Although mulberry leaf (Morus alba L., ML) and Siraitia grosvenorii (SG) individually demonstrate anti-diabetic properties, their combined efficacy against type 2 diabetes mellitus (T2DM) remains unexplored. This study systematically explored the multi-target mechanisms and synergistic potential of the MLSG combination (MLSG) for T2DM intervention. We evaluated the in vitro inhibitory activities of MLSG, ML, and SG on α-amylase and α-glucosidase, alongside antioxidant capacity assessments through DPPH/ABTS radical scavenging, reducing power, and FRAP assays. Bioactive metabolites were identified using non-targeted metabolomics, while core targets and pathways were predicted using network pharmacology and validated through molecular docking. The results reveal MLSG’s significantly enhanced inhibition of α-amylase (IC₅₀ = 14.06 mg/mL) and α-glucosidase (IC₅₀ = 0.02 mg/mL) compared to individual extracts, exhibiting 1.3–15.5-fold higher potency with synergistic effects (combination index < 1). MLSG also showed improved antioxidant capacity, outperforming SG in DPPH/ABTS⁺ scavenging and reducing power (p < 0.05), and surpassing ML in ABTS⁺ scavenging, reducing power, and FRAP values (p < 0.05). Metabolomics identified 26 MLSG-derived metabolites with anti-T2DM potential, and network analysis pinpointed 26 active components primarily targeting STAT3, AKT1, PIK3CA, EGFR, and MAPK1 to regulate T2DM pathways. Molecular docking confirmed strong binding affinities between these components and core targets. Collectively, MLSG exerts potent synergistic anti-T2DM effects through dual-enzyme inhibition, elevated antioxidant activity, and multi-target pathway regulation, providing a solid foundation for developing MLSG as functional food ingredients.

Depression is a common mood disorder, and growing evidence has revealed the critical role of gut microbiota in its onset and progression. The gut–brain axis, which connects the central nervous system and intestinal microecology, offers new strategies for depression intervention. In this study, an acute depression model was established in mice using lipopolysaccharide (LPS), and the potential antidepressant effects and mechanisms of Bifidobacterium animalis CP-9 were investigated. The results indicated that CP-9 may exert antidepressant effects through multiple pathways, including modulation of peripheral and central inflammatory responses, restoration of gut microbiota balance, enhancement of short-chain fatty acid (SCFA) production, and regulation of neurotransmitter metabolism such as γ-aminobutyric acid (GABA) and 5-hydroxytryptamine (5-HT). Notably, intervention with CP-9 at a dose of 10⁸ CFU/mL significantly alleviated depressive-like behaviors in mice, suggesting its promising potential in the prevention and treatment of mood disorders.