Honokiol alleviates LPS-induced acute lung injury by inhibiting NLRP3 inflammasome-mediated pyroptosis via Nrf2 activation in vitro and in vivo

Abstract Background Honokiol (HKL) has been reported to ameliorate lipopolysaccharide (LPS)-induced acute lung injury (ALI). However, its potential mechanism of its protective effects remains unclear. In this study, the protective mechanism of HKL on LPS-induced ALI was explored in vivo and in vitro...

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Autores principales:	Yuhan Liu, Jiabin Zhou, Yingying Luo, Jinxiao Li, Luorui Shang, Fangyuan Zhou, Shenglan Yang
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Acute lung injury Honokiol NLRP3 inflammasome Pyroptosis Nrf2 Lipopolysaccharide Other systems of medicine RZ201-999
Acceso en línea:	https://doaj.org/article/ef230416b9994822a6e9b831a8c47c7a
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spelling	oai:doaj.org-article:ef230416b9994822a6e9b831a8c47c7a2021-12-05T12:07:05ZHonokiol alleviates LPS-induced acute lung injury by inhibiting NLRP3 inflammasome-mediated pyroptosis via Nrf2 activation in vitro and in vivo10.1186/s13020-021-00541-z1749-8546https://doaj.org/article/ef230416b9994822a6e9b831a8c47c7a2021-11-01T00:00:00Zhttps://doi.org/10.1186/s13020-021-00541-zhttps://doaj.org/toc/1749-8546Abstract Background Honokiol (HKL) has been reported to ameliorate lipopolysaccharide (LPS)-induced acute lung injury (ALI). However, its potential mechanism of its protective effects remains unclear. In this study, the protective mechanism of HKL on LPS-induced ALI was explored in vivo and in vitro. Methods In vivo, the SD rats were intratracheally instilled with LPS (5 mg/kg) to establish an acute lung injury model and then treated with HKL (1.25/2.5/5 mg/kg) or ML385 (30 mg/kg) intraperitoneally. In vitro, the human bronchial epithelial cell line (BEAS-2B) was stimulated with LPS and ATP to induce pyroptosis and treated with HKL (12.5/25/50 μM). Small interfering RNA (siRNA) technique was used to knockdown Nrf2 in BEAS-2B cells. The protein and mRNA expression levels of Nrf2, HO-1, NLRP3, ASC, CASP1, and GSDMD in cells and lung tissues were detected by western blot and real time-PCR. The expression levels of interleukin (IL)-1β, IL-18, MPO, MDA, and SOD in bronchoalveolar lavage fluid (BALF) and supernatant were determined by ELISA. The degree of pathological injury of lung tissue was evaluated by H&E staining. Results The results showed that HKL could alleviate oxidative stress and inflammatory responses by regulating the levels of MPO, MDA, SOD, IL-1β, IL-18 in supernatant. And it could also inhibit the expression levels of NLRP3, ASC, CASP1, GSDMD via activation of Nrf2 in BEAS-2B cells. Further studies revealed that HKL could attenuate the pathological injury in LPS-induced ALI rats, and the molecular mechanism was consistent with the results in vitro. Conclusions Our study demonstrated that HKL could alleviate LPS-induced ALI by reducing the oxidative stress and inhibiting NLRP3 inflammasome-mediated pyroptosis, which was partly dependent on the Nrf2 activation. Graphical AbstractYuhan LiuJiabin ZhouYingying LuoJinxiao LiLuorui ShangFangyuan ZhouShenglan YangBMCarticleAcute lung injuryHonokiolNLRP3 inflammasomePyroptosisNrf2LipopolysaccharideOther systems of medicineRZ201-999ENChinese Medicine, Vol 16, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Acute lung injury Honokiol NLRP3 inflammasome Pyroptosis Nrf2 Lipopolysaccharide Other systems of medicine RZ201-999
