Neuropsychiatric Disease and Treatment (Jun 2023)
Leonurine Alleviates Cognitive Dysfunction and Reduces Oxidative Stress by Activating Nrf-2 Pathway in Alzheimer’s Disease Mouse Model
Abstract
Yue Xie,1,* Yaning Jin,2,* Shuyue Li,3 Baoxi Shen,4 Liping Ma,5 Lujie Zuo,6 Ya Gao,3 Guofeng Yang3 1Department of Neurology, the Second Medical Center and National Clinical Research Center for Geriatric Disease, Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China; 2Chaoyang Second Retired Cadre Rest Center of Beijing Garrison, Beijing, 100853, People’s Republic of China; 3Department of Geriatrics, the Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China; 4Department of Neurosurgery, the First Medical Centre, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing, 100853, People’s Republic of China; 5Department of Neurology, Xinzhou People’s Hospital, Shanxi, 034000, People’s Republic of China; 6Department of Otolaryngology, Head and Neck Surgery, Children’s Hospital of Hebei Province, Shijiazhuang, Hebei, 050000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ya Gao; Guofeng Yang, Department of Geriatrics, the Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China, Email [email protected]; [email protected]: Alzheimer’s disease (AD) is the most common type of dementia, impacting approximately 50 million individuals globally. However, the current treatments available for AD are only symptomatic and have limited efficacy. This study aimed to investigate whether Leonurine could alleviate cognitive dysfunction in a mouse model of AD and explore its underlying molecular mechanisms.Methods: In this study, male APP/PS1 mice were orally administered Leonurine for two consecutive months. The cognitive functions of the mice were then evaluated using novel object recognition (NOR) and Morris water maze (MWM) tests. Hippocampal neuronal damage was observed through Nissl staining, Aβ levels were determined through ELISA, oxidative stress activity was detected through biochemical methods, and the nuclear factor erythroid-2-related factor 2 (Nrf-2) pathway was analyzed using western blot and real-time quantitative polymerase chain reaction analysis.Results: Our results demonstrated that Leonurine treatment markedly improved cognitive functions, as indicated by the improved performance in the model. Additionally, histopathology showed a reduction in hippocampal neuronal damage. This can be attributed to the potential of Leonurine to reduce Aβ 1-40 and Aβ 1-42 levels and alleviate oxidative stress. Its antioxidant effect is linked to the activation of the Nrf-2 signaling pathway in APP/PS1 mice, which promotes Nrf-2 nuclear translocation and expression of HO-1 and NQO-1.Conclusion: These findings suggest that Leonurine could be explored further as it could emerge as a promising drug for AD treatment.Keywords: Alzheimer’s disease, cognitive deficit, Leonurine, Nrf-2, oxidative stress
