Adaptogens, Bioregulatory Systems Medicine and Network Pharmacology

Have you ever wondered how life on Earth has managed to survive in the midst of volcanos, ice ages and asteroids? The answer is adaptation. Humans are remarkably adaptable. We’ve been able to adjust to almost any condition on the planet, while continuing to thrive as a civilization.

Think about this:

  • No other species lives in such a variety of places, including the Arctic, in deserts, in jungles, at sea, or in barren wastelands.
  • No other species has the ability to eat and digest such a wide variety of foods.
  • No other species is able to reconstruct their living environment to the degree that humans do.

Charles Darwin said it well: “It is not the strongest or the most intelligent of the species that survives. It is the one that is most adaptable to change.

Hormesis: The Key to Adaptation

The biological phenomenon of this adaptogenic quality of life is called “hormesis.” The principal pillars of my approach to health are to enhance adaptation, energy transfer efficiency, protection, and reproduction (hormonal health). Perhaps the most important of these is adaptation, but really, they are all interconnected. Everything is networked. Thus, the best approach to health is to support the networks of the body as a whole, to enhance robustness and our ability to auto-regulate and auto-organize at the molecular, cellular, and organ system levels. 

This is why adaptogenic formulas are the first step in building and enhancing robust health, and the most important supplemental support you can provide to your body. Every other supplement you take should be secondary to adaptogenic formulations.

Our approach to health and healing is not a fixed line, but a circle that is alive and in constant motion. It is not functional, but rather responsive, so although everything in our body has a function, ultimately what makes us alive and human is how our bodies respond.  Response implies a life-force that activates and regulates all components of energy transfer. This life-force is capable of listening to the “orchestra” (ie; network) and providing direction while constantly adapting. To function is robotic and programmed, while response is connected to wisdom and is alive. 

Medicine today continues to view the body in a fragmented way, including body systems, parts, genes, and microbiomes. Very few people, particularly in the medical profession, see the whole, but we have complex diseases that are characterized as polygenic and multifactorial. We are therefore best served with medicines—specifically plant medicines—that are pleotrophic, gentle, nourishing, strengthening, and assist in normalizing, or auto-regulating.

Thinking Outside the Current Medical Model

Herbal formulations contain multiple components that dock to multiple target sites and synergistically exert beneficial effects throughout a wide range of pathways. Through many years of clinical practice, I’ve realized that it is neither possible or appropriate to try and fit herbal medicine into or alongside the current conventional model. That is why I developed the Mederi Care model as a new way of thinking and combining various approaches that is inclusive of both holistic and allopathic medicine. The soul of this approach, however, is rooted in botanical medicine, combined with nutritional supplementation, food as medicine, life-style modifications, and spiritual care. Once this foundation is in place, then it is appropriate to evaluate if more specific, “heroic” (ie; pharmaceutical) medicine is needed, and if so, where it fits within the whole systems, unitive approach.

The molecular pathways that govern human disease consist of molecular circuits that coalesce into complex, overlapping networks. These network pathways are presumably regulated in a coordinated fashion, but such regulation has been difficult to decipher using only reductionistic principles. The emerging paradigm of “network medicine” proposes to utilize insights garnered from network topology (ie; the static position of molecules in relation to their neighbors) as well as network dynamics (ie; the unique flux of information through the network) to understand better the pathogenic behavior of complex molecular interconnections that traditional methods fail to recognize.[1]

Bioregulatory Systems Medicine

Bioregulatory Systems Medicine (BrSM) is a comprehensive, innovative approach in medicine. It embraces the complexity of diseases by supporting the general idea of autoregulation and addressing underlying dysregulating biological networks.

The objective of Bioregulatory Systems within the Mederi Care approach is to improve patient outcomes by supporting a patient’s autoregulatory capacity. This is accomplished through the Mederi Care toolboxes, specifically botanical and nutritional medicine, which is applied in a gentle, synergistic way. Botanical and nutritional medicine practiced within Mederi Care is primarily directed at enhancement of ‘Self-regulating Internal Community Networks,’ supporting and even directing, while allowing the freedom to improvise.

