阿尔茨海默病（AD）是老年人失去记忆和认知功能的不可逆进行性脑部疾病。尽管药物疗法取得了显著进展，但有效的药理干预仍很少见。石榴、覆盆子、蓝莓和栗子中都含有一种活性抗氧化多酚物质-锁阳鞭甙（PU），其拥有强大的抗氧化和抗炎性质，引起了广泛的关注。本研究重点研究PU对老年小鼠神经保护作用及其潜在机制。在本研究中，我们首先评估了PU对BV2小胶质细胞介导的N2a细胞损伤所致神经炎症的保护作用。在活体外D-半乳糖（D-gal）诱导的脑衰老模型中，PU减轻了学习和记忆障碍，预防了神经炎症，这表现在微胶质细胞激活和星形胶质细胞增生减少。此外，PU减少了丙二醛（MDA）和活性氧（ROS）的水平，并抑制了NLRP3炎性小体的激活，减少了炎性细胞因子（如白细胞介素6（IL-6）、肿瘤坏死因子-α（TNF-α）、白细胞介素18（IL-18）和白细胞介素1β（IL-1β））的水平在加速老化和自然衰老的小鼠模型中。PU有效改善了老年小鼠的神经炎症、学习和记忆障碍和氧化还原平衡，可作为AD的潜在治疗药物。©2023 John Wiley＆Sons Ltd.

Alzheimer's disease (AD) is an irreversible, progressive brain disorder characterized by loss of memory and cognitive dysfunction in the aged. Despite remarkable advances in drug therapy, effective pharmacological interventions are rare. Punicalagin (PU) is an active antioxidant polyphenol found in pomegranates, raspberries, blueberries, and chestnuts that has attracted considerable attention owing to its strong antioxidant and anti-inflammatory properties. The current study focused on the neuroprotective effect of PU on aging mice and its potential mechanisms. In this study, we first evaluated the protective effect of PU on neuro-2a (N2a) cell damage mediated by BV2 microglia-induced neuroinflammation. The in vivo D-galactose (D-gal)-induced brain aging model demonstrated that PU ameliorated deficits in learning and memory and prevented neuroinflammation, which was evident from the decrease in microglial activation and astrocytosis. Furthermore, PU reduced the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) and inhibited NLRP3 inflammasome activation, reducing the levels of inflammatory cytokines, such as interleukin-6 (IL-6), tumor necrosis factor-a (TNF-a), interleukin-18 (IL-18), and interleukin-1 beta (IL-1β) in both accelerated aging and naturally senescent mouse models. PU effectively improved neuroinflammation, learning and memory deficits, and redox homeostasis in aging mice, and it could be a potential therapeutic agent for AD.© 2023 John Wiley & Sons Ltd.