Bushen-Yizhi formula ameliorates cognitive dysfunction through SIRT1/ER stress pathway in SAMP8 mice
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Shi-Jie Zhang1,*, Ting-Ting Xu1,*, Lin Li1, Yu-Min Xu1, Zi-Ling Qu1, Xin-Chen Wang1, Shui-Qing Huang1, Yi Luo1, Na-Chuan Luo1, Ping Lu1, Ya-Fei Shi1, Xin Yang2 and Qi Wang1
1Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou 510405, China
2Department of Pharmacy, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou 510700, China
*These authors contributed equally to this work
Xin Yang, email: [email protected]
Qi Wang, email: [email protected]
Keywords: aging, dementia, Bushen-Yizhi formula, SIRT1, ER stress
Received: April 03, 2017 Accepted: April 25, 2017 Published: May 04, 2017
The Chinese formula Bushen-Yizhi (BSYZ) has been reported to ameliorate cognitive dysfunction. However the mechanism is still unclear. In this study, we employ an aging model, SAMP8 mice, to explore whether BSYZ could protect dementia through SIRT1/endoplasmic reticulum (ER) stress pathway. Morris water maze and the fearing condition test results show that oral administration of BSYZ (1.46 g/kg/d, 2.92 g/kg/d and 5.84 g/kg/d) and donepezil (3 mg/kg/d) shorten the escape latency, increase the crossing times of the original position of the platform and the time spent in the target quadrant, and increase the freezing time. BSYZ decreases the activity of acetylcholinesterase (AChE), and increases the activity of choline acetyltransferase (ChAT) and the concentration of acetylcholine (Ach) in both hippocampus and cortex. In addition, western blot results (Bcl-2, Bax and Caspase-3) and TUNEL staining show that BSYZ prevents neuron from apoptosis, and elevates the expression of neurotrophic factors, including nerve growth factor (NGF), postsynapticdensity 95 (PSD95) and synaptophysin (SYN), in both hippocampus and cortex. BSYZ also increases the protein expression of SIRT1 and alleviates ER stress-associated proteins (PERK, IRE-1α, eIF-2α, BIP, PDI and CHOP). These results indicate that the neuroprotective mechanism of BSYZ might be related with SIRT1/ER stress pathway.
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