褐藻源富可汀是从褐藻中提取的最丰富的海洋类胡萝卜素，具有抗氧化、抗炎和神经保护作用，可能有助于治疗神经性疾病。术后认知功能障碍（POCD）是一种以学习和记忆障碍为主的神经症状，主要影响老年人术后。然而，目前对该症状尚无有效治疗方法。本研究评估了富可汀对手术后老年小鼠POCD的神经保护作用。 使用卤莽膦作为阳性对照。通过行为测试分析富可汀对POCD的有益效果。采用酶联免疫吸附法（ELISA）测定前炎症细胞因子。通过Western blotting分析分析Akt和ERK信号通路的关键蛋白的表达。通过免疫组化染色研究微胶质细胞和星形胶质细胞的形态。通过抗氧化酶活性测定测定抗氧化超氧化物歧化酶（SOD）和过氧化氢酶（CAT）的活性。100-200mg/kg的富可汀显著减轻了老年小鼠术后的认知功能障碍，与姜黄素具有类似的效力。此外，富可汀和姜黄素显著增加了pAkt的表达，阻止了微胶质细胞和星形胶质细胞的激活，并抑制了前炎症介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）的分泌。此外，富可汀和姜黄素提高了ERK通路并显著增加了抗氧化酶的活性。最重要的是，ERK通路抑制剂U0126和Akt通路抑制剂抑酮霉素显著减弱了富可汀对术后老年小鼠的认知增强作用，以及对神经炎症的抑制和抗氧化应激的减轻作用。富可汀可能通过激活Akt和ERK信号通路抑制神经炎症并增强抗氧化能力，作为功能性食品或药物用于POCD的治疗。 版权所有 © 2023 Elsevier GmbH.

Fucoxanthin is the most abundant marine carotenoid derived from brown seaweeds, possesses antioxidant, anti-inflammatory, and neuroprotective properties, and might be benefit for the treatment of neurological disorders. Post-operative cognitive dysfunction (POCD) is a neurological symptom with learning and memory impairments, mainly affecting the elderly after surgery. However, there is no effective treatments for this symptom.In this study, we evaluated the neuroprotective effects of fucoxanthin against POCD in aged mice after surgery.The animal model of POCD was established in 12 - 14 month aged mice with a laparotomy. Curcumin was used as a positive control. The beneficial effects of fucoxanthin on POCD was analyzed by behavioral tests. Pro-inflammatory cytokines were measured by Enzyme-linked Immunosorbent Assay (ELISA). And the expressions of key proteins in the Akt and ERK signaling pathways were analyzed by Western blotting analysis. The morphology of microglial cells and astrocytes was explored by immunohistochemical staining. The activity of antioxidant superoxide dismutase (SOD) and catalase (CAT) were measured by anti-oxidative enzyme activity assays.Fucoxanthin at 100 - 200 mg/kg significantly attenuated cognitive dysfunction, with a similar potency as curcumin, in aged mice after surgery. In addition, fucoxanthin and curcumin significantly increased the expression of pAkt, prevented the activation of microglial cells and astrocytes, and inhibited the secretion of pro-inflammatory interleukin-1β (IL - 1β) and tumor necrosis factor-α (TNF-α). Furthermore, fucoxanthin and curcumin elevated the ERK pathway and potently increased the activity of antioxidant enzymes. Most importantly, U0126, an inhibitor of the ERK pathway, and wortmannin, an inhibitor of the Akt pathway, significantly abolished the cognitive-enhancing effects, as well as the inhibition of neuroinflammation and the reduction of oxidative stress, induced by fucoxanthin in aged mice after surgery.Fucoxanthin might be developed as a functional food or drug for the treatment of POCD by inhibiting neuroinflammation and enhancing antioxidant capacity via the activation of the Akt and ERK signaling pathways.Copyright © 2023. Published by Elsevier GmbH.