The Phytoneuroendocrine System: Connecting Plants to Human Systems Biology

Abstract

Traditional medicine, exemplified by systems such as Ayurveda, inherently adopts a holistic framework. This framework extends beyond mere consideration of the human body to encompass broader systems of health, integrating elements of nature, particularly plants. Over time, there has been a notable integration between traditional medical philosophies and modern scientific methodologies. This integration is evident in published works that blend these disciplines, resulting in the creation of innovative terminology, such as «Ayurnutrigenomics».

Concurrently, the lexicon within medical science has evolved to highlight the connection of body systems, as illustrated by terms like «gut-brain axis», which emphasize the relationship between physiological and psychological factors. This integration of perspectives is further demonstrated by terms such as «psychoneuroendocrine» and «mind-heart-body», reflecting a holistic approach to health. Alongside the emergence of these novel terms, there has been a proliferation of literature exploring the diverse functions of plants, particularly focusing on phytonutrients such as those found in the polyphenol category of compounds.

In many ways, these emerging findings suggest a fundamental relationship between humans and plants, aligning with the principles of traditional medicine and indicating a profound connection between the two. Thus, in harmony with the increasing recognition of the interconnectedness between human systems biology, the study of phytochemicals, and the ability of plants to influence neuroendocrine responses, this article proposes a new term: the phytoneuroendocrine system.

Traditional Chinese medicine (TCM) and Ayurveda have historically emphasized the interconnectedness of organ systems and the holistic nature of the body as integral components of their frameworks.¹ In contrast, allopathic medicine and the scientific lineage have tended to adopt a divergent approach, focusing on increased categorization and description of organ systems, often examining phenomena at the cellular level to deepen understanding. Although these divergent patterns of thinking may appear distinct, they ultimately provide complementary perspectives for understanding the complexity of human existence.²

One approach adopts a macroscopic view, focusing on the intricate patterns responsible for holistic health encompassing body, mind, and spirit. In contrast, the other approach employs a more microscopic, methodical approach to dissect underlying mechanisms. As the clinical understanding of how interconnected body systems mutually influence each other gains prominence, and as the scientific community acknowledges the significance of systems biology, there arises a critical need to consistently update the terminology used within the scientific and medical domains.

In the past 75 years, there have been notable shifts in medical terminology, with the introduction of terms that intricately interconnect various disciplines.³ Words such as “Psychoneuroimmune,” “Psychoneuroendocrine,” and “Psychoneuroendocrineimmune” have been invented and integrated into the scientific literature to illustrate the growing recognition of the interconnectedness between the body and mind, or the interfaces between the mind, heart, and body.^2-8 These terms may be presented with or without hyphens, or even condensed into acronyms like PNEI or PINE.^10-12 Regardless of their specific structure, there is a common theme emphasizing the interconnectedness of these terms, akin to building blocks, signifying a shared scientific and medical framework that fosters dialogue between psychology and physiology.

These terms have evolved to encompass concepts such as the placebo effect, the impact of emotions on immune modulation, the pathways through which stress influences inflammatory-immune responses, and the role of hormones in mental health.^13-16 Additionally, we observe the use of hyphenated terms like “brain-gut axis” stemming from this foundational lexicon of mind-body terminology. However, these terms now focus on specific organs, such as the brain and gut, rather than broader systems like neurology or gastroenterology.^17-19

Similarly, new terms are being built to bridge the realms of science and ancient healing traditions. Examples include “Ayurgenomics”,^20,21 “Ayurnutrigenomics”,²² “Ayurpharmacoepidemiology”,²³ “Ayurceuticals”,²³ and “ZHENG-omics”,²⁴ which are now prominently featured in indexed scientific publications. These terms reflect the convergence of constitutional genomics with concepts such as doshas in Ayurveda and elemental phenotypic imbalances in TCM. Auspiciously, through the introduction of these terms, we witness the fusion of body systems and the integration of scientific principles with the art of traditional healing in innovative ways.

These observable shifts in language may potentially alter the thought landscape regarding the feasible integration of scientific methods into integrative medicine. In a less tangible manner, a linguistic foundation is being established to facilitate acceptance, reconciliation, and even collaboration between the seemingly distinct paradigms of traditional healing and modern science.²² In alignment with these principles, I introduced the term “Phytoneuroendocrine system” during my presentation at Dr. Jeffrey Bland’s Personalized Lifestyle Medicine Institute Thought Leaders Consortium in Seattle, WA, in October 2023. At the heart of my presentation was the fundamental principle of aligning with nature to enhance human health.

Phytoneuroendocrine System

The phytoneuroendocrine system refers to the complex network of interactions between phytochemicals found in plants and the human neuroendocrine system, influencing neurotransmitter production, hormone regulation, and overall neuroendocrine function.²² It embodies the bidirectional communication pathways between plants and humans, highlighting the therapeutic potential of plant-based interventions in modulating human health and well-being.^23-24 In the sections to follow, examples of this human-plant interrelationship will be detailed for illustration.

