Abstract
Vascular dementia (VaD) is the second cause of dementia after Alzheimer’s disease. Ligustilide (LIG) is one of the main active ingredients of traditional Chinese medicines, such as Angelica. Studies have reported that LIG could protect against VaD. However, the mechanism is still confused. In this study, we employed a bilateral common carotid artery occlusion rat model to study. LIG (20 or 40 mg/kg/day) and Nimodipine (20 mg/kg) were orally administered to the VaD rats for four weeks. Morris water maze test showed that LIG effectively ameliorated learning and memory impairment in VaD rats. LIG obviously reduced neuronal oxidative stress damage and the level of homocysteine in the brain of VaD rats. Western blot results showed that pro-apoptotic protein Bax and cleaved caspase 3 increased and anti-apoptotic protein Bcl-2 decreased in the hippocampi of VaD rats. But after LIG treatment, these changes were reversed. Moreover, Nissl staining result showed that LIG could reduce neuronal degeneration in VaD rats. Furthermore, LIG enhanced the expressions of P-AMPK and Sirtuin1(SIRT1) in VaD rats. In conclusion, these studies indicated that LIG could ameliorate cognitive impairment in VaD rats, which might be related to AMPK/SIRT1 pathway activation.
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This work was supported by the National Natural Science Foundation of China (82004430 and 81673717); the Natural Science Foundation of Guangdong (2021A1515011478 and 2018A0303130053) and Guangdong Provincial Key Laboratory of Research on Emergency in TCM (2017B030314176).
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Shi-Jie Zhang designed the experiments. Dong Peng carried out the experiments and wrote the manuscript. Dan Luo supported the animal work. Han-Zi Qiao, Hong-Yu Tan, Yi-Xue Wang, Li-Jun Qiao supported the materials. Dong Peng, Ye-Feng Cai and Shi-Jie Zhang modified the manuscript. Qi Wang supported the experimental platform. Li Guan and Shi-Jie Zhang supervised this work
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Peng, D., Qiao, HZ., Tan, HY. et al. Ligustilide ameliorates cognitive impairment via AMPK/SIRT1 pathway in vascular dementia rat. Metab Brain Dis 37, 1401–1414 (2022). https://doi.org/10.1007/s11011-022-00947-0
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DOI: https://doi.org/10.1007/s11011-022-00947-0