Lichen secondary metabolite atraric acid alleviates chronic intermittent hypoxia-induced liver injury by activating autophagy to inhibit the NF-κB pathway

<p indent="0mm">Chronic intermittent hypoxia (CIH) is an alternating state of recurrent hypoxia and reoxygenation triggered by disorders such as sleep apnea, leading to systemic oxidative stress and organ damage. In this study, we investigate the protective effect and mechanism of atraric acid (AA), a secondary metabolite produced by lichens, against CIH-induced liver injury. By establishing a CIH mouse model <sc>(10 h/d,</sc> oxygen cycling 5%–21% for 4 weeks) and an <italic>in vitro</italic> model of AML-12 cell hypoxia/reoxygenation (H/R), combined with H&amp;E staining, biochemical assays (ALT/AST/MDA/CAT/T-AOC/GSH-Px), qPCR, western blotting, immunofluorescence and flow cytometry (JC-1 detection of the mitochondrial membrane potential) were performed. The results show that AA significantly reduces alanine aminotransferase (ALT)/aspartate aminotransferase (AST) levels, inhibits the elevation of hepatic malondialdehyde (MDA), restores the activities of catalase (CAT), total antioxidant capacity (T-AOC), and glutathione peroxidase (GSH-Px) in CIH mice, ameliorates mitochondrial dysfunction; activates autophagy; and reduces the expression of inflammatory factors. Mechanistically, AA reduces the release of downstream proinflammatory factors by blocking NF-κB nuclear translocation through the inhibition of IκBα phosphorylation. The activation of autophagic flow by AA is accompanied by a significant increase in LC3-II/I protein expression. Furthermore, autophagy blockade impedes the role of AA in alleviating inflammatory oxidative stress and mitochondrial dysfunction in the CIH-induced injury model, confirming that autophagy activation is necessary for the protective effect of AA. In conclusion, the present study reveals that AA alleviates oxidative stress and mitochondrial dysfunction, as well as NF-κB signaling, through the activation of autophagy, providing a novel therapeutic strategy for CIH-associated liver injury.