Hovenia dulcis Fruit Peduncle Polysaccharides Modulate Glutamate Metabolism and Tight Junction Protein Expressions to Attenuate the Neurotoxic Effects of Alcohol on Mice

Objective: This study aimed to investigate the protective effects of Hovenia dulcis fruit peduncle polysaccharides (HDPs) on alcohol-induced neurobehavioral alterations in mice and to elucidate whether HDPs mitigate alcohol-induced neuronal damage by modulating glutamate metabolic pathway and the expression of tight junction protein. Methods: Male C57BL/6 mice were administered alcohol intragastrically at a dose of 114 μL/20 g for 14 d to establish an alcohol exposure model, and an intervention group was set up for HDPs intervention (114 μL/20 g alcohol+100 mg/kg HDPs). Behavioral experiments (open field test, elevated plus maze test) were used to assess changes in neurobehavior, gas chromatography was used to determine ethanol concentrations in mouse blood. γ-H2AX fluorescence was used to detect DNA damage in mouse hippocampal tissue, and immunohistochemical analysis was used to detect the expression of tight junction proteins Claudin-1 and ZO-1 in mouse brain tissue. Metabolites in mouse brain tissue were analyzed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) metabolomics technology. Results: HDPs effectively reduced blood ethanol concentration in alcohol-exposed mice (from 4.69±0.29 g/L to 1.64±0.104 g/L) and ameliorated alcohol-induced neurobehavioral abnormalities. In the open field test, compared to the alcohol group, HDPs intervention significantly increased total distance traveled (27340±3304 cm, P<0.05) and average velocity (67.4±13.4 cm/s, P<0.05), while reduced immobility time by 29% (P<0.05). The elevated plus maze test revealed that HDPs treatment decreased closed-arm dwelling time (195.6±10.3 s, P<0.05) and increased open-arm entries by 26% (P<0.05) compared to the alcohol group. Additionally, HDPs alleviated alcohol-induced oxidative brain damage by reducing ROS levels (5.4%) and MDA content (29.5%) (P<0.05) respectively, while enhanced total antioxidant capacity (T-AOC) by 10.9%. It upregulated hippocampal expression of tight junction proteins Claudin-1 (2.2-fold) and ZO-1 (10%). HDPs also modulated glutamatergic metabolic pathways, elevating brain levels of glycine, glutathione, and succinate by 19.7%, 25% and 22.6% respectively. Conclusion: HDPs can effectively alleviate the neurobehavioral impact of alcohol on mice. The mechanism may involve antioxidant activity, protection of tight junction proteins, and modulation of glutamate metabolic pathways, providing a theoretical basis for the development and application of Hovenia dulcisis resources in the food field.