It is inevitable for living beings to be away from stress. Chronic stress remains an etiology and also risk factor for progression of several pathological conditions. In this consideration to manage stress, adaptogens are employed. The present investigation is aimed to evaluate adaptogenic/antistress activity of a novel proprietary polyherbal formulation (PHF) in rodents and its plausible anti-stress mechanisms were identified in in vitro cell assays. Rats were exposed to chronic variable stress paradigm for sixteen days and PHF was administered concurrently at various dose levels. Immobility time of rats during forced swim test and serum cortisol levels were measured. Additionally adaptogenic activity of PHF to stress was evaluated in mice using swim endurance model with pre-treatment for ten days. To understand the defending mechanism, PHF was tested for corticotropin releasing hormone receptor 1 (CRHR1) antagonistic activity in Chinese hamster ovary-K1 (CHO-K1) cells. Also, effect on cortisol release and mRNA expression of 11β- hydroxysteroid dehydrogenase type 1 (11β-HSD1) against forskolin (10 μM) stimulated human adrenocarcinoma (H295R) cell were analyzed. PHF at all dose levels was found to decrease immobility time significantly during FST and reduced serum cortisol significantly at 15 mg/kg when compared to stressed group. PHF treatment was found to enhance swimming time significantly upto ~1.7 fold during swim endurance test when compared to untreated group. PHF (100 μg/mL) showed antagonistic effect of 26 % against CRF induced CRHR1 activity. Also, PHF (40 μg/mL) showed inhibition of cortisol release by 90.31 % and downregulated 11β- HSD1 expression by 11.5 fold in forskolin stimulated H295R cells. PHF demonstrated adaptogenic/antistress activity against chronic stress by its antagonistic effect on CRHR1, inhibition of cortisol release and downregulation of 11β-HSD1 expression.

Keywords : Anti-Fatigue, Physical Endurance, Chronic Variable Stress, CRHR1, Phytocee, 11β-HSD1 Expression.