Sedative effects of physcion and its modulatory interaction with diazepam: in vivo and in silico evaluation

Physcion (PHY), an anthraquinone derivative, has demonstrated various biological properties, including antioxidant and anti-inflammatory effects. This study aimed to evaluate the sedative activity of PHY in Swiss mice using in vivo and in silico approaches. The thiopental sodium (TS)-induced sleep model, fireplace test, and hole cross test were employed to assess sedation along with molecular docking studies. PHY significantly (p < 0.05) reduced sleep latency (17.29 ± 2.33 min) and increased sleep duration (162.85 ± 8.38 min) compared to controls at higher doses. It also significantly increased (p < 0.05) jump time and decreased the number of hole crosses. Co-administration of PHY with diazepam (DZP) enhanced sedation, while Co-administration with flumazenil (FLN) attenuated it, suggesting modulation of GABA_A receptors. In silico molecular docking revealed a strong binding affinity (- 8.1 kcal/mol) of PHY with GABA_A receptor subunits α1 and β2, comparable to DZP. Pharmacokinetic and toxicity predictions showed favorable profiles, supporting the potential of PHY as a sedative agent. Overall, PHY exhibited significant sedative effects likely mediated through the GABAergic pathway.