Cu-Zhi-Yi-Hao (CZYH), an empirical formula of traditional Chinese medicine (TCM), has been used for amnesia treatment in clinical practice. However, its underlying pharmacological mechanism has not been fully illuminated. The current study was designed to investigate the neuroprotective effect of CZYH on a β-amyloid 25-35- (Aβ_25-35-) induced learning and memory deficit rat model. CZYH (200, 400, or 800 mg/kg), donepezil (1.0 mg/kg), or distilled water was given to Aβ_25-35-stimulated animals for 17 days consecutively. The Morris water maze test revealed that CZYH (400 or 800 mg/kg) administration improved the Aβ_25-35-induced cognitive impairments in rats, and Nissl staining demonstrated that CZYH mitigated the Aβ-caused neuron loss. In addition, CZYH treatment markedly inhibited the activation of microglia as evidenced by a decreased level of IBA-1 and increased YM-1/2 protein expression. The protein expression levels of TNF-α, IL-1β, and COX-2 were also repressed by CZYH. Besides, CZYH treatment alleviated Aβ-induced IκB-α degradation and NF-κB p65 phosphorylation, as well as reduced the JNK phosphorylation level. In conclusion, the present study suggests that CZYH could improve learning and memory abilities and relieve neuron loss in Aβ_25-35-induced rats, at least partly through inhibition of the neuroinflammatory response via inhibiting the JNK-dependent NF-κB activation, indicating that CZYH might be a promising formula for the treatment of AD.

中文翻译：

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CZYH通过调节JNK和NF-κB途径减轻β-淀粉样蛋白诱导的认知障碍和炎症反应。

Cu-Zhi-Yi-Hao（CZYH）是传统中药（TCM）的经验公式，已在临床实践中用于健忘症治疗。但是，其潜在的药理机制尚未完全阐明。目前的研究旨在探讨CZYH对一个神经保护作用β淀粉样蛋白25-35-（A β _25-35 - ）引起的学习记忆减退大鼠模型。CZYH（200，400，或800毫克/千克），多奈哌齐（1.0mg / kg的），或蒸馏水给予阿β _25-35刺激的动物17天连续。Morris水迷宫测试中，发现CZYH（400或800毫克/公斤）施用改善了甲β _25-35在诱导大鼠认知障碍和尼氏染色证实CZYH减轻在A β -caused神经元丢失。此外，CZYH处理可明显抑制小胶质细胞的活化，这可通过IBA-1水平降低和YM-1 / 2蛋白表达水平升高来证明。CZYH也抑制TNF - α，IL- 1β和COX-2的蛋白表达水平。此外，CZYH治疗可减轻的β诱导我κ B- α降解和NF- κ乙P65磷酸化，以及降低了JNK的磷酸化水平。总之，目前的研究表明，CZYH可以提高学习和记忆能力，减轻神经元丢失在一个β _25-35诱导的大鼠中，至少部分地通过抑制经由抑制JNK依赖性NF-所述神经炎性响应的κ乙激活，表明CZYH可能是治疗AD的一个有前途的公式。