Inhibition of Inflammation and Regulation of AQPs/ENaCs/Na+-K+-ATPase Mediated Alveolar Fluid Transport by Total Flavonoids Extracted From Nervilia fordii in Lipopolysaccharide-induced Acute Lung Injury

Aims: The occurrence of vascular permeability pulmonary edema in acute lung injury (ALI) is related to the imbalance of alveolar fluid transport. Regulating the active transport of alveolar fluid by aquaporins (AQPs), epithelial sodium channels (ENaCs), and Na+-K+-ATPase can effectively reduce the e...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Shuomiao Yin, Meizhu Ding, Long Fan, Xuhua Yu, Ziyao Liang, Lei Wu, Zhiling Gao, Lin Lin, Yuanbin Chen
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	acute lung injury nervilia fordii flavonoids lipopolysaccharide aquaporins epithelial sodium channel Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/d90a5d59ebe6482aa9901316842e16fc
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:d90a5d59ebe6482aa9901316842e16fc
record_format	dspace
spelling	oai:doaj.org-article:d90a5d59ebe6482aa9901316842e16fc2021-11-30T14:39:09ZInhibition of Inflammation and Regulation of AQPs/ENaCs/Na+-K+-ATPase Mediated Alveolar Fluid Transport by Total Flavonoids Extracted From Nervilia fordii in Lipopolysaccharide-induced Acute Lung Injury1663-981210.3389/fphar.2021.603863https://doaj.org/article/d90a5d59ebe6482aa9901316842e16fc2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.603863/fullhttps://doaj.org/toc/1663-9812Aims: The occurrence of vascular permeability pulmonary edema in acute lung injury (ALI) is related to the imbalance of alveolar fluid transport. Regulating the active transport of alveolar fluid by aquaporins (AQPs), epithelial sodium channels (ENaCs), and Na+-K+-ATPase can effectively reduce the edema fluid in the alveolar cavity and protect against ALI. We evaluated the therapeutic effects of total flavonoids, extracted from Nervilia fordii (TFENF), and investigated its potential mechanisms of alveolar fluid transport in a rat ALI model.Materials and methods: A model of lipopolysaccharide (LPS, 5 mg/kg)-induced ALI was established in Sprague-Dawley (SD) rats through the arteriae dorsalis penis. SD rats were divided into six groups, including the vehicle, LPS model, TFENF (6 mg/kg, 12 mg/kg, 24 mg/kg), and dexamethasone group (DEX group, 5 mg/kg). The wet-to-dry (W/D) lung weight ratio, oxygenation index, and histopathological observation were used to evaluate the therapeutic effect of TFENF. The mRNA expression of AQPs, ENaCs, and pro-inflammatory cytokines was determined using real-time polymerase chain reaction, whereas protein expression was determined using immunohistochemistry. The Na+-K+-ATPase activity was assessed using enzyme-linked immunosorbent assay.Results: LPS significantly stimulated the production of inflammatory mediators including tumor necrosis factor (TNF)-α and interleukin (IL)-1β, and disrupted the water transport balance in the alveolar cavity by inhibiting AQPs/ENaCs/Na+-K+-ATPase. Pretreatment with TFENF reduced the pathological damage and W/D ratio of the lungs and ameliorated the arterial blood oxygen partial pressure (PaO2) and oxygenation index. TFENF further decreased the mRNA level of TNF-α and IL-1β; increased the expression of AQP-1, AQP-5, αENaC, and βENaC; and increased Na+-K+-ATPase activity. Moreover, the regulation of AQPs, βENaC, and Na+-K+-ATPase and the inhibition of TNF-α and IL-1β by TFENF were found to be dose dependent.Conclusion: TFENF protects against