Efficacy of Aqueous Extract of Chinese Caterpillar Mushroom Ophiocordyceps sinensis (Ascomycota) Against Simulated Altitude Stress and Subacute Toxicity Studies

Exposure to high altitude severely impacts performance of unacclimatized individuals and contraindi-cations 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 cy-tokine NF-??B, 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.