Anxiolytic Activity of Morellic Acid: Modulation of Diazepam's Anxiolytic Effects, Possibly Through GABAergic Interventions

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ABSTRACT Background Numerous studies suggest that morellic acid (MOR), highly available in Garcinia plants, has different physiological activities, including anti‐cancer, anti‐oxidant, and anti‐microbial activity. Aim In this investigation, we aimed to demonstrate the anxiolytic activity, along with the mechanism behind this activity of MOR, using in vivo and in silico studies. Methods For this, we used different doses of MOR (5 and 10 mg/kg) and administered this drug intraperitoneally to Swiss albino mice (male and female). Diazepam (DZP), a positive allosteric modulator of the GABA A receptor, was used as a positive control at a dose of 2 mg/kg (i.p), and vehicle was used as a control group. In this test, various test protocols are used to assess the behavioral patterns of mice, including swing, hole cross, light–dark testing, and open field testing. Results This investigation revealed that MOR remarkably reduced the locomotor activity of mice in a dose‐dependent manner and produced calming behaviors like DZP. However, the findings showed that the combination of MOR and DZP synergistically reduced the locomotion of mice compared to the single therapy. On the other hand, from the computational study, the result demonstrated that MOR exhibited the highest binding scores (−9.2 kcal/mol) towards the GABA A receptor α3 subunit and −7.6 kcal/mol towards the GABA A α2 receptor. Whereas, DZP showed −6.6 and −7.3 kcal/mol docking affinity and FLU exerted −6.2 and −6.3 kcal/mol docking scores towards the GABA A receptor α2 and α3 subunits, respectively. The ligand interacted with the receptor by forming different hydrogen and hydrophobic bonds. Conclusion However, it is recommended that more precise and comprehensive preclinical investigations be required to demonstrate the exact mechanism behind the anxiolytic effects and conduct clinical trials to determine efficacy and safety.

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