Nature’s Cure: Phytotherapy

Utilization of herbal remedies for health purposes has been in the market for centuries. Historical examples of healing diseases with plant-based approaches (curcumin as an anti-inflammatory agent, berberine as an antidiuretic, etc.) lay emphasis on the potential of using plant substances as tools in drug discovery (Nasim et al., 2022). With the emergence of pharmacognosy - a field that focuses on the natural compounds derived from living organisms such as fungi, plants, or animals - and the rapid development of synthetic medicinal drugs, using plants for the sake of human health has been a popular debate in drug discovery. It is known that many commercialized drugs found in the market today include substances that are derived either directly or indirectly from plant species (De Smet, 1997). Thus, the use of plants in the medicinal field has a long history, including serious diseases that yet remain uncured. It has been observed that there is an increased use of plant compounds (plant-derived and crude herbal medicine) worldwide in regard to coping with mild health problems and aging (Cragg & Newman, 2013). Although this is the case, additional chemical substances used in the process of drug research carry the potential of causing severe side effects and higher costs such as increased toxicity in humans or threatening environmental conservation. This article reveals why and how plants may play a critical role in medicinal research by serving as a healthier, more economical, and sustainable substitute.

What is Phytotherapy?

The term phytotherapy refers to “finding therapy from plants” when translated from its Greek origin, 'phyton' meaning 'plant', and 'therapeia' meaning 'treatment' (Leite et al., 2021). In broader words, medicinal products that are derived from plant-derived substances can be called phytotherapeutics. These substances are produced within the plant metabolism in response to environmental conditions such as temperature, light, or the presence of pathogens. Their abundance differs depending on the biological activity of plants (Allegra et al., 2023). Traditional use of herbal medicines throughout centuries has been the blueprint for modern phytotherapeutic research. There are numerous plant-based medical alternatives on the market that potentially serve as therapeutic agents for human illnesses (such as herbal teas and plant essential oils, see Figure 1). In fact, there are even some bioactive materials found in plant extracts that can act as antiviral agents and are considered to positively affect the immune system of humans.

Figure 1: Dried herbs (photo from Shutterstock).

Herbalism vs. Phytotherapy

The misconception between herbalism and phytotherapy is a complex phenomenon influenced by many factors including culture. Although the ultimate goal may be the same for both approaches, using plants as a means of treatment, their origin and motivation differ immensely. Herbalism focuses on the use of plants in various cultures as traditional cues to find solutions for diseases. So, the healing property of the herbs comes from the legacy of the relationship between traditional knowledge of plants and the culture that comes along with it. Phytotherapy, on the other hand, is based on a more scientific approach that relies on medical practices and experimental research (Heinrich, 2017). Nevertheless, it is challenging to draw strict boundaries between the two due to the fact that some phytotherapeutic approaches are considered as traditional remedies rather than medical approaches due to cultural familiarity.

Why Herbal Medicines in the First Place?

The high number of undiscovered plant species and their uses would potentially draw attention to the future of modern phytotherapy. Given the existence of numerous plant extracts that can act as defense molecules, intake of these substances by humans may facilitate the process of healing. Since herbal medicines are derived from natural compounds, they can serve as a biological option for treatments with minimal side effects instead of synthetic drugs (Saller et al., 1998). Another advantage of using plant-derived medicine rather than synthetic drugs is due to the high costs of commercial drugs. Alternative herbal medicines also act as a more economical therapy option.

Figure 2: Phytotherapy research (Sciencesoft, n.d.)

What Makes a Plant Suitable for Drug Discovery?

Like other organisms, plants also have their own metabolism that allows them to manage homeostasis while being "alive". They have their own way of maintaining life, including processes such as respiration, photosynthesis, and organic molecule synthesis accomplished through a series of chemical reactions. Plant metabolism results in the synthesis of certain low molecular weight organic compounds that can be categorized into three main groups: primary metabolites, secondary metabolites, and hormones.

Primary metabolites are directly involved in the development of the plant, while secondary metabolites are more functional against environmental stressors. So, plant secondary metabolites are not considered to be essential for the development of the plant, but rather important in defense response signaling. Hormones, on the other hand, can act as regulators of primary and secondary plant metabolism while managing organismal regulation (Erb & Kliebenstein, 2020). Phytotherapeutic approaches depend on the use of secondary metabolites of plants and their regenerative characteristics. These metabolites are usually synthesized when the plant is trying to defend itself from the environment and exhibit antiviral, antibiotic, and antifungal properties (Hussein & El-Anssary, 2019). Therefore, plant secondary metabolites serve as an important source of molecules for plant research as well as new treatments for human health.

