SSTTRREEESSS!! Stress refers to a wide range of phenomena and situations that humans are exposed to throughout their lifetimes1. In our modern, fast-paced world, stress has become ever-present and unavoidable. Research has recognized stress as a contributing factor in the development of a number of diseases. If not kept under control, the effects of stress on the body’s immune system and overall health can be detrimental. While it may be difficult to limit our exposure to stressors, helping the body cope with its unwanted effects may be possible using a variety of techniques, including natural adaptogens. But, what exactly are adaptogens?
The broad definition of adaptogens refers to natural substances that increase a body’s resistance to physically, biologically or chemically harmful factors, and have the ability to restore its inner balance (homeostasis) and normal functionality.2 The term adaptogen was initially coined by pharmacologist N. V. Lazarev in 1947 and, later, adopted widely in the USSR to refer to a substance that has the capability to increase “non-specific” resistance of an organism to adverse influences. More recently, this definition has been updated to “a new class of metabolic regulators which increase the ability of an organism to adapt to environmental factors and to avoid damage from such factors”.3 In simpler terms, adaptogens help the body adapt to stress. Exactly how they work, and what specific effects they might exert in protecting the human body from the harmful effects of stress, is not yet thoroughly understood. However, it has been postulated that the beneficial stress-protective effects of adaptogens are related to the regulation of homeostasis via the hypothalamic-pituitary adrenal axis, as well as the associated stress response mediators, such as NO, molecular chaperones, and cortisol.4
Plants are an excellent source of phytoadaptogens and there is an evolutionary reason behind this fact. Plants synthesize phytochemicals, such as the bitter tasting alkaloids, the psychoactive cannabinoids, and stimulants like caffeine and ephedrine, as feeding deterrents.5 In turn, organisms that consume plants have developed a complex metabolic mechanism designed to degrade and eliminate these potentially toxic substances. To protect itself from toxicity, the human body has evolved a characteristic, three-step response to ingested noxious phytochemicals. As the first step, at low concentrations, it activates the adaptive stress response, at somewhat higher concentrations, noxious but non-toxic effects are observed, while toxic response takes place at very high concentrations.5 Therefore, in humans, the exposure to phytochemicals is both transient and limited.
While exposure to high doses of phytochemicals may have detrimental effects, low doses typically have stimulatory and beneficial effects, and exert protection against higher doses of the same substance, as well as a range of different other stressors.5 In response to mild stressors, the human body releases the stress hormones neuropeptide Y (NPY) and heat shock protein 72 (Hsp72) into systemic circulation, in an effort to increase tolerance and initiate adaptation.4 Thus, in research studies, NPY and Hsp72 have been used as biomarkers of adaptogenic activity and the innate stress defense response.
Most of the early research on adaptogens took place in the former USSR and Scandinavian countries in the 1980s. Today, an increasing body of literature on adaptogens indicates that they are still a hot research topic in the scientific community. Consequently, several assays targeting the evaluation of adaptogenic effects of a test substance have been developed in the recent decades, and are extensively utilized to evaluate herbal extracts, phytochemicals and plant-based food products. With core expertise in testing and research of phytonutrients, Brunswick Labs has joined the mission to expand adaptogenic research by performing in vitro investigations in human neuroglia cells. This article will give an overview of two such assays conducted at Brunswick Labs.
Cellular NPY expression assay. Neuropeptide Y is an important peptide neurotransmitter in the brain and the autonomic nervous system of humans. It is 36 amino acid residues long and widely distributed in the central and peripheral nervous system.6 NPY is released in response to physiological and psychological stressors, such as chronic fatigue, strenuous exercise, and a high-fat, high-sugar diet.7 Past research studies have pointed to the role of NPY in adaptation to stress, and improvement in mood and cognition. In the cellular NPY assay, the impact of a test material on NPY expression is quantitatively evaluated in human neuroglia cells.
Cellular Hsp72 expression assay. The heat shock protein 72 (Hsp72) functions as a chaperone and as a cytokine; its dual function is referred to as chaperokine activity. As a chaperone, it binds important antigenic peptides and transports them to antigen presenting cells (APC), while as a cytokine it stimulates the release of proinflammatory cytokines.4 Previous research has shown that Hsp70 may be used as a molecular biomarker for adaptogenic activity. In the cellular Hsp72 assay, the impact of a test material on Hsp72 expression is quantitatively evaluated in human neuroglia cells.
European and US regulatory agencies have recognized the need to somehow address the emerging research on adaptogens. The European Medicines Agency considers the concept of adaptogen suitable for the assessment of traditional herbal medicinal products, while cautioning that further studies of adaptogenic action are needed in the pre-clinical and clinical arena.8 The US Food and Drug Administration regulates the labeling of adaptogenic activity of dietary supplements and plant-based products under the umbrella of structure/function claim regulations. Brunswick Labs facilitates the ongoing research on adaptogens by making the assessment and interpretation of in vitro adaptogenic activity available to the food, pharma and biotechnology companies interested in meeting the structure/function claim requirements for their products. The scientific team at Brunswick Labs can also help guide product testing, provide interpretation of testing results, and assist with science-backed marketing of products.
- 1. Seely D, Singh R. Adaptogenic Potential of a Polyherbal Natural Health Product: Report on a Longitudinal Clinical Trial. Evid Based Complement Alternat Med. 2007;4(3):375-80.
- 2. Levin O. Phytoadaptogens – protection against stress? (Abstract) Harefuah. 2015;154(3):183-6, 211.
- 3. Panossian A., Wikman G., Wagner H. Plant adaptogens. III. Earlier and more recent aspects and concepts on their mode of action.Phytomedicine 1999;6:287–30010.
- 4. Panossian A, Wikman G, Kaur P, Asea A. Adaptogens Stimulate Neuropeptide Y and Hsp72 Expression and Release in Neuroglia Cells. Front Neurosci. 2012;6:6.
- 5. Lee J, Jo D-G, Park D, Chung HY, Mattson MP. Adaptive Cellular Stress Pathways as Therapeutic Targets of Dietary Phytochemicals: Focus on the Nervous System. Pharmacol Rev. 2014;66:815-868.
- 6. Tatemoto K (2004). “Neuropeptide Y: History and Overview”. In Michel MC. Handbook of Experimental Pharmacology. 162. Springer. pp. 2–15.
- 7. Kuo LE, Czarnecka M, Kitlinska JB, et al. Chronic Stress, Combined with a High-Fat/High-Sugar Diet, Shifts Sympathetic Signaling toward Neuropeptide Y and Leads to Obesity and the Metabolic Syndrome. Ann N Y Acad Sci. 2008;1148:232-237.
- 8. EMEA/HMPC/102655/2007.Reflection Paper on the Adaptogenic Concept. European Medicines Agency, London, May 8th, 2008.
Author Jasenka Piljac Zegarac is a scientist and freelance writer. She holds a PhD in biology and a BS degree in biochemistry, and contributes on a regular basis to several health and science blogs. Her research articles have gathered more than 1200 citations. She may be contacted for assistance with a variety of science and medical writing projects. Find Jasenka on LinkedIn.