Trilobatin Alleviates Cognitive Deficits and Pathologies in an Alzheimer's Disease Mouse Model. (5th November 2021)

• Record Type: Journal Article
• Authors: Ding, Jiuyang; Huang, Jian; Yin, Dan; Liu, Ting; Ren, Zheng; Hu, Shanshan; Ye, Yuanliang; Le, Cuiyun; Zhao, Na; Zhou, Hongmei; Li, Zhu; Qi, Xiaolan; Huang, Jiang
• Other Names: Wu Xu Academic Editor.
• Is Part Of: Oxidative medicine and cellular longevity. Volume 2021(2021)
• Publication Date: 2021-11-05
• Subjects: Oxidative stress -- Periodicals; Cells -- Aging -- Periodicals; Cells -- Aging; Oxidative stress; Oxidative Stress -- Periodicals; Cell Aging -- Periodicals; Periodicals; 611.0181
• DOI: 10.1155/2021/3298400
• Languages: English
• ISSNs: 1942-0900

Abstract

Abstract : Alzheimer's disease (AD) is the most common neurodegenerative disease nowadays that causes memory impairments. It is characterized by extracellular aggregates of amyloid-beta (A β ), intracellular aggregates of hyperphosphorylated Tau (p-Tau), and other pathological features. Trilobatin (TLB), a natural flavonoid compound isolated from Lithocarpus polystachyus Rehd., has emerged as a neuroprotective agent. However, the effects and mechanisms of TLB on Alzheimer's disease (AD) remain unclear. In this research, different doses of TLB were orally introduced to 3×FAD AD model mice. The pathology, memory performance, and Toll-like receptor 4- (TLR4-) dependent inflammatory pathway protein level were assessed. Here, we show that TLB oral treatment protected 3×FAD AD model mice against the A β burden, neuroinflammation, Tau hyperphosphorylation, synaptic degeneration, hippocampal neuronal loss, and memory impairment. The TLR4, a pattern recognition immune receptor, has been implicated in neurodegenerative disease-related neuroinflammation. We found that TLB suppressed glial activation by inhibiting the TLR4-MYD88-NF κ B pathway, which leads to the inflammatory factor TNF- α, IL-1 β, and IL-6 reduction. Our study shows that TLR4 might be a key target of TLB in AD treatment and suggests a multifaceted target of TLB in halting AD. Taken together, our findings suggest a potential therapeutic effect of TLB in AD treatment.