[en] Klebsiella pneumoniae (Kpn) is an important pathogen of hospital-acquired pneumonia, which can lead to sepsis and death in severe cases. In this study, we simulated pneumonia induced by Kpn infection in mice to investigate the therapeutic effect of naringin (NAR) on bacterial-induced lung inflammation. Mice infected with Kpn exhibited increases in white blood cells (WBC) and neutrophils in the peripheral blood and pathological severe injury of the lungs. This injury was manifested by increased expression of the inflammatory cytokines interleukin (IL)- 18, IL-1β, tumor necrosis factor-α (TNF-α) and IL-6, and elevated the expression of NLRP3 protein. NAR treatment could decrease the protein expression of NLRP3, alleviate lung inflammation, and reduce lung injury in mice caused by Kpn. Meanwhile, molecular docking results suggest NAR could bind to NLRP3 and Surface Plasmon Resonance (SPR) analyses also confirm this result. In vitro trials, we found that pretreated with NAR not only inhibited nuclear translocation of nuclear factor (NF)-κB protein P65 but also attenuated the protein interaction of NLRP3, caspase-1 and ASC and inhibited the assembly of NLRP3 inflammasome in mice AMs. Additionally, NAR could reduce intracellular potassium (K+) efflux, inhibiting NLRP3 inflammasome activation. These results indicated that NAR could protect against Kpn-induced pneumonia by inhibiting the overactivation of the NLRP3 inflammasome signaling pathway. The results of this study confirm the efficacy of NAR in treating bacterial pneumonia, refine the mechanism of action of NAR, and provide a theoretical basis for the research and development of NAR as an anti-inflammatory adjuvant.
Disciplines :
Veterinary medicine & animal health
Author, co-author :
Jing, Xiao-Han; Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Sciences (CAAS), China, Engineering and Technology Research Center of Traditional Chinese Veterinary Medicine of Gansu Province, China, Key Laboratory of Veterinary Pharmaceutical Development of Ministry of Agriculture and Rural Affairs of P.R. China, China
Zhao, Guan-Yu; College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou, Gansu 730000, China
Wang, Gui-Bo; Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Sciences (CAAS), China, Engineering and Technology Research Center of Traditional Chinese Veterinary Medicine of Gansu Province, China, Key Laboratory of Veterinary Pharmaceutical Development of Ministry of Agriculture and Rural Affairs of P.R. China, China
Huang, Qi-Lin; Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Sciences (CAAS), China, Engineering and Technology Research Center of Traditional Chinese Veterinary Medicine of Gansu Province, China, Key Laboratory of Veterinary Pharmaceutical Development of Ministry of Agriculture and Rural Affairs of P.R. China, China
Zou, Wen-Shu; Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Sciences (CAAS), China, Engineering and Technology Research Center of Traditional Chinese Veterinary Medicine of Gansu Province, China, Key Laboratory of Veterinary Pharmaceutical Development of Ministry of Agriculture and Rural Affairs of P.R. China, China
Huang, Li-Na; School of Pharmacy, State Key Laboratory of Applied Organic Chemistry, Lanzhou University, China
Li, Wei; Lanzhou Center for Disease Control and Prevention, Lanzhou, China. Electronic address: 349665516@qq.com
Qiu, Zheng-Ying; Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Sciences (CAAS), China, Engineering and Technology Research Center of Traditional Chinese Veterinary Medicine of Gansu Province, China, Key Laboratory of Veterinary Pharmaceutical Development of Ministry of Agriculture and Rural Affairs of P.R. China, China. Electronic address: qiumoying@163.com
Xin, Ruihua ; Université de Liège - ULiège > TERRA Research Centre ; Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Sciences (CAAS), China, Engineering and Technology Research Center of Traditional Chinese Veterinary Medicine of Gansu Province, China, Key Laboratory of Veterinary Pharmaceutical Development of Ministry of Agriculture and Rural Affairs of P.R. China, China. Electronic address: xinruihua@caas.cn
Language :
English
Title :
Naringin alleviates pneumonia caused by Klebsiella pneumoniae infection by suppressing NLRP3 inflammasome.
This work was supported by the National Key Research and Development Program of China ( 2022YFD180110304 ), National Natural Science Foundation of China ( 32002328 ), Natural Science Foundation of Gansu Province ( 22JR5RA038 ), Key Research and Development fund of Gansu Province , China ( 21YF5FA166 ), Central government guides local science and technology development fund projects in Gansu province ( 22ZY1QA012 ). Lanzhou Science and Technology Project , China ( 2021–1-159 , 2022-RC-21 ).This work was supported by the National Key Research and Development Program of China (2022YFD180110304), National Natural Science Foundation of China (32002328), Natural Science Foundation of Gansu Province (22JR5RA038), Key Research and Development fund of Gansu Province, China (21YF5FA166), Central government guides local science and technology development fund projects in Gansu province (22ZY1QA012). Lanzhou Science and Technology Project, China (2021–1-159, 2022-RC-21).
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