Department of Geriatrics, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang, China.
Key Laboratory of Diagnosis and Treatment of Aging and Physic-chemical Injury Diseases of Zhejiang Province, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Commun Biol. 2024 Jul 28;7(1):912. doi: 10.1038/s42003-024-06615-6.
Alzheimer's disease (AD) is the most common cause of dementia characterized by amyloid-β (Aβ) deposition, tau hyperphosphorylation, and neuroinflammation. Naringenin (NRG), a natural flavonoid widely present in citrus fruits, has been reported can penetrate the blood-brain barrier and exert anti-inflammatory effects in the central nervous system. Here, we investigate the protective effects of long-term NRG treatment on AD. The novel object recognition test and Morris water maze test reveal that NRG treatment can improve the learning and memory ability of APP/PS1 mice. Besides, we find that NRG can significantly reduce Aβ deposition, microglial and astrocytic activation, and pro-inflammatory cytokine levels in APP/PS1 mice. Results further show that NRG effectively decreases pro-inflammatory cytokines in LPS/Aβ-stimulated BV2 cells. Lastly, the molecular mechanistic study reveals that NRG attenuates neuroinflammatory responses via inhibition of the MAPK signaling pathway in vivo and in vitro. Overall, NRG may emerge as a promising compound for the prevention and treatment of AD.
阿尔茨海默病（AD）是最常见的痴呆症类型，其特征是淀粉样蛋白-β（Aβ）沉积、tau 过度磷酸化和神经炎症。柚皮素（NRG）是一种广泛存在于柑橘类水果中的天然类黄酮，据报道它可以穿透血脑屏障并在中枢神经系统发挥抗炎作用。在这里，我们研究了长期 NRG 治疗对 AD 的保护作用。新物体识别测试和 Morris 水迷宫测试表明，NRG 治疗可以提高 APP/PS1 小鼠的学习和记忆能力。此外，我们发现 NRG 可以显著减少 APP/PS1 小鼠中的 Aβ 沉积、小胶质细胞和星形胶质细胞激活以及促炎细胞因子水平。结果进一步表明，NRG 可有效降低 LPS/Aβ 刺激的 BV2 细胞中的促炎细胞因子。最后，分子机制研究表明，NRG 通过体内和体外抑制 MAPK 信号通路来减轻神经炎症反应。总的来说，NRG 可能成为预防和治疗 AD 的一种有前途的化合物。
