Astragaloside IV Protects from PM2.5-Induced Lung Injury by Regulating Autophagy via Inhibition of PI3K/Akt/mTOR Signaling in vivo and in vitro

Caixia Pei,* Fei Wang,* Demei Huang, Shihua Shi, Xiaomin Wang, Yilan Wang, Shuiqin Li, Yongcan Wu, Zhenxing Wang Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, People’s Republic of China*These authors contributed equally to this wor...

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Autores principales: Pei C, Wang F, Huang D, Shi S, Wang X, Wang Y, Li S, Wu Y, Wang Z
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Publicado: Dove Medical Press 2021
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spelling oai:doaj.org-article:22eabfdd05b4479d910bb32622ec052d2021-12-02T15:03:23ZAstragaloside IV Protects from PM2.5-Induced Lung Injury by Regulating Autophagy via Inhibition of PI3K/Akt/mTOR Signaling in vivo and in vitro1178-7031https://doaj.org/article/22eabfdd05b4479d910bb32622ec052d2021-09-01T00:00:00Zhttps://www.dovepress.com/astragaloside-iv-protects-from-pm25-induced-lung-injury-by-regulating--peer-reviewed-fulltext-article-JIRhttps://doaj.org/toc/1178-7031Caixia Pei,* Fei Wang,* Demei Huang, Shihua Shi, Xiaomin Wang, Yilan Wang, Shuiqin Li, Yongcan Wu, Zhenxing Wang Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhenxing Wang; Yongcan WuHospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, People’s Republic of ChinaEmail wangzhenxing@vip.tom.com; appleofcan@163.comIntroduction: Prolonged exposure to air polluted with airborne fine particulate matter (PM2.5) can increase respiratory disease risk. Astragaloside IV (AS-IV) is one of the main bioactive substances in the traditional Chinese medicinal herb, Astragalus membranaceus Bunge. AS-IV has numerous pharmacological properties; whereas there are few reports on the prevention of PM2.5-induced lung injury by AS-IV through modulation of the autophagic pathway. This study aimed to investigate the protective effects and the underlying mechanisms of AS-IV in PM2.5-induced lung injury rats and rat alveolar macrophages (NR8383 cells).Methods: The pneumotoxicity model was established by intratracheal injection of PM2.5 in rats, and PM2.5 challenge in NR8383 cells. The severity of lung injury was evaluated by wet weight to dry weight ratio and McGuigan pathology scoring. Inflammatory factors and oxidative stress were detected through ELISA. The expressions of p-PI3K, p-Akt, and p-mTOR proteins were analyzed by immunohistochemistry. Immunofluorescence and transmission electron microscopy were used to detect autophagosomes. The expressions of autophagy marker protein (LC3B and p62), PI3K/Akt/mTOR signaling and NF-κB translocation were detected by Western blot in lung tissue and NR8383 cells.Results: After PM2.5 stimulation, rats showed severe inflammation and oxidative stress, along with inhibition of autophagy in lung tissue. AS-IV not only decreased pulmonary inflammation and oxidative stress by inhibiting nuclear factor kappa B translocation, but also regulated autophagy by inhibiting PI3K/Akt/mTOR signaling. After treatment with 3-methyladenine (a classic PI3K inhibitor, blocking the formation of autophagosomes), the protective effect of AS-IV on PM2.5-induced lung injury was further strengthened. In parallel, using Western blot, immunohistochemistry, and transmission electron microscopy, we demonstrated that AS-IV restore autophagic flux mainly through regulating the degradation of autophagosomes rather than suppressing the formation in vivo and in vitro.Conclusion: Our data indicated that AS-IV protects from PM2.5-induced lung injury in vivo and in vitro by inhibiting the PI3K/Akt/mTOR pathway to regulate autophagy and inflammation.Keywords: PM2.5, lung injury, astragaloside IV, autophagy, inflammationPei CWang FHuang DShi SWang XWang YLi SWu YWang ZDove Medical Pressarticlepm2.5lung injuryastragaloside ivautophagyinflammationPathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 14, Pp 4707-4721 (2021)
institution DOAJ
collection DOAJ
language EN
topic pm2.5
lung injury
astragaloside iv
autophagy
inflammation
Pathology
RB1-214
Therapeutics. Pharmacology
RM1-950
spellingShingle pm2.5
lung injury
astragaloside iv
