Taohong siwu decoction ameliorates cognitive dysfunction through SIRT6/ER stress pathway in Alzheimer's disease.
Taohong siwu decoction ameliorates cognitive dysfunction through SIRT6/ER stress pathway in Alzheimer's disease.
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DOI：
10.1016/j.jep.2023.116580
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发表时间：
2023-05
影响因子：
5.4
通讯作者：
Hong‐Yu Tan;Can Wan;Guangping Wu;Li Qiao;Ye-Feng Cai;Qi Wang;Shi-Jie Zhang
中科院分区：
文献类型：
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作者：
Hong‐Yu Tan;Can Wan;Guangping Wu;Li Qiao;Ye-Feng Cai;Qi Wang;Shi-Jie Zhang
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很强的神经药理活性，但TSD对抗AD的作用和机制仍不清楚。研究目的探讨TSD是否可以通过SIRT6/ER应激通路有效改善认知缺陷。材料和方法本文使用APP/PS1小鼠、AD模型和HT-22细胞系。通过灌胃法给小鼠施用不同剂量的 TSD（4.25、8.50 和 17.00 g/kg/d），持续 10 周。行为测试后，使用丙二醛（MDA）和超氧化物歧化酶（SOD）试剂盒测量氧化应激水平。使用尼氏染色和蛋白质印迹分析来检测神经元功能。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应激相关蛋白水平。结果行为测试显示，口服TSD的APP/PS1小鼠在目标象限中停留的时间更长，在目标象限中穿越的次数更多，具有更高的识别系数，并且在目标象限中停留的时间更长。 中部地区。此外，TSD 可以改善 APP/PS1 小鼠的氧化应激并抑制神经元凋亡。此外，在 APP/PS1 小鼠和 Aβ1-42 处理的 HT22 细胞中，TSD 可以上调 SIRT6 蛋白表达并抑制 ER 传感蛋白（如 p-PERK 和 ATF6）表达。结论根据上述研究结果，TSD 可以通过调节 SIRT6/ER 应激途径缓解 AD 认知功能障碍。
Ethnopharmacological relevanceA 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 studyTo investigate whether TSD could be effective in ameliorating cognitive deficits through SIRT6/ER stress pathway.Materials and methodsHerein, 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.ResultsBehavioral 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 Aβ1-42-treated HT22 cells.ConclusionAccording to the abovementioned findings, TSD could alleviate cognitive dysfunction in AD by modulating the SIRT6/ER stress pathway.