Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Acute lung injury inhibition by juglone in LPS induced sepsis mouse model involves Sirt1 activation

Qiong Hu¹, Chunai Yang², Fenshuang Zheng¹, Hongdan Duan¹, Yangshan Fu¹, Zhongfeng Cheng¹

¹Emergency Department, The Second People's Hospital of Kunming, Kunming, Yunnan 650204; ²Emergency Department, The Second People's Hospital of Yunnan Province, Kunming, Yunnan 650021, China.

For correspondence:- Zhongfeng Cheng Email: chengzf222@sina.com

Accepted: 16 April 2020 Published: 31 May 2020

Citation: Hu Q, Yang C, Zheng F, Duan H, Fu Y, Cheng Z. Acute lung injury inhibition by juglone in LPS induced sepsis mouse model involves Sirt1 activation. Trop J Pharm Res 2020; 19(5):1001-1007 doi: 10.4314/tjpr.v19i5.14

© 2020 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To investigate the effect of juglone on LPS induced lung injury in a mouse model and in TC 1 cell line.

Methods: Edema formation in lungs were measured by determination of lung wet/dry weight. expressions of various proteins were assessed by western blot assay, while Sirt1 level was assessed using immunohistochemistry. Mice were randomly assigned to nine groups of 10 mice each: normal control, untreated and seven juglone treatment groups. Acute lung injury was induced in mice by injecting LPS (10 mg/kg) via intraperitoneal route (ip). The treatment groups were given 10, 20, 30, 40, 50, 60 and 100 µM of juglone, ip, respectively.

Results: The levels of MMP-9, IL-6, IL-1β and iNOS were significantly higher in acute lung injury induced mice compared than the control group (p < 0.05). Treatment of the mice with juglone significantly decreased LPS-induced up-regulation of inflammatory cytokines in a dose-dependent manner. The production of inflammatory cytokines was almost completely inhibited in the mice treated with 100 mg/kg dose of juglone, while treatment of the LPS-stimulated TC 1 cells with juglone up-regulated the expression of Sirt1 mRNA. Down-regulation of Sirt1 expression by siRNA inhibited the effect of juglone on LPS-induced increase in inflammatory cytokine production.

Conclusion: Juglone prevents lung injury in mice via up-regulation of Sirt1 expression. Therefore, juglone might be useful for the development of a treatment strategy for lung injury.

Keywords: Inflammatory, Sirtuin, Edema, Cytokines, Lung injury, TC 1 lung alveolar epithelial cells, Sirt1