The poet and philosopher Mark Nepo says: “To be the best we can be, we have to meet the outer world with our inner world. I’ve always believed in the amazing resilience of the human spirit.” Nepo believed that life has been made just hard enough that we need one another. Through experiences of great suffering and great love, we are reduced to what is essential.

The most effective way to reduce the possibility of poor health and disease is to keep the root system healthy and robust. Adaptogenic herbs in combination have a synergistic and pleotropic effect.

Synergism Enhances the Actions of Plant Medicines

Synergistic plant medicines contain bioregulatory properties. Their actions are determined by both chemistry and synergy, as their biological activity often results from the additive or synergistic effects of their components.

Synergy means behavior of whole systems unpredicted by the behavior of their parts.”

― Buckminster Fuller

These synergistic strategies can be much more comprehensive and broader in their scope of effects than single-component drugs[2]. This concept is not new to science. Synergy is an ubiquitous phenomenon in nature, and is widely used in numerous scientific disciplines, including thermodynamics, biophysics, biochemistry, molecular biology, and neurobiology.[3]

Herbal medicines are often combinations of botanical extracts that have additive or synergistic effects.  For example, combining the four herbal (S. baicalensis, D. morifolium, G. uralensis and R. rubescens) extracts significantly enhanced their activity compared with extracts alone in a prostate cancer model.[4]

It is important not to confuse synergistic effect with additive effect. Synergy occurs when two or more drugs/compounds are combined to produce a total effect that is greater than the sum of the individual agents while an additive effect is an add up of individual effects where each individual agent is not affecting the other (no interactions).[5]

The synergy of biological effects of plants in medicine is well documented, and encompasses synergistic multitarget effects, physicochemical effects based on improved solubility, antagonization of resistance mechanisms, and elimination or neutralization of toxic substances.[6] As such, multi-combination and/or multi-system low dose medications, preferably of natural origin, are well suited for the bioregulatory medical approach and offer the potential for a graded response to treatment.[7]

Generally speaking, herbal and nutritional medicine within this model exhibits four fundamental advantages of a multicomponent, combinatorial strategy over a single-component strategy:

1. Synergistic effects target a wider range of information flow in disease-related biological networks;

2. Modest modulation allows for more efficient control of biological networks;

3. Low concentrations ensure higher safety of the whole combination;

4. Drug resistance is much less probable.[8]

According to Traditional Chinese medicine (TCM), every living thing is sustained by the balance of two opposing forces of energy, Yin and Yang. Together they make up Qi (pronounced ‘chee’), which is the vital energy that flows in, through and around the body.

Network Pharmacology: A New Way of Understanding Herbal Formulations

Network pharmacology stems from several pioneering works. The holistic theory and practice of TCM, as well as other herbal medicine systems, play a key role in the origin and rapid development of network pharmacology. The original hypothesis referring to the biological associations between TCM syndromes, herbal formula, and molecular networks was proposed in 1999 and 2002.[9]

Network pharmacology has been used to study multiple protein/gene target diseases. It describes the relationship between biological systems, drugs, and diseases from the perspective of the network. This is consistent with the holistic pattern differentiation theory of TCM[10] as well as Mederi medicine.

Mitochondrial Network Medicine

The mitochondrial network is constantly in a dynamic and regulated balance of fusion and fission processes, which is known as mitochondrial dynamics. Mitochondria make physical contact with almost every other membrane in the cell, thus impacting all cellular functions.[11] 

“Qi,” as noted above, describes energy-dependent body functions. This can broadly be correlated with mitochondria-energy dynamics.

[12]

The term adaptogen was first proposed in 1940 by a scientist from the USSR. Lazarev described Schisandra chinensis and other herbs as plant-derived adaptogens that non-specifically enhance human physiology.[13]

Adaptogens are the material basis of the bodily response to the external environment and can act on the immune system and the stress response system, as shown below.

