Unlocking the Power of Herbal Medicine through Synergy and Network Pharmacology

The noblest foundation for medicine is love. It is love that teaches us the art of healing. Without love, true healing can never be born.” – Paracelsus

In order to deepen our understanding and appreciation for the immense healing value of herbal medicine, it is essential to understand its global impact on biological networks.

Biological networks are formed when multiple biological pathways, which are inherently complex, interact with each other to accomplish a task. These network interactions are highly dynamic and responsive to changes in the physiological state. Understanding this environment leads to a better understanding of the root cause of diseases that occur as a result of metabolic processes that become derailed. In fact, cancer is now increasingly studied from the perspective of dysregulated pathways rather than as a disease resulting from mutations of individual genes.

Just as everything around us is in motion and changing, so is everything within us. Just as nature has an intelligence guiding the ‘Life Force,’ the same can be said for our internal self.

Like all living organisms, plants share several key characteristics or functions, including order, sensitivity or response to the environment, adaptation, reproduction, growth, and development, which work together in a coordinated fashion to sustain life. This is one of the reasons they are so ideally suited as healing medicines for us and the planet.

In recent years, there has been a resurgence of interest in herbal medicine as more people seek natural and holistic approaches to health and well-being. This renewed interest has led to a growing body of scientific research aimed at understanding the mechanisms by which herbal medicines exert their therapeutic effects. One of the key concepts emerging from this research is the idea of synergy – the notion that the combined action of multiple compounds within a plant can produce a more potent and effective therapeutic effect than any single compound alone. This concept of synergy is central to the practice of herbal medicine. It forms the basis for developing new therapeutic strategies that harness the full potential of plant-based remedies.

Modern society has often misunderstood the role of herbs and herbal medicine in health and disease. In our attempts to comprehend this ancient practice, we’ve tried to apply our current understanding of health, disease, and treatment terminology to herbal medicine. However, using single herbs as alternatives to drug therapies is not the same thing, and this approach may lead to misunderstandings.

Herbal medicines are botanical mixtures containing synergistic combinations of plant compounds. These mixtures differ significantly from purified, isolated compounds commonly found in pharmaceutical drugs. Herbal medicines work by modulating the activity of target networks underlying disease phenotypes more efficiently than purified compounds, thanks to favorable “synergistic” interactions. This means that the various components within the herbal mixture work together to enhance each other’s beneficial effects, leading to a more holistic approach to treatment.

In many traditional healing systems, such as Traditional Chinese Medicine and Ayurveda, herbal medicines have been used for centuries to treat a wide range of ailments. These systems recognize the importance of the complex interplay between the various compounds found in plants, and they emphasize the importance of treating the individual as a whole rather than just focusing on specific symptoms or diseases.

As we continue to learn more about the intricate relationships between plants, their compounds, and our bodies, it is essential to maintain an open and curious mindset. We must strive to expand our understanding of herbal medicine and its potential benefits. By doing so, we can work towards a more integrative and holistic approach to healthcare, which ultimately benefits everyone.

The Essence of Holistic Healing: Exploring Traditional Herbal Medicine

A holistic view of traditional or traditional herbal medicine (THM) aligns with a new generation of medical research focused on networks and systems. This approach recognizes the complex interactions between various components in herbal medicine and the body’s systems to achieve a more comprehensive understanding of the healing process.[1]

Many researchers have explored the therapeutic mechanisms of THM formulas using omics approaches, such as genomics, proteomics, and metabolomics. These cutting-edge techniques have allowed them to shift from a “one-target, one-drug” to a “multi-targets, multi-components” paradigm, advancing our knowledge of how these herbal remedies work on a molecular level.

This has dramatically advanced the digitalization and internationalization of THM, as data from these studies can be compiled, analyzed, and shared with researchers and practitioners worldwide. The growing body of evidence supporting THM’s efficacy has also helped bridge the gap between traditional and modern medicine, fostering greater collaboration and understanding between these two fields.

