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Inflammation. 2019 Mar 19. doi: 10.1007/s10753-019-00990-7. [Epub ahead of print]

Dihydromyricetin Alleviates Sepsis-Induced Acute Lung Injury through Inhibiting NLRP3 Inflammasome-Dependent Pyroptosis in Mice Model.

Author information

1
Trauma center/Department of Emergency and Traumatic Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, 1095 Jiefang avenue, Wuhan, 430030, Hubei Province, China, People's Republic of China.
2
Trauma center/Department of Emergency and Traumatic Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, 1095 Jiefang avenue, Wuhan, 430030, Hubei Province, China, People's Republic of China. lezhfei@163.com.

Abstract

Increasing evidence demonstrates that pyroptosis, pro-inflammatory programmed cell death, is linked to acute lung injury (ALI). Dihydromyricetin (DHM) has been reported to exert anti-inflammatory effects by inhibiting NLRP3 inflammasome activation in vascular endothelial cells. However, the effects of DHM on NLRP3 inflammasome-induced pyroptosis in ALI remain elusive. In the present study, male BALB/c mice were subjected to cecal ligation and puncture (CLP), and DHM (50, 100, 150 mg/kg) was orally administered (once per day, for 3 days) 2 h after CLP. After 72 h, lung histopathology was examined, and the wet/dry (W/D) ratio, inflammatory infiltration, total protein concentration, total cell, and neutrophil counts were detected. Myeloperoxidase (MPO), interleukin (IL)-6, TNF-α, IL-1β, and IL-18 levels in bronchoalveolar lavage fluid (BALF) were measured by ELISA. Additionally, the expression of NLRP3 signaling pathway proteins were detected by Western blotting. The results revealed that in BALF, DHM (150 mg/kg) treatment significantly reduced the CLP-induced lung histopathological injury, inflammatory cell infiltration, total cell and neutrophil number, and total protein and albumin concentration. DHM treatment significantly inhibited the CLP-induced NLRP3 inflammasome pathway (NLRP3, ASC, caspase-1, gasdermin D (Gsdmd), IL-1β, and IL-18). In conclusion, these results demonstrate that DHM protects against CLP-induced ALI by inhibiting NLRP3 inflammasome activation and subsequent pyroptosis.

KEYWORDS:

NLRP3 inflammasome; acute lung injury; dihydromyricetin; pyroptosis; sepsis

PMID:
30887396
DOI:
10.1007/s10753-019-00990-7

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