Abietic Acid Enhances the Sedative Activity of Diazepam: In vivo Approach along with Receptor Binding Affinity and Molecular Interaction with the GABAergic System

This study evaluated the sedative activity of abietic acid (AA) through a thiopental sodium (TS)-induced sleep model in mice. AA (5, 10, and 20 mg/kg) and diazepam (DZP) (2 mg/kg) were provided, followed by TS (20 mg/kg) after 30 min to induce sleep. Sleep latency and total sleeping time were documented over a 4 h period. Additionally, molecular docking studies were conducted to examine the interactions of AA with GABA_A (Protein Data Bank: 6X3X) receptors, which hold two subunits of α1 and β2, alongside pharmacokinetic and toxicity assessments. The results indicated that AA significantly (p < 0.05) provided the fast onset of sleeping and extended sleeping time in a dose-dependent manner. The combination of AA (20 mg/kg) with DZP further enhanced sedation, yielding a prolonged sleep duration and a reduced sleep latency, indicating a synergistic effect. In addition, in silico analysis expressed that AA exhibited a strong binding affinity for GABA_A receptors (-7.9 kcal/mol), comparable to DZP (-8.4 kcal/mol). Furthermore, AA demonstrated favorable pharmacokinetic properties and drug-likeness. Overall, these findings suggest that AA possesses potent sedative effects, likely mediated through interactions with the GABAergic system, warranting further investigation for its therapeutic potential in sleep disorders.