Modified (−)-gallocatechin gallate-enriched green tea extract rescues age-related cognitive deficits by restoring hippocampal synaptic plasticity

• Published in: Biochemistry and biophysics reports Vol. 29; p. 101201
• Main Authors: Ahn, Ji-Woong, Kim, Sohyun, Ko, Sukjin, Kim, Young-Hwan, Jeong, Ji-Hyun, Chung, Seungsoo
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2022; Elsevier
• Subjects: Aging; Gallocatechin gallate; Hippocampus; Long-term potentiation; Memory; HPLC-PDA; MWM; Gallocatechin gallate; DMSO; fEPSPs; Long-term potentiation; Memory; EGCG; PKA; LTP; GCG; NMDARs; MTT; SC; Aging; aCSF; GTE; TTX; HTP-GTE; Hippocampus; DIC; GTE, conventional green tea extract; MWM, Morris water maze; EGCG, (−)-epigallocatechin-3-gallate; fEPSPs, field excitatory postsynaptic potentials; DIC, differential interference contrast; LTP, long-term potentiation; HTP-GTE, GCG-enriched green tea extract; GCG, (−)-gallocatechin gallate; TTX, tetrodotoxin; NMDARs, N-Methyl-d-aspartate receptors; MTT, methylthiazolyldiphenyl-tetrazolium bromide; aCSF, artificial cerebrospinal fluid; HPLC-PDA, high performance liquid chromatography photometric diode array; DMSO, dimethyl sulfoxide; PKA, protein kinase A; SC, Schaffer collateral
• ISSN: 2405-5808; 2405-5808
• DOI: 10.1016/j.bbrep.2022.101201

Aging leads to cognitive impairments characterized by reduced hippocampal functions that are associated with impairment of long-term potentiation of CA1 synapses. Here, we assessed the safety and efficacy of modified (−)-gallocatechin gallate (GCG)-enriched green tea extract (HTP-GTE) in ameliorating the cognitive dysfunctions in late middle-aged murine model. We developed a novel HTP-GTE that was enriched with GCG via epimerization that involved heating. We compared the effects of oral administrations of conventional green tea and HTP-GTE in young and aged male C57/BL6 mice, and examined the changes in the hippocampal functions related to aging process. The functional outcome was assessed by the electrophysiological experiments to measure the long-term potentiation (LTP). HTP-GTE improved the age-related cognitive impairments via restoring long-term synaptic plasticity. We also identified that GCG was the main active component responsible for the HTP-GTE effect. The main molecular pathway in ameliorating the age-related cognitive dysfunctions involved protein kinase A (PKA) which was shown to be modulated by HTP-GTE. Thus, HTP-GTE has a therapeutic potential as a dietary supplement which may aid to rescue the impaired cognitive functions at the early phase of aging process through the modulation of LTP threshold. ●HTP-GTE has a potential to improve the age-related impairment of hippocampal-dependent spatial memory function.●The active ingredient in the HTP-GTE is GCG.●Cognitive dysfunction at the beginning of aging process can be rescued by GCG-enriched HTP-GTE.