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Inflammopharmacology. 2018 Apr;26(2):635-643. doi: 10.1007/s10787-017-0398-0. Epub 2017 Oct 7.

Acacetin attenuates mice endotoxin-induced acute lung injury via augmentation of heme oxygenase-1 activity.

Author information

1
Emergency Department, General Hospital of Chinese People's Liberation Army, No. 28 Fuxing Road, Haidian District, Beijing, 100853, People's Republic of China.
2
Emergency Department, General Hospital of Chinese People's Liberation Army, No. 28 Fuxing Road, Haidian District, Beijing, 100853, People's Republic of China. TanshiLi07@163.com.

Abstract

Acacetin, a natural product, has a wide spectrum of biological activities such as antioxidant properties. In the present study, we examined whether Acacetin has any beneficial role on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and, if so, whether its effect is mediated via heme oxygenase-1 (HO-1), an antioxidant enzyme playing an important role in ALI. Male BALB/c mice were stimulated with LPS intratracheal instillation to induce ALI. Acacetin was administrated 2 h after LPS challenge. Samples were harvested 10 h after LPS administration. We demonstrated that LPS challenge significantly induced lung histological alterations such as inflammation and edema. Acacetin administration notably attenuated these changes and reduced tumor necrosis factor-α and interleukin-1β in lung tissues. The LPS-induced reactive oxygen species generation was markedly suppressed by Acacetin. Furthermore, Acacetin treatment significantly elevated pulmonary HO-1 and nuclear factor erythroid-2-related factor 2 (Nrf2) activities. However, the beneficial action of Acacetin was markedly abolished when pretreated with zinc protoporphyrin, an inhibitor of HO-1. In in vitro studies, Acacetin notably increased the HO-1 expression in pulmonary microvascular endothelial cells. During knockdown of Nrf2 by siRNA, the effect of Acacetin on HO-1 expression was significantly reversed. Acacetin attenuates LPS-induced ALI in mice. This protective effect of Acacetin may be mediated, in part, through an HO-1-dependent pathway.

KEYWORDS:

Acacetin; Acute lung injury; Heme oxygenase-1

PMID:
28988328
DOI:
10.1007/s10787-017-0398-0
[Indexed for MEDLINE]

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