Arctigenin attenuates ischemic stroke via SIRT1-dependent inhibition of NLRP3 inflammasome

Zhang, Shimeng; Jiang, Liangjun; Che, Fengyuan; Lu, Yucheng; Xie, Zhongxiang; Wang, Hao

doi:10.1016/j.bbrc.2017.08.062

Cited by 64 publications

(49 citation statements)

References 30 publications

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“…Accumulating scientific evidence suggests that neuroinflammation and oxidative stress are the main pathological processes responsible for the impairment of neurological function in MCAO [26,29,44,45]. Clinically, Eze, a NPC1L1 inhibitor, is mainly used as a treatment for hypercholesterolemia; however, in addition to its lipid-lowering activity, several studies have reported that Eze may attenuate ischemic-related oxidative stress and inflammation [14,19].…”

Section: Discussionmentioning

confidence: 99%

Ezetimibe Attenuates Oxidative Stress and Neuroinflammation via the AMPK/Nrf2/TXNIP Pathway after MCAO in Rats

Wang

Matei

et al. 2020

Oxidative Medicine and Cellular Longevity

114

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Oxidative stress and neuroinflammation play essential roles in ischemic stroke-induced brain injury. Previous studies have reported that Ezetimibe (Eze) exerts antioxidative stress and anti-inflammatory properties in hepatocytes. In the present study, we investigated the effects of Eze on oxidative stress and neuroinflammation in a rat middle cerebral artery occlusion (MCAO) model. One hundred and ninety-eight male Sprague-Dawley rats were used. Animals assigned to MCAO were given either Eze or its control. To explore the downstream signaling of Eze, the following interventions were given: AMPK inhibitor dorsomorphin and nuclear factor erythroid 2-related factor 2 (Nrf2) siRNA. Intranasal administration of Eze, 1 h post-MCAO, further increased the endogenous p-AMPK expression, reducing brain infarction, neurologic deficits, neutrophil infiltration, microglia/macrophage activation, number of dihydroethidium- (DHE-) positive cells, and malonaldehyde (MDA) levels. Specifically, treatment with Eze increased the expression of p-AMPK, Nrf2, and HO-1; Romo-1, thioredoxin-interacting protein (TXNIP), NOD-like receptor protein 3 (NLRP3), Cleaved Caspase-1, and IL-1β were reduced. Dorsomorphin and Nrf2 siRNA reversed the protective effects of Eze. In summary, Eze decreases oxidative stress and subsequent neuroinflammation via activation of the AMPK/Nrf2/TXNIP pathway after MCAO in rats. Therefore, Eze may be a potential therapeutic approach for ischemic stroke patients.

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Section: Discussionmentioning

confidence: 99%

Ezetimibe Attenuates Oxidative Stress and Neuroinflammation via the AMPK/Nrf2/TXNIP Pathway after MCAO in Rats

Wang

Matei

et al. 2020

Oxidative Medicine and Cellular Longevity

114

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“…An important inflammatory pathway involved in ischemia/reperfusion injury is NLRP3 activation by mitochondria-derived ROS, with production of IL-1β [44]. Sulfide decreases NF-κB translocation [45], preventing NLRP3 activation and cytokine production.…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective effects of ammonium tetrathiomolybdate, a slow-release sulfide donor, in a rodent model of regional stroke

Mendonça¹,

Cardoso²,

Michels³

et al. 2020

ICMx

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Background: Several therapeutic strategies to rescue the brain from ischemic injury have improved outcomes after stroke; however, there is no treatment as yet for reperfusion injury, the secondary damage caused by necessary revascularization. Recently we characterized ammonium tetrathiomolybdate (ATTM), a drug used as a copper chelator over many decades in humans, as a new class of sulfide donor that shows efficacy in preclinical injury models. We hypothesized that ATTM could confer neuroprotection in a relevant rodent model of regional stroke.Methods and results: Brain ischemia was induced by transient (90-min) middle cerebral artery occlusion (tMCAO) in anesthetized Wistar rats. To mimic a clinical scenario, ATTM (or saline) was administered intravenously just prior to reperfusion. At 24 h or 7 days post-reperfusion, rats were assessed using functional (rotarod test, spontaneous locomotor activity), histological (infarct size), and molecular (antioxidant enzyme capacity, oxidative damage, and inflammation) outcome measurements. ATTM-treated animals showed improved functional activity at both 24 h and 7-days post-reperfusion, in parallel with a significant reduction in infarct size. These effects were additionally associated with increased brain antioxidant enzyme capacity, decreased oxidative damage, and a late (7-day) effect on proinflammatory cytokine levels and nitric oxide products.Conclusion: ATTM confers significant neuroprotection that, along with its known safety profile in humans, provides encouragement for its development as a novel adjunct therapy for revascularization following stroke.

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“…The studies reported that the activation of the NLRP3 inflammasome leads to the development and release of inflammatory cytokines IL-1b and IL-18, suggesting the role for the NLRP3 inflammasome in the initiation and development of cerebral ischemia (Rathinam et al, 2012;Gao et al, 2017). Accumulating amounts of evidence have indicated that NLRP3 inflammasome activation was closely related with postischemic inflammation after stroke, which was critical in neuronal cell death in ischemic stroke (Zhang et al, 2017;Alishahi et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective Effects of Qingnao Dripping Pills Against Cerebral Ischemia via Inhibiting NLRP3 Inflammasome Signaling Pathway: In Vivo and In Vitro

Zhang

Zeng

et al. 2020

Front. Pharmacol.

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Arctigenin attenuates ischemic stroke via SIRT1-dependent inhibition of NLRP3 inflammasome

Cited by 64 publications

References 30 publications

Ezetimibe Attenuates Oxidative Stress and Neuroinflammation via the AMPK/Nrf2/TXNIP Pathway after MCAO in Rats

Ezetimibe Attenuates Oxidative Stress and Neuroinflammation via the AMPK/Nrf2/TXNIP Pathway after MCAO in Rats

Neuroprotective effects of ammonium tetrathiomolybdate, a slow-release sulfide donor, in a rodent model of regional stroke

Neuroprotective Effects of Qingnao Dripping Pills Against Cerebral Ischemia via Inhibiting NLRP3 Inflammasome Signaling Pathway: In Vivo and In Vitro

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