Integrative Network Pharmacology: Evaluating the Therapeutic Potential of Ayurvedic Herbs and Formulations

Ayurveda, an ancient system of medicine originating in India, utilizes a wide array of herbs and polyherbal formulations to address complex diseases. These remedies are characterized by their ability to target multiple pathways and restore balance within the body. However, the empirical nature of Ayurvedic treatments and their lack of mechanistic clarity have limited their acceptance in evidence-based medicine. Network pharmacology, which integrates systems biology and pharmacology, emerges as a powerful tool to analyze the multi-target and multi-component nature of Ayurvedic formulations. This review highlights the synergy between Ayurveda and network pharmacology, focusing on their application to unravel the molecular basis of efficacy and safety.

Network pharmacology adopts a holistic perspective, emphasizing the complex interactions between drugs, targets, and pathways within biological networks. Unlike conventional single-target drug discovery, this approach acknowledges the polypharmacological nature of bioactive compounds. By integrating computational tools, molecular databases, and omics technologies, network pharmacology facilitates the mapping of intricate interactions, thereby providing a systems-level understanding of disease mechanisms and therapeutic effects.

Relevance of Network Pharmacology to Ayurvedic Research: Ayurvedic herbs and formulations often contain a plethora of bioactive compounds, each contributing to therapeutic efficacy. Network pharmacology enables the identification of active constituents, their molecular targets, and the pathways they influence. Key benefits include:

1.    Multi-target Profiling: Ayurvedic treatments frequently act on multiple molecular targets. Network pharmacology helps decipher these interactions, elucidating their cumulative therapeutic effects.

2.          Synergistic Mechanisms: The efficacy of polyherbal formulations arises from the synergy between compounds. Network models help identify synergistic interactions and optimize formulations for maximum efficacy.

3.   Disease-Target Mapping: Ayurveda classifies diseases holistically, while modern medicine categorizes them mechanistically. Network pharmacology bridges this gap by mapping Ayurvedic interventions onto molecular disease pathways.

Applications of Network Pharmacology in Ayurvedic Evaluation

1.       Therapeutic Target Identification: Studies leveraging network pharmacology have identified molecular targets for Ayurvedic herbs such as Withania somnifera (Ashwagandha) and Curcuma longa (Turmeric). These targets include inflammatory cytokines, oxidative stress markers, and apoptotic regulators.

2.      Drug Repositioning: Ayurvedic remedies with known clinical efficacy can be repositioned for modern applications. For instance, Tinospora cordifolia (Giloy) has been explored for its immunomodulatory effects using network analysis.

3.        Pathway Elucidation: Network pharmacology has revealed that herbs like Phyllanthus emblica (Amla) modulate key pathways such as NF-κB and PI3K-Akt, contributing to their anti-inflammatory and antioxidant properties.

4.     Adverse Effect Prediction: The polypharmacological profile of Ayurvedic formulations can lead to unintended side effects. Network-based toxicity prediction models assist in identifying potential adverse interactions.

