The Potency of Plant-Based Medicinal Compounds Based on Environment

  40% of pharmaceutical drugs are derived from plants. Crazy, right? I don’t know about you, but when I hear “plant-based medicine,” my mind does not go to the leading prescription drugs in the U.S. Yet, if you’ve ever had a headache, you can thank that willow tree outside your window for being a main component of aspirin. If you’ve ever had a cold, thank licorice root for being an ingredient in cough drops. Going even further, when a person close to you is having symptoms of heart failure, the foxglove plant can be used to help their injured heart pump blood more efficiently and even treat abnormal heart rhythms! Plant-based medicine sounds much more serious now, doesn’t it? 

I came upon this topic by visiting a botanical garden in Washington D.C. on vacation. The moment I saw that there was a medicinal plants section, I bolted to it and started reading all the information there was on the plaques. One of the information boards said, “Did you know? The concentration of medicinal compounds in plants can differ depending on the environment in which a plant grows.” I couldn’t stop thinking about it the rest of the visit, and I wondered what sort of environmental factors specifically contributed to the concentration of the compounds. So, I hypothesized that obviously, factors like soil and sunlight could be a baseline. However, I wondered what was going on chemically. Did different compounds require different environmental factors to grow? If so, why? What was the chemical transaction between the plant and the environment in terms of each factor? I had a ton of questions, so I began to research.

Different Types of Plant-Derived Compounds

  I began to broadly search for information about medicinal plants themselves before diving into specific factors that affect them. I had no background on medicinal plants, and the question of what exactly happens when these organisms produce medicinal compounds needed to be answered before anything else. When discussing what types of compounds plants produce, it’s important to separate them into two categories– primary and secondary metabolites. Of course, science is famous for giving complex names to very simple things, so allow me to explain what these categories actually mean.

Primary metabolites are the chemical compounds directly involved in the normal processes that are essential or of primary importance for plant life. By “normal processes,” I mean the common ones of growth, development, and reproduction. Some examples of primary metabolites are amino acids (the building blocks of proteins) and nucleotides (the building blocks of DNA). The word “metabolite” refers to the product that is produced during metabolism, which is the digestive process. In the case of plants, the process of photosynthesis, turning energy from sunlight into usable chemical energy called ATP, powers the production of metabolites. Thus, photosynthesis is dubbed as a metabolic pathway, as it is a pathway through which energy is produced to create these metabolites. So, mush the words primary and metabolite together, and you basically get the essential compounds to plant life that are metabolites, the products of metabolism. You may be thinking, “medicinal compounds must be a primary metabolite because of how long you’re going on about them…” But, you’d be wrong!

Medicinal compounds are actually grouped within the category of secondary metabolites. This is because the production of medicinal compounds are NOT essential for plant life, although they are pretty important, but rather an adaptive stress response to environmental extremes. An adaptive stress response is triggered due to an external threat to a plant, which in turn produces a substance that can aid the plant in survival, or in our case, be repurposed for usage in medicine. So, essentially, the types of plant-derived compounds that we use in medicine are produced directly because of specific survival responses from plants. Isn’t that cool to think about?

Before moving on to specifics, however, it’s important to recognize there are limitations to the production of medicinal compounds as secondary metabolites. It’s notable that not every secondary metabolite can be utilized for medical usage, and sometimes, a slight overdose of a medicinal plant can be fatal. Already, we have a very small area to work with, but there’s more. Their production is tightly regulated, restricted to specific plant tissues, developmental stages, or in response to certain stimuli. It isn’t some sort of randomized process either, in fact, it is a highly ordered series of biochemical reactions that occur with respect and regard to the plant’s development. The production of secondary metabolites is also restricted to certain plant groups, developed through the process of natural selection or evolutionary adaptation for survival in tough environments. But, even with all these limitations, scientists have been able to conduct research that strongly suggests that the synthesis of such compounds is under the control of the plant’s environment. After finishing this broad research, I found that this conclusion made sense because it directly correlates to the adaptive stress response in plants. But, I had a further question to answer: what sort of environmental factors have the most noticeable impact on the production of secondary metabolites?

Environmental Factors that Affect Secondary Metabolite Production

  Just a note that I’ll add in before I dive into specifics: I will only be considering abiotic stressors (or, non-living, environmental stressors) in this paper. There are also biotic stressors (living stressors) that trigger secondary metabolite production, such as viruses, bacteria, and fungi. This is just a smaller portion of environmental factors, when in fact, there are many more things that can affect secondary compound production!

Poor Light Quality (Wavelength)

From the research I gathered, it seems that changes in light affect the largest group of plants when it comes to secondary metabolite production. This was a pretty logical conclusion when considering stress responses, as development in plants is inarguably dependent on light and its quality. Light not only affects the production of secondary metabolites, but primary metabolites as well. Photosynthetic carbon fixation, which is the ability to turn inorganic carbon into organic compounds, and biomass accumulation, the ability to store energy from the sun as renewable energy, are two huge processes that would be affected by light stress. Furthermore, harmful wavelengths of light can cause great damage to plant DNA itself and the photosynthetic process. Based on all these examples, it comes as no surprise that extremes in light quality are effective triggers to the stress response that produces secondary metabolites. In fact, because light is such an effective trigger, plants have evolved to perceive harmful light signals and convert them into outputs that are beneficial to them. Research has specifically shown that light at a wavelength of 280-315 nanometers, which is considered UV-B radiation, is a stressor that impacts the synthesis of a vast variety of secondary metabolites.

A good example of a response to light stressors is found in the Arabidopsis plant (Arabidopsis thaliana), which has many adaptive responses to UV-B radiation. Most notably, it deploys antioxidants– defenses that prevent or reduce damage by oxidation– by producing a certain class of chemicals called flavonoids. Because of its effective use as an antioxidant, it has been highly effective in preventing lipid peroxidation, a process that is linked to type 2 diabetes. Research has shown that it may help with insulin signaling and secretion, which is vital considering that type 2 diabetes is caused by a lower rate of insulin production and insulin resistance. Additionally, flavonoids have been shown to have anticancer, antiviral, and anti-inflammatory properties. Because flavonoids are naturally found in plants, they exist in many of our foods and drinks in varying quantities. They can be found in tea, wine, soybeans, and citrus fruits as well. Such compounds can contribute to our health significantly, making it all the more intriguing to know what natural processes go into the making of it.

Lack of Soil Nutrients

When researching the response to nutrient deficiency, I was surprised at how specific the stress responses were according to what sort