Oxypinnatanine promotes non-rapid eye movement sleep in mice

The flowers and leaves of Hemerocallis fulva var. sempervirens, Akinowauregusa in Japanese, were eaten to cure insomnia in Okinawa, Japan. We found that H. fulva var. sempervirens contained oxypinnatanine, a unique derivative of glutamic acid or glutamine with a furfuryl group isolated from only a few plants. In this study, we demonstrated by electroencephalographic analyses that an oral administration of oxypinnatanine (5, 15 and 30 mg/kg) to mice at light-off time increased non-rapid eye movement (non-REM, NREM) sleep in a dose-dependent manner. During the 3-h period after the administration, oxypinnatanine (30 mg/kg) increased the total time of NREM sleep by 84%, by increasing the number of stage transitions from wakefulness to NREM sleep by 76% and the number of NREM sleep bouts twofold, and by decreasing the mean episode duration of wakefulness by 54% without changing the mean episode duration of NREM sleep, the amount of rapid eye movement sleep or rebound insomnia after the induction of NREM sleep. Therefore, oxypinnatanine is an effective sleep-promoting substance of H. fulva var. sempervirens.