Evaluating ginkgetin from Ginkgo biloba as a novel agent for sleep promotion through molecular docking and in vivo studies

Abstract

Objectives: Sleep impacts the well-being and quality of life of millions. Given conventional pharmacotherapy's limitations and side effects, the quest for adequate and proper sleep promotion is imperative. This study aims to identify a suitable and effective compound for sleep by examining qualified herbal compounds in the PubChem database using in silico methods. Ultimately, the extracted compound (ginkgetin, a bioactive flavonoid from Ginkgo biloba) through molecular docking by considering the GABAA receptors will be evaluated through the in vivo method in an animal model to serve as proof for the findings from the molecular docking process.

Materials and methods: Utilizing a comprehensive approach, this research employed molecular docking to screen 2299 phytochemicals for their affinity towards the GABAA receptor, focusing on the GABA, benzodiazepine, and steroid-binding sites. Ginkgetin emerged as a top candidate due to its high binding affinity. Subsequent in vivo electrophysiological assessments in rats treated with G. biloba extract containing ginkgetin evaluated alterations in sleep architecture, REM, and NREM sleep phases.

Results: Molecular docking identified ginkgetin as possessing the highest binding affinity among the screened phytochemicals. In vivo studies corroborated these findings, demonstrating that rats treated with Ginkgo biloba extract significantly enhanced REM and NREM sleep compared to controls.

Conclusion: Ginkgetin, derived from G. biloba, shows promising potential as a novel therapeutic agent for sleep disorders, supported by its strong affinity to key receptor sites and its efficacy in modulating sleep architecture in vivo. These findings contribute to the expanding evidence base for the therapeutic use of G. biloba in sleep promotion and underscore the need for further research to elucidate the mechanisms and clinical applicability of ginkgetin in sleep disorder treatment.

Keywords: GABAA receptor; Ginkgetin; Ginkgo biloba; Molecular docking; Sleep.

Figure 1

Analysis method: High-performance thin layer chromatography

Figure 2

Molecular interaction profile of ginkgetin with GABAA receptor binding sites

Figure 3

Correlation of predicted binding energies by AutoDock4 and Vina

Figure 4

Comparative effects of Ginkgo biloba and valerian extracts on sleep architecture

Figure 5

Hypnogram of Ginkgo biloba extract administration