Oxyphylla A ameliorates cognitive deficits and alleviates neuropathology via the Akt-GSK3β and Nrf2-Keap1-HO-1 pathways in vitro and in vivo murine models of Alzheimer's disease

• Published in: Journal of advanced research Vol. 34; pp. 1 - 12
• Main Authors: Bian, Yaqi, Chen, Yan, Wang, Xiufen, Cui, Guozhen, Ung, Carolina Oi Lam, Lu, Jia-Hong, Cong, Weihong, Tang, Benqin, Lee, Simon Ming-Yuen
• Format: Journal Article
• Language: English
• Published: Egypt Elsevier B.V 01.12.2021; Elsevier
• Subjects: Alzheimer Disease - drug therapy; Alzheimer’s disease; Amyloid beta proteins; Amyloid beta-Peptides - metabolism; Animals; Caproates; Cognition; Cognitive Dysfunction - drug therapy; Cognitive Dysfunction - etiology; Cresols; Disease Models, Animal; Glycogen Synthase Kinase 3 beta; Kelch-Like ECH-Associated Protein 1; Mice; NF-E2-Related Factor 2 - metabolism; Oxidative Stress; oxyphylla A; Proto-Oncogene Proteins c-akt; SAMP8; APP; NQO1; Oxidative stress; MWM; AD; Alzheimer’s disease; oxyphylla A; Amyloid beta proteins; HO-1; PHF; Aβ; NFTs; ARE; PD; SAMP8 mice; Nrf2; GSK3; AOE; ROS; SAMP8; Keap1; RLU; pRL-TK; ARE, antioxidant response element; ARE, antioxidant responsive element; PD, Parkinson’s disease; AD, Alzheimer’s disease; Aβ, amyloid beta; NFTs, neurofibrillary tangles; AOE, ethanolic extract of Alpinia oxyphylla; GSK3, glycogen synthase kinase 3; MWM, Morris Water Maze; Nrf2, erythroid-derived 2-related factor 2; NQO1, NAD(P)H:quinone oxidoreductase1; RLU, relative luciferase units; PHF, paired helical filaments; pRL-TK, Renilla luciferase reporter plasmid; ROS, reactive oxygen species; SAMP8 mice, senescence-accelerated mouse prone 8; Keap1, Keleh-like ECH-associated protein; HO-1, heme oxygenase-1; APP, amyloid precursor protein
• ISSN: 2090-1232; 2090-1224
• DOI: 10.1016/j.jare.2021.09.002

[Display omitted] Alzheimer’s disease (AD) is a progressive brain disorder, and one of the most common causes of dementia and amnesia. Due to the complex pathogenesis of AD, the underlying mechanisms remain unclear. Although scientists have made increasing efforts to develop drugs for AD, no effective therapeutic agents have been found. Natural products and their constituents have shown promise for treating neurodegenerative diseases, including AD. Thus, in-depth study of medical plants, and the main active ingredients thereof against AD, is necessary to devise therapeutic agents. In this study, N2a/APP cells and SAMP8 mice were employed as in vitro and in vivo models of AD. Multiple molecular biological methods were used to investigate the potential therapeutic actions of oxyphylla A, and the underlying mechanisms. Results showed that oxyphylla A, a novel compound extracted from Alpinia oxyphylla, could reduce the expression levels of amyloid precursor protein (APP) and amyloid beta (Aβ) proteins, and attenuate cognitive decline in SAMP8 mice. Further investigation of the underlying mechanisms showed that oxyphylla A exerted an antioxidative effect through the Akt-GSK3β and Nrf2-Keap1-HO-1 pathways. Conclusions. Taken together, our results suggest a new horizon for the discovery of therapeutic agents for AD.