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Plants from all over the world such as Eleutherococcus senticosus, Panax ginseng, Raponticum carthamoides, Rhodiola rosea, Withania somnifera and Ocimum sanctum have been extensively evaluated for their adaptogenic potential. However, none of them has been successfully introduced as an adaptogen in the clinic. This paper discusses some of the problems in evaluation of adaptogens which have precluded their inclusion as clinically useful drugs. We further discuss our results with six rasayana plants from Ayurveda, which were studied for their adaptogenic potential. The whole, aqueous, standardized extracts of selected plants (Tinospora cordifolia, Asparagus racemosus, Emblica officinalis, Withania somnifera, Piper longum and Terminalia chebula) were administered orally to experimental animals, in a dose extrapolated from the human dose, following which they were exposed to a variety of biological, physical and chemical stressors. These plants were found to offer protection against these stressors, as judged by using markers of stress responses and objective parameters for stress manifestations. Using a model of cisplatin induced alterations in gastrointestinal motility, the ability of these plants to exert a normalizing effect, irrespective of direction of pathological change was tested. All the plants reversed the effects of cisplatin on gastric emptying, while Tinospora cordifolia and Asparagus racemosus also normalized cisplatin induced intestinal hypermotility. Tinospora cordifolia was also tested for its ability to modulate the changes occurring in the phagocytic activity of peritoneal macrophages after exposure of rats to either carbon tetrachloride or horse serum. It was found to normalize the phagocytic function irrespective to the direction of change, complying to the definition of an adaptogen. All the plant drugs were found to be safe in both acute and subacute toxicity studies. Studies on the mechanisms of action of the plants revealed that they all produced immunostimulation. The protection offered by Tinospora cordifolia against stress induced gastric mucosal damage was lost if macrophage activity was blocked. Emblica officinalis strengthened the defence mechanisms against free radical damage induced during stress. The effect of Emblica officinalis appeared to depend on the ability of target tissues to synthesize prostaglandins. Recent data obtained with Tinospora cordifolia suggest that it may induce genotypic adaptation, further opening the arena for more research and experimentation.

Secondary infections are the most common cause of mortality in the immunocompromised host. A recent therapeutic approach has aimed at bolstering the host's defence mechanism to assist in eradication of infection, using naturally occurring and synthetic substances like BCG, C. pamum, muramyl dipeptide and glucans. Tinospora cordifolia (TC), Asparagus racemosus (AR) and Withania somnifera (WS) are plants prescribed in Ayurveda, the Indian traditional system of medicine, as agents to strengthen host defence mechanisms. The present article reviews the effects of TC, AR and W S in diverse experimental infections. TC, AR and WS protected rats against caecal Ligation induced abdominal sepsis and mice against Escherichia coli peritonitis. This was associated with a faster bacteremia clearance. Myelosuppression induced by single and multiple doses of cyclophosphamide was reversed. Mortality due to Staphylococcus aumus sepsis in neutropenic and hemisplenectomized mice was reduced in treated animals. Candida albicans sepsis induced mortality was also reduced by the plants. The plants induced leucocytosis with predominant neutrophilia associated with stimulation of phagocytic and bactericidal capacity of neutrophils and macrophages. In view of their oral efficacy and relative lack of adverse effects, AR, TC and WS show promise as useful immunomodulators.

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