Evaluating Prophylactic Efficacy of Terminalia Arjuna ROXB EX DC Wight and ARN Santalum Album L and Nymphaea X Rubra Roxb Ex Andrews for Acute Mountain Sickness

Abstract

Acute mountain sickness (AMS) is the highest prevalent illness occurring on rapid ascends to high altitude. The absence of the suitable animal model, clinical diagnostic markers and specific drugs to mitigate symptoms associated with AMS still remains an enigma. The present study was designed for the development of an animal model for acute hypobaric hypoxia-induced alterations in fluid and electrolyte balance, cerebral vascular leakage (CVL), and hypovolemia in rats. Further, we studied, the prophylactic efficacy of poly-herbal formulation comprising of Terminalia arjuna (T. arjuna), Santalum album (S. album) and Nymphaea rubra (N. rubra) during combined hypoxia dehydration (CHD) stress. For acute hypobaric hypoxia study, the altitude was optimized by exposing animals at different altitudes viz., 10,000, 15,000, 20,000, 25,000, 27,000 and 30,000 ft. For dehydration studies, animals were exposed to dehydration stress for 72 hrs. During CHD stress animals were exposed to dehydration for 60 hrs and then the animals were exposed to acute hypobaric hypoxia at the altitude of 27,000 ft. For phyto-prophylactics studies, T. arjuna and S. album extracts were administered to hypoxic animals (27,000 ft.) at the doses of 150 and 200 mg/kg respectively and N. rubra extract at the dose of 200 mg/kg was administered to dehydrated animals. A poly-herbal formulation with an optimized composition of T. arjuna, S. album and N. rubra was prepared and toxicity studies were conducted according to the guidelines provided by the organization for economic corporation and development. Glomerular filtration rate was estimated by Tc-99mDTPA, plasma volume and CVL was estimated by using Evan s blue and sodium fluorescein dye respectively. Renin, angiotensin-II, aldosterone, ANP, TNF-and#945;, IL-16, IL-1and#946; and S100B were estimated by ELISA kits. The expression of RAGE and NF-and#954;B were studied by commercially available antibodies. RBC fragility was estimated by isotonicity and flow cytometric methods.