Emulsified Mulberry Extract Alleviates CUMS-Induced Anxiety- and Depressive-Like Behaviors in Mice in Association with Gut Microbiota and Short-Chain Fatty Acids.
Zhang X, Wang Z, et al. • Journal of agricultural and food chemistry • 2026
Emulsified mulberry extract (EME) alleviated anxiety- and depression-like behaviors more effectively than aqueous mulberry extract (AME) in CUMS-exposed mice by remodeling the gut microbiota-SCFA axis, enhancing colonic barrier integrity, reducing neuroinflammation, and modulating the hypothalamic-pituitary-adrenal axis.
Key Findings
Results
Emulsified mulberry extract (EME) alleviated anxiety- and depression-like behaviors more effectively than aqueous mulberry extract (AME) in mice exposed to chronic unpredictable mild stress (CUMS).
The study used male C57BL/6J mice exposed to CUMS as the animal model of anxiety and depression.
EME demonstrated superior efficacy compared to AME in behavioral outcomes.
EME exhibited superior colloidal stability and dispersion compared to AME.
The emulsification process was identified as enhancing the overall bioactivity of whole-component mulberry extracts.
Results
Metabolomic profiling revealed higher relative abundances of carbohydrates, eicosanoids, and flavonoids in EME compared to AME.
Metabolomic profiling was used to compare the chemical composition of EME and AME.
EME showed higher relative abundances of carbohydrates, eicosanoids, and flavonoids.
Mulberry is described as a traditional medicinal and edible plant rich in polysaccharides and flavonoids.
The enhanced bioavailability of these components in emulsified form may contribute to the superior behavioral effects of EME.
Results
EME remodeled the gut microbiota-short-chain fatty acid (SCFA) axis in CUMS-exposed mice.
EME treatment altered gut microbiota composition in CUMS-exposed mice.
Changes in gut microbiota were associated with changes in short-chain fatty acid (SCFA) production.
Correlation analyses linked gut microbiota composition, SCFAs, HPA axis activity, and behavioral phenotypes.
The gut microbiota-SCFA axis was identified as a key mechanistic pathway underlying EME's effects.
Results
EME enhanced colonic barrier integrity and reduced systemic inflammatory markers in CUMS-exposed mice.
EME treatment enhanced colonic barrier integrity.
EME reduced serum lipopolysaccharide (LPS) levels, indicating decreased gut permeability and endotoxin translocation.
EME reduced proinflammatory cytokine levels in serum.
These effects suggest EME attenuated CUMS-induced gut-brain inflammatory signaling.
Results
EME decreased stress hormone levels and elevated 5-hydroxytryptamine (serotonin) in CUMS-exposed mice.
EME treatment decreased stress hormone levels, indicating modulation of the hypothalamic-pituitary-adrenal (HPA) axis.
Correlation analyses linked HPA axis activity to behavioral phenotypes.
These neurochemical changes are consistent with the observed alleviation of anxiety- and depression-like behaviors.
Results
EME suppressed hippocampal glial activation and preserved neuronal integrity in CUMS-exposed mice.
EME suppressed hippocampal glial activation, indicating reduced neuroinflammation in a brain region critical for mood regulation.
EME preserved neuronal integrity in the hippocampus.
Hippocampal glial activation is associated with neuroinflammatory processes that contribute to anxiety and depression.
These neuroprotective effects were among the proposed mechanisms underlying EME's behavioral effects.
Results
Correlation analyses linked gut microbiota composition, SCFAs, HPA axis activity, and behavioral phenotypes in a mechanistic framework.
Correlation analyses were performed to connect multiple biological axes affected by EME treatment.
Gut microbiota, SCFAs, HPA axis activity, and behavioral phenotypes were all significantly correlated.
These correlations supported the proposed gut-brain axis mechanism underlying EME's anxiolytic and antidepressant effects.
The findings suggest that the gut microbiota-SCFA axis mediates EME's effects on stress hormones and ultimately behavior.
What This Means
This research suggests that turning mulberry plant extract into an emulsion (a stable mixture where the extract is dispersed in tiny droplets, similar to how oil and water are combined in salad dressing) makes it significantly more effective at reducing anxiety- and depression-like behaviors in mice. The study compared this emulsified mulberry extract (EME) to a standard water-based extract (AME) in mice subjected to chronic mild stress, a common animal model for studying anxiety and depression. The emulsified form appeared to preserve more of the beneficial compounds found in mulberry, including carbohydrates, flavonoids, and other bioactive molecules.
The researchers found that EME worked through multiple interconnected biological pathways. It reshaped the community of bacteria living in the gut and boosted the production of short-chain fatty acids (beneficial compounds that gut bacteria make from fiber). This in turn appeared to strengthen the gut lining, reduce the leakage of bacterial toxins into the bloodstream, and lower levels of inflammation-promoting proteins. EME also reduced stress hormone levels (linked to the body's stress response system), raised serotonin (a mood-regulating brain chemical), and reduced inflammation and cellular damage in the hippocampus, a brain region important for emotional regulation.
This research suggests that the way a plant extract is prepared — in this case, converting it into an emulsion — can significantly affect how well it works in the body. The findings point to mulberry extract emulsions as a potential natural, food-based approach to supporting emotional wellbeing, likely by improving the health of the gut-brain connection. While these results are promising, the study was conducted in mice, and further research would be needed to determine whether these effects translate to humans.
Zhang X, Wang Z, Wu S, Hao J, Jia X, Zhao Z, et al.. (2026). Emulsified Mulberry Extract Alleviates CUMS-Induced Anxiety- and Depressive-Like Behaviors in Mice in Association with Gut Microbiota and Short-Chain Fatty Acids.. Journal of agricultural and food chemistry. https://doi.org/10.1021/acs.jafc.6c03546