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Purpose: To investigate the anti-depressant-like activity of curculigoside from Curculigo orchioides Gaertn and its underlying mechanism(s). Methods: Antidepressant-like activity was determined in mice through forced swimming test (FST), tail suspending test (TST), and open field test (OFT). Mechanism of action was investigated by measuring levels of dopamine (DA), norepinephrine (NE), and 5-hydroxytryptamine (5-HT) in chronic mild stress (CMS) rats using high-performance liquid chromatography-electron capture detector (HPLC-ECD). Western blotting was used to investigate the effect of curculigoside on the expression of brain-derived neurotrophic factor (BDNF) protein in rats. Results: In FST and TST, treatment of mice with curculigoside (10, 20, 40 mg/kg, p.o.) significantly reduced immobility time, which was, however, unaffected by locomotor activity when assessed in the OFT. The treatment led to significant increases in DA, NE and 5-HT, and up-regulation of BDNF protein expression in the hippocampus of the CMS rats. Conclusion: These results demonstrate that curculigoside exerts significant anti-depressant-like activity on mice, the mechanism of which involves increase in the levels of DA, NE, 5-HT, and up-regulation of BDNF expression. Thus, curculigoside can be considered a potential drug candidate for the treatment of depressive disorders. Keywords: Curculigo orchioides Gaertn, Curculigoside, Antidepressant-like activity, Behavioral studies

Anti-depressant-like effect of curculigoside isolated from <i>Curculigo orchioides</i> Gaertn root