Affiliation:
1. Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education Zunyi Medical University China
2. Department of Hospital Infection Management People's Hospital of WeiNing County Bijie China
3. Department of Clinical Medicine Zunyi Medical University China
4. Department of Gastroenterology, Digestive Disease Hospital Affiliated Hospital of Zunyi Medical University China
Abstract
It was reported that the Wnt/β‐catenin pathway is involved in the regulation of aerobic glycolysis and that brain glycolytic dysfunction results in the development of Alzheimer's disease (AD). Icariin (ICA), an active component extracted from Epimedii Folium, has been reported to produce neuroprotective effects in multiple models of AD, but its underlying mechanism remains to be fully described. We aimed to investigate the protective effects of ICA on animal and cell models of AD and confirm whether the Wnt/β‐catenin pathway has functions in the neuroprotective function of ICA. The 3 × Tg‐AD mice were treated with ICA. HT22 cells, the Aβ25‐35 peptide and Dickkopf‐1 (DKK1) agent (a specific inhibitor of the Wnt/β‐catenin pathway) were used to further explore the underlying mechanism of ICA that produces anti‐AD effects. Behavioral examination, western blotting assay, staining analysis, biochemical test, and lactate dehydrogenase (LDH) assays were applied. We first demonstrated that ICA significantly improved cognitive function and autonomous behavior, reduced neuronal damage, and reversed the protein levels and activities of glycolytic key enzymes, and expression of protein molecules of the canonical Wnt signaling pathway, in 3 × Tg‐AD mice back to wild‐type levels. Next, we further found that ICA increased cell viability and effectively improved the dysfunctional glycolysis in HT22 cells injured by Aβ25‐35. However, when canonical Wnt signaling was inhibited by DKK1, the above effects of ICA on glycolysis were abolished. In summary, ICA exerts neuroprotective effects in 3 × Tg‐AD animals and AD cellular models by enhancing the function of glycolysis through activation of the Wnt/β‐catenin pathway.
Funder
National Natural Science Foundation of China
Cited by
2 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献