One of the most significant pathologies of Alzheimer’s disease (AD), an irreversible and progressive neurodegenerative disease that causes cognitive impairment, is the neuroinflammation facilitating the accumulation of amyloid-β (Aβ) peptide. Hence, the inhibition of abnormal neuroinflammatory response is considered a promising therapeutic approach for AD. Picrorhiza kurroa Bentham, Scrophulariae (PK) is a medicinal herb that has been traditionally used for the treatment of various diseases, including inflammation. This study aims to report the significance of PK treatment in markedly improving spatial learning memory and dramatically decreasing Aβ levels in Tg6799 mice, also known 5xFAD mice, which have five familial AD (FAD) mutations. Remarkably, these effects correlated with reversal of disease-related microglial neuroinflammation, as evidenced by shifting microglia phenotypes from the inflammatory form to the anti-inflammatory form and inhibiting the nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain containing 3 inflammasome activity. Moreover, PK administration induced silent information regulator type1/peroxisome proliferator-activated receptor-γ signaling, resulting in a decrease of β-secretase 1 (BACE1) expression, which involved in Aβ production. Overall, this study suggests that PK exhibits a neuroprotective effect by inducing alternative activation of microglia and downregulating the BACE1 expression, thereby ameliorating the disease pathophysiology and reversing the cognitive decline related to Aβ deposition in AD mice.

中文翻译：

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Picrorhiza kurroa 通过抑制 5xFAD 小鼠的 NLRP3 炎症小体激活和 BACE1 表达来预防记忆缺陷。

阿尔茨海默病 (AD) 是一种导致认知障碍的不可逆和进行性神经退行性疾病，其最重要的病理之一是促进淀粉样蛋白-β (Aβ) 肽积累的神经炎症。因此，抑制异常的神经炎症反应被认为是一种很有前途的 AD 治疗方法。苦参边沁玄参 (PK) 是一种药草，传统上用于治疗各种疾病，包括炎症。本研究旨在报告 PK 治疗在显着改善空间学习记忆和显着降低 Tg6799 小鼠（也称为 5xFAD 小鼠）中的 Aβ 水平的意义，这些小鼠具有五个家族性 AD (FAD) 突变。值得注意的是，这些作用与疾病相关的小胶质细胞神经炎症的逆转相关，这可以通过将小胶质细胞表型从炎症形式转变为抗炎形式并抑制核苷酸结合寡聚结构域、富含亮氨酸的重复序列和含有 3 个炎性体的 pyrin 结构域来证明活动。此外，PK 给药诱导沉默信息调节因子 1 型/过氧化物酶体增殖物激活受体-γ 信号传导，导致参与 Aβ 产生的 β-分泌酶 1 (BACE1) 表达降低。总体而言，这项研究表明，PK 通过诱导小胶质细胞的替代激活和下调 BACE1 表达而表现出神经保护作用，从而改善疾病的病理生理学并逆转 AD 小鼠与 Aβ 沉积相关的认知衰退。