Triethylene glycol-like effects of Ashwagandha (Withania somnifera (L.) Dunal) root extract devoid of withanolides in stressed mice

BACKGROUND: The objective of the study is to compare stress resistance-promoting effect of triethylene glycol (TEG) and root extract of Ashwagandha (Withania somnifera) i.e. withanolide-free root extract of Withania somnifera (WFWS). MATERIALS AND METHODS: Mice groups treated orally with 10 mg/kg TEG or WFWS (3.3, 10, 33.3, or 100 mg/kg) for 12 consecutive days were subjected to foot shock stress-triggered hyperthermia test on the 1(st), 5(th), 7(th) and 10(th) day and to marble-burying test on the following 2 days. Effects of treatment on stress-triggered alteration in body weight, core temperature, blood glucose, insulin and cortisol level were quantified and statistically analyzed. RESULTS: WFWS doses up to 10 mg/kg/day were as effective as TEG in affording protection against stress-triggered alteration in body weight, core temperature and marble-burying behavior. Protection against stress-triggered alteration in blood glucose and insulin level, as well as antidepressants or anxiolytic-like activities in the behavioral test, were observed in the higher two WFWS doses (33.3 and 100 mg/kg) treated groups only. CONCLUSION: Ashwagandha metabolites other than withanolides contribute to its stress resistance increasing effects. The observations suggest that modulation of physiological functions of gut microbiota may be involved in the mode of action of Withania somnifera root extracts.