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

High‐mobility group box1 (HMGB1) induces inflammatory injury, and emerging reports suggest that it is critical for brain ischemia reperfusion. Engeletin, a natural Smilax glabra rhizomilax derivative, is reported to possess anti‐inflammatory activity. Herein, we examined the mechanism of engeletin‐m...

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Autores principales: Xu, Yangyang, Zhang, Jie, Gao, Fei, Cheng, Wenna, Zhang, Ye, Wei, Chuanmei, Zhang, Shuping, Gao, Xinfu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10273068/
https://www.ncbi.nlm.nih.gov/pubmed/37132060
http://dx.doi.org/10.1111/jcmm.17758
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author Xu, Yangyang
Zhang, Jie
Gao, Fei
Cheng, Wenna
Zhang, Ye
Wei, Chuanmei
Zhang, Shuping
Gao, Xinfu
author_facet Xu, Yangyang
Zhang, Jie
Gao, Fei
Cheng, Wenna
Zhang, Ye
Wei, Chuanmei
Zhang, Shuping
Gao, Xinfu
author_sort Xu, Yangyang
collection PubMed
description High‐mobility group box1 (HMGB1) induces inflammatory injury, and emerging reports suggest that it is critical for brain ischemia reperfusion. Engeletin, a natural Smilax glabra rhizomilax derivative, is reported to possess anti‐inflammatory activity. Herein, we examined the mechanism of engeletin‐mediated neuroprotection in rats having transient middle cerebral artery occlusion (tMCAO) against cerebral ischemia reperfusion injury. Male SD rats were induced using a 1.5 h tMCAO, following by reperfusion for 22.5 h. Engeletin (15, 30 or 60 mg/kg) was intravenously administered immediately following 0.5 h of ischemia. Based on our results, engeletin, in a dose‐dependent fashion, reduced neurological deficits, infarct size, histopathological alterations, brain edema and inflammatory factors, namely, circulating IL‐1β, TNF‐α, IL‐6 and IFN‐γ. Furthermore, engeletin treatment markedly reduced neuronal apoptosis, which, in turn, elevated Bcl‐2 protein levels, while suppressing Bax and Cleaved Caspase‐3 protein levels. Meanwhile, engeletin significantly reduces overall expressions of HMGB1, TLR4, and NF‐κB and attenuated nuclear transfer of nuclear factor kappa B (NF‐κB) p65 in ischemic cortical tissue. In conclusion, engeletin strongly prevents focal cerebral ischemia via suppression of the HMGB1/TLR4/NF‐κB inflammatory network.
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spelling pubmed-102730682023-06-17 Engeletin alleviates cerebral ischemia reperfusion‐induced neuroinflammation via the HMGB1/TLR4/NF‐κB network Xu, Yangyang Zhang, Jie Gao, Fei Cheng, Wenna Zhang, Ye Wei, Chuanmei Zhang, Shuping Gao, Xinfu J Cell Mol Med Original Articles High‐mobility group box1 (HMGB1) induces inflammatory injury, and emerging reports suggest that it is critical for brain ischemia reperfusion. Engeletin, a natural Smilax glabra rhizomilax derivative, is reported to possess anti‐inflammatory activity. Herein, we examined the mechanism of engeletin‐mediated neuroprotection in rats having transient middle cerebral artery occlusion (tMCAO) against cerebral ischemia reperfusion injury. Male SD rats were induced using a 1.5 h tMCAO, following by reperfusion for 22.5 h. Engeletin (15, 30 or 60 mg/kg) was intravenously administered immediately following 0.5 h of ischemia. Based on our results, engeletin, in a dose‐dependent fashion, reduced neurological deficits, infarct size, histopathological alterations, brain edema and inflammatory factors, namely, circulating IL‐1β, TNF‐α, IL‐6 and IFN‐γ. Furthermore, engeletin treatment markedly reduced neuronal apoptosis, which, in turn, elevated Bcl‐2 protein levels, while suppressing Bax and Cleaved Caspase‐3 protein levels. Meanwhile, engeletin significantly reduces overall expressions of HMGB1, TLR4, and NF‐κB and attenuated nuclear transfer of nuclear factor kappa B (NF‐κB) p65 in ischemic cortical tissue. In conclusion, engeletin strongly prevents focal cerebral ischemia via suppression of the HMGB1/TLR4/NF‐κB inflammatory network. John Wiley and Sons Inc. 2023-05-02 /pmc/articles/PMC10273068/ /pubmed/37132060 http://dx.doi.org/10.1111/jcmm.17758 Text en © 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Xu, Yangyang
Zhang, Jie
Gao, Fei
Cheng, Wenna
Zhang, Ye
Wei, Chuanmei
Zhang, Shuping
Gao, Xinfu
Engeletin alleviates cerebral ischemia reperfusion‐induced neuroinflammation via the HMGB1/TLR4/NF‐κB network
title Engeletin alleviates cerebral ischemia reperfusion‐induced neuroinflammation via the HMGB1/TLR4/NF‐κB network
title_full Engeletin alleviates cerebral ischemia reperfusion‐induced neuroinflammation via the HMGB1/TLR4/NF‐κB network
title_fullStr Engeletin alleviates cerebral ischemia reperfusion‐induced neuroinflammation via the HMGB1/TLR4/NF‐κB network
title_full_unstemmed Engeletin alleviates cerebral ischemia reperfusion‐induced neuroinflammation via the HMGB1/TLR4/NF‐κB network
title_short Engeletin alleviates cerebral ischemia reperfusion‐induced neuroinflammation via the HMGB1/TLR4/NF‐κB network
title_sort engeletin alleviates cerebral ischemia reperfusion‐induced neuroinflammation via the hmgb1/tlr4/nf‐κb network
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10273068/
https://www.ncbi.nlm.nih.gov/pubmed/37132060
http://dx.doi.org/10.1111/jcmm.17758
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