spellingShingle	Acute lung injury Honokiol NLRP3 inflammasome Pyroptosis Nrf2 Lipopolysaccharide Other systems of medicine RZ201-999 Yuhan Liu Jiabin Zhou Yingying Luo Jinxiao Li Luorui Shang Fangyuan Zhou Shenglan Yang Honokiol alleviates LPS-induced acute lung injury by inhibiting NLRP3 inflammasome-mediated pyroptosis via Nrf2 activation in vitro and in vivo
description	Abstract Background Honokiol (HKL) has been reported to ameliorate lipopolysaccharide (LPS)-induced acute lung injury (ALI). However, its potential mechanism of its protective effects remains unclear. In this study, the protective mechanism of HKL on LPS-induced ALI was explored in vivo and in vitro. Methods In vivo, the SD rats were intratracheally instilled with LPS (5 mg/kg) to establish an acute lung injury model and then treated with HKL (1.25/2.5/5 mg/kg) or ML385 (30 mg/kg) intraperitoneally. In vitro, the human bronchial epithelial cell line (BEAS-2B) was stimulated with LPS and ATP to induce pyroptosis and treated with HKL (12.5/25/50 μM). Small interfering RNA (siRNA) technique was used to knockdown Nrf2 in BEAS-2B cells. The protein and mRNA expression levels of Nrf2, HO-1, NLRP3, ASC, CASP1, and GSDMD in cells and lung tissues were detected by western blot and real time-PCR. The expression levels of interleukin (IL)-1β, IL-18, MPO, MDA, and SOD in bronchoalveolar lavage fluid (BALF) and supernatant were determined by ELISA. The degree of pathological injury of lung tissue was evaluated by H&E staining. Results The results showed that HKL could alleviate oxidative stress and inflammatory responses by regulating the levels of MPO, MDA, SOD, IL-1β, IL-18 in supernatant. And it could also inhibit the expression levels of NLRP3, ASC, CASP1, GSDMD via activation of Nrf2 in BEAS-2B cells. Further studies revealed that HKL could attenuate the pathological injury in LPS-induced ALI rats, and the molecular mechanism was consistent with the results in vitro. Conclusions Our study demonstrated that HKL could alleviate LPS-induced ALI by reducing the oxidative stress and inhibiting NLRP3 inflammasome-mediated pyroptosis, which was partly dependent on the Nrf2 activation. Graphical Abstract
format	article
author	Yuhan Liu Jiabin Zhou Yingying Luo Jinxiao Li Luorui Shang Fangyuan Zhou Shenglan Yang
author_facet	Yuhan Liu Jiabin Zhou Yingying Luo Jinxiao Li Luorui Shang Fangyuan Zhou Shenglan Yang
author_sort	Yuhan Liu
title	Honokiol alleviates LPS-induced acute lung injury by inhibiting NLRP3 inflammasome-mediated pyroptosis via Nrf2 activation in vitro and in vivo
title_short	Honokiol alleviates LPS-induced acute lung injury by inhibiting NLRP3 inflammasome-mediated pyroptosis via Nrf2 activation in vitro and in vivo
title_full	Honokiol alleviates LPS-induced acute lung injury by inhibiting NLRP3 inflammasome-mediated pyroptosis via Nrf2 activation in vitro and in vivo
title_fullStr	Honokiol alleviates LPS-induced acute lung injury by inhibiting NLRP3 inflammasome-mediated pyroptosis via Nrf2 activation in vitro and in vivo
title_full_unstemmed	Honokiol alleviates LPS-induced acute lung injury by inhibiting NLRP3 inflammasome-mediated pyroptosis via Nrf2 activation in vitro and in vivo
title_sort	honokiol alleviates lps-induced acute lung injury by inhibiting nlrp3 inflammasome-mediated pyroptosis via nrf2 activation in vitro and in vivo
publisher	BMC
publishDate	2021
url	https://doaj.org/article/ef230416b9994822a6e9b831a8c47c7a
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Honokiol alleviates LPS-induced acute lung injury by inhibiting NLRP3 inflammasome-mediated pyroptosis via Nrf2 activation in vitro and in vivo

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