Relationship Between Plant-Based Chronobiotics and Circadian Rhythms

Although the concept is not novel and has long been fundamental in traditional medicine, scientific studies increasingly recognize the mechanisms associated with the disruption of circannual and circadian rhythms. Among the various approaches to synchronize with day-night cycles, including maintaining adequate sleep, consistent mealtimes, and regular physical activity, preclinical studies suggest that consuming specific seasonal plant foods may improve functionality during these natural rhythms. Chronobiotic phytochemicals such as polyphenols have demonstrated the ability to regulate the neuroendocrine system, particularly the signaling pathways involving the hypothalamus-pituitary-pineal nexus.

Seasonal Influence on Polyphenol Production and Metabolism

Polyphenols, constituting one of the largest categories of phytochemicals with approximately 8000 compounds, undergo synthesis modulation by environmental factors such as water availability, light intensity, temperature variations, and soil salinity, thus establishing a connection with seasonal changes.²⁵ A study revealed that rats exposed to light conditions simulating winter light exposure exhibited the highest concentrations of metabolites derived from grapes they had consumed, compared to conditions simulating spring, summer, and autumn light exposure.²⁶ In essence, the study demonstrates that grape polyphenols exhibit increased metabolism under simulated winter conditions compared to other light simulations. Additionally, this study indicates that organic grapes display superior bioavailability and metabolism of polyphenols compared to conventionally grown grapes, as evidenced by higher serum concentrations of metabolites.

Impact of Seasonal Consumption on Fat Tissue Accumulation

An intriguing animal study investigated the effects of consuming oranges from different hemispheres out of season, revealing that such consumption led to fat tissue accumulation.²⁷ The study analyzed approximately 39 phytochemicals in the fruits, with the oranges from the southern and northern hemispheres differing in 24 of them. This phenomenon aligns with the xenohormesis theory, which suggests that humans respond to bioactive compounds, including polyphenols and other chronobiotic phytochemicals, in food to adapt to the environment or changing seasons. These responses may affect neuroendocrine markers such as hypothalamic signaling, hormone levels (leptin, insulin, and melatonin), and fat storage and metabolism.^25,28

Seasonal Consumption of Sweet Cherries and Adipose Tissue Metabolism

This phenomenon was also observed with sweet cherries, typically consumed during the spring and summer months when days are longer. The metabolism of adipose tissue exhibited variations in animals based on the photoperiod or whether the fruit was consumed in or out of season, which was simulated by varying hours of light exposure.²⁹ Consumption of cherries out of season correlated with an increased propensity for fat accumulation in the animals.

Polyphenols and their Role in Psychoneuroendocrine Health

In addition to their seasonal modulation of the neuroendocrine system, polyphenols have been linked to conditions closely associated with the psychoneuroendocrine system, such as reducing the risk of depressive and anxiety disorders. They exert multifaceted effects on the gut-brain axis by influencing neurotransmitter systems, neurotrophic factors, inflammatory pathways, oxidative stress markers, and rebalancing the gut microbiome.^30-32 Moreover, certain polyphenols, such as flavonoids, have demonstrated activity as GABA-alpha receptor agonists, thereby exerting anxiolytic effects.³³ Additionally, phenolics known as coumarins function as monoamine oxidase-B inhibitors.³⁴ These phytochemicals may also have signaling impacts on the hypothalamus-pituitary-adrenal axis (HPA-axis).³⁵

Furthermore, while not yet fully elucidated, I anticipate broader effects of these compounds on what I term the “SPHPTPHLPMGAK axis,” an acronym encapsulating the comprehensive endocrine system intercommunication recognized in science, extending beyond the HPA axis to include the skin, pineal gland, hypothalamus, pituitary gland, thyroid gland, parathyroid gland, heart, liver, pancreas, muscle, gonads, adrenals, and kidneys.

Interconnection Between Plants and Human Physiology

My observations across nature, traditional medicine, and scientific inquiry underscore the means of conscious environmental cues emanating from plants.^36,37 The intricate intelligence of plants, coupled with the diverse array of phytochemicals they contain, enriches our comprehension of human physiology.²⁰ Therefore, I propose not only the formal adoption of the term “Phytoneuroendocrine system” to summarize the profound connection between humans and plants through our intricate neuroendocrinology but also its utilization as a symbolic emblem for the comprehensive integration of plants, nature, and rhythmic patterns into our mindset, particularly within the domain of healing arts.

The diverse spectrum of plants constitutes an indispensable aspect of our human existence, offering far more than mere nutritional sustenance. They furnish us with means of survival, fortitude, and enhanced functionality, and contribute to an enriched, more vibrant quality of life.^38,39 This aligns perfectly with the inherent capability of our neuroendocrine systems to foster well-being in our daily lives.

Conclusion

The exploration of the phytoneuroendocrine system highlights the complex relationship between humans and plants, illuminating how plant-derived compounds influence our neuroendocrine function. Through the lens of traditional medicine, scientific inquiry, and observations of nature, we recognize the profound impact of phytochemicals on human physiology and well-being. By embracing the integration of plants, nature, and rhythmic patterns into our healthcare paradigm, we open doors to novel approaches in the healing arts, fostering resilience, vitality, and an enhanced quality of life. This holistic perspective offers promising avenues for future research and clinical application, highlighting the importance of nurturing our connection with the natural world for optimal health and wellness.