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In the present study, oral supplementation of l-arginine in rats was evaluated for its anti-stress and adaptogenic activity using the cold (5°C)–hypoxia (428 mmHg)–restraint (C-H-R) animal model. A dose-dependent study of l-arginine was carried out at doses of 12.5, 25.0, 50.0, 100.0, 200.0 and 500.0 mg/kg body weight, administered orally 30 min prior to C-H-R exposure. The time taken by the rat to attain a rectal temperature of 23°C (Trec 23°C) during C-H-R exposure and its recovery to Trec 37°C at normal atmospheric pressure and 32 ± 1°C were used as biomarkers of anti-stress and adaptogenic activity. Biochemical parameters related to lipid peroxidation, anti-oxidants, cell membrane permeability, nitric oxide and stress, with and without administration of the least effective l-arginine dose, were measured in rats on attaining Trec 23°C and Trec 37°C. The least effective adaptogenic dose of l-arginine was 100.0 mg/kg body weight. The C-H-R exposure of control rats, on attaining Trec 23°C, resulted in a significant increase in plasma malondialdehyde (MDA), blood lactate dehydrogenase (LDH) and a decrease in blood catalase (CAT) and plasma testosterone levels. On recovery (Trec 37°C) of control rats, there was a further decrease in CAT and plasma testosterone, and an increase in LDH. l-Arginine supplementation resulted in a significant decrease in plasma MDA, an increase in blood superoxide dismutase (SOD), CAT levels maintained at control values and a lower increase in LDH compared with controls (45.3 versus 58.5% and 21.5 versus 105.2%) on attaining Trec 23°C during C-H-R exposure and on recovery to Trec 37°C. The results suggested that l-arginine possesses potent anti-stress activity during C-H-R exposure and recovery from C-H-R-induced hypothermia.

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Substances which enhance endurance for physical and mental work and increase non-specific resistance to stress during a prolonged stay in physiologically adverse habitats are called 'adaptogens'. Panax ginseng is well known for its anti-stress and adaptogenic properties. In the present study, adaptogenic activity by the intake of a herbo-vitamin-mineral preparation (HVMP) containing P. ginseng and multivitamin-mineral preparation (MVMP) was evaluated using the cold-hypoxia-restrained (C-H-R) animal model. The aim was to determine whether the cold tolerance and recovery from acute hypothermia mediated by P. ginseng was modified by simultaneous intake of additional vitamins and minerals. Results suggest that the adaptogenic effect of HVMP was more or less the sum total of its two components P. ginseng and MVMP. In HVMP, P. ginseng was found to be effective for developing resistance to cooling and MVMP helped in stimulating faster recovery from acute hypothermia.

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The results show that the a new species of withanolide, 1-oxo-5beta, 6beta-epoxy-witha-2-ene-27-ethoxy-olide (compound-1) could prove to be an effective agent to counteract C-H-R stress.