LPS-induced ALI, at least in part, through the suppression of inflammatory cytokines and regulation of the active transport capacity of AQPs/ENaCs/Na+-K+-ATPase. These findings suggest the therapeutic potential of TFENF as phytomedicine to treat inflammation and pulmonary edema in ALI.Shuomiao YinMeizhu DingLong FanXuhua YuZiyao LiangLei WuLei WuZhiling GaoLin LinLin LinYuanbin ChenYuanbin ChenFrontiers Media S.A.articleacute lung injurynervilia fordiiflavonoidslipopolysaccharideaquaporinsepithelial sodium channelTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	acute lung injury nervilia fordii flavonoids lipopolysaccharide aquaporins epithelial sodium channel Therapeutics. Pharmacology RM1-950
spellingShingle	acute lung injury nervilia fordii flavonoids lipopolysaccharide aquaporins epithelial sodium channel Therapeutics. Pharmacology RM1-950 Shuomiao Yin Meizhu Ding Long Fan Xuhua Yu Ziyao Liang Lei Wu Lei Wu Zhiling Gao Lin Lin Lin Lin Yuanbin Chen Yuanbin Chen Inhibition of Inflammation and Regulation of AQPs/ENaCs/Na+-K+-ATPase Mediated Alveolar Fluid Transport by Total Flavonoids Extracted From Nervilia fordii in Lipopolysaccharide-induced Acute Lung Injury
description	Aims: The occurrence of vascular permeability pulmonary edema in acute lung injury (ALI) is related to the imbalance of alveolar fluid transport. Regulating the active transport of alveolar fluid by aquaporins (AQPs), epithelial sodium channels (ENaCs), and Na+-K+-ATPase can effectively reduce the edema fluid in the alveolar cavity and protect against ALI. We evaluated the therapeutic effects of total flavonoids, extracted from Nervilia fordii (TFENF), and investigated its potential mechanisms of alveolar fluid transport in a rat ALI model.Materials and methods: A model of lipopolysaccharide (LPS, 5 mg/kg)-induced ALI was established in Sprague-Dawley (SD) rats through the arteriae dorsalis penis. SD rats were divided into six groups, including the vehicle, LPS model, TFENF (6 mg/kg, 12 mg/kg, 24 mg/kg), and dexamethasone group (DEX group, 5 mg/kg). The wet-to-dry (W/D) lung weight ratio, oxygenation index, and histopathological observation were used to evaluate the therapeutic effect of TFENF. The mRNA expression of AQPs, ENaCs, and pro-inflammatory cytokines was determined using real-time polymerase chain reaction, whereas protein expression was determined using immunohistochemistry. The Na+-K+-ATPase activity was assessed using enzyme-linked immunosorbent assay.Results: LPS significantly stimulated the production of inflammatory mediators including tumor necrosis factor (TNF)-α and interleukin (IL)-1β, and disrupted the water transport balance in the alveolar cavity by inhibiting AQPs/ENaCs/Na+-K+-ATPase. Pretreatment with TFENF reduced the pathological damage and W/D ratio of the lungs and ameliorated the arterial blood oxygen partial pressure (PaO2) and oxygenation index. TFENF further decreased the mRNA level of TNF-α and IL-1β; increased the expression of AQP-1, AQP-5, αENaC, and βENaC; and increased Na+-K+-ATPase activity. Moreover, the regulation of AQPs, βENaC, and Na+-K+-ATPase and the inhibition of TNF-α and IL-1β by TFENF were found to be dose dependent.Conclusion: TFENF protects against LPS-induced ALI, at least in part, through the suppression of inflammatory cytokines and regulation of the active transport capacity of AQPs/ENaCs/Na+-K+-ATPase. These findings suggest the therapeutic potential of TFENF as phytomedicine to treat inflammation and pulmonary edema in ALI.
