Mechanism of Baicalein in Brain Injury After Intracerebral Hemorrhage by Inhibiting the ROS/NLRP3 Inflammasome Pathway

Chen, Xuan; Zhou, Yue; Wang, Shanshan; Wang, Wei

doi:10.1007/s10753-021-01569-x

Cited by 20 publications

(12 citation statements)

References 32 publications

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“…It was reported that in intracerebral hemorrhage brain injury model, ROS was elevated, and NLRP3 inflammasome pathway was activated [47]. It also reported that ROS scavenger may inhibit NLRP3 inflammatory response and alleviate brain injury [47]. Another study proved during ischemia/reperfusion injury, mitochondria malfunction caused ROS accumulation and stimulated NLRP3 inflammasome activation [48].…”

Section: Discussionmentioning

confidence: 98%

“…Although a variety of external or host-derived stimuli, such as mitochondrial dysfunction, ion flux, and lysosomal damage are involved in the activation of NLRP3 inflammasome [43], recent studies focused on mitochondrial autophagy and subsequent oxidative stress [44][45][46]. It was reported that in intracerebral hemorrhage brain injury model, ROS was elevated, and NLRP3 inflammasome pathway was activated [47]. It also reported that ROS scavenger may inhibit NLRP3 inflammatory response and alleviate brain injury [47].…”

Section: Discussionmentioning

confidence: 99%

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The Mechanism of TNF-α-Mediated Accumulation of Phosphorylated Tau Protein and Its Modulation by Propofol in Primary Mouse Hippocampal Neurons: Role of Mitophagy, NLRP3, and p62/Keap1/Nrf2 Pathway

Zhang

Song

Ding

et al. 2022

Oxidative Medicine and Cellular Longevity

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Background. Neuroinflammation-induced phosphorylated Tau (p-Tau) deposition in central nervous system contributes to neurodegenerative disorders. Propofol possesses neuroprotective properties. We investigated its impacts on tumor necrosis factor-α (TNF-α)-mediated p-Tau deposition in neurons. Methods. Mouse hippocampal neurons were exposed to propofol followed by TNF-α. Cell viability, p-Tau, mitophagy, reactive oxygen species (ROS), NOD-like receptor protein 3 (NLRP3), antioxidant enzymes, and p62/Keap1/Nrf2 pathway were investigated. Results. TNF-α promoted p-Tau accumulation in a concentration- and time-dependent manner. TNF-α (20 ng/mL, 4 h) inhibited mitophagy while increased ROS accumulation and NLRP3 activation. It also induced glycogen synthase kinase-3β (GSK3β) while inhibited protein phosphatase 2A (PP2A) phosphorylation. All these effects were attenuated by 25 μM propofol. In addition, TNF-α-induced p-Tau accumulation was attenuated by ROS scavenger, NLRP3 inhibitor, GSK3β inhibitor, or PP2A activator. Besides, compared with control neurons, 100 μM propofol decreased p-Tau accumulation. It also decreased ROS and NLRP3 activation, modulated GSK3β/PP2A phosphorylation, leaving mitophagy unchanged. Further, 100 μM propofol induced p62 expression, reduced Keap1 expression, triggered the nuclear translocation of Nrf2, and upregulated superoxide dismutase (SOD) and heme oxygenase-1 (HO-1) expression, which was abolished by p62 knockdown, Keap1 overexpression, or Nrf2 inhibitor. Consistently, the inhibitory effect of 100 μM propofol on ROS and p-Tau accumulation was mitigated by p62 knockdown, Keap1 overexpression, or Nrf2 inhibitor. Conclusions. In hippocampal neurons, TNF-α inhibited mitophagy, caused oxidative stress and NLRP3 activation, leading to GSK3β/PP2A-dependent Tau phosphorylation. Propofol may reduce p-Tau accumulation by reversing mitophagy and oxidative stress-related events. Besides, propofol may reduce p-Tau accumulation by modulating SOD and HO-1 expression through p62/Keap1/Nrf2 pathway.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

The Mechanism of TNF-α-Mediated Accumulation of Phosphorylated Tau Protein and Its Modulation by Propofol in Primary Mouse Hippocampal Neurons: Role of Mitophagy, NLRP3, and p62/Keap1/Nrf2 Pathway

Zhang

Song

Ding

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…Furthermore, andrographolide significantly reduces the TNF-a and IL-6 levels by inhibiting the NF-kB signaling pathway (132). Other active ingredients in herbal medicine, such as verbascoside, cordycepin, and baicalein, inhibit inflammation and cell death and protect neurons following ICH by suppressing NLRP3 expression (136)(137)(138). Because of the common pharmacological actions, these drugs are likely to lessen pyroptosis after ICH.…”

