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1. Adaptogens Wellness Wednesdays 12/4/19 – Aspen, CO Dr. John Hughes, DO

2. Adaptogens • Increase the resistance to stress • Decrease sensitivity to stressors (stress protection effect) • Stimulate the body’s overall physiology • Limit fatigue • All of the above create “heterostasis” – a condition of the body better adapted than normal homeostasis

3. Popular Adaptogens and their Pharmacological Effects Pharmacological profile of adaptogens: summary of in vitro or in animal studies. Regulatory System: effect Pharmacological Effects Rhodiola Eleutherococcus Schisandra Stress-system (neuro-endocrine- immune complex): Anti-stress/stress- mimetic/ stress- protective CNS-stimulating: enhancing of physical performance, cognitive performance (learning and memory) + + + Neuroprotective + + Hepatoprotective + + + Cardioprotective + + Gastroprotective + + Oxidative stress/Radioprotectiv e + + + Anti-atherosclerosis + + Vasodilatatory/hypot ensive + Anti-hyperglycemic + Anti- inflammatory/allergy + + + Immunotropic + + + Antidepressive + Anxiolytic + +

4. Why Adaptogens Work Adaptogens are complex phenolics or tetracyclic triterpenoids/ steroids Phenolics: Structure is similar to catecholamines which are mediators of the sympathoadrenal system (SAS) early in the stress response Tetracyclic triterpenoids: Structurally resemble the corticosteroid stress hormones for long-term protective inactivation of the stress system Also, the monoterpene glucoside rosiridin from Rhodiola rosea, was found to inhibit monoamine oxidases A and B which may benefit depression and senile dementia


6. Can Adaptogens Extend Life?

7. What Happens Cellularly with Stress • Mitochondria: create oxygen-containing radicals that can damage native or repair proteins by distorting their 3-D structure • With stressors: infection, cold, heat, radiation, physical load, emotional stress, a cascade of “signalling” proteins/enzymes (eg JNK) • JNK: limits neuronal development, activates the immune system, and begins programmed cell death (apoptosis)

8. Adaptogen Cellular Response • ADAPT-232 • Decreases NO, cortisol and JNK under stress • Stimulate/activate the expression of Hsp70 and p-FoxO1 • With the following results: • Enhances the repair of damaged proteins, inhibits the stress-induced expression of NO genes, inhibits JNK and consequently apoptotic death and suppression of immune system via activation of GR and other mechanisms. • Maintains normal ATP levels the anti-fatigue and anti-depressive effects of adaptogens and with normal cognitive function (e.g., good attention, memory and learning). • Increased long-term resistance to stress and increased life span

9. Effects of Chronic Stress on Humans Brain/Spine: –volume reductions of some structures (such as the PFC) –decreased neuronal plasticity due to dendritic atrophy and neuronal death –decreased spine density –Stressed Brains and Depressed brains look morphologically similar Immune system: –psychological stress induces the same response as infections and causes tissue damage –increase the levels of circulating cytokines and of various biomarkers of inflammation

10. Effects of Chronic Stress on Humans Cardiovascular system: -stress induces the release of noradrenaline by sympathetic nerve fibers targeting blood vessels –promoting cell division and leukocyte mobilization into the bloodstream –resulting in enhanced recruitment of inflammatory cells in atherosclerotic plaques, higher levels of proteases and increased plaque fragility –Interestingly, beta blockers (blocking noradrenaline) limit or reverse the buildup of athelerosclerotic plaques Joints: Proinflammatory cytokines induced by stress Adaptogenic activity: Exercise counteracts stress, Glandular therapy targeting the hypothalamus, pituitary, and adrenals