[en] Necrotizing enterocolitis (NEC) is a fatal intestinal disease in premature infants, and is characterized by intestinal inflammation and disruption of the intestinal barrier. The protective effects of sodium butyrate (NaB) against NEC have been documented, however, the underlying fundamental processes remain unknown. To address this deficit, we used the NEC neonatal rat model to confirm the intestinal protective effect of NaB. We then used network pharmacology and confirmed a role for NaB in the attenuation of NEC and this was associated with the NLRP3 inflammasome and the NF-κB signaling pathway. These results were verified by proteome analysis in vivo, and molecular docking analysis was used to explore the potential underlying mechanisms, revealing a suppressive function of NaB on NEC, which may be caused by its interaction with the TLR4-mediated NF-κB signaling pathway. An in vitro cell model (LPS-stimulated IEC-6 cells) was then established to confirm the docking results. Results using assays involving the NLRP3 (MCC950) and TLR4 (TAK-242) inhibitors suggested that NaB protected intestinal cells from inflammatory injuries during NEC by suppressing the TLR4/MyD88/NF-κB/NLRP3/cleaved caspase-1/GSDMD inflammasome pathway. These findings indicated that NaB can be used as a potential modulatory and therapeutic candidate for the treatment of NEC.
Disciplines :
Food science
Author, co-author :
Gao, Yanan; Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China. zhengnan@caas.cn
Yang, Liting; Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China. zhengnan@caas.cn ; Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing 100193, China
Wu, Hongya; Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China. zhengnan@caas.cn
Yao, Qianqian ; Université de Liège - ULiège > TERRA Research Centre
Wang, Jiaqi; Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China. zhengnan@caas.cn
Zheng, Nan ; Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China. zhengnan@caas.cn
This study was supported by the National Key R&D Program of China (2022YFD1600104), the earmarked fund for CARS (CARS-36), the Agricultural Science and Technology Innovation Program (ASTIP-IAS12).
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