autophagy
inflammation
Pathology
RB1-214
Therapeutics. Pharmacology
RM1-950
Pei C
Wang F
Huang D
Shi S
Wang X
Wang Y
Li S
Wu Y
Wang Z
Astragaloside IV Protects from PM2.5-Induced Lung Injury by Regulating Autophagy via Inhibition of PI3K/Akt/mTOR Signaling in vivo and in vitro
description Caixia Pei,* Fei Wang,* Demei Huang, Shihua Shi, Xiaomin Wang, Yilan Wang, Shuiqin Li, Yongcan Wu, Zhenxing Wang Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhenxing Wang; Yongcan WuHospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, People’s Republic of ChinaEmail wangzhenxing@vip.tom.com; appleofcan@163.comIntroduction: Prolonged exposure to air polluted with airborne fine particulate matter (PM2.5) can increase respiratory disease risk. Astragaloside IV (AS-IV) is one of the main bioactive substances in the traditional Chinese medicinal herb, Astragalus membranaceus Bunge. AS-IV has numerous pharmacological properties; whereas there are few reports on the prevention of PM2.5-induced lung injury by AS-IV through modulation of the autophagic pathway. This study aimed to investigate the protective effects and the underlying mechanisms of AS-IV in PM2.5-induced lung injury rats and rat alveolar macrophages (NR8383 cells).Methods: The pneumotoxicity model was established by intratracheal injection of PM2.5 in rats, and PM2.5 challenge in NR8383 cells. The severity of lung injury was evaluated by wet weight to dry weight ratio and McGuigan pathology scoring. Inflammatory factors and oxidative stress were detected through ELISA. The expressions of p-PI3K, p-Akt, and p-mTOR proteins were analyzed by immunohistochemistry. Immunofluorescence and transmission electron microscopy were used to detect autophagosomes. The expressions of autophagy marker protein (LC3B and p62), PI3K/Akt/mTOR signaling and NF-κB translocation were detected by Western blot in lung tissue and NR8383 cells.Results: After PM2.5 stimulation, rats showed severe inflammation and oxidative stress, along with inhibition of autophagy in lung tissue. AS-IV not only decreased pulmonary inflammation and oxidative stress by inhibiting nuclear factor kappa B translocation, but also regulated autophagy by inhibiting PI3K/Akt/mTOR signaling. After treatment with 3-methyladenine (a classic PI3K inhibitor, blocking the formation of autophagosomes), the protective effect of AS-IV on PM2.5-induced lung injury was further strengthened. In parallel, using Western blot, immunohistochemistry, and transmission electron microscopy, we demonstrated that AS-IV restore autophagic flux mainly through regulating the degradation of autophagosomes rather than suppressing the formation in vivo and in vitro.Conclusion: Our data indicated that AS-IV protects from PM2.5-induced lung injury in vivo and in vitro by inhibiting the PI3K/Akt/mTOR pathway to regulate autophagy and inflammation.Keywords: PM2.5, lung injury, astragaloside IV, autophagy, inflammation
format article
author Pei C
Wang F
Huang D
Shi S
Wang X
Wang Y
Li S
Wu Y
Wang Z
author_facet Pei C
Wang F
Huang D
Shi S
Wang X
Wang Y
Li S
Wu Y
Wang Z
author_sort Pei C
title Astragaloside IV Protects from PM2.5-Induced Lung Injury by Regulating Autophagy via Inhibition of PI3K/Akt/mTOR Signaling in vivo and in vitro
title_short Astragaloside IV Protects from PM2.5-Induced Lung Injury by Regulating Autophagy via Inhibition of PI3K/Akt/mTOR Signaling in vivo and in vitro
title_full Astragaloside IV Protects from PM2.5-Induced Lung Injury by Regulating Autophagy via Inhibition of PI3K/Akt/mTOR Signaling in vivo and in vitro
title_fullStr Astragaloside IV Protects from PM2.5-Induced Lung Injury by Regulating Autophagy via Inhibition of PI3K/Akt/mTOR Signaling in vivo and in vitro
title_full_unstemmed Astragaloside IV Protects from PM2.5-Induced Lung Injury by Regulating Autophagy via Inhibition of PI3K/Akt/mTOR Signaling in vivo and in vitro
title_sort astragaloside iv protects from pm2.5-induced lung injury by regulating autophagy via inhibition of pi3k/akt/mtor signaling in vivo and in vitro
publisher Dove Medical Press
publishDate 2021
url https://doaj.org/article/22eabfdd05b4479d910bb32622ec052d
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