Plant secondary metabolites can be classified into four alkaloids, terpenoids, phenolic compounds, and sulfur-containing compounds. These bioactive compounds can either be synthesized naturally by the plant or, can be produced in laboratory conditions by manipulating plant cells. Since these compounds are known to have the ability to cause toxicity in both humans and animals, there is a high demand for research on plant secondary metabolites (Guerriero, 2018).

Figure 3: Organic compounds synthesized in plant metabolism (Erb & Kliebenstein, 2020).

Isolating plant secondary metabolites from the plant species includes various molecular biology techniques such as cloning and chromatography. In order to understand their potential role in pharmacology, the genes that code for the synthesis of bioactive compounds are isolated and the signaling pathways are analyzed. By this, it can be revealed whether these compounds interact on their own. In the following steps, disease-bearing tissue samples are utilized in vitro and treated with plant compounds to deal with health problems. Studies on the production of an alkaloid, Berbeline, from Coptidis rhizoma revealed that it plays a critical role in the management of several neurodegenerative diseases such as Alzheimer's and schizophrenia.

Before a plant can be considered a phytotherapeutic agent, standardization of herbal medicine is essential. Plant metabolism can easily be affected by external stimulators, therefore, standardizing allows one to make sure that the amount of bioactive compounds present within the plant stays within a range (Gary et al, 2012). In other words, standardization refers to adjustment of the composition of the drug in such a way that it is arranged according to the content of pre-existing drugs that are derived from plants.

Plant Microbiome

In their natural environment, plants tend to associate with multiple groups of microorganisms that support their survival. In fact, the composition of plant microbiome can even differ within the same species, depending on environmental conditions. It is possible to analyze the plant microbiome in three domains: the rhizosphere (found in soil), the phyllosphere (mostly leaves and stem tissue), and the endosphere (intracellular interactions). This reveals that the survival of a plant in nature does not only depend on itself, but also on other organisms that facilitate its growth and fitness. In other words, the microbiome of a plant can alter the type and amount of secondary metabolites produced by this plant species.

Figure 4: Interactions of plant secondary metabolites and microbiome (Pang et al., 2021).

The plant synthesizes the secondary metabolites into the environment or the rhizosphere by using ATP as an energy source. These are then either utilized by the root microbiome to modulate interactions between organisms (Pang et al., 2021) or phyllosphere. Therefore, the secondary metabolites produced by the plant do not solely depend on the plant itself, but also on the microbiome. This emphasizes the significance of plant research in the medicinal field, since the amount and content of plant secondary metabolites production can be altered in vitro to increase yields and can improve our understanding as of how these metabolites function.

Modern Drug Discoveries From Plants

Some examples of plant-derived medicines that have already been utilized in the health sector include:

• Quinine, an alkaloid isolated from the bark of Calendula officinalis that has been used as an antimalarial drug and has been in the field for a long time (Cragg & Newman, 2013).

• Phenanthrenes, which are commonly present in orchids and have been known to have anti-tumor properties in specific human cancer cell lines (Teoh, 2016).

• Ginko balboa extract has been shown to be associated with nerve regeneration in mice, and hence, serves as a candidate for fighting against various neurological diseases (Lin et al., 2017).

• Extracts derived from Coptidis Rhizoma are shown to increase the number of myelinated axons within the brain, thus, may be critical for certain nervous system diseases such as Alzheimer’s.

• Morphine, which can be isolated from Papaver somniferum, has been used as a painkiller for millennia (Yeshi et al., 2022).

What are the Risks?

Although herbal medicines may seem like a more sustainable and healthier treatment approach, it should not be overlooked that herbal medicines include active substances that can potentially interact with other drugs or treatments (Izzo & Ernst, 2001). This can result in no observable effects of the drugs on the patient. In fact, it can be even possible for the interaction to result in toxicity. Another point to consider is that the process of harvesting plants can cause significant harm to the nature, leading to questions about the conservation of biodiversity. So, although research on medicinal plants is supported by the World Health Organization (WHO), it is possible for phytotherapeutic approaches to result in a loss in nature’s biota (Sen& Samantha, 2014). Nevertheless, the potential of plant research and finding cures for serious illnesses could outcompete this adverse situation, provided that research is done in accordance with regulations.

Figure 5: Some plant compounds and their uses (Mohiuddin, 2019).

Conclusion

Plant metabolism—in particular, the production of secondary metabolites—plays an essential role in the defense mechanism of the plant to survive under threat conditions. The biological nature of these metabolites enables them to serve as critical sources for drug development against serious human diseases. Following the traditional herbal-based treatments, there is an increasing demand for a healthier, more sustainable, and cheaper version of disease treatment globally. Hence, the area of phytotherapy has started to become more popular in the modern era. Besides having all the benefits, it is essential not to forget the downsides of phytotherapeutic approaches in regard to human health and conservation of the environment. Therefore, the use of plants in the medicinal field needs to be performed under strict regulations that would minimize the undesired effects and the damage that results from those.

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