Targeting the PI3K/AKT signaling pathway with PNU120596 protects against LPS-induced acute lung injury.

Autor:	Hou Z; Department of Anesthesiology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421001, PR China., Yang F; Department of Anesthesiology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421001, PR China.; Department of Anesthesiology, General Hospital, Hunan University of Medicine, Huaihua 418000, PR China., Zhang Q; Department of Anesthesiology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421001, PR China., Wang Y; Department of Anesthesiology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421001, PR China., Liu J; Department of Anesthesiology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421001, PR China., Liang F; Department of Anesthesiology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421001, PR China.
Jazyk:	angličtina
Zdroj:	The Journal of pharmacy and pharmacology [J Pharm Pharmacol] 2024 Nov 04; Vol. 76 (11), pp. 1508-1520.
DOI:	10.1093/jpp/rgae076
Abstrakt:	Objectives: This study investigated the potential therapeutic benefits of PNU120596, a positive allosteric modulator of the α7 nicotinic acetylcholine receptor (α7nAChR), in mitigating acute lung injury (ALI) induced by lipopolysaccharide (LPS) in a mouse model. Specifically, we sought to examine the impact of PNU120596 on the PI3K/AKT signaling pathway in the context of ALI. Methods: ALI was induced in mice by LPS administration, and the protective effects of PNU120596 were assessed. Lung injury, lung function, and the inflammatory response were evaluated. Additionally, the activation of the PI3K/AKT signaling pathway was examined, along with the levels of inflammatory factors and oxidative stress markers. Key Findings: PNU120596 significantly ameliorated LPS-induced lung injury, improved lung function, and reduced the inflammatory response in the mouse model of ALI. Furthermore, we observed that PNU120596 inhibited the activation of the PI3K/AKT signaling pathway, which was associated with decreased levels of inflammatory factors and oxidative stress markers. Conclusions: PNU120596 exhibits promising therapeutic potential for the treatment of acute lung injury, potentially by targeting the PI3K/AKT signaling pathway. These findings suggest that modulation of the α7 nicotinic acetylcholine receptor with PNU120596 may offer a viable strategy for the management of ALI, warranting further investigation and potential clinical applications. (© The Author(s) 2024. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
Databáze:	MEDLINE
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