Sedative and hypnotic effects of Polygala tenuifolia willd. saponins on insomnia mice and their targets

Polygala tenuifolia Willd. has been widely used in the treatment of cancer, forgetfulness, depression and other diseases. The purpose of this study was to investigate the sleep-enhancing effect and mechanism of P. tenuifolia saponins (PTS). The total saponin (YZ-I) and purified saponin (YZ-II) fractions were extracted and ICR mice model of insomnia was established by p-chlorophenylalanine (PCPA) induction to observe anxiety and depression behaviors. Effects of YZ-I and YZ-II on the levels of neurotransmitters, hormones, and inflammation cytokines were detected by ELISA, RT-qPCR and western blotting. The results showed that YZ-I and YZ-II reduced the immobility time of mice and prolonged the sleep time of mice and significantly increased the concentrations of 5-HT, NE, PGD2, IL-1β and TNF-α. YZ-I and YZ-II regulated GABAARα2, GABAARα3, GAD65/67, 5-HT1A and 5-HT2A, while regulated the levels of inflammatory cytokines such as DPR, PGD2, iNOS and TNF-α to exert sedative and hypnotic effects. PTS are mainly achieved sedative and hypnotic effects by altering serotonergic, GABAergic and immune systems, but the effects and mechanisms of action of YZ-I were different from YZ-II.