Lactiplantibacillus plantarum fermentation enhances the antidepressant effects of Hemerocallis citrina Baroni in chronic restraint stress mice.

ETHNOPHARMACOLOGICAL RELEVANCEHemerocallis citrina Baroni (H. citrina), referred to as 'Forgetting Sadness Grass,' is a traditional Chinese medicine (TCM) known for its antidepressant effects. Fermentation is an ancient processing method for TCM. Whether fermentation affects the antidepressant effect of H. citrina is unknown.

AIMIn this study, we aim to evaluate the effect of fermented and unfermented H. citrina on chronic restraint stress-induced depression and the underlying mechanism.

MATERIALS AND METHODSH. citrina was co-fermented with Lactiplantibacillus plantarum strains LZU-J-TSL-6 and LZU-J-LZ1-1 to produce fermented H. citrina (FH). Both H. citrina and FH were evaluated for effects on depression and anxiety in chronic restraint stress (CRS) mice.

RESULTSFermentation increased flavonoids and phenols while reducing terpenoids. Both H. citrina and FH exhibited antidepressant effects, with FH showing superior efficacy in alleviating depressive symptoms. Specifically, FH effectively alleviated weight loss, behavioral abnormalities, and hippocampal pathological damage caused by CRS, while significantly reducing serum levels of cortisol and inflammatory factors, and increasing hippocampal serotonin (5-HT) level. Moreover, FH can restore CRS-induced gut microbiota dysbiosis by promoting the colonization of beneficial microbes, such as Lactobacillus, and inhibiting the growth of harmful microbes, like Bacteroides_H. Importantly, we discovered that the antidepressant effects of FH are closely associated with substances such as L-theanine and myo-inositol, as well as with the metabolic pathways of alanine, aspartic acid, and glutamic acid.

CONCLUSIONOur findings suggest that fermentation alters the composition of active ingredients in H. citrina and enhance its role in depression. It highlights the potential therapeutic application of FH in treating depression.