Effects of Adaptogens on the Central Nervous System and the Molecular Mechanisms Associated with Their Stress—Protective Activity.docVIP

Pharmaceuticals 2010, 3, 188-224; doi:10.3390/ph3010188 OPEN ACCESS pharmaceuticals ISSN 1424-8247 /journal/pharmaceuticals Review Effects of Adaptogens on the Central Nervous System and the Molecular Mechanisms Associated with Their Stress—Protective Activity Alexander Panossian * and Georg Wikman Swedish Herbal Institute Research Development, Sp?rv?gen 2, SE-432 96 ?skloster, Sweden * Author to whom correspondence should be addressed; E-Mail: ap@shi.se; Tel.: +46 Fax: +46-3023098. Received: 14 December 2009; in revised form: 11 January 2010 / Accepted: 16 January 2010 / Published: 19 January 2010 Abstract: Adaptogens were initially defined as substances that enhance the “state of non- specific resistance” in stress, a physiological condition that is linked with various disorders of the neuroendocrine-immune system. Studies on animals and isolated neuronal cells have revealed that adaptogens exhibit neuroprotective, anti-fatigue, antidepressive, anxiolytic, nootropic and CNS stimulating activity. In addition, a number of clinical trials demonstrate that adaptogens exert an anti-fatigue effect that increases mental work capacity against a background of stress and fatigue, particularly in tolerance to mental exhaustion and enhanced attention. Indeed, recent pharmacological studies of a number of adaptogens have provided a rationale for these effects also at the molecular level. It was discovered that the stress—protective activity of adaptogens was associated with regulation of homeostasis via several mechanisms of action, which was linked with the hypothalamic- pituitary-adrenal axis and the regulation of key mediators of stress response, such as molecular chaperons (e.g., HSP70), stress-activated c-Jun N-terminal protein kinase 1 (JNK1), Forkhead box O (FOXO) transcription factor DAF-16, cortisol and nitric oxide. Keywords: adaptogens; herbal medicine; fatigue; Hsp70;