Section: Direct Regulation Of Nlrp3mentioning

confidence: 99%

Perspectives on the mechanism of pyroptosis after intracerebral hemorrhage

et al. 2022

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Intracerebral hemorrhage (ICH) is a highly harmful neurological disorder with high rates of mortality, disability, and recurrence. However, effective therapies are not currently available. Secondary immune injury and cell death are the leading causes of brain injury and a poor prognosis. Pyroptosis is a recently discovered form of programmed cell death that differs from apoptosis and necrosis and is mediated by gasdermin proteins. Pyroptosis is caused by multiple pathways that eventually form pores in the cell membrane, facilitating the release of inflammatory substances and causing the cell to rupture and die. Pyroptosis occurs in neurons, glial cells, and endothelial cells after ICH. Furthermore, pyroptosis causes cell death and releases inflammatory factors such as interleukin (IL)-1β and IL-18, leading to a secondary immune-inflammatory response and further brain damage. The NOD-like receptor protein 3 (NLRP3)/caspase-1/gasdermin D (GSDMD) pathway plays the most critical role in pyroptosis after ICH. Pyroptosis can be inhibited by directly targeting NLRP3 or its upstream molecules, or directly interfering with caspase-1 expression and GSDMD formation, thus significantly improving the prognosis of ICH. The present review discusses key pathological pathways and regulatory mechanisms of pyroptosis after ICH and suggests possible intervention strategies to mitigate pyroptosis and brain dysfunction after ICH.

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“…In addition, the presence of excessive ROS will directly cause the production of acute pro-inflammatory cytokines, including tumor necrosis factor α (TNF-α) and interleukin-10 (IL-10). ROS also can cause the activation of nuclear factor-κB (NF-κB), which has a critical role in promoting the inflammatory reaction ( Ma et al, 2014 ; Chen et al, 2022 ). During ICH-induced inflammation, the neutrophil activation causes damage to the respiratory chain, releasing excessive amounts of ROS and nitric oxide.…”

Section: The Role Of Oxidative Stress In the Pathophysiology Of Intra...mentioning

confidence: 99%

Regulation of nuclear factor erythroid-2-related factor 2 as a potential therapeutic target in intracerebral hemorrhage

Zhang

Liu

et al. 2022

Front. Mol. Neurosci.

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Hemorrhagic stroke can be categorized into several subtypes. The most common is intracerebral hemorrhage (ICH), which exhibits significant morbidity and mortality, affecting the lives of millions of people worldwide every year. Brain injury after ICH includes the primary injury that results from direct compression as well as stimulation by the hematoma and secondary brain injury (SBI) that is due to ischemia and hypoxia in the penumbra around the hematoma. A number of recent studies have analyzed the mechanisms producing the oxidative stress and inflammation that develop following hematoma formation and are associated with the ICH induced by the SBI as well as the resulting neurological dysfunction. Nuclear factor erythroid-2-related factor 2 (Nrf2) is a critical component in mediating oxidative stress and anti-inflammatory response. We summarize the pathological mechanisms of ICH focusing on oxidative stress and the regulatory role of Nrf2, and review the mechanisms regulating Nrf2 at the transcriptional and post-transcriptional levels by influencing gene expression levels, protein stability, subcellular localization, and synergistic effects with other transcription factors. We further reviewing the efficacy of several Nrf2 activators in the treatment of ICH in experimental ICH models. Activation of Nrf2 might produce antioxidant, anti-inflammatory, and neuron-protection effects, which could potentially be a focus for developing future treatments and prevention of ICH.

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Mechanism of Baicalein in Brain Injury After Intracerebral Hemorrhage by Inhibiting the ROS/NLRP3 Inflammasome Pathway

Cited by 20 publications

References 32 publications

The Mechanism of TNF-α-Mediated Accumulation of Phosphorylated Tau Protein and Its Modulation by Propofol in Primary Mouse Hippocampal Neurons: Role of Mitophagy, NLRP3, and p62/Keap1/Nrf2 Pathway

The Mechanism of TNF-α-Mediated Accumulation of Phosphorylated Tau Protein and Its Modulation by Propofol in Primary Mouse Hippocampal Neurons: Role of Mitophagy, NLRP3, and p62/Keap1/Nrf2 Pathway

Perspectives on the mechanism of pyroptosis after intracerebral hemorrhage

Regulation of nuclear factor erythroid-2-related factor 2 as a potential therapeutic target in intracerebral hemorrhage

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