As a result, THM is gaining increased recognition and acceptance within the global medical community, and its potential applications continue to expand. This holistic approach to healthcare holds great promise for improving patient outcomes and advancing our understanding of the intricate relationships between natural remedies and the human body.

Traditional Chinese Medicine (TCM) and Network Pharmacology

One of the oldest systems of THM, traditional Chinese medicine (TCM), has given rise to a new method featuring holistic and systematic “network targets.” This core theory and method of network pharmacology seeks to understand the network-based biological basis of complex diseases, THM syndromes, and herbal treatments.

THM Network Pharmacology Methods

THM network pharmacology methods prioritize:

  1. Disease-associated genes,
  2. Predicting target profiles and pharmacological actions of herbal compounds,
  3. Revealing drug-gene-disease co-module associations,
  4. Screening synergistic multi-compounds from herbal formulations in a high-throughput manner,
  5. Interpreting the combinatorial rules and network regulation effects of herbal formulations,
  6. Identifying disease and syndrome biomarkers based on biological networks.

These network-based methods have proven effective for discovering bioactive compounds and elucidating the mechanisms of action of herbal formulations.

Systems biology-driven omics approaches have boosted TCM research from multiple perspectives.

(A) Prescribed ingredients of TCM formula recorded in Chinese Pharmacopoeia (2020 edition). (B) The TCM quality control (fingerprint-based chemical ingredients analysis methods and genomics-related biological ingredients analysis methods). (C) Multi-omics approaches, including genomics, transcriptomics, microbiome, and metabolomics, could be utilized for investigating the therapeutic mechanism of the TCM formula for treating various diseases. (D) Network pharmacology analysis for screening the bioactive compounds and potential targets for TCM formulas in treating various diseases. (E) The databases for TCM research. The current databases serve as a link across TCM formulas, ingredients, bioactive compounds, targets (proteins/genes), and various diseases.[2]

Systems Pharmacology and Network Pharmacology Approaches

Systems pharmacology and network pharmacology approaches have been introduced to decipher complex mechanisms of action (MOAs) in networks of biomolecules. These approaches explore the pharmacological effects of multi-component herbal medicines acting on multiple disease targets from a holistic perspective.

From the tiniest molecules to entire organ systems, human health and disease are influenced by the flow of regulatory information throughout a vast, interconnected network.[3]

Adaptogens: Nourishing Our Roots

Like a tree’s roots nourish and support the tree, our bodies have roots that need nourishment. Adaptogens are our root medicines. They are herbs that enhance recovery, normalize and regulate multiple organ systems, are non-specific, non-toxic, demonstrate global beneficial effects in the body, and have been extensively studied. Their profound abilities impact all the body’s networks, including both the endocrine and nervous systems, to support the body in maintaining homeostasis and allostatic balance.[4]

The mechanism of action of plant adaptogens is complex and pleotrophic, producing a multitude of effects. Panax ginseng, Eleutherococcus senticosus, Rhaponticum carthamoides, Rhodiola rosea, and Schisandra chinensis are a few of my favorite adaptogens for their ability to aid in recovery from illness, physical weakness, memory impairment, and other conditions.

Adaptogens: Enhancing Adaptability and Combating Stress

Adaptogens are well-known for their ability to mitigate the effects of prolonged stress, enhancing the dynamic range of healthy stability. They improve energy pathways, improving efficiency within cellular energy transfer networks related to oxygen, glucose, lipid, and amino acid metabolism. Adaptogens enhance adaptation, enabling better adaptability and, more importantly, protecting us from the stress and allostatic overload induced by our lifestyle and environment. Adaptogens strengthen the neuroendocrine hub, the reservoir of our hormonal self, helping anabolic restoration and recovery from the catabolic effects of aging and stress.

