Astaxanthin Mitigates Neurocognitive Deficits in D-Galactose-Induced Brain Aging: Targeting HMGB1/TLR4 / NF-κB signaling pathway

Introduction: D-galactose (D-gal) caused brain aging and cognitive decline. Astaxanthin (ASX) has anti-inflammatory and antioxidant impacts.Objective: to demonstrate the underlying mechanisms and the neuroprotective impact of ASX in D-gal-induced cognitive impairmentsMaterial & methods: Thirty male Wister albino rats were split into three groups: control, D-gal, and D-gal+ASX. Rats were subjected to the NOR and EPM tests, and after they were killed, the hippocampus gene expression of HMGB1, TLR4, NF-kB, and BDNF was evaluated, along with measurements of MDA, SOD, TNF-α, and IL-6. GFAP and NF-kB hippocampus immunoreaction were performed. Results: In contrast to the control group, D-gal had higher hippocampal GFAP and NF-kB immunoreaction and a significantly lower discrimination index of the NOR test, time in the open arms of EPM, SOD, and gene expression of BDNF, D-gal also demonstrated cognitive impairment with significantly higher MDA, TNF-α, IL-6, and hippocampal gene expression of HMGB1, TLR4, and NF-kB. D-gal-induced brain alterations were significantly ameliorated by ASX.Conclusion: By down-regulating the HMGB1/TLR4/NF-kB signaling cascade, improving gliosis, and utilizing neurotrophic, antioxidant, and anti-inflammatory pathways, ASX mitigated D-gal-induced cognitive impairments.