Sleep-promoting effects and potential mechanisms of Apocynum venetum leaf extract (VENETRON®): Effects of acute and chronic treatment on the sleep-wake profiles in mice.

Ethnopharmacological Relevance: Apocynum venetum L. has long been used to promote relaxation and alleviate anxiety. It has been prescribed to treat insomnia, reduce psychological stress, and support overall well-being.

Aim Of The Study: This study aimed to evaluate the sleep-promoting effects of A. venetum leaf extract (VENETRON®; VNT) and investigate its underlying mechanisms using in vitro, in vivo, and in silico assays.

Methods: A pentobarbital-induced sleep test, combined with an analysis of sleep architecture, was used to assess the sleep-enhancing properties of VNT. The binding affinity of VNT for the GABA receptor was evaluated using in vitro binding assays. Additionally, the primary components of VNT were analyzed through in silico molecular docking to explore its mechanism of action.

Results: VNT reduced sleep latency in a dose-dependent manner and extended the duration of non-rapid-eye-movement sleep without affecting delta activity. Chronic administration sustained its sleep-promoting effects without causing withdrawal (WD) symptoms. In vitro experiments demonstrated that VNT has considerable affinity for the benzodiazepine (BZD) binding site on the γ-aminobutyric acid type A (GABA) receptor. Furthermore, in vivo studies demonstrated that flumazenil antagonized the hypnotic effects of VNT, confirming its modulation of GABA-BZD receptors.

Conclusion: Our findings indicate that VNT promotes sleep by modulating the BZD site of the GABA receptor. Furthermore, its sustained hypnotic effects without WD symptoms suggest its potential as a safer alternative to conventional hypnotics.