Plant adaptogens. III. Earlier and more recent aspects and concepts on their mode of action.

Stimulus-response coupling systems responsible for defence and adaptation of organism to stressors are multi-target and very complicated pharmacological systems, including the neuroendocrine (stress) and immune system. The mode of action of adaptogens is basically associated with the stress-system (neuroendocrine-immune complex) and can be directed on the various targets of the system involved in regulation (activation and inhibition) of stimulus-response coupling. However, clinical studies performed according to the most modern standards are quite limited. On the other hand there is an extensive amount of clinical experience and also established use in self care etc. These aspects are planned to be dealt within a subsequent article which will be devoted to the application in three areas: self care, adjuvants in medicine and curative action in some diseases. At this stage, nevertheless, it seems possible to define some most important "stress-markers" for evaluation of efficiency of adaptogens in experimental and clinical pharmacological studies. They can be both activating (catecholamines, LT-s, cytokines, NO, etc.--"switch on" system--which activates energetic and other resources of the organism), and deactivating (corticosteroids and PGE2-endogenous mediators of cellular communications, which protect cells and whole organism from overreacting to the activating messengers--"switch off" system) stress-messengers. The balance between the activities of the "switch on" and "switch off" systems reflects the well being of the organism. It could be established on different levels of the homeostasis (heterostasis) with different levels of the sensitivity to stressors (Figure 8). The response of stress system--"reactivity" is different at the various levels of heterostasis and depends on adaptation--capacity of the organism (or a cell) to protect itself. In the process of adaptation to stressor's effects the basal levels mediators of switch on (e.g. NO) and switch of (e.g. cortisol) systems are increasing but their balance (the ratio) does not change. In other words, adaptogens increase the capacity of stress system to respond to external signals at the higher level of the equilibrium of activating and deactivating mediators of stress response. Consequently, plant adaptogens can be defined as "smooth" pro-stressors which reduce reactivity of host defense systems and decrease damaging effects of various stressors due to increased basal level of mediators involved in the stress-response. In further studies of adaptogens it seems important to find correlation between adaptogenic activity (a decrease in the "reactivity" of the organism--the basal level of activating and deactivating messengers: ILs, LTB4, NO, PGE2, cortisol, but not their ratio) and their therapeutic efficiency (symptomatic evaluation).