Tiliroside Attenuates NLRP3 Inflammasome Activation in Macrophages and Protects against Acute Lung Injury in Mice
Chao Zhong,
Jing Yang,
Keke Deng,
Xiaoya Lang,
Jiangtao Zhang,
Min Li,
Liang Qiu,
Guoyue Zhong,
Jun Yu
Affiliations
Chao Zhong
Center for Translational Medicine, College of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang 330004, China
Jing Yang
Center for Translational Medicine, College of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang 330004, China
Keke Deng
Center for Translational Medicine, College of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang 330004, China
Xiaoya Lang
Center for Translational Medicine, College of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang 330004, China
Jiangtao Zhang
Center for Translational Medicine, College of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang 330004, China
Min Li
Center for Traditional Chinese Medicine Resources and Ethnic Medicine, Jiangxi University of Chinese Medicine, Nanchang 330004, China
Liang Qiu
Center for Translational Medicine, College of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang 330004, China
Guoyue Zhong
Center for Traditional Chinese Medicine Resources and Ethnic Medicine, Jiangxi University of Chinese Medicine, Nanchang 330004, China
Jun Yu
Department of Cardiovascular Sciences, Center for Metabolic Disease Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA
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.