Antidepressant-like Effects of Polygonatum humile Fisch via Serotonergic System in Mouse Model: Involvement of the Serotonin Subunit 6 Receptor

Polygonatum humile Fisch is commonly called Sookjuk in Korea. The roots of P. humile are typically used in traditional medicine as an anti-rheumatic, demulcent, and sedative agent. The aim of this study was to evaluate the potential of the P. humile extracts to treat depression. Mice were administered P. humile water extract (PH) and were subjected to the forced swim test (FST), tail suspension test (TST), and open-field test (OFT). The levels of brain monoamines including serotonin (5-HT), norepinephrine, and dopamine were evaluated. In addition, the PH antidepressant-like effects were studied based on the regulation of 5-HT-mediated Ca2+ and extracellular signal-regulated kinase 1/2 (ERK1/2) in human 1321N1 cells stably expressing the 5-HT subunit 6 receptor (5-HT6). In FST and TST, PH (300 mg/kg) significantly reduced the immobility time without changing the locomotor activity in mice. In addition, PH enhanced the level of 5-HT in the mice brain. The results further indicated an inhibitory activity of PH on both   the 5-HT6 receptor expression level and the 5-HT6 receptor dependent downstream signal   pathway ERK1/2.These findings indicated antidepressant-like effects of PH  as evidenced by decreased immobility time in mice through a 5-HT6 receptor antagonistic mechanism.