Lippia grata Schauer: Essential Oil as a Source of the Phytotherapeutic Thymol for the Treatment of Seizures and Anxiety Induced by Alcohol Withdrawal in Adult Zebrafish.

Lippia grata Schauer, a species of the Verbenaceae family, is native to the Northeastern region of Brazil and widely distributed in the Seasonally Dry Tropical Forest. Commonly known as "alecrim-da-chapada," this medicinal plant stands out for its antimicrobial and pharmacological properties, mainly due to its essential oils rich in thymol and carvacrol. These compounds confer antifungal, antibiotic, anti-inflammatory, antioxidant, and antitumor activities, highlighting their potential in folk medicine. Based on this, the present study aimed to use in silico and in vivo tests in adult zebrafish as an alternative method to investigate the therapeutic potential of the essential oil of Lippia grata (EOLg) and its main constituent thymol (2-isopropyl-5-methylphenol) in the treatment of seizures and anxiety induced by alcohol withdrawal. Initially, adult zebrafish (n = 6/group) were treated with EOLg and thymol (0.01 or  0.1 or 1.0 mg/mL; 20 µL; oral administration) and assessed for anxiolytic, convulsive, and acute toxicity effects after 96 h. Subsequently, the potential anxiolytic-like, anticonvulsant effects, the possible GABAergic mechanism, and the efficacy of the samples in treating anxiety induced by alcohol withdrawal in adult zebrafish were investigated. Furthermore, molecular docking simulations of thymol with GABAergic receptors were performed. Preliminary results showed that EOLg and thymol were nontoxic and did not exhibit sedative effects in ZFa. Both demonstrated anticonvulsant and anxiolytic effects involving GABAA receptors and were effective in treating anxiety induced by alcohol withdrawal in the chronic test. These in vivo effects were corroborated by the potential interaction between thymol and the GABAA receptor identified in the in silico analysis.