Luteolin attenuates LPS-induced damage in IPEC-J2 cells by enhancing mitophagy via AMPK signaling pathway activation

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Background: Luteolin (LUT), a flavonoid compound widely present in natural plants, has been extensively studied for its diverse biological properties, involving anti-inflammatory,antioxidant, anti-apoptosis and other properties. Methods: The aim of this study was to investigate the effect of LUT on lipopolysaccharide (LPS)-induced Intestinal Porcine Epithelial Cell line-J2 (IPEC-J2 cells) damage and its underlying mechanism. Results: The experiment showed that LPS treatment induced injury in IPEC-J2 cells, leading to tight junction disruption, ROS accumulation, and cell apoptosis. Remarkably, LUT attenuated LPS-induced IPEC-J2 cells damage by the up-regulation of Zonula Occludens-1(ZO-1), Occludin, and Claudin protein 1 (Claudin-1) protein expression levels.Besides, LUT increased the activities of CAT, and SOD and prevented 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 Interleukin-6 (IL-6) expression. Moreover, LUT attenuated LPS-induced apoptosis 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 (Caspase-3), Cysteine - aspartic acid protease 9 (Caspase-9) and Bcl-2-associated X protein (Bax). Furthermore, LUT upregulated the AMP-activated protein kinase (AMPK)/Unc-51 like autophagy activating kinase (ULK) signaling pathway and Parkin-RBR E3 ubiquitin protein ligase (Parkin)/PTEN induced putative kinase 1 (PINK1)-mediated mitophagy in a dose-dependent manner. When AMPK was knocked down by short-hairpin 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. Conclusion: In summary, LUT exhibits the ability to protect against LPS-induced damage to intestinal tight junctions by enhancing mitophagy through AMPK activation.

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