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ORIGINAL RESEARCH article
Front. Nutr.
Sec. Nutritional Immunology
Volume 12 - 2025 | doi: 10.3389/fnut.2025.1552890
This article is part of the Research Topic Health Effects of Natural Compounds from Plant View all 3 articles
Luteolin attenuates LPS-induced damage in IPEC-J2 cells by enhancing mitophagy via AMPK signaling pathway activation
Provisionally accepted
Jianyun Yuan Ke Zhang Lingling Yang Xinyi Cheng Jinyan Chen Xiaoquan Guo 
Huabin Cao 
Caiying Zhang Chenghong Xing 
Guoliang Hu *
Yu Zhuang *- Jiangxi Agricultural University, Nanchang, China
Luteolin (LUT), a flavonoid compound widely present in natural pla nts, has been extensively studied for its diverse biological properties, invo lving anti-inflammatory, antioxidant, anti-apoptosis and other properties. The aim of this study was to investigate the effect of LUT on lipopolysacc haride (LPS)-induced Intestinal Porcine Epithelial Cell line -J2 (IPEC-J2 cells) damage and its underlying mechanism. Results showed that LPS tre atment induced injury in IPEC-J2 cells, leading to tight junction disruptio n, ROS accumulation, and cell apoptosis. Remarkably, LUT attenuated LP S-induced IPEC-J2 cells damage by the up-regulation of Zonula Occluden s-1(ZO-1), Occludin, and Claudin protein 1(Claudin-1) protein expressio n levels. Besides, LUT increased the activities of CAT, and SOD and prev ented LPS-induced MDA and ROS production. LUT suppressed Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation in LPS-induced IPEC-J2 cells, reducing (Interleukin-1beta) IL-1β and Int erleukin-6(IL-6) expression. Moreover, LUT attenuated LPS-induced apo ptosis in IPEC-J2 cells by up-regulating expression of B-cell lymphoma 2 (Bcl-2) and down-regulating expression of Cysteine-aspartic acid protease 3 3 (Caspase-3), Cysteine -aspartic acid protease 9 (Caspase-9) and Bcl-2associated X protein (Bax). Furthermore, LUT upregulated the AMP -acti vated protein kinase (AMPK)/Unc -51 like autophagy activating kinase (ULK) signaling pathway and Parkin -RBR E3 ubiquitin protein ligase (P arkin)/PTEN induced putative kinase 1 (PINK1) -mediated mitophagy in a dose -dependent manner. When AMPK was knocked down by short -ha irpin RNA (shRNA), the protective effects of LUT against LPS -induced IPEC -J2 cell damage were weakened, as evidenced by the accumulation of excessive ROS and impaired mitophagy. In summary, LUT exhibits the ability to protect against LPS-induced damage to intestinal tight junctions by enhancing mitophagy through AMPK activation.
Keywords: Luteolin, lipopolysaccharide, AMPK, IPEC-J2 cells, Mitoph agy
Received: 29 Dec 2024; Accepted: 06 Mar 2025.
Copyright: © 2025 Yuan, Zhang, Yang, Cheng, Chen, Guo, Cao, Zhang, Xing, Hu and Zhuang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Guoliang Hu, Jiangxi Agricultural University, Nanchang, China
Yu Zhuang, Jiangxi Agricultural University, Nanchang, China
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