Oxidative stress is a key component of the pathological cascade in subarachnoid hemorrhage (SAH). Fucoxanthin (Fx) possesses a strong antioxidant property and has shown neuroprotective effects in acute brain injuries such as ischemic stroke and traumatic brain injury. Here, we investigated the beneficial effects of Fx against SAH-induced oxidative insults and the possible molecular mechanisms. Our data showed that Fx could significantly inhibit SAH-induced reactive oxygen species production and lipid peroxidation, and restore the impairment of endogenous antioxidant enzymes activities. In addition, Fx supplementation improved mitochondrial morphology, ameliorated neural apoptosis, and reduced brain edema after SAH. Moreover, Fx administration exerted an improvement in short-term and long-term neurobehavior functions after SAH. Mechanistically, Fx inhibited oxidative damage and brain injury after SAH by deacetylation of forkhead transcription factors of the O class and p53 via sirtuin 1 (Sirt1) activation. EX527, a selective Sirt1 inhibitor, significantly abated Fx-induced Sirt1 activation and abrogated the antioxidant and neuroprotective effects of Fx after SAH. In primary neurons, Fx similarly suppressed oxidative insults and improved cell viability. These effects were associated with Sirt1 activation and were reversed by EX527 treatment. Taken together, our study explored that Fx provided protection against SAH-induced oxidative insults by inducing Sirt1 signaling, indicating that Fx might serve as a potential therapeutic drug for SAH.

氧化应激是蛛网膜下腔出血（SAH）病理级联的关键组成部分。岩藻黄质（Fx）具有很强的抗氧化性能，并在缺血性中风和颅脑外伤等急性脑损伤中显示出神经保护作用。在这里，我们研究了Fx对SAH诱导的氧化损伤的有益作用以及可能的分子机制。我们的数据表明，Fx可以显着抑制SAH诱导的活性氧生成和脂质过氧化，并恢复内源性抗氧化酶活性的损害。此外，Fx补充剂改善了SAH后的线粒体形态，改善了神经细胞凋亡，并减少了脑水肿。此外，Fx给药可改善SAH后短期和长期的神经行为功能。机械上，Fx通过经由Sirtuin 1（Sirt1）激活使O类叉头转录因子和p53脱乙酰化，从而抑制SAH后的氧化损伤和脑损伤。EX527是一种选择性Sirt1抑制剂，可显着减轻Fx诱导的Sirt1活化，并消除SAH后Fx的抗氧化和神经保护作用。在原代神经元中，Fx同样抑制了氧化损伤并改善了细胞活力。这些作用与Sirt1激活有关，并通过EX527处理逆转。综上所述，我们的研究探索了Fx通过诱导Sirt1信号传导来提供针对SAH诱导的氧化损伤的保护作用，表明Fx可能作为SAH的潜在治疗药物。