The non-specific response mode, especially the hormone response mode, occurs when homeostasis is not the driving force.[14]

Schisandra Fortifies Mitochondrial (Qi) Antioxidant Status

Schisandra

Schisandra berry or Wu-Wei-Zi, meaning the “the fruit of five tastes” in Chinese, is a commonly used herb in TCM. Ancient Chinese herbalists noted the berry’s beneficial effect on the “Qi” of the five visceral organs.  Schisandra is one of the main researched primary adaptogens that I use in adaptogenic formulations.  It is perhaps my favorite adaptogen, but I believe combination formulas have many advantages over single herbs.

Schisandra berry is well-known for it’s “Qi-invigorating” properties. The herb has been shown to fortify mitochondrial antioxidant status, thereby offering the body generalized protection against noxious challenges, both of internal and external origin. Given the indispensable role of the mitochondrion in generating cellular energy, the linking of Schisandra chinensis berry extract (SCBE) to the safeguarding of mitochondrial function provides a biochemical explanation for its “Qi-invigorating” action.[15]

SCBE is a potent adaptogen, and has been shown to improve disease and stress tolerance, while increasing energy, endurance, and physical performance.

SCBE is helpful in the treatment of neurological, cardiovascular, and gastrointestinal disorders. It has been shown to decrease fatigue, relieve insomnia, reduce obesity, and provide protection from mitochondrial dysfunction. SCBE stimulates immunity, acts as a tonic, and exerts antioxidant, anti-inflammatory, antiviral, anticancer, anti-aging, anti- diabetic, and liver- and skin-protecting activities.

Effects of Schisandra chinensis fruit extracts and their bioactive compounds in mitochondria.

[16]

SCBE has been shown to restore impaired mitochondrial function, acting as a mitoprotective agent. Studies show that schisandrin, the identified active ingredient in SCBE, restored cytochrome c oxidase activity, and protected the opening of mitochondrial permeability transition. Furthermore, schisandrin improved ATP production, citrate synthase activity, and the process of mitochondrial fusion and fission.[17]

Recent studies investigating the various active compounds within schisandra identified a total of 78 compounds consisting of 13 prototype lignans and 65 metabolites (including isomers).[18]

Combining schisandra extract with other adaptogens and tonic herbs provides hundreds to thousands of active compounds swimming together, bathing the cells and molecules throughout the body. Complex formulas no longer act like the single herb, but in an entirely new way. Think of an orchestra, and perhaps what a single member playing an instrument might sound like. Then consider the entire orchestra, and all of the instruments working in harmony. As a jazz musician and an herbalist with an interest in network pharmacology, this is a perfect analogy for the way that herbs work together when combined in appropriate formulations.

On Pubmed alone, there are now 30 articles illustrating the increasing interest in network pharmacology and traditional herbal medicine.[19] Understanding network pharmacology and Bioregulatory Systems Medicineis the foundation of Mederi Care. I am grateful that this comprehensive, harmonious system of healing is gaining the recognition it deserves.

References


[1] Chan SY, Loscalzo J. The emerging paradigm of network medicine in the study of human disease. Circ Res. 2012 Jul 20;111(3):359-74. doi: 10.1161/CIRCRESAHA.111.258541. PMID: 22821909; PMCID: PMC3425394

[2] Lila MA. 2007. From beans to berries and beyond: Teamwork between plant chemicals for protection of optimal human health. Ann. N. Y. Acad. Sci.1114:372–80

[3] Corning PA. 1998. “The synergism hypothesis”: On the concept of synergy and its role in the evolution of complex systems. J. Soc. Evol. Syst.21(2):133–72

[4] Adams LS, Seeram NP, Hardy ML, Carpenter C, Heber D. Analysis of the interactions of botanical extract combinations against the viability of prostate cancer cell lines. Evid Based Complement Alternat Med. 2006 Mar;3(1):117-24. doi: 10.1093/ecam/nel001.

