异甘草素通过激活 PI3K/AKT/GSK-3β 通路预防β-淀粉样蛋白相关认知障碍。
Isorhapontigenin prevents β‑amyloid‑associated cognitive impairments through activation of the PI3K/AKT/GSK‑3β pathway.
机构信息
Department of Geriatrics Neurology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China;
Department of Geriatrics Neurology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
出版信息
Acta Neurobiol Exp (Wars). 2022;82(3):389-397. doi: 10.55782/ane-2022-037.
Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disease that is the most common cause of dementia in the elderly. Aβ1‑42 is significantly associated with memory deficits and it can increase the level of acetylcholine, promote the activity of acetylcholinesterase (AChE), and cause cognitive dysfunction. Isorhapontigenin (ISO) is a stilbene derivative that has antioxidant, anti‑tumor, and anti‑inflammatory effects. However, it is still unclear whether ISO can affect β‑amyloid‑associated cognitive impairments. In this study, we found that ISO improved cognitive dysfunction induced by Aβ1‑42 in rats. It inhibited the Aβ‑induced activation of M1 microglia and reduced the release of inflammatory cytokines. It alleviated amyloid beta‑induced oxidative stress and led to an overall improvement in AD symptoms. Cellularly, we found that ISO alleviated Aβ‑induced inflammation and oxidative stress by activating the PI3K/AKT/GSK‑3β pathway and ultimately improved cognitive dysfunction in AD rats.
阿尔茨海默病（AD）是一种慢性进行性神经退行性疾病，是老年人中最常见的痴呆症病因。Aβ1-42 与记忆缺陷显著相关，它可以增加乙酰胆碱水平，促进乙酰胆碱酯酶（AChE）的活性，并导致认知功能障碍。异甘草素（ISO）是一种芪类衍生物，具有抗氧化、抗肿瘤和抗炎作用。然而，目前尚不清楚 ISO 是否会影响与β-淀粉样蛋白相关的认知障碍。在这项研究中，我们发现 ISO 可改善 Aβ1-42 诱导的大鼠认知功能障碍。它抑制 Aβ 诱导的 M1 小胶质细胞激活，并减少炎症细胞因子的释放。它减轻了淀粉样β诱导的氧化应激，从而整体改善 AD 症状。在细胞水平上，我们发现 ISO 通过激活 PI3K/AKT/GSK-3β 通路缓解了 Aβ 诱导的炎症和氧化应激，最终改善了 AD 大鼠的认知功能障碍。
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