Throughout human history, medicinal plants have been recognised and used. Before humans ever set foot on the planet, medicinal plants were already in existence (Shastri et al., 2021). Only the plant kingdom's essential function in maintaining life has allowed for man's survival on our planet (Kokate, et al., 2016). Early civilisations revered medicinal plants and used them to cure illnesses and improve human health (Jindal et al., 2018). Man and plants have had a strong association throughout the evolution of human civilisation, and interest in plant based medicines has only grown as our knowledge of human illness has grown (Modi, 2017). According to Tapsell et al. (2006), plants possess the capacity to produce an extensive range of chemical compounds that are essential for carrying out crucial biological processes and protecting themselves against herbivorous animals, fungi, and insects. Surgery and medicine have a long and distant history. The Rigveda (3500–1800 BC) has the oldest accounts of the medicinal qualities of certain plants in India. Subsequently, significant writings by Charaka and Susruta emerged (Norman & Farmworth, 2009). The first English book that provided a really scientific analysis of plants was William Turner's New Herbal, published in 1551 (Wallis & Churchill, 2018). There are thought to be between 25000 and 75000 species of higher plants on the planet. The Traditional System of Medicine (TSM) has used a realistic estimate of around 10%. However, it's possible that just 1% of these (250–750 species) have been shown in scientific research to be therapeutically useful when taken by humans in extract form. Natural products may come from terrestrial, marine, or aquatic sources and are produced from higher plants, microorganisms, or animals. The therapeutic preparations made from these basic materials were either crude drugs, like dried herbs, or extracts of them that were always made from a combination of several ingredients. Many of these supposedly therapeutic plants became the subject of chemical research with the introduction of European scientific techniques, which resulted in the isolation of active components. There has been constant work in this field since 1800 AD, during which time the active principles of several well-known medicinal plants were identified and their chemical analyses conducted. These substances, either in their pure form or as well-characterized extracts, were quickly isolated and characterised, and soon thereafter they were included in the pharmacopoeias of several nations. This is the point of convergence between contemporary medicine and herbal therapy (Handa, 2012). Plants are a major source of raw materials for many key pharmaceuticals in contemporary medicine, even if synthetic drugs have revolutionised the treatment of certain ailments. However, millions of people who live in rural areas and rely on traditional healers are unable to afford these synthetic medications; however, careful application of medicinal plants may always cure fatal illnesses9. The three medical systems that make up the Indian system of medicine (TSM) are Ayurveda, Siddha, and Unani, which are respectively practiced by Vaidyas, Siddhars, and Hakims. Indian System of Medicines includes the medications used in Ayurvedic, Siddha, and Unani systems of therapy. According to Bhatacharjee (2010), the medication and Cosmetic Act defines the ISM as "all medicines, intended for internal or external use in diagnosis, treatment, mitigation or prevention of disease or disorder in human beings or animals, including Ayurvedic, Siddha, and Unani drug".

A basic definition of herb is "crude drugs of vegetable origin utilised for the treatment of disease states, often of a chronic nature, or to attain or maintain a condition of improved health." Herbs may signify many different things. Herbal medicines prepared from various components of herbs or plants are referred to as "Phytopharmaceuticals," "Phytomedicinal," or "Phytomedicine." They are available in a variety of formulations and dosage forms, including as powder, tincture, cream, pills, capsules, and elixir, as well as parental preparations. Herbal medicine does not refer to a specific isolated or active ingredient produced from plants, such as digoxin or reserpine pills (Miles, 2021).

The broad biological activity, greater safety margins, and lower cost of herbal medications make them highly sought-after for basic healthcare in both developed and poor nations. They also provide treatments for age-related illnesses that are not currently treated by mainstream medicine, such as immune system problems, memory loss, osteoporosis, etc. Because of the rising rate of adverse medication responses and the high cost of the current medical system, interest in herbal medicines among the general public, academic community, and government is expanding rapidly.

Standardisation is a process to guarantee that each medication package supplied has the right ingredients in the right amounts to provide its intended therapeutic effect (Thaibinh, 2014). Plant-derived goods have seen tremendous demand in affluent nations in recent years. The demand for these goods as cosmetics, nutraceuticals, and medications is rising. In India, there are over 6000 producers of herbal remedies. Ayurvedic medications are produced in more than 4000 units. Due to strict regulatory rules, a shortage of trained labour, infrastructure, and dependable procedures, most businesses make their products on a highly tentative basis. Establish robust, focused, and sensitive quality control systems using a combination of modern and classic instrumental techniques of analysis to ensure that the quality of raw materials, materials used during processing, and final products are all well-coordinated. One of the most important metrics for ensuring the effectiveness of herbal medicines is standardisation. All procedures used in manufacturing and quality assurance that provide repeatable quality are referred to as "standardisation." It also involves mixing herbal medicines or herbal drug preparations, including excipients, or altering the herbal drug preparation to include a certain amount of an ingredient or combination of compounds having established medicinal effects, as appropriate. "Evaluation" of a medication refers to verifying its identification, assessing its quality and purity, and identifying any adulteration. It is difficult to standardise herbal medications since a variety of variables might affect their bioefficacy and repeatable therapeutic impact. Care should be taken to ensure the quality of herbal products, starting with the correct identification of the plants, the season and collecting location, their extraction, the purifying process, and, in the case of polyherbal medications, the rationalisation of the combination (Ansari, 2005).

