Theaflavin-3,3'-digallate ameliorates learning and memory impairments in mice with premature brain aging induced by D-galactose

Yichou Cao; Yunyi Zhang; Zehan Jia; Huining Jia; Yuanchen Sun; Hongxia Yuan; Yongle Bian; BingJie Xu; Jing Fu; Fenju Qin

doi:10.1016/j.physbeh.2023.114077

Theaflavin-3,3'-digallate ameliorates learning and memory impairments in mice with premature brain aging induced by D-galactose

Physiol Behav. 2023 Mar 15:261:114077. doi: 10.1016/j.physbeh.2023.114077. Epub 2023 Jan 11.

Authors

Yichou Cao¹, Yunyi Zhang¹, Zehan Jia¹, Huining Jia¹, Yuanchen Sun¹, Hongxia Yuan¹, Yongle Bian¹, BingJie Xu¹, Jing Fu², Fenju Qin³

Affiliations

¹ School of Chemistry and Life Sciences, Suzhou University of Science and Technology, Suzhou 215009, China.
² Key Laboratory of Bio-resources of Shaanxi Province, College of Biological Science and Engineering, Shaanxi University of Technology, Hanzhong 723001, Shaanxi, China; Qinba State Key Laboratory of biological resources and ecological environment (Cultivation), Shaanxi University of Technology, Hanzhong 723001, Shaanxi, China. Electronic address: fujing@snut.edu.cn.
³ School of Chemistry and Life Sciences, Suzhou University of Science and Technology, Suzhou 215009, China. Electronic address: qinfenju@usts.edu.cn.

PMID: 36638877
DOI: 10.1016/j.physbeh.2023.114077

Abstract

Age-related neurodegenerative diseases accompanied by learning and memory deficits are growing in prevalence due to population aging. Cellular oxidative stress is a common pathomechanism in multiple age-related disorders, and various antioxidants have demonstrated therapeutic efficacy in patients or animal models. Many plants and plant extracts possess potent antioxidant activity, but the compounds responsible are frequently unknown. Identification and evaluation of these phytochemicals is necessary for optimal targeted therapy. A recent study identified theaflavin-3,3'-digallate (TFDG) as the most potent among a large series of phytochemical antioxidants. Here we examined if TFDG can mitigate learning and memory impairments in the D-galactose model of age-related neurodegeneration. Experimental mice were injected subcutaneously with D-galactose (120 mg/kg) for 56 days. In treatment groups, different doses of TFDG were administered daily by gavage starting on day 29 of D-galactose injection. Model mice exhibited poor learning and memory in the novel object recognition and Y-maze tests, reduced brain/body mass ratio, increased brain glutamate concentration and acetylcholinesterase activity, decreased brain acetylcholine concentration, and lower choline acetyltransferase, glutaminase, and glutamine synthetase activities. Activities of antioxidant enzymes glutathione peroxidase and superoxide dismutase were also reduced, while the concentration of malondialdehyde, a lipid peroxidation product, was elevated. Further, antioxidant genes Nrf2, Prx2, Gsh-px1, and Sod1 were downregulated in brain. Each one of these changes was dose-dependently reversed by TFDG. TFDG is an effective antioxidant response inducer and neuroprotectant that can restore normal neurotransmitter metabolism and ameliorate learning and memory dysfunction in the D-galactose model of age-related cognitive decline.

Keywords: Aging model; Antioxidant enzyme; Antioxidant gene; Learning and memory; Theaflavin-3,3′-digallate.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetylcholinesterase / metabolism
Aging
Aging, Premature*
Animals
Antioxidants* / metabolism
Antioxidants* / pharmacology
Antioxidants* / therapeutic use
Brain / metabolism
Galactose / metabolism
Galactose / toxicity
Maze Learning
Memory Disorders / chemically induced
Memory Disorders / drug therapy
Memory Disorders / metabolism
Mice
Oxidative Stress
Superoxide Dismutase / metabolism

Substances

Antioxidants
Galactose
theaflavin-3,3'-digallate
Acetylcholinesterase
Superoxide Dismutase