Astaxanthin attenuates carrageenan-induced oxidative stress and inflammation in mice brain: possible role of the wnt/β-catenin signaling pathway

Astaxanthin (AST) is a red pigment carotenoid with various pharmacological effects. It exerts powerful antioxidant and anti-inflammatory activities. However, there is still limited and sometimes contrasting data regarding the exact mechanism of AST in different inflammation models. This study aimed to investigate whether AST attenuates oxidative stress and the inflammatory response in a mouse model of carrageenan (CAR)-induced inflammation and whether the wnt/β-catenin signaling pathway is involved in these potential protective effects. Thirty-two male mice were randomly divided into four equal groups and pretreated with AST at 5 and 10 mg/kg doses for 14 days before CAR injection. The anti-inflammatory and anti-nociceptive effects of AST were assessed using the hot-plate test. Antioxidant enzyme activity and gene expression were evaluated by spectrophotometric analysis and qRT-PCR, respectively. Our findings demonstrated that AST produced neuroprotective effects, as evidenced by significantly reduced levels of malondialdehyde (MDA) and markedly increased levels of glutathione (GSH) and catalase (CAT) activity, as well as an increased latency of pain response on the hot plate. Furthermore, AST exhibited anti-inflammatory effects, as indicated by a significant reduction in the expression of glycogen synthase kinase 3β (gsk3β), tumor necrosis factor-alpha (tnf-α), and interleukin 6 (il-6) genes, alongside markedly increased expression of β-catenin and wnt genes in the brain. In summary, our data indicate that AST pretreatment modulates CAR-induced oxidative stress and inflammation by promoting antioxidant enzyme activity, suppressing inflammatory cytokines, and activating the wnt/β-catenin signaling pathway.