Planta Medica - PLANTA MED , vol. 75, no. 09, 2009

Molecular chaperons mediated pathways of stress protective and anti-aging effects of adaptogens
A Panossian, G Wikman, P Kaur, A Asea

Abstract
The aim of our studies on plant adaptogens, e.g. ADAPT-232 forte - a fixed combination of standardized extracts of Eleutherococcus senticocus (Rupr. et Maxim) Harms root, Schisandra chinensis (Turzc) Baill., root, Rhodiola rosea L., root, was to give a rationale to their antifatigue, stress-protective and life-span enhancing effects on the molecular level. In several studies on animals we demonstrated that these effects are associated with the regulation of key mediators of stress response, such as molecular chaperons (e.g. Hsp70) [1], stress-activated c-Jun N-terminal protein kinase (JNK1) [2], Forkhead box O (FoxO) transcription factor DAF-16 [3], cortisol [2,4] and nitric oxide (NO) [2]. Adaptogens prevent stress-induced NO increase [2], which is known to inhibit the production of cellular energy (ATP) through two mechanisms: inhibition of mitochondrial respiration by inhibition of cytochrome P450 and the inhibition of glycolysis [5]. That results in increased performance and endurance [1]. The key point of the mechanism of action of ADAPT-232 is up-regulation, of a "stress sensor" protein Hsp70 [1], which plays an important role in cell survival and apoptosis. Hsp70 inhibits the NOS II gene expression and interacts with glucocorticoid receptors directly and via the JNK pathway affecting thereof the circulating cortisol and NO. Adaptogen-induced up-regulation of Hsp70 triggers stress-induced JNK-1 and DAF-16-mediated pathways of regulation the resistance to stress, resulting in enhanced mental and physical performance and increased of longevity [6].

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[5] Brown, G.C. (2001) Biochim. Biophys. Acta 1504:46-57.
[6] Panossian, A. and Wikman, G. (2009) Curr. Clin. Pharmacol. In press.