桃红四物汤通过 SIRT6/ER 应激途径改善阿尔茨海默病认知功能障碍。
Taohong siwu decoction ameliorates cognitive dysfunction through SIRT6/ER stress pathway in Alzheimer's disease.
机构信息
Department of Neurology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China; Department of Neurology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China; Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, China.
Department of Neurology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China; Department of Neurology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China.
出版信息
J Ethnopharmacol. 2023 Oct 5;314:116580. doi: 10.1016/j.jep.2023.116580. Epub 2023 May 2.
ETHNOPHARMACOLOGICAL RELEVANCE
A growing number of people suffer from Alzheimer's disease (AD), but there is currently no effective treatment yet. Taohong Siwu Decoction (TSD) has been proved to take strong neuropharmacological activity on dementia, but the effect and mechanism of TSD against AD are still elusive.
AIM OF STUDY
To investigate whether TSD could be effective in ameliorating cognitive deficits through SIRT6/ER stress pathway.
MATERIALS AND METHODS
Herein, the APP/PS1 mice, an AD model, and HT-22 cell lines were utilized. Different dosages of TSD (4.25, 8.50 and 17.00 g/kg/d) were administered to the mice for 10 weeks by gavage. Following the behavioral tests, oxidative stress levels were measured using malondialdehyde (MDA) and superoxide dismutase (SOD) kits. Nissl staining and Western blot analyses were used to detect the neuronal function. Then, immunofluorescence and Western blot analysis were applied to evaluate silent information regulator 6 (SIRT6) and ER Stress related protein levels in APP/PS1 mice and HT-22 cells.
RESULTS
Behavioral tests revealed that APP/PS1 mice administered with TSD orally took more time in the target quadrant, crossed more times in the target quadrant, had a higher recognition coefficient, and spent more time in the central region. In addition, TSD could ameliorate oxidative stress and inhibit neuronal apoptosis in APP/PS1 mice. Furthermore, TSD could up-regulate the SIRT6 protein expression and inhibit ER sensing proteins expressions, such as p-PERK and ATF6, in APP/PS1 mice and Aβ-treated HT22 cells.
CONCLUSION
According to the abovementioned findings, TSD could alleviate cognitive dysfunction in AD by modulating the SIRT6/ER stress pathway.
民族药理学相关性
越来越多的人患有阿尔茨海默病（AD），但目前尚无有效的治疗方法。桃红四物汤（TSD）已被证明对痴呆具有强烈的神经药理学活性，但 TSD 对 AD 的作用和机制仍不清楚。
研究目的
研究桃红四物汤（TSD）是否通过 SIRT6/ER 应激通路有效改善认知功能障碍。
材料与方法
本研究采用 APP/PS1 小鼠 AD 模型和 HT-22 细胞系。通过灌胃给予不同剂量的 TSD（4.25、8.50 和 17.00 g/kg/d），连续给药 10 周。行为学测试后，采用 MDA 和 SOD 试剂盒检测氧化应激水平。尼氏染色和 Western blot 分析检测神经元功能。然后，应用免疫荧光和 Western blot 分析评估 APP/PS1 小鼠和 HT-22 细胞中沉默信息调节因子 6（SIRT6）和 ER 应激相关蛋白的水平。
结果
行为学测试结果显示，TSD 灌胃给药的 APP/PS1 小鼠在目标象限停留时间更长，穿越目标象限次数更多，识别系数更高，在中央区域停留时间更长。此外，TSD 可改善 APP/PS1 小鼠的氧化应激和抑制神经元凋亡。进一步研究表明，TSD 可上调 SIRT6 蛋白表达，并抑制 APP/PS1 小鼠和 Aβ 处理的 HT22 细胞中 ER 感知蛋白 p-PERK 和 ATF6 的表达。
结论
根据上述研究结果，TSD 可能通过调节 SIRT6/ER 应激通路缓解 AD 患者的认知功能障碍。
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