Enhancing Cellular Defense Mechanisms with Adaptogens

Enhancing Cellular Defense Mechanisms with Adaptogens

Aging is associated with a decrease in adaptive abilities along with increased vulnerability to stress. At the same time, aging is a complex process involving a persistent activation of some stress response systems, often involving transcriptional reprogramming, and the activation of vitagenes, which can be consider a ‘geroprotective’ adaptation.13   Environmental stressors induce specific and predictable epigenetic changes that can eventually result in an adaptive response to the stimulus. It seems likely that mild stress-induced hormetic response involves mechanisms similar to those that underlie developmental epigenetic adaptations.

The illustration below shows the involvement of hormesis in the epigenetic processes that determine age-related disorders and longevity.14


Dose–response curve depicting the quantitative features of hormesis

Hormesis is a biological phenomenon whereby a beneficial effect (improved health, stress tolerance, growth or longevity) results from exposure to low doses of an agent that is otherwise toxic or lethal when given at higher doses.

The Role of Adaptogens in Hormesis

Botanical and dietary compounds, such as polyphenols, have recently been shown to be neuroprotective through the activation of hormetic pathways, including vitagenes. Hormesis provides the foundation of neuroprotective responses, and offers a framework for explaining the common measurable features of their dose response relationships, their mechanistic foundations, and their relationship to the concept of biological plasticity as well as providing a key insight for improving the accuracy of the therapeutic dose of pharmaceutical agents.15

Adaptogenic formulas allow for the modulation of endogenous cellular defense mechanisms, and represent an innovative approach to therapeutic intervention in chronic diseases and aging.

Adaptogenic formulations are the foundation of botanical medicine and their unique mode of beneficial actions include the expansion of “homeodynamic space.” A crucial component of the homeodynamic space is the stress response, in which a living system senses disturbance and initiates a series of events for maintenance, repair, adaptation, remodeling and survival.

Adapting to stressors provides a wider dynamic range of stability, also referred as the homeodynamic space. Adaptogenic formulas strengthen and maintain expansiveness of the homeodynamic space, mitigating the negative impact of aging on this important aspect of health and healing. In this way, they offer protection against a wide variety of environmental assaults and emotional and physical stressors.

What is an Adaptogen?

The general pharmacodynamic characteristics of an adaptogenic substance were defined by Brekhman and Dardymov (1969) as follows:

  • An adaptogen is almost non-toxic to the recipient;
  • An adaptogen tends to be non-specific in its pharmacological properties and acts by increasing the resistance of the organism to a broad spectrum of adverse biological, chemical, and physical factors;
  • An adaptogen tends to be a regulator having a normalizing effect on the various organ systems of the recipient organism.

One mode of action of adaptogens has been associated with the neuroendocrine-immune system and the system involved in regulation (activation and inhibition) of stimulus-response coupling, which are responsible for defense and adaptation of the organism to stressors.16-18 Although useful, this classic reductionist model is insufficient for explaining the mechanistic aspects of the physiological notion of “adaptability” and the adaptogenic activity of adaptogens.

To consider adaptogens in a broader sense, they are associated with stress hormones and key mediators of homeostasis. In this context, the mechanisms of action of adaptogens are specifically related to stress-protective activity and increased adaptability of the organism. Adaptogens exhibit multiple protective effects against chronic inflammation, atherosclerosis, neurodegenerative cognitive impairment, metabolic disorders, cancer, and other aging-related diseases.

Current uses of adptogens are mainly related to stress-induced fatigue and cognitive function, mental illness, and behavioral disorders. It is very unlikely that the pharmacological activity of any phytochemical is specific and associated only with one type of receptor, particularly adaptogenic compounds, which affect key mediators of the adaptive stress response at intracellular and extracellular levels of communication. Therefore, their prophylactic use by healthy subjects to ameliorate stress and prevent age-related diseases appears to be justified. 19

Beginning in the early 1960’s, extensive human and animal research on adaptogenic plant extracts has consistently shown that adaptogens enhance stress resistance by promoting vitality and enhancing physical and mental performance. Adaptogens improve health by enhancing the four life requirements, which are 1) Energy, 2) Adaptation, 3) Protection, and 4) Reproduction.  Adaptogens aid in all aspects of response, and then normalize and restore function.

In my experience, the value of adaptogenic formulas for health and vitality is their ability to enhance the four Rs: Recognition, Response, Recovery, and Revitalize.

