Exposure to high altitude severely impacts performance of unacclimatized individuals and
contraindications associated with
synthetic drugs ascertain the need for development of herbal drugs. Thus, the present study investigated the adaptogenic potential of Ophiocordyceps sinensis aqueous extract (CSAQ) using simulated altitude stress models such as severe
hypoxia (SH) in
hermetic vessel, cold restraint (CR) at 4°C, and hypobaric
hypoxia (HBH) at 7,620 meter, ~ 282 mm Hg. To further address safety limits of extract, subacute toxicity studies were conducted in rats orally administered with CSAQ (0, 100, 500 and 1000 mg/kg) in a single dose/day for 28 days. Results revealed that animals administered with CSAQ increased convulsion time and core body temperature during SH and CR stress. CSAQ modulated thermogenic response by upregulating
uncoupling protein 1 and maintaining metabolic homeostasis. Further, CSAQ improved
antioxidant status (
glutathione and 2,3-diposhphoglycerate), attenuated pro-inflammatory
cytokine NF-κB, and augmented
hypoxia inducible factor and nuclear erythroid 2 related factor 2 in HBH exposed animals. Toxicity studies revealed no observed adverse effect level with 1000 mg/kg extract in
body weight gain, organ/
body weight ratio, hematological variables, biochemical parameters and histoarchitecture of vital organs. In conclusion, CSAQ initiated dose dependent adaptive response and exhibited high safety margins, which strongly suggests the therapeutic potential of CSAQ in mitigating high altitude maladies.