Taohong siwu decoction ameliorates cognitive dysfunction through SIRT6/ER stress pathway in Alzheimer's disease

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. To investi...

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Bibliographic Details
Published in:Journal of ethnopharmacology 2023-10, Vol.314, p.116580-116580, Article 116580
Main Authors: Tan, Hong-Yu, Wan, Can, Wu, Guang-Liang, Qiao, Li-Jun, Cai, Ye-Feng, Wang, Qi, Zhang, Shi-Jie
Format: Article
Language:English
Subjects:
Alzheimer's disease
Endoplasmic reticulum stress
SIRT6
Taohong siwu decoction
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Summary: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. To investigate whether TSD could be effective in ameliorating cognitive deficits through SIRT6/ER stress pathway. 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. 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 Aβ1-42-treated HT22 cells. According to the abovementioned findings, TSD could alleviate cognitive dysfunction in AD by modulating the SIRT6/ER stress pathway. This study suggested that Taohong Siwu Decoction (TSD) could improve cognitive dysfunction in APP/PS1 mice. The mechanism studies showed that TSD could ameliorate oxidative stress, decrease neuronal apoptosis, activate SIRT6 and relieve ER stress in APP/PS1 mice and HT22 cells. [Display omitted] •TSD improves cognitive dysfunction in APP/PS1 mice.•TSD ameliorates oxidative stress and inhibit neuronal apoptosis in APP/PS1 mice.•TSD activates SIRT6 and relieves ER stress in APP/PS1 mice and HT22 cells.
ISSN:0378-8741
1872-7573
DOI:10.1016/j.jep.2023.116580