Exploring herbal medicine through synergy and network pharmacology offers a promising pathway to a more holistic and integrative approach to healthcare. By targeting multiple pathways and systems within the body, these potent plant compounds offer a comprehensive approach to addressing the multifaceted nature of stress and its impact on our well-being.

Overall, adaptogens trigger pleiotropic genes, molecular mechanisms, and cellular signaling pathways that mediate adaptive and defense responses, resulting in multitarget modes of action simultaneously and, therefore, in nonspecific pleiotropic pharmacological activity.

Pleiotropy is the result of the effect of adaptogen on a single gene that impacts multiple signaling pathways, biological processes, physiological functions, and phenotype characteristics. Various cells use the gene transcription mechanism that triggers numerous downstream signaling pathways and molecular networks that collectively affect multiple molecular targets, resulting in many pharmacological activities (nonspecific effect).

The rationale of specific and nonspecific pleiotropic actions of adaptogens.

The specific molecular targets and adaptive stress response signaling mechanisms involved in nonspecific modes of action of adaptogens are identified.[5]

Plants have been an essential source of human medicine for millennia.  I believe we are ready for a new holistic, interdisciplinary approach to studying medicinal plants that combines methods and insights from various disciplines, including evolutionary ecology, molecular biology/biochemistry, ethnopharmacology, and bio-regulatory network medicine.  This may then facilitate a breakthrough in science and healing that would, in turn, lead to rapid advancements in the promotion of human health and well-being.  THM views medicinal plants and people as partners in healing.  It is time to see plant medicines as symbiotic partners that can reshape modern medicine, improve human health, and extend human lifespans.[i]

[i] Charles C. Davis, Patrick Choisy, Medicinal plants meet modern biodiversity science,Current Biology,Volume 34, Issue 4, 2024, Pages R158-R173, ISSN 0960 9822,https://doi.org/10.1016/j.cub.2023.12.038.

[1] Pulok Kumar Mukherjee, Subhadip Banerjee, Amit Kar, Sushil K. Chaudhary, Pardeep K. Bhardwaj, Pallab Kanti Haldar, Nanaocha Sharma, Chapter 21 – Synergy and network pharmacology—Establishing the efficacy of herbal medicine, Editor(s): Pulok K. Mukherjee, Evidence-Based Validation of Herbal Medicine (Second Edition), Elsevier, 2022, Pages 501-510, ISBN 9780323855426, https://doi.org/10.1016/B978-0-323-85542-6.00017-2.

[2] Zhu X, Yao Q, Yang P, Zhao D, Yang R, Bai H, Ning K. Multi-omics approaches for in-depth understanding of therapeutic mechanism for Traditional Chinese Medicine. Front Pharmacol. 2022 Nov 25;13:1031051. doi: 10.3389/fphar.2022.1031051. PMID: 36506559; PMCID: PMC9732109.

[3] Goldman AW, Burmeister Y, Cesnulevicius K, Herbert M, Kane M, Lescheid D, McCaffrey T, Schultz M, Seilheimer B, Smit A, St Laurent G 3rd, Berman B. Bioregulatory systems medicine: an innovative approach to integrating the science of molecular networks, inflammation, and systems biology with the patient’s autoregulatory capacity? Front Physiol. 2015 Aug 19;6:225. doi: 10.3389/fphys.2015.00225. 

[4] Todorova V, Ivanov K, Delattre C, Nalbantova V, Karcheva-Bahchevanska D, Ivanova S. Plant Adaptogens-History and Future Perspectives. Nutrients. 2021 Aug 20;13(8):2861. doi: 10.3390/nu13082861. PMID: 34445021; PMCID: PMC8398443.

[5] Panossian A, Efferth T. Network Pharmacology of Adaptogens in the Assessment of Their Pleiotropic Therapeutic Activity. Pharmaceuticals (Basel). 2022 Aug 25;15(9):1051. doi: 10.3390/ph15091051. PMID: 36145272; PMCID: PMC9504187.

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