Changliang He1,2, Jia Yang1,2, Xiaolin Jiang1,2, Xiaoxia Liang1,2, Lizi Yin1,2, Zhongqiong Yin1,2, Yi Geng3, Zhijun Zhong4, Xu Song1,2, Yuanfeng Zou1,2, Lixia Li1,2, Wei Zhang1,2, Cheng Lv1,2. 1. Department of Pharmacy, College of Veterinary Medicine, Sichuan Agricultural University , Chengdu , China. 2. College of Veterinary Medicine, Natural Medicine Research Center, Sichuan Agricultural University , Chengdu , China. 3. Department of Basic Veterinary, College of Veterinary Medicine, Sichuan Agricultural University , Chengdu , China. 4. College of Veterinary Medicine, Sichuan Agricultural University, Sichuan Province Key Laboratory of Animal Disease and Human Health, Key Laboratory of Environmental Hazard and Human Health of Sichuan Province , Chengdu , China.
Abstract
Background: The pharmacological application of kaempferol, a natural flavonol present in different plant species, has been demonstrated to have extensive anti-inflammatory, anti-apoptotic, anti-oxidative, and anti-cancer effects. Pyroptosis is an inflammatory form of programed cell death by membranolysis and associated leakage of cytoplasm. This study investigated the molecular mechanism of kaempferol-induced effects on the pyroptosis in splenic lymphocytes (SLCs) isolated from mice. Methods: Lipopolysaccharide (LPS)-primed and adenosine triphosphate (ATP)-stimulated SLCs were used to establish the pyroptosis model. The kaempferol pretreatment was tested in the model. Results: The results show that kaempferol alleviates LPS-ATP mediated damage by increasing cell viability, improving membrane integrity, and decreasing the release of IL1b and IL-18. Kaempferol reduces pyroptosis by suppressing the expression and activity of caspase-1, increasing the protein expression of Toll-like receptor 4 (TLR4) and NOD-like receptor 3 (NLRP3), and inhibition of the decomposition of gasdermin D (GSDMD). Conclusions: Our data suggest that kaempferol exhibits anti-pyroptosis activities, which warrants further detailed investigation.
Background: The pharmacological application of kaempferol, a natural flavonol present in different plant species, has been demonstrated to have extensive anti-inflammatory, anti-apoptotic, anti-oxidative, and anti-cancer effects. Pyroptosis is an inflammatory form of programed cell death by membranolysis and associated leakage of cytoplasm. This study investigated the molecular mechanism of kaempferol-induced effects on the pyroptosis in splenic lymphocytes (SLCs) isolated from mice. Methods: Lipopolysaccharide (LPS)-primed and adenosine triphosphate (ATP)-stimulated SLCs were used to establish the pyroptosis model. The kaempferol pretreatment was tested in the model. Results: The results show that kaempferol alleviates LPS-ATP mediated damage by increasing cell viability, improving membrane integrity, and decreasing the release of IL1b and IL-18. Kaempferol reduces pyroptosis by suppressing the expression and activity of caspase-1, increasing the protein expression of Toll-like receptor 4 (TLR4) and NOD-like receptor 3 (NLRP3), and inhibition of the decomposition of gasdermin D (GSDMD). Conclusions: Our data suggest that kaempferol exhibits anti-pyroptosis activities, which warrants further detailed investigation.