  • Recognize. Recognition is the first step to any response. When the body comes into contact with a pathogen such as a flu virus, the first step is to identify the invader so that the immune system can mount an appropriate response. Another way to think of this is awareness. The immune system cannot respond until it is aware of what is wrong. In the event of cancer, the failure of the immune system to recognize cancer cells as abnormal occurs in all stages of the disease, including initiation, progression, angiogenesis, and invasion.
  • Respond. Once the body is aware of a physiological need, it mounts a response. For example, digestion begins as a response to food entering the mouth, which triggers the secretion of digestive enzymes. After food is digested, hydrochloric acid and enzymes are turned off, and the body produces bicarbonates to buffer the acids. If we don’t respond appropriately because our energy is diverted elsewhere, then we either don’t make enough digestive enzymes, or we make too much, or we don’t make bicarbonates because we never fully digested what we ate.

All of these unhealthy responses are often caused by stress, but in most cases, the root cause is never addressed. For example, enzyme deficiency (caused by stress) is the primary cause of acid reflux. Antacids are usually prescribed to quell the excess acid, but the real problem has not been addressed. By blocking acid production, we don’t feel discomfort, but the body is unable to digest and assimilate nutrients, and thus, cannot maintain optimal health.

  • Recovery. Once we respond to stress, we must recover from that response, turn down or off certain metabolic switches, and turn others back on. An important aspect of recovery is anabolic restoration. When energy goes to the surface it is catabolic. When we recover it is anabolic.
  • Revitalize. All energy systems or organ networks require that we restore their energy reserves. If energy reserves are not sufficiently replenished, an individual will not be able to effectively heal.

Adaptogens improve the efficacy of energy transfer, which include catabolic activities that involve oxygen, glucose, and fats for optimal efficient energy production, as well as anabolic processes utilizing amino acids to build up all tissues and cells of the body. Anabolic restoration is an essential feature of adaptogens.

The Subtle Energetics of Adaptogens

The idea that energetic relationships within the body give rise to adaptation and healing, such as the vis medicatrix naturae (the healing power of nature), is a pivotal concept of naturopathic and herbal medicine. Vital to an understanding of healing is an exploration of aspects of energy utilization including the impact of belief systems, lifestyle choices, sexuality, and spirituality.

Energetic relationships are important and relevant, yet because they cannot be methodically analyzed and explained on a biological or physiological level, they are misconstrued and largely ignored in modern-conventional medicine. The language and approach of traditional healing systems is better suited to explore and understand the concepts and interrelationships that are essential for the creation and maintenance of optimal health.

Adaptogens act to normalize homeostasis, optimize metabolism, and improve resistance to a variety of adverse factors. All of my protocols are built on a foundation of adaptogenic formulations. Just has a building has framework, so does a supportive protocol of botanical and nutritional remedies.

Mederi Medicine utilizes five medicinal toolboxes, and multiple interwoven treatments or modalities, to provide synergistic effects—not merely additive or opposing effects, but optimizing a harmonious effect whereby the combination is significantly better in every way, in comparison to any of these medicines alone.

In summation, a house should not be built by beginning at the top and working down. You must first create a strong foundation. In the same way, people with health issues must return to their foundation, creating a solid base from which they can rebuild their health.

In physical terms, this means supporting the body with optimal nutrition, rest, and appropriate exercise. This is where adaptogenic tonics provide fundamental support. This special class of botanical and nutritional medicines works on a foundational level to sustain everything else you do to improve your health by nonspecifically enhancing and balancing the ‘whole,’ (the life force). In terms of the mind and emotions, we must learn to calm the mind, to forgive, to love, and to live with integrity in our relationships with others and ourselves. And in terms of spirit, we must nourish our connection to God through prayer and reflection. By attending to all of these aspects of our being, we can find our way back to true health.

Saint John of the Cross, a Carmelite priest and a great mystic, taught the monks a humble exercise; to sit and contemplate where they could view the open sky, hills, trees, fields, and growing plants, and to call upon the beauty of these things to praise God. This simple meditation on Nature reminds us of Divine Power, and the wisdom and goodness that exist in Her. If we stop for a moment to consider the origin, magnitude, beauty, fullness, activity, and order of all things, we cannot doubt the beneficence of God.

I offer this prayer to you and our world:

Dear Lord,

Nourish us,

Shed your light upon all of our thoughts,

Breathe holy inspiration into our hearts and minds,

Bring peace to the world and us.



