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Background  Herbal therapies are potential alternatives and adjuncts for depression treatment. The present study aims to investigate the antidepressant-like effects of hydroalcoholic  Hemerocallis citrina  extracts and its potential neuropharmacological components.    Methods  Hydroalcoholic  H. citrina  extracts were phytochemically analyzed. Behavioral models, including tail suspension tests and open field tests, were performed to evaluate the antidepressant-like effects of the extracts. A possible mechanism was explored by analyzing brain monoamine neurotransmitters. Toxicity and histopathological analyses were performed to determine whether or not the extracts are safe for oral administration.    Results  The antidepressant-like effects of hydroalcoholic  H. citrina  extracts were mainly related to flavonoids, especially rutin and hesperidin. The extract prepared using 75% ethanol (i.e., HCE75) exhibited the highest active flavonoid content and activity. Orally administered 400 mg/kg of HCE75 significantly induced an antidepressant-like effect, whereas the combination of equivalent rutin and hesperidin dosages exhibited the same profiles. Isobologram analysis showed sub-additive antidepressant interactions between rutin and hesperidin. HCE75 (400 mg/kg, p.o.) increased the serotonin and dopamine levels in the central nervous system. Mortality and lesions were not observed upon oral administration of up to 5000 mg/kg HCE75.    Conclusions  The antidepressant-like effects of hydroalcoholic  H. citrina  extracts are mainly related to flavonoids, especially rutin and hesperidin. The serotonergic and dopaminergic systems may have major roles. The active extract is toxicologically safe for oral administration.

Antidepressant-like effects of the hydroalcoholic extracts of Hemerocallis Citrina and its potential active components