Emulsified Mulberry Extract Alleviates CUMS-Induced Anxiety- and Depressive-Like Behaviors in Mice in Association with Gut Microbiota and Short-Chain Fatty Acids.

Mulberry, a traditional medicinal and edible plant rich in polysaccharides and flavonoids, has potential in regulating emotional behaviors. This study compared emulsified mulberry extract (EME) and aqueous mulberry extract (AME) on anxiety- and depression-like behaviors in male C57BL/6J mice exposed to chronic unpredictable mild stress (CUMS), and explored the underlying mechanisms of EME. EME alleviated anxiety- and depression-like behaviors more effectively than AME, with superior colloidal stability and dispersion. Metabolomic profiling revealed higher relative abundances of carbohydrates, eicosanoids, and flavonoids in EME. EME remodeled the gut microbiota-short-chain fatty acid (SCFA) axis, enhanced colonic barrier integrity, reduced serum lipopolysaccharide and proinflammatory cytokines, decreased stress hormone levels, elevated 5-hydroxytryptamine, and suppressed hippocampal glial activation while preserving neuronal integrity. Correlation analyses linked gut microbiota, SCFAs, hypothalamic-pituitary-adrenal axis activity, and behavioral phenotypes. These findings indicate that emulsification enhances the bioactivity of whole-component mulberry extracts, supporting their potential as natural food-based interventions for emotional disorders.