Anxiolytic-Like Effect of Underground Parts of Ajuga remota Benth (Lamiaceae) and Its Bioactive Constituents in Mice: A Behavioral Study

Several undesirable side effects as well as tolerance and physical dependence associated with use of benzodiazepine (BZD) derivatives for the management of anxiety are important challenges which motivate the search for safer and better tolerated anxiolytic compounds devoid of dependence. This study isolated the potential active constituents from methanol underground parts of Ajuga remota (Lamiaceae) with anxiolytic-like effects. In vivo anxiolytic activity in mice of the samples and diazepam (positive control) was assessed using the hole board and elevated plus maze (EPM) experiments. Chromatographic procedures led to the isolation of harpagide (1), 8-O-acetylharpagide (2), 2,3- diacetylharpagide (3), 6,8-acetylharpagide-O-2,3-diacetylglycoside (4), 6-rhamnosylharpagide (5), 6-galloyl-7,8- dehydroharpagide (6), cyasterone (7) and ergosterone-5,8-endoperoxide (8) from the methanol extracts. Oral administration of cyasterone (7) and ergosterone-5,8-endoperoxide (8) (5 mg/kg) increased the duration of open arm exploration and number of head-dips in EPM and hole-board tests, respectively (P≤0.05) compared to negative control. However, compound 1, 2, 3, and 4 elicited negative responses in open arm in EPM. Compounds 7 and 8 (25 and 50 mg/kg) showed dose dependent (P≤0.01) rise in number and duration of head-dips comparable to the anxiolytic effect of diazepam which suggests their potential use for management of anxiety disorder.