  1. K. Pon, J. R. Lane, E. K. Sloan, M. L. Halls. The 2-adrenoceptor activates a positive cAMP-calcium feed forward loop to drive breast cancer cell invasion. The FASEB Journal, 2015; 30 (3): 1144 DOI:10.1096/fj.15-277798
  2. Liu, D., et. al. β2-AR signaling controls trastuzumab resistance-dependent Pathway, Oncogene (2016) 35, 47–58
  3. Partecke LI. Et. al., Chronic stress increases experimental pancreatic cancer growth, reduces survival and can be antagonised by betaadrenergic receptor blockade, Pancreatology. 2016 MayJun;16(3):42333. doi: 10.1016/j.pan.2016.03.005. Epub 2016 Mar 23.
  4. Pasquier, E., et. al. Propranolol potentiates the anti-angiogenic effects and antitumor efficacy of chemotherapy agents: implication in breast cancer treatment, Oncotarget, October, Vol.2, No 10, 2011
  5. Chow W , Amaya CN , Rains S , Chow M , Dickerson EB , Bryan BA., Growth Attenuation of Cutaneous Angiosarcoma With Propranolol-Mediated β-Blockade, JAMA Dermatol. 2015 Sep 16:1-4. doi: 10.1001/jamadermatol.2015.2554.
  6. Calvani, Maura, et. al.Norepinephrine promotes tumor microenvironment reactivity through β3-adrenoreceptors during melanoma progression, Oncotarget, Vol. 6, No.7, 2014 Oct.
  7. De Couck M, Maréchal R, Moorthamers S, Van Laethem JL, Gidron Y. Vagal nerve activity predicts overall survival in metastatic pancreatic cancer, mediated by inflammation. Cancer 2016 Feb;40:47-51. doi: 10.1016/j.canep.2015.11.007. Epub 2015 Nov 24.
  8. Demirovic DRattan SI. Establishing cellular stress response profiles as biomarkers of homeodynamics, health and hormesis, Exp Gerontol.2013 Jan;48(1):94-8. doi: 10.1016/j.exger.2012.02.005. Epub 2012 Feb 22.
  9. Rattan, SI, 2004. Aging intervention, prevention, and therapy through hormesis. J. Gerontol. Biol. Sci. 59A, 705–709.
  10. Rattan SI, Hormesis in aging, Ageing Res Rev.2008 Jan;7(1):63-78. Epub 2007 Aug 31.
  11. Davies, Kevin, JA, Adaptive homeostasis, Molecular Aspects of Medicine 2016;49:1-7
  12. Lushchak VI. Dissection of the Hormetic Curve: Analysis of Components and Mechanisms. Dose-Response. 2014;12:466-479
  13. Vaiserman, Am., Hormesis, Adaptive Epigenetic Reorganization, and Implications for Human Health and Longevity, Dose-Response, 8:16–21, 2010, DOI: 10.2203/dose-response.09-014.
  14. Vittorio Calabrese, Carolin Cornelius, Albena T. Dinkova-Kostova, Edward J. CalabreseMark P. Mattson, Cellular Stress Responses, The Hormesis Paradigm, and Vitagenes: Novel Targets for Therapeutic Intervention in Neurodegenerative Disorders, Antioxid Redox Signal. 2010 Dec 1; 13(11): 1763–1811.
  15. Calabrese V, Cornelius C, Dinkova-Kostova AT, Iavicoli I, Di Paola R, Koverech A, Cuzzocrea S, Rizzarelli E, Calabrese EJ. Biochim Biophys Acta. 2012 May; 1822(5):753-83. Epub 2011 Nov 6.
  16. Panossian A, Wikman G, Wagner H, 1999. Plant Adaptogens Ш, Earlier and More RecentAspects and Concepts on Their Mode of Action. Phytomedicine: 6(4): 287-99
  17. Panossian A, 2003. Adaptogens, Tonic Herbs for Fatigue and Stress. Alternative & Complementary Therapies, 9(6):327-31.
  18. Panossian A, Wagner H, 2005. Stimulating effect of adaptogens: an overview with particular reference to their efficacy following single dose administration. Phytother Res, Oct. 19 (10): 819-38
  19. Panossian A, Understanding adaptogenic activity: specificity of the pharmacological action of adaptogens and other phytochemicals, Ann N Y Acad Sci.2017 Jun 22. doi: 10.1111/nyas.13399.
   Send article as PDF   

Leave a Reply

Your email address will not be published. Required fields are marked *