[5] Zhou, Xian et al. “Synergistic Effects of Chinese Herbal Medicine: A Comprehensive Review of Methodology and Current Research.” Frontiers in pharmacology vol. 7 201. 12 Jul. 2016, doi:10.3389/fphar.2016.00201

[6] Wagner H. Synergy research: approaching a new generation of phytopharmaceuticals. Fitoterapia. 2011 Jan;82(1):34-7. 

[7] Bioregulatory Systems Medicine. White Paper. Published February 2019 – Copyright © Biologische Heilmittel Heel GmbH. Rights Reserved

[8] Kong DX, Li XJ, Zhang HY. Where is the hope for drug discovery? Let history tell the future. Drug Discov Today. 2009 Feb;14(3-4):115-9. 

[9] Li S. (2007). Framework and practice of network-based studies for Chinese herbal formulaZhong Xi Yi Jie He Xue Bao. 5, 489–493.  10.3736/jcim20070501

[10] Zhang R, Zhu X, Bai H, Ning K. Network Pharmacology Databases for Traditional Chinese Medicine: Review and Assessment. Front Pharmacol. 2019 Feb 21;10:123.

[11] Pijuan J, Cantarero L, Natera-de Benito D, Altimir A, Altisent-Huguet A, Díaz-Osorio Y, Carrera-García L, Expósito-Escudero J, Ortez C, Nascimento A, Hoenicka J, Palau F. Mitochondrial Dynamics and Mitochondria-Lysosome Contacts in Neurogenetic Diseases. Front Neurosci. 2022 Jan 31;16:784880.

[12] Tian J, Huang Y, Wu T, Huang HD, Ko KM, Zhu BT, Chen J. The Use of Chinese Yang/Qi-Invigorating Tonic Botanical Drugs/Herbal Formulations in Ameliorating Chronic Kidney Disease by Enhancing Mitochondrial Function. Front Pharmacol. 2021 Jun 24;12:622498. doi: 10.3389/fphar.2021.622498. PMID: 34248614; PMCID: PMC8264145.

[13] Liao LY, He YF, Li L, Meng H, Dong YM, Yi F, Xiao PG. A preliminary review of studies on adaptogens: comparison of their bioactivity in TCM with that of ginseng-like herbs used worldwide. Chin Med. 2018 Nov 16;13:57.

[14] Panossian A, Wikman G, Wagner H. Plant adaptogens. III. Earlier and more recent aspects and concepts on their mode of action. Phytomedicine. 1999 Oct;6(4):287-300.

[15] Ko KM, Chiu PY. Biochemical basis of the “Qi-invigorating” action of Schisandra berry (wu-wei-zi) in Chinese medicine. Am J Chin Med. 2006;34(2):171-6. 

[16] Kopustinskiene DM, Bernatoniene J. Antioxidant Effects of Schisandra chinensis Fruits and Their Active Constituents. Antioxidants (Basel). 2021 Apr 18;10(4):620. doi: 10.3390/antiox10040620.

[17] Piao, Z.; Song, L.; Yao, L.; Zhang, L.; Lu, Y. Schisandrin restores the amyloid -induced impairments on mitochondrial function, energy metabolism, biogenesis, and dynamics in rat primary hippocampal neurons. Pharmacology 2021, 1–11.

[18] Wu Z, Jia M, Zhao W, Huang X, Yang X, Chen D, Qiaolongbatu X, Li X, Wu J, Qian F, Lou Y, Fan G. Schisandrol A, the main active ingredient of Schisandrae Chinensis Fructus, inhibits pulmonary fibrosis through suppression of the TGF-β signaling pathway as revealed by UPLC-Q-TOF/MS, network pharmacology and experimental verification. J Ethnopharmacol. 2022 May 10;289:115031. doi: 10.1016/j.jep.2022.115031. Epub 2022 Jan 26. PMID: 35091014.

