Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
Department of Anatomy, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
Neurotox Res. 2021 Apr;39(2):266-276. doi: 10.1007/s12640-020-00269-y. Epub 2020 Aug 27.
A high dose of dexamethasone induces neurodegeneration by initiating the inflammatory processes that lead to neural apoptosis. A dexamethasone administration model induces overproduction of amyloid-β (Aβ) and tau protein hyperphosphorylation and shows abnormalities of cholinergic function similar to Alzheimer's disease (AD). This study aimed to investigate the protective effect of hexahydrocurcumin on the brain of dexamethasone-induced mice. The results showed that hexahydrocurcumin and donepezil attenuated the levels of amyloid precursor protein and β-secretase mRNA by reverse transcription polymerase chain reaction, decreased the expression of hyperphosphorylated tau, and improved synaptic function. Moreover, we found that hexahydrocurcumin treatment could decrease interleukin-6 levels by attenuating p65 of nuclear factor kappa-light-chain-enhancer (NF-κB) of activated beta cells. In addition, hexahydrocurcumin also decreased oxidative stress, as demonstrated by the expression of 4-hydroxynonenal and thereby prevented apoptosis. Therefore, our finding suggests that hexahydrocurcumin prevents dexamethasone-induced AD-like pathology and improves memory impairment.
大剂量地塞米松通过启动导致神经细胞凋亡的炎症过程诱导神经退行性变。地塞米松给药模型诱导淀粉样β（Aβ）和tau 蛋白过度产生以及胆碱能功能异常，类似于阿尔茨海默病（AD）。本研究旨在探讨六氢姜黄素对地塞米松诱导的小鼠大脑的保护作用。结果表明，六氢姜黄素和多奈哌齐通过逆转录聚合酶链反应降低淀粉样前体蛋白和β-分泌酶 mRNA 的水平，降低过度磷酸化的 tau 的表达，并改善突触功能。此外，我们发现六氢姜黄素处理可以通过抑制激活的β细胞中核因子κB（NF-κB）的 p65 来降低白细胞介素-6 水平。此外，六氢姜黄素还降低了氧化应激，表现为 4-羟壬烯醛的表达，从而防止了细胞凋亡。因此，我们的研究结果表明，六氢姜黄素可预防地塞米松诱导的 AD 样病理并改善记忆障碍。
