Abstract
Phytol (PHY), a chlorophyll side chain diterpenoid possesses many health benefits, including neurological activities. A previous report evaluated its anti-depressive effects in mice without any possible mechanism. Our current study aimed at the evaluation of anti-depressive effect of PHY with possible molecular mechanisms through in vivo and in silico studies. For this, adult male mice were randomly divided into six individual groups (n = 6), namely control (vehicle), two standards (DZP: diazepam at 2 m/kg, FLU: flumazenil at 0.1 mg/kg), three test groups (PHY at 25, 50, and 75 mg/kg), and three combined groups with the GABA agonist drug DZP (2 mg/kg) and/or a GABA antagonist drug FLU (0.1 mg/kg) with PHY at 75 mg/kg. Thirty minutes after treatment, each animal was subjected to tail-suspension and forced-swimming tests and their immobility time was counted for five minutes. The in silico studies were also performed with GABAA receptor α2 and α5 subunits to investigate possible molecular mechanism behind this neurological effect of the test samples. The results demonstrate that PHY significantly (p < 0.05) and dose-dependently reduced the immobility time (IMT) in both protocols. It also significantly (p < 0.05) increased the IMT values with DZP-2, while reducing this parameter with FLU-01. In in silico studies PHY exhibited the binding affinities with α2 and α5 subunits of GABAA receptor by − 5.2 and − 6.9 kcal/mol, respectively. Taken together, PHY exerted an antidepressant capacity in mice. It modulated the effects of DZP and FLU. PHY may expert its antidepressant capacity possibly through interacting with α2 and α5 subunits of the GABAA receptor. PHY may be one of the good candidates for management of depression.