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-hour period. Additionally, molecular docking studies were conducted to examine the interactions of AA with GABAA (PDB: 6X3X) receptors which hold two subunits of α1 and β2, alongside pharmacokinetic and toxicity assessments. The results indicated that AA significantly (p > 0.05) delayed the onset of sleep and extended sleeping time in a dose-dependent manner. The sleep latency was 23.67 ± 3.21, 19.67 ± 1.81, and 9.33 ± 0.80 min, while sleep duration increased to 146.50 ± 3.05, 176 ± 3.84, and 248.66 ± 2.45 min at AA doses of 5, 10, and 20 mg/kg, respectively. The combination of AA (20 mg/kg) with DZP further enhanced sedation, yielding a prolonged sleep duration of 248.66 ± 2.45 min and a reduced sleep latency of 4.17 ± 0.31 min, indicating a synergistic effect. In addition, in silico analysis expressed that AA exhibited a strong binding affinity for GABAA 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.