Luteolin Confers Cerebroprotection after Subarachnoid Hemorrhage by Suppression of NLPR3 Inflammasome Activation through Nrf2-Dependent Pathway

Luteolin (LUT) possesses multiple biologic functions and has beneficial effects for cardiovascular and cerebral vascular diseases. Here, we investigated the protective effects of LUT against subarachnoid hemorrhage (SAH) and the involvement of underlying molecular mechanisms. In a rat model of SAH,...

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Autores principales:	Zi-Huan Zhang, Jia-Qiang Liu, Cheng-Di Hu, Xin-Tong Zhao, Fei-Yun Qin, Zong Zhuang, Xiang-Sheng Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Hindawi Limited 2021
Materias:	Cytology QH573-671
Acceso en línea:	https://doaj.org/article/65063c5072e24a52b9934cd9e1dfaca9
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spelling	oai:doaj.org-article:65063c5072e24a52b9934cd9e1dfaca92021-11-15T01:19:10ZLuteolin Confers Cerebroprotection after Subarachnoid Hemorrhage by Suppression of NLPR3 Inflammasome Activation through Nrf2-Dependent Pathway1942-099410.1155/2021/5838101https://doaj.org/article/65063c5072e24a52b9934cd9e1dfaca92021-01-01T00:00:00Zhttp://dx.doi.org/10.1155/2021/5838101https://doaj.org/toc/1942-0994Luteolin (LUT) possesses multiple biologic functions and has beneficial effects for cardiovascular and cerebral vascular diseases. Here, we investigated the protective effects of LUT against subarachnoid hemorrhage (SAH) and the involvement of underlying molecular mechanisms. In a rat model of SAH, LUT significantly inhibited SAH-induced neuroinflammation as evidenced by reduced microglia activation, decreased neutrophil infiltration, and suppressed proinflammatory cytokine release. In addition, LUT markedly ameliorated SAH-induced oxidative damage and restored the endogenous antioxidant systems. Concomitant with the suppressed oxidative stress and neuroinflammation, LUT significantly improved neurologic function and reduced neuronal cell death after SAH. Mechanistically, LUT treatment significantly enhanced the expression of nuclear factor-erythroid 2-related factor 2 (Nrf2), while it downregulated nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome activation. Inhibition of Nrf2 by ML385 dramatically abrogated LUT-induced Nrf2 activation and NLRP3 suppression and reversed the beneficial effects of LUT against SAH. In neurons and microglia coculture system, LUT also mitigated oxidative stress, inflammatory response, and neuronal degeneration. These beneficial effects were associated with activation of the Nrf2 and inhibitory effects on NLRP3 inflammasome and were reversed by ML385 treatment. Taken together, this present study reveals that LUT confers protection against SAH by inhibiting NLRP3 inflammasome signaling pathway, which may be modulated by Nrf2 activation.Zi-Huan ZhangJia-Qiang LiuCheng-Di HuXin-Tong ZhaoFei-Yun QinZong ZhuangXiang-Sheng ZhangHindawi LimitedarticleCytologyQH573-671ENOxidative Medicine and Cellular Longevity, Vol 2021 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cytology QH573-671
spellingShingle	Cytology QH573-671 Zi-Huan Zhang Jia-Qiang Liu Cheng-Di Hu Xin-Tong Zhao Fei-Yun Qin Zong Zhuang Xiang-Sheng Zhang Luteolin Confers Cerebroprotection after Subarachnoid Hemorrhage by Suppression of NLPR3 Inflammasome Activation through Nrf2-Dependent Pathway
description	Luteolin (LUT) possesses multiple biologic functions and has beneficial effects for cardiovascular and cerebral vascular diseases. Here, we investigated the protective effects of LUT against subarachnoid hemorrhage (SAH) and the involvement of underlying molecular mechanisms. In a rat model of SAH, LUT significantly inhibited SAH-induced neuroinflammation as evidenced by reduced microglia activation, decreased neutrophil infiltration, and suppressed proinflammatory cytokine release. In addition, LUT markedly ameliorated SAH-induced oxidative damage and restored the endogenous antioxidant systems. Concomitant with the suppressed oxidative stress and neuroinflammation, LUT significantly improved neurologic function and reduced neuronal cell death after SAH. Mechanistically, LUT treatment significantly enhanced the expression of nuclear factor-erythroid 2-related factor 2 (Nrf2), while it downregulated nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome activation. Inhibition of Nrf2 by ML385 dramatically abrogated LUT-induced Nrf2 activation and NLRP3 suppression and reversed the beneficial effects of LUT against SAH. In neurons and microglia coculture system, LUT also mitigated oxidative stress, inflammatory response, and neuronal degeneration. These beneficial effects were associated with activation of the Nrf2 and inhibitory effects on NLRP3 inflammasome and were reversed by ML385 treatment. Taken together, this present study reveals that LUT confers protection against SAH by inhibiting NLRP3 inflammasome signaling pathway, which may be modulated by Nrf2 activation.
format	article
author	Zi-Huan Zhang Jia-Qiang Liu Cheng-Di Hu Xin-Tong Zhao Fei-Yun Qin Zong Zhuang Xiang-Sheng Zhang
author_facet	Zi-Huan Zhang Jia-Qiang Liu Cheng-Di Hu Xin-Tong Zhao Fei-Yun Qin Zong Zhuang Xiang-Sheng Zhang
author_sort	Zi-Huan Zhang
title	Luteolin Confers Cerebroprotection after Subarachnoid Hemorrhage by Suppression of NLPR3 Inflammasome Activation through Nrf2-Dependent Pathway
title_short	Luteolin Confers Cerebroprotection after Subarachnoid Hemorrhage by Suppression of NLPR3 Inflammasome Activation through Nrf2-Dependent Pathway
title_full	Luteolin Confers Cerebroprotection after Subarachnoid Hemorrhage by Suppression of NLPR3 Inflammasome Activation through Nrf2-Dependent Pathway
title_fullStr	Luteolin Confers Cerebroprotection after Subarachnoid Hemorrhage by Suppression of NLPR3 Inflammasome Activation through Nrf2-Dependent Pathway
title_full_unstemmed	Luteolin Confers Cerebroprotection after Subarachnoid Hemorrhage by Suppression of NLPR3 Inflammasome Activation through Nrf2-Dependent Pathway
title_sort	luteolin confers cerebroprotection after subarachnoid hemorrhage by suppression of nlpr3 inflammasome activation through nrf2-dependent pathway
publisher	Hindawi Limited
publishDate	2021
url	https://doaj.org/article/65063c5072e24a52b9934cd9e1dfaca9
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Luteolin Confers Cerebroprotection after Subarachnoid Hemorrhage by Suppression of NLPR3 Inflammasome Activation through Nrf2-Dependent Pathway

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