format	article
author	Shuomiao Yin Meizhu Ding Long Fan Xuhua Yu Ziyao Liang Lei Wu Lei Wu Zhiling Gao Lin Lin Lin Lin Yuanbin Chen Yuanbin Chen
author_facet	Shuomiao Yin Meizhu Ding Long Fan Xuhua Yu Ziyao Liang Lei Wu Lei Wu Zhiling Gao Lin Lin Lin Lin Yuanbin Chen Yuanbin Chen
author_sort	Shuomiao Yin
title	Inhibition of Inflammation and Regulation of AQPs/ENaCs/Na+-K+-ATPase Mediated Alveolar Fluid Transport by Total Flavonoids Extracted From Nervilia fordii in Lipopolysaccharide-induced Acute Lung Injury
title_short	Inhibition of Inflammation and Regulation of AQPs/ENaCs/Na+-K+-ATPase Mediated Alveolar Fluid Transport by Total Flavonoids Extracted From Nervilia fordii in Lipopolysaccharide-induced Acute Lung Injury
title_full	Inhibition of Inflammation and Regulation of AQPs/ENaCs/Na+-K+-ATPase Mediated Alveolar Fluid Transport by Total Flavonoids Extracted From Nervilia fordii in Lipopolysaccharide-induced Acute Lung Injury
title_fullStr	Inhibition of Inflammation and Regulation of AQPs/ENaCs/Na+-K+-ATPase Mediated Alveolar Fluid Transport by Total Flavonoids Extracted From Nervilia fordii in Lipopolysaccharide-induced Acute Lung Injury
title_full_unstemmed	Inhibition of Inflammation and Regulation of AQPs/ENaCs/Na+-K+-ATPase Mediated Alveolar Fluid Transport by Total Flavonoids Extracted From Nervilia fordii in Lipopolysaccharide-induced Acute Lung Injury
title_sort	inhibition of inflammation and regulation of aqps/enacs/na+-k+-atpase mediated alveolar fluid transport by total flavonoids extracted from nervilia fordii in lipopolysaccharide-induced acute lung injury
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/d90a5d59ebe6482aa9901316842e16fc
work_keys_str_mv	AT shuomiaoyin inhibitionofinflammationandregulationofaqpsenacsnakatpasemediatedalveolarfluidtransportbytotalflavonoidsextractedfromnerviliafordiiinlipopolysaccharideinducedacutelunginjury AT meizhuding inhibitionofinflammationandregulationofaqpsenacsnakatpasemediatedalveolarfluidtransportbytotalflavonoidsextractedfromnerviliafordiiinlipopolysaccharideinducedacutelunginjury AT longfan inhibitionofinflammationandregulationofaqpsenacsnakatpasemediatedalveolarfluidtransportbytotalflavonoidsextractedfromnerviliafordiiinlipopolysaccharideinducedacutelunginjury AT xuhuayu inhibitionofinflammationandregulationofaqpsenacsnakatpasemediatedalveolarfluidtransportbytotalflavonoidsextractedfromnerviliafordiiinlipopolysaccharideinducedacutelunginjury AT ziyaoliang inhibitionofinflammationandregulationofaqpsenacsnakatpasemediatedalveolarfluidtransportbytotalflavonoidsextractedfromnerviliafordiiinlipopolysaccharideinducedacutelunginjury AT leiwu inhibitionofinflammationandregulationofaqpsenacsnakatpasemediatedalveolarfluidtransportbytotalflavonoidsextractedfromnerviliafordiiinlipopolysaccharideinducedacutelunginjury AT leiwu inhibitionofinflammationandregulationofaqpsenacsnakatpasemediatedalveolarfluidtransportbytotalflavonoidsextractedfromnerviliafordiiinlipopolysaccharideinducedacutelunginjury AT zhilinggao inhibitionofinflammationandregulationofaqpsenacsnakatpasemediatedalveolarfluidtransportbytotalflavonoidsextractedfromnerviliafordiiinlipopolysaccharideinducedacutelunginjury AT linlin inhibitionofinflammationandregulationofaqpsenacsnakatpasemediatedalveolarfluidtransportbytotalflavonoidsextractedfromnerviliafordiiinlipopolysaccharideinducedacutelunginjury AT linlin inhibitionofinflammationandregulationofaqpsenacsnakatpasemediatedalveolarfluidtransportbytotalflavonoidsextractedfromnerviliafordiiinlipopolysaccharideinducedacutelunginjury AT yuanbinchen inhibitionofinflammationandregulationofaqpsenacsnakatpasemediatedalveolarfluidtransportbytotalflavonoidsextractedfromnerviliafordiiinlipopolysaccharideinducedacutelunginjury AT yuanbinchen inhibitionofinflammationandregulationofaqpsenacsnakatpasemediatedalveolarfluidtransportbytotalflavonoidsextractedfromnerviliafordiiinlipopolysaccharideinducedacutelunginjury
_version_	1718406533582159872

Inhibition of Inflammation and Regulation of AQPs/ENaCs/Na+-K+-ATPase Mediated Alveolar Fluid Transport by Total Flavonoids Extracted From Nervilia fordii in Lipopolysaccharide-induced Acute Lung Injury

Ejemplares similares