Standardization by marker compound

Chromatography has produced the finest standardisation tool to date. It explains the chemical holiness and botanical identification of the plant. Finger print analysis and marker compound testing are two examples of such techniques. Herb secondary metabolites are regarded as marker chemicals. With the aid of contemporary, high-tech instruments like HPTLC, HPLC, and others, several chromatographic techniques are used to analyse the marker chemicals in herbs (Bhanu & Zafar, 2003).

Current status of standardization

The World Health Organisation has stressed the significance of using contemporary methods to guarantee quality control of herbs and herbal mixtures. To preserve the quality of herbs, a number of pharmacopoeias, including German Commission – E, Japanese Pharmacopoeia, United States Pharmacopoeia, British Herbal Compendium, and others, provide monographs. The Indian Ayurvedic Pharmacopoeia offers fundamental quality standards for eighty popular herbal Ayurvedic medications. Chinese Herbal Pharmacopoeia has 1751 monographs on substances and articles, BHP has 233 monographs and quality control tests, and BHC has 84 monographs on medicinal plants. 330 monographs on drugs used in German folk medicine are available from German Commission E.

Over a very long period of time, there have been a few developments in drug research. The amount of newly accumulated compounds entering the market as pharmaceuticals has declined, even while high throughput motions are still available. Furthermore, the amount of repairs that are implemented immediately after transportation in the commercial areas is growing. It is evident that the revelation process has to be revisited (Patwardhan, 2014). Standard facts and generally typical items may determine that the current drug transparency standoff has to be broken urgently. More than 100 novel, conventional thing-based leads are reportedly under clinical development, according to a study. Between 1981 and 2002, about 60% of anticancer and 75% of severely organized to infectious drugs were seen to have normal initial phases. Various stimulating mixtures (bioactives) from conventional game-plan sources may serve as incomprehensible first mixtures and phases for normal prescription arrangements. The majority of these blends are often essential for regularly taking common drugs, and because of their safety and security, they are generally preferred over other manufactured compounds that are novel for human usage. Many specialists believe that concentrating on plants that are portrayed in outdated literature would be more appropriate and acceptable (Holland, 1994). Thus far, remarkable successes using bioactives derived from botanicals (stable plants) have been addressed. Among them, quinghaosu and artemisinin from Chinese medicine stand out the most. Ayurvedic strategies have given rise to a variety of bioactive particles, such as phyllanthins as antivirals, curcumine for compounding, mucuna pruriens for Parkinson's disease, guggulsterons as hypolipidemic coordinated well-informed authorities, picrosides for hepatic security, phyllanthins for mental assistance, phyllanthins for vitiligo, and withanolides as immunomodulators (Patwardhan et al., 2014).

By and large medication transparency follows the one quality/one goal/one drug approach, yet a multi-target, multi-fixing showing plan may be the genuinely staggering framework. Drug openness need not be confined every entrance to the divulgence of a single molecule. Today, we are managing polygenic circumstances and not just bound ailments, consequently multi-target approaches are gigantic (Zimmermann et al., 2007). Way of life issues like heaviness, diabetes, cardiovascular troubles and enhancements can be directed multi-alloted approach. By honesty of the degree of plans, commonplace concentrates can administer different targets in the interim and may make synergistic impacts. Thusly, the improvement of normalized, synergistic, shielded strong regions for and definitions with acceptable careful confirmation can offer a wise and better other decision.

While network pharmacology offers transformative potential, certain challenges persist:

·              Data Standardization: Variability in Ayurvedic formulations and a lack of standardized databases complicate network analysis.

·         Integration of Traditional Knowledge: Incorporating Ayurvedic concepts, such as doshas and rasayana, into computational models requires innovative frameworks.

·              Experimental Validation: Computational predictions need rigorous experimental validation to ensure translational relevance.

Future research should focus on integrating artificial intelligence, machine learning, and omics technologies with network pharmacology to refine the evaluation of Ayurvedic interventions. Collaborative efforts between traditional medicine practitioners and modern scientists are essential to unlock the full therapeutic potential of Ayurveda.

Network pharmacology represents a paradigm shift in the scientific evaluation of Ayurvedic herbs and formulations. By providing mechanistic insights into their multi-target actions, this approach not only validates traditional knowledge but also paves the way for the development of novel therapeutic strategies. As the synergy between Ayurveda and network pharmacology continues to evolve, it holds immense promise for advancing holistic healthcare and addressing complex diseases in a scientifically rigorous manner.