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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| Format: | Article |
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MDPI AG
2023-11-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/22/7527 |
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| author | Chao Zhong Jing Yang Keke Deng Xiaoya Lang Jiangtao Zhang Min Li Liang Qiu Guoyue Zhong Jun Yu |
| author_facet | Chao Zhong Jing Yang Keke Deng Xiaoya Lang Jiangtao Zhang Min Li Liang Qiu Guoyue Zhong Jun Yu |
| author_sort | Chao Zhong |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T16:34:19Z |
| format | Article |
| id | doaj.art-73d6e6f940a34baa87aa407daa653044 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T16:34:19Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-73d6e6f940a34baa87aa407daa6530442023-11-24T14:58:06ZengMDPI AGMolecules1420-30492023-11-012822752710.3390/molecules28227527Tiliroside Attenuates NLRP3 Inflammasome Activation in Macrophages and Protects against Acute Lung Injury in MiceChao Zhong0Jing Yang1Keke Deng2Xiaoya Lang3Jiangtao Zhang4Min Li5Liang Qiu6Guoyue Zhong7Jun Yu8Center for Translational Medicine, College of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang 330004, ChinaCenter for Translational Medicine, College of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang 330004, ChinaCenter for Translational Medicine, College of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang 330004, ChinaCenter for Translational Medicine, College of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang 330004, ChinaCenter for Translational Medicine, College of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang 330004, ChinaCenter for Traditional Chinese Medicine Resources and Ethnic Medicine, Jiangxi University of Chinese Medicine, Nanchang 330004, ChinaCenter for Translational Medicine, College of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang 330004, ChinaCenter for Traditional Chinese Medicine Resources and Ethnic Medicine, Jiangxi University of Chinese Medicine, Nanchang 330004, ChinaDepartment of Cardiovascular Sciences, Center for Metabolic Disease Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USAThe 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.https://www.mdpi.com/1420-3049/28/22/7527tilirosideNLRP3 inflammasomemacrophagesAMPKmitochondrial damageacute lung injury |
| spellingShingle | Chao Zhong Jing Yang Keke Deng Xiaoya Lang Jiangtao Zhang Min Li Liang Qiu Guoyue Zhong Jun Yu Tiliroside Attenuates NLRP3 Inflammasome Activation in Macrophages and Protects against Acute Lung Injury in Mice Molecules tiliroside NLRP3 inflammasome macrophages AMPK mitochondrial damage acute lung injury |
| title | Tiliroside Attenuates NLRP3 Inflammasome Activation in Macrophages and Protects against Acute Lung Injury in Mice |
| title_full | Tiliroside Attenuates NLRP3 Inflammasome Activation in Macrophages and Protects against Acute Lung Injury in Mice |
| title_fullStr | Tiliroside Attenuates NLRP3 Inflammasome Activation in Macrophages and Protects against Acute Lung Injury in Mice |
| title_full_unstemmed | Tiliroside Attenuates NLRP3 Inflammasome Activation in Macrophages and Protects against Acute Lung Injury in Mice |
| title_short | Tiliroside Attenuates NLRP3 Inflammasome Activation in Macrophages and Protects against Acute Lung Injury in Mice |
| title_sort | tiliroside attenuates nlrp3 inflammasome activation in macrophages and protects against acute lung injury in mice |
| topic | tiliroside NLRP3 inflammasome macrophages AMPK mitochondrial damage acute lung injury |
| url | https://www.mdpi.com/1420-3049/28/22/7527 |
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