Abstract: Objective: This study aimed to investigate the effect and underlying mechanism of epigallocatechin gallate (EGCG) on improving memory function in mice with chronic alcoholic encephalopathy. Methods: First, bioinformatics approaches were employed to screen for potential genes through which EGCG improved chronic alcoholic encephalopathy and to predict its targeted signaling pathways. Then, male Kunming mice were used to establish a chronic alcoholic encephalopathy model via gavage with gradient concentrations of alcohol, and the mice in the intervention groups received gavage of EGCG at different doses. The general status of mice in each group was observed. The step-down and Morris water maze (MWM) tests were conducted to evaluate memory function in mice. After killing the animals, brain tissues were collected for pathological observation and to detect the activity of superoxide dismutase (SOD), as well as the contents of malondialdehyde (MDA) and glutathione (GSH). Western blot was used to determine the expression of proteins related to the predicted signaling pathways in brain tissues. Results: Bioinformatics analysis identified 263 genes that overlap between chronic alcoholic encephalopathy and oxidative damage (potential genes through which EGCG improves chronic alcoholic encephalopathy via its antioxidant effects). Among these, the key ones were the genes encoding albumin (ALB), protein kinase B (AKT) serine/threonine kinase 1 (AKT1), and tumor protein p53 (TP53), and the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway was a critical pathway involved. The animal experiments showed that EGCG intervention improved the general status of mice with chronic alcoholic encephalopathy. It prolonged the latency and reduced the number of errors in the step-down test, shortened escape latency in the MWM directional navigation test, and increased the number of crossings over the platform location, as well as the proportion of swimming time and distance traveled in the target quadrant in the MWM spatial probe test. Meanwhile, EGCG improved the pathological features of the hippocampus, increased the activity of SOD and the content of GSH, and decreased the content of MDA in brain tissues. Additionally, EGCG increased the phosphorylation levels of PI3K (p-PI3K) and AKT (p-AKT) in brain tissues, thereby activating the PI3K/AKT signaling pathway. Conclusion: EGCG can improve memory function in mice with chronic alcoholic encephalopathy, and its underlying mechanism may be related to the activation of the PI3K/AKT signaling pathway and the reduction of oxidative damage in brain tissues.

Key words: epigallocatechin gallate; chronic alcoholic encephalopathy; memory function; step-down test; Morris water maze test; bioinformatics analysis; phosphatidylinositol 3-kinase/protein kinase B signaling pathway; oxidative damage