Astaxanthin Alleviates Ischemia-Reperfusion Injury by Regulating the JAK2/STAT3 Signaling Pathway

Cerebral ischemia-reperfusion injury (CIRI) is a leading cause of death worldwide, yet effective treatments remain limited. Astaxanthin (AST) has been shown to significantly ameliorate cerebral I/R injury; however, the underlying mechanisms are not fully understood. In this study, an oxygen-glucose deprivation/reoxygenation (OGD/R) model was used to simulate cerebral ischemia in vitro, with treatment of AST or a JAK2 agonist. Cell viability was assessed using the MTT assay, apoptosis was analyzed by flow cytometry, and oxidative damage was evaluated by measuring 8-hydroxy-2'-deoxyguanosine (8-OHdG), 4-hydroxy-2-nonenal (4-HNE), malondialdehyde (MDA), and reactive oxygen species (ROS). Western blotting was performed to detect pro-inflammatory factors (tumor necrosis factor-alpha: TNF-α; interleukin-1 beta: IL-1β; interleukin-6: IL-6; monocyte chemoattractant protein-1: MCP-1) and the protein expression of key components of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway (phospho-JAK2: p-JAK2; phospho-STAT3: p-STAT3). Additionally, an in vivo middle cerebral artery occlusion and reperfusion (MCAO/R) model was employed to further validate the effects of AST. The results showed that OGD/R significantly reduced PC12 cell viability, increased apoptosis, and elevated the levels of oxidative damage markers and pro-inflammatory factors. AST treatment promoted cell proliferation, inhibited apoptosis, and markedly reduced the levels of 8-OHdG, 4-HNE, MDA, ROS, TNF-α, IL-1β, IL-6, and MCP-1. Furthermore, OGD/R activated the JAK2/STAT3 signaling pathway, whereas AST alleviated cell damage by inhibiting the expression of p-JAK2 and p-STAT3. Activation of the JAK2/STAT3 pathway significantly abolished the protective effects of AST against OGD/R-induced PC12 cell damage. In vivo experiments further demonstrated that AST effectively alleviated ischemia-reperfusion injury in rats. In conclusion, AST exerts its protective effects through inhibition of the JAK2/STAT3 signaling pathway.