Baicalein suppresses lipopolysaccharide-induced acute lung injury by regulating Drp1-dependent mitochondrial fission of macrophages

Acute lung injury (ALI) and its serious form, the acute respiratory distress syndrome (ARDS) are devastating diseases without effective chemotherapy. Exuberant or uncontrolled proinflammation responses in the lung, also known as “cytokine storms”, is one of the main culprits in the pathogenesis of o...

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Autores principales:	Cheng Jiang, Jiechun Zhang, Huiwen Xie, Huiting Guan, Rui Li, Caixia Chen, Hongzhen Dong, You Zhou, Wei Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2022
Materias:	Baicalein Macrophage Mitochondrial dysfunction Dynamin-related protein 1 Inflammation Acute lung injury Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/5cfaa02f1178453dbd8db4bb20ed199e
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spelling	oai:doaj.org-article:5cfaa02f1178453dbd8db4bb20ed199e2021-11-20T04:55:50ZBaicalein suppresses lipopolysaccharide-induced acute lung injury by regulating Drp1-dependent mitochondrial fission of macrophages0753-332210.1016/j.biopha.2021.112408https://doaj.org/article/5cfaa02f1178453dbd8db4bb20ed199e2022-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S075333222101194Xhttps://doaj.org/toc/0753-3322Acute lung injury (ALI) and its serious form, the acute respiratory distress syndrome (ARDS) are devastating diseases without effective chemotherapy. Exuberant or uncontrolled proinflammation responses in the lung, also known as “cytokine storms”, is one of the main culprits in the pathogenesis of organ failure, and anti-inflammatory therapy is essential to alleviate ALI/ARDS-associated injuries. Emerging evidence suggests that baicalein has potent anti-inflammatory and antioxidant properties. However, the underlined mechanism of baicalein to mitigate inflammation in ALI remains unclear. Herein, we demonstrated a critical role for baicalein in suppressing the inflammatory response of LPS-activated macrophages. We found that mitochondria function was restored in the condition of baicalein. Interestingly, results showed that mitochondrial dysfunction positively correlates with inflammatory cytokine generation at each corresponding baicalein concentration. Further mRNA analysis revealed that baicalein mitigates mitochondrial defects via attenuation of dynamin-related protein 1 (Drp1) expression. These reprogrammed mitochondria prevent their function shift from the ATP synthesis to reactive oxygen species (ROS) production after the LPS challenge, thereby dampening NF-κB-dependent inflammatory cytokine transcription. Baicalein reduces the production of inflammatory mediators TNF-α, MIP-1, IL-6, and diminishes neutrophil influx and severity of endotoxin-mediated ALI. Taken together, our results show that baicalein may serve as a new clinical therapeutic strategy in ALI by modulating Drp1-induced mitochondrial impairment, restraining inflammatory responses, and reducing the severity of lung injury.Cheng JiangJiechun ZhangHuiwen XieHuiting GuanRui LiCaixia ChenHongzhen DongYou ZhouWei ZhangElsevierarticleBaicaleinMacrophageMitochondrial dysfunctionDynamin-related protein 1InflammationAcute lung injuryTherapeutics. PharmacologyRM1-950ENBiomedicine & Pharmacotherapy, Vol 145, Iss , Pp 112408- (2022)
institution	DOAJ
collection	DOAJ
language	EN
topic	Baicalein Macrophage Mitochondrial dysfunction Dynamin-related protein 1 Inflammation Acute lung injury Therapeutics. Pharmacology RM1-950
spellingShingle	Baicalein Macrophage Mitochondrial dysfunction Dynamin-related protein 1 Inflammation Acute lung injury Therapeutics. Pharmacology RM1-950 Cheng Jiang Jiechun Zhang Huiwen Xie Huiting Guan Rui Li Caixia Chen Hongzhen Dong You Zhou Wei Zhang Baicalein suppresses lipopolysaccharide-induced acute lung injury by regulating Drp1-dependent mitochondrial fission of macrophages
description	Acute lung injury (ALI) and its serious form, the acute respiratory distress syndrome (ARDS) are devastating diseases without effective chemotherapy. Exuberant or uncontrolled proinflammation responses in the lung, also known as “cytokine storms”, is one of the main culprits in the pathogenesis of organ failure, and anti-inflammatory therapy is essential to alleviate ALI/ARDS-associated injuries. Emerging evidence suggests that baicalein has potent anti-inflammatory and antioxidant properties. However, the underlined mechanism of baicalein to mitigate inflammation in ALI remains unclear. Herein, we demonstrated a critical role for baicalein in suppressing the inflammatory response of LPS-activated macrophages. We found that mitochondria function was restored in the condition of baicalein. Interestingly, results showed that mitochondrial dysfunction positively correlates with inflammatory cytokine generation at each corresponding baicalein concentration. Further mRNA analysis revealed that baicalein mitigates mitochondrial defects via attenuation of dynamin-related protein 1 (Drp1) expression. These reprogrammed mitochondria prevent their function shift from the ATP synthesis to reactive oxygen species (ROS) production after the LPS challenge, thereby dampening NF-κB-dependent inflammatory cytokine transcription. Baicalein reduces the production of inflammatory mediators TNF-α, MIP-1, IL-6, and diminishes neutrophil influx and severity of endotoxin-mediated ALI. Taken together, our results show that baicalein may serve as a new clinical therapeutic strategy in ALI by modulating Drp1-induced mitochondrial impairment, restraining inflammatory responses, and reducing the severity of lung injury.
format	article
author	Cheng Jiang Jiechun Zhang Huiwen Xie Huiting Guan Rui Li Caixia Chen Hongzhen Dong You Zhou Wei Zhang
author_facet	Cheng Jiang Jiechun Zhang Huiwen Xie Huiting Guan Rui Li Caixia Chen Hongzhen Dong You Zhou Wei Zhang
author_sort	Cheng Jiang
title	Baicalein suppresses lipopolysaccharide-induced acute lung injury by regulating Drp1-dependent mitochondrial fission of macrophages
title_short	Baicalein suppresses lipopolysaccharide-induced acute lung injury by regulating Drp1-dependent mitochondrial fission of macrophages
title_full	Baicalein suppresses lipopolysaccharide-induced acute lung injury by regulating Drp1-dependent mitochondrial fission of macrophages
title_fullStr	Baicalein suppresses lipopolysaccharide-induced acute lung injury by regulating Drp1-dependent mitochondrial fission of macrophages
title_full_unstemmed	Baicalein suppresses lipopolysaccharide-induced acute lung injury by regulating Drp1-dependent mitochondrial fission of macrophages
title_sort	baicalein suppresses lipopolysaccharide-induced acute lung injury by regulating drp1-dependent mitochondrial fission of macrophages
publisher	Elsevier
publishDate	2022
url	https://doaj.org/article/5cfaa02f1178453dbd8db4bb20ed199e
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Baicalein suppresses lipopolysaccharide-induced acute lung injury by regulating Drp1-dependent mitochondrial fission of macrophages

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