Boropinol-B is a phenylpropanoid compound originally isolated from Boronia pinnata Sm. (Rutaceae). This study aimed to evaluate the sedative–hypnotic effects of Boropinol-B and explore the underlying mechanisms.

Pentobarbital sodium-induced sleep mouse model and caffeine-induced insomnia mouse model were used to investigate the sedative effects of Boropinol-B. Pharmacokinetics profiles of Boropinol-B in rats were evaluated by high-performance liquid chromatography. The effects of Boropinol-B on the γ-aminobutyric acid (GABA)ergic system were investigated using ELISA assay and patch-clamp technique. Immunohistochemistry and immunofluorescence were carried out to assess the effects of Boropinol-B on sleep-related brain nucleus.

Boropinol-B showed significant sedative effects, including reduced sleep latency, increased sleep duration in pentobarbital sodium-treated mice and decreased locomotor activity in insomnia mice. Pharmacokinetics studies demonstrated that Boropinol-B had a rapid onset of action, a short half-life and no accumulation. It increased the GABA level in mice’s brain, and promoted chloride ions influx mediated by the γ-aminobutyric acid type A (GABA_A) receptors in neurons. Also, it increased the c-Fos positive ratio of GABAergic neurons in ventrolateral preoptic nucleus and decreased c-Fos expression in tuberomammillary nucleus.

Boropinol-B showed significant sedative–hypnotic effects in mice by activating the GABA_A receptors and stimulating the sleep-related brain nucleus.