Xanthohumol ameliorates memory impairment and reduces the deposition of β-amyloid in APP/PS1 mice via regulating the mTOR/LC3II and Bax/Bcl-2 signalling pathways

• Published in: Journal of pharmacy and pharmacology 2021-09, Vol.73 (9), p.1230-1239
• Main Authors: Sun, Xiao-Lei, Zhang, Jia-Bao, Guo, Yun-Xiang, Xia, Tian-Shuang, Xu, Ling-Chuan, Rahmand, Khalid, Wang, Guo-Ping, Li, Xiao-Jin, Han, Ting, Wang, Na-Ni, Xin, Hai-Liang
• Format: Article
• Language: English
• Subjects: Amyloid beta-Peptides - metabolism; Amyloid beta-Protein Precursor - metabolism; Animals; Apoptosis; Autophagy; bcl-2-Associated X Protein - metabolism; Flavonoids - pharmacology; Hippocampus - drug effects; Hippocampus - metabolism; Humulus - chemistry; Male; Maze Learning; Memory - drug effects; Memory Disorders - drug therapy; Memory Disorders - metabolism; Mice, Transgenic; Microtubule-Associated Proteins - metabolism; Neuroinflammatory Diseases - drug therapy; Neuroinflammatory Diseases - metabolism; Neuroprotective Agents - pharmacology; Oxidative Stress - drug effects; Phytotherapy; Plant Extracts - pharmacology; Presenilin-1 - metabolism; Propiophenones - pharmacology; Signal Transduction; TOR Serine-Threonine Kinases - metabolism
• ISSN: 0022-3573; 2042-7158
• DOI: 10.1093/jpp/rgab052

Abstract Objectives Xanthohumol (XAN) is a unique component of Humulus lupulus L. and is known for its diverse biological activities. In this study, we investigated whether Xanthohumol could ameliorate memory impairment of APP/PS1 mice, and explored its potential mechanism of action. Methods APP/PS1 mice were used for in vivo test and were treated with N-acetylcysteine and Xanthohumol for 2 months. Learning and memory levels were evaluated by the Morris water maze. Inflammatory and oxidative markers in serum and hippocampus and the deposition of Aβ in the hippocampus were determined. Moreover, the expression of autophagy and apoptosis proteins was also evaluated by western blot. Key findings Xanthohumol significantly reduced the latency and increased the residence time of mice in the target quadrant. Additionally, Xanthohumol increased superoxide dismutase level and reduced Interleukin-6 and Interleukin-1β levels both in serum and hippocampus. Xanthohumol also significantly reduced Aβ deposition in the hippocampus and activated autophagy and anti-apoptotic signals. Conclusions Xanthohumol effectively ameliorates memory impairment of APP/PS1 mice by activating mTOR/LC3 and Bax/Bcl-2 signalling pathways, which provides new insight into the neuroprotective effects of Xanthohumol.