin‐1β (IL‐1β) in the brain tissue.ResultsCompared with the tMCAO group, Sal B significantly improved neurological deficits, reduced infarct size, attenuated cerebral edema, and downregulated the expression of pro‐inflammatory mediators TLR4, p‐p38MAPK, p‐JNK, nuclear NF‐κB, and IL‐1β in brain tissue after I/R injury.ConclusionWe found that Sal B protects brain tissues from I/R injury by activating its anti‐inflammatory properties.

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Biliverdin modulates the Nrf2/A20/eEF1A2 axis to alleviate cerebral ischemia-reperfusion injury by inhibiting pyroptosis

Cited by 4 publications

References 69 publications

Exploring the causal association between genetically determined circulating metabolome and hemorrhagic stroke

Exploring the causal association between genetically determined circulating metabolome and hemorrhagic stroke

Causal relationship between human blood metabolites and risk of ischemic stroke: a Mendelian randomization study

Neuroprotective mechanism of salvianolic acid B against cerebral ischemia–reperfusion injury in mice through downregulation of TLR4, p‐p38MAPK, p‐JNK, NF‐κB, and IL‐1β

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