Engeletin alleviates cerebral ischemia <scp>reperfusion‐induced</scp> neuroinflammation via the <scp>HMGB1</scp>/<scp>TLR4</scp>/<scp>NF‐κB</scp> network

Xu, Yangyang; Zhang, Jie; Gao, Fei; Cheng, Wenna; Zhang, Ye; Wei, Chuanmei; Zhang, Shuping; Gao, Xinfu

doi:10.1111/jcmm.17758

Cited by 15 publications

(10 citation statements)

References 36 publications

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“…It has been determined that HMGB1/TLR4/NF-κB inflammatory network and its downstream mediators (IL-1β and TNF-α) as well as NLRP3 inflammasomemediated neuroinflammatory responses in the brain (Su et al, 2022;Xu et al, 2023). Investigation on ASD patients reveals a higher level of pro-inflammatory cytokines, including IL-1β and TNF-α (Chan et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Maternal separation stress through triggering of the neuro‐immune response in the hippocampus induces autistic‐like behaviors in male mice

Reisi‐Vanani,

Lorigooini,

Bijad

et al. 2023

Intl J of Devlp Neuroscience

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Autism spectrum disorder (ASD) is the fastest‐growing neurodevelopmental disease throughout the world. Neuro‐immune responses from prenatal to adulthood stages of life induce developmental defects in synaptic signaling, neurotransmitter imbalance, and even structural changes in the brain. In this study, we aimed to focus on the possible role of neuroinflammatory response in the hippocampus in development of the autistic‐like behaviors following maternal separation (MS) stress in mice. To do this, mice neonates daily separated from their mothers from postnatal day (PND) 2 to PND 14 for 3 h. During PND45–60, behavioral tests related to autistic‐like behaviors including three‐chamber sociability, Morris water maze (MWM), shuttle box, resident‐intruder, and marble burying tests were performed. Then, hippocampi were dissected out, and the gene expression of inflammatory mediators including TNF‐α, IL‐1β, TLR4, HMGB1, and NLRP3 was assessed in the hippocampus using RT‐PCR. Results showed that MS mice exerted impaired sociability preference, repetitive behaviors, impaired passive avoidance, and spatial memories. The gene expression of inflammatory mediators significantly increased in the hippocampi of MS mice. We concluded that MS stress probably via activating of the HMGB1/TLR4 signaling cascade in the hippocampus induced autistic‐like behaviors in mice.

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Section: Discussionmentioning

confidence: 99%

Maternal separation stress through triggering of the neuro‐immune response in the hippocampus induces autistic‐like behaviors in male mice

Reisi‐Vanani,

Lorigooini,

Bijad

et al. 2023

Intl J of Devlp Neuroscience

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“…For example, nuclear factor-kappa B (NF-κB) and the subsequent transcription of various pro-inflammatory genes were activated afterward. This results in the production and secretion of pro-inflammatory cytokines including TNF-α, IL-1β, and IL-6 ( Xie et al, 2019 ; Xu et al, 2023 ). HMGB1 can also promote the expression and activity of MMPs, especially MMP-9, thus altering the function of TJPs and consequently increasing BBB permeability ( Richard et al, 2017 ).…”

Section: Inflammatory Markersmentioning

confidence: 99%

Emerging diagnostic markers and therapeutic targets in post-stroke hemorrhagic transformation and brain edema

Yao,

Liu,

et al. 2023

Front. Mol. Neurosci.

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Stroke is a devastating condition that can lead to significant morbidity and mortality. The aftermath of a stroke, particularly hemorrhagic transformation (HT) and brain edema, can significantly impact the prognosis of patients. Early detection and effective management of these complications are crucial for improving outcomes in stroke patients. This review highlights the emerging diagnostic markers and therapeutic targets including claudin, occludin, zonula occluden, s100β, albumin, MMP-9, MMP-2, MMP-12, IL-1β, TNF-α, IL-6, IFN-γ, TGF-β, IL-10, IL-4, IL-13, MCP-1/CCL2, CXCL2, CXCL8, CXCL12, CCL5, CX3CL1, ICAM-1, VCAM-1, P-selectin, E-selectin, PECAM-1/CD31, JAMs, HMGB1, vWF, VEGF, ROS, NAC, and AQP4. The clinical significance and implications of these biomarkers were also discussed.

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“… 15 , 16 In addition, it has been shown to exert neuroprotective activity, suppressing the production of reactive oxygen species and mitigating the severity of ischemia/reperfusion injury and Alzheimer's disease. 17 , 18 Preliminary research conducted by our group further revealed that engeletin can alleviate depressive‐like behaviours induced by chronic restraint stress through its ability to modulate the brain‐derived neurotrophic factor (BDNF)/TrkB/mTORC1 signalling axis, thereby enhancing synaptic plasticity. 19 However, no research to date has evaluated the effects of engeletin on the regulation of the M1/M2 polarization of microglia.…”

Section: Introductionmentioning

confidence: 99%

Engeletin alleviates depressive‐like behaviours by modulating microglial polarization via the LCN2/CXCL10 signalling pathway

Zhang,

Song,

Huo

et al. 2024

J Cellular Molecular Medi

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Microglial polarization and associated inflammatory activity are the key mediators of depression pathogenesis. The natural Smilax glabra rhizomilax derivative engeletin has been reported to exhibit robust anti‐inflammatory activity, but no studies to date have examined the mechanisms through which it can treat depressive symptoms. We showed that treatment for 21 days with engeletin significantly alleviated depressive‐like behaviours in chronic stress social defeat stress (CSDS) model mice. T1‐weighted imaging (T1WI), T2‐weighted imaging (T2WI) imaging revealed no significant differences between groups, but the bilateral prefrontal cortex of CSDS mice exhibited significant increases in apparent diffusion coefficient and T2 values relative to normal control mice, with a corresponding reduction in fractional anisotropy, while engeletin reversed all of these changes. CSDS resulted in higher levels of IL‐1β, IL‐6, and TNF‐a production, enhanced microglial activation, and greater M1 polarization with a concomitant decrease in M2 polarization in the mPFC, whereas engeletin treatment effectively abrogated these CSDS‐related pathological changes. Engeletin was further found to suppress the LCN2/C‐X‐C motif chemokine ligand 10 (CXCL10) signalling axis such that adeno‐associated virus‐induced LCN2 overexpression ablated the antidepressant effects of engeletin and reversed its beneficial effects on the M1/M2 polarization of microglia. In conclusion, engeletin can alleviate CSDS‐induced depressive‐like behaviours by regulating the LCN2/CXCL10 pathway and thereby altering the polarization of microglia. These data suggest that the antidepressant effects of engeletin are correlated with the polarization of microglia, highlighting a potential avenue for future design of antidepressant strategies that specifically target the microglia.

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Engeletin alleviates cerebral ischemia reperfusion‐induced neuroinflammation via the HMGB1/TLR4/NF‐κB network

Cited by 15 publications

References 36 publications

Maternal separation stress through triggering of the neuro‐immune response in the hippocampus induces autistic‐like behaviors in male mice

Maternal separation stress through triggering of the neuro‐immune response in the hippocampus induces autistic‐like behaviors in male mice

Emerging diagnostic markers and therapeutic targets in post-stroke hemorrhagic transformation and brain edema

Engeletin alleviates depressive‐like behaviours by modulating microglial polarization via the LCN2/CXCL10 signalling pathway

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