Tiliroside Attenuates NLRP3 Inflammasome Activation in Macrophages and Protects against Acute Lung Injury in Mice

The Nod-like receptor family PYRIN domain containing 3 (NLRP3) inflammasome is a multiprotein signaling complex that plays a pivotal role in innate immunity, and the dysregulated NLRP3 inflammasome activation is implicated in various diseases. Tiliroside is a natural flavonoid in multiple medicinal...

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Bibliographic Details
Published in:Molecules (Basel, Switzerland) Switzerland), 2023-11, Vol.28 (22), p.7527
Main Authors: Zhong, Chao, Yang, Jing, Deng, Keke, Lang, Xiaoya, Zhang, Jiangtao, Li, Min, Qiu, Liang, Zhong, Guoyue, Yu, Jun
Format: Article
Language:English
Subjects:
acute lung injury
Acute respiratory distress syndrome
Adenosine triphosphate
AMPK
Bioflavonoids
Chemokines
Cytokines
Ethylenediaminetetraacetic acid
Flavones
Flavonoids
Health aspects
Homeostasis
Inflammation
Kinases
Macrophages
Medicine, Botanic
Medicine, Herbal
mitochondrial damage
NLRP3 inflammasome
Protein kinases
Proteins
Reactive oxygen species
tiliroside
Type 2 diabetes
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Summary:The Nod-like receptor family PYRIN domain containing 3 (NLRP3) inflammasome is a multiprotein signaling complex that plays a pivotal role in innate immunity, and the dysregulated NLRP3 inflammasome activation is implicated in various diseases. Tiliroside is a natural flavonoid in multiple medicinal and dietary plants with known anti-inflammatory activities. However, its role in regulating NLRP3 inflammasome activation and NLRP3-related disease has not been evaluated. Herein, it was demonstrated that tiliroside is inhibitory in activating the NLRP3 inflammasome in macrophages. Mechanistically, tiliroside promotes AMP-activated protein kinase (AMPK) activation, thereby leading to ameliorated mitochondrial damage as evidenced by the reduction of mitochondrial reactive oxygen species (ROS) production and the improvement of mitochondrial membrane potential, which is accompanied by attenuated NLRP3 inflammasome activation in macrophages. Notably, tiliroside potently attenuated lipopolysaccharide (LPS)-induced acute lung injury in mice, which has been known to be NLRP3 inflammasome dependent. For the first time, this study identified that tiliroside is an NLRP3 inflammasome inhibitor and may represent a potential therapeutic agent for managing NLRP3-mediated inflammatory disease.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules28227527