摘要Objective:This study investigated the antidepression mechanisms of Xiaoyaosan(XYS),a classic Chinese prescription,from the perspective of energy metabolism in the brain and intestinal tissues.Methods:Chronic unpredictable mild stress model-a classic depression rat model-was established.Effects of XYS on behaviors and gastrointestinal motility of depressed rats were investigated.Effects of XYS on energetic charge(EC),adenosine triphosphate-related enzymes,and key enzymes of energy meta-bolism in both hippocampus and jejunum tissues of depressed rats were investigated using high-performance liquid chromatography,biochemical analysis,and real-time quantitative polymerase chain reaction,respectively.Spearman correlation analysis was conducted to construct a correlation network of"behavior-brain energy metabolism-intestinal energy metabolism"of depression.Results:XYS significantly reduced the abnormal behaviors that observed in depressed rats and increased the EC and the activity of Na+-K+-adenosine triphosphatase(ATPase)and Ca2+-Mg2+-ATPase in hippocam-pus and jejunum tissues of depressed rats.XYS restored the key energetic pathways that had been inter-rupted by depression,including glycolysis,tricarboxylic acid cycle,and oxidative phosphorylation.Furthermore,XYS exhibited antidepressive effects in terms of regulating energy metabolism in tissues of both brain and intestine.Conclusion:XYS significantly corrected the disturbances in EC and energy metabolism-related enzymes of both brain and intestinal tissues,alleviating both core and concomitant symptoms of depression.The current findings underscore the role of energy metabolism in the antidepressive activity of XYS,pro-viding a fresh perspective on depression,and novel research strategies for revealing the mechanism of actions of traditional Chinese medicines on multi-site and multi-symptom diseases.