Roudoukou-Suanzaoren Ameliorates Chronic Restraint-Induced Anxiety- and Depression-Like Behaviors in Mice via the Gut-Brain Axis.

RS alleviates chronic restraint stress-induced anxiety- and depression-like behaviors in mice.

• Behavioral analyses demonstrated that RS treatment ameliorated CRS-induced anxiety- and depression-like behaviors.
• The study used a chronic restraint stress (CRS) mouse model to induce anxiety and depression.
• Histopathological analyses confirmed that RS attenuates neuropathological damage in relevant brain regions.
• The underlying mechanism is likely mediated by the CREB/BDNF/TrkB signaling pathway.

RS reduces proinflammatory cytokines in tissues and modulates hippocampal glial cell populations.

• RS reduces proinflammatory cytokines in tissues.
• RS decreases hippocampal microglial numbers.
• RS increases astrocyte numbers in the hippocampus.
• These effects suggest RS exerts anti-inflammatory actions in the brain relevant to anxiety and depression.

RS attenuates colonic injury and restores intestinal barrier integrity in CRS-exposed mice.

• RS attenuates colonic injury induced by chronic restraint stress.
• RS restores intestinal permeability disrupted by CRS.
• RS upregulates tight-junction proteins in the colon.
• These intestinal effects are part of the proposed gut-brain axis mechanism underlying RS's antianxiety and antidepression effects.

RS improves gut microbiota dysbiosis induced by chronic restraint stress.

• RS treatment improved gut microbiota dysbiosis caused by CRS.
• Modulation of gut microbiota is identified as one of the key mechanisms by which RS exerts its antianxiety and antidepression effects.
• The gut microbiota changes are linked to the gut-brain axis pathway.

The main chemical constituents of RS include flavonoids, terpenoids, alkaloids, and phenylpropanoids.

• RS is a combination of Roudoukou (nutmeg) and Suanzaoren (sour jujube seed), an ancient TCM-derived beverage.
• Chemical characterization identified four major classes of constituents: flavonoids, terpenoids, alkaloids, and phenylpropanoids.
• These constituents are proposed to underlie the pharmacological activity of RS against anxiety and depression.