[19] Lai, Xinxing et al. “Editorial: Network Pharmacology and Traditional Medicine.” Frontiers in pharmacology vol. 11 1194. 4 Aug. 2020, doi:10.3389/fphar.2020.01194

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Health Optimization and Adaptogens

Health Optimization and Adaptogens – An Effective Strategy Against Pathogens

In general, I am astonished by how little attention is placed on the value and importance of good health in our society. In the face of the current pandemic, with underlying co-morbidities present in an estimated 60% of the population, increasing the risk of death from complications, there is an even greater urgency to educate our communities and urge our citizens to adopt the key components to optimal health. For example, there is now a clear association between diabetes and increased mortality and severity in COVID-19 pneumonia, and ocular symptoms of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2).[1] These and many other underlying conditions can be successfully managed by applying the fundamental building blocks to optimal health and wellness, which include nutrition, botanical medicine, lifestyle, and diet. The more robust our health at the molecular, cellular, and organ system levels, the better equipped we are to resist and recover from disease.

Continue reading “Health Optimization and Adaptogens”

Whose Dietary Supplements Can You Trust and Why?

For more than four decades I’ve been involved in the dietary supplement business, from my humble beginnings working in a natural foods store to creating my own line of the highest quality supplements available on the market.

It has been a long, challenging, and educational road. And I understand—from an insider’s viewpoint—just how difficult it is to know whom you can trust when it comes to choosing the most effective dietary supplements.

Continue reading “Whose Dietary Supplements Can You Trust and Why?”

Neuroplasticity, Brain Health, Mood and ‘Smarty Plants’

Our brains have the remarkable capacity to adapt and change throughout our lives. This ability to form and reorganize neural pathways in response to learning, experience, injury, disease, or aging is called neuroplasticity.

“Everybody can be great, because everybody can serve. You only need a heart full of grace, a soul generated by love.”

~ Dr. Martin Luther King

Neuroplasticity helps the brain process sensory input along with creating suitable adaptive responses to stimuli. Neurons must have purpose to survive, and those with weak or ineffective connections are pruned. Through a variety of structural and molecular mechanisms, neurons compensate for injury or disease.

Continue reading “Neuroplasticity, Brain Health, Mood and ‘Smarty Plants’”

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

adaptogens

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. Continue reading “Enhancing Cellular Defense Mechanisms with Adaptogens”

Adaptogens – Essential Support for Restoration, Protection, Resilience, and Longevity

In my observation, far too many people today are merely surviving instead of thriving. I attribute most of the erosion of well being and resilience—including the growing prevalence of chronic, degenerative diseases—to the increased stressors of contemporary society. Although the role of stress in disease has long been recognized, it is now more fully understood through the advances of scientific research.

Perhaps the biggest breakthrough in cancer has been the discovery of the relationship between the sympathetic nervous system and cancer growth and reoccurrence. This was first detected though observational research showing a strong association between cancer patients on beta-blockers and a reduction in reoccurrence rates, a slowing of cancer growth, and decreased angiogenesis. 1-6 Researchers studying the relationship of vagal nerve activity (measured through heart rate variability) and the neuro-modulation of tumors found improved overall survival rate in cancer patients when the parasympathetic nervous system (the system responsible for calming the body) is activated.7

These are exciting discoveries, and support my life’s work on the importance of using herbal adaptogens and nervines to help the body adapt to physical and emotional stressors. Neither disease nor treatment of disease, including natural approaches through health optimization, can be described in a linear reductionist model, which is what almost everyone attempts to do. It is the collective effect of the perturbations in multiple underlying networks that result in the symptoms of disease, thus effective treatment should be directed at strengthening and harmonizing all systems of the organism. Continue reading “Adaptogens – Essential Support for Restoration, Protection, Resilience, and Longevity”