Effect of Valerian Extract on GABRB3 Gene MRNA Expression and Sedation in BALB/C Mice

Background: Valerian, also known as Setwall, Baldrianwurzel, or Phu is an herbaceous perennial plant from Europe and Asia, ubiquitously dispersed in almost all countries with a pH of 6-7. Valeriana officinalis is often used to treat sleep disorders, anxiety, fatigue, seizures, epilepsy, and depression as traditional medicine for 2000 years. The main constituent of Valeriana officinalis is Valerenic acid with hydroxyl and acetone group derivatives. Valerenic acid has anxiolytic, tranquilizing, and sleep-inducing effects that have been demonstrated in both animal studies and clinical trials. Valerenic acid inhibits catabolism-enzyme induced breakdown of Gamma-Aminobutyric Acid (GABA) in the brain resulting in sedation. Gamma-aminobutyric acid is the most important brain inhibitory neurotransmitter with key roles in the regulation and function of the central nervous system. The sedative effect of Valerian extract is facilitated by the GABAA receptor β3 subunit. GABRB3 gene is a ligand-gated ion channel that encodes the GABAA receptor β3 subunit. GABRB3 also functions as a receptor for diazepam and other anesthetic drugs (i.e. phenobarbital). Valerian influences the presynaptic component of GABA-ergic neurons that affect the release of synaptic GABA. Valerian also inhibits GABA reuptake and GABA catabolism by inhibiting the enzyme GABA transaminase. On that basis, this study aims to determine the effect of valerian extract on GABRB3 gene mRNA expression and sedative effect in BALB/c mice. Objective: This is an experimental study using an animal model, with a posttest-only control group design to determine the effect of Valerian extract on GABRB3 gene mRNA expression and sedative effect in BALB/c mice. Methods: Twenty selected BALB/c mice were randomly allocated into four groups; each group consisting of 5 mice. Group A (negative control) was given 5 ml of aqua dest (distilled water). Group B (positive control) was given 0.025 mg/10 g of diazepam. Group C (treatment group 1) was given 2.5 mg/10 g of Valerian extract, and group D (treatment group 2) was given 5 mg/10 g of Valerian extract. The drugs were administered for seven days through a gastric gavage. Rotarod test was performed on the seventh day. A blood sample of 1 ml was taken on the first day before drug administration and after the rotarod test on the seventh day to be analyzed using RT-PCR. Results: GABRB3 gene mRNA expression showed a significant increase in group B, C, and D (p <0.0001). There was a significant difference between group C and D. The examination of motor coordination functions (Rotarod test) showed a significant difference (p<0.05) between group A and group B, between group A and group C, and between group A and group D. There was no significant difference between group B and both group C and D. Conclusions: GABRB3 gene mRNA expression was increased significantly after the administration of Valerian extract. Based on the Rotarod test, Valerian extract and Diazepam had a clinically similar sedation effect. A higher dose of Valerian extract does not yield a higher level of GABRB3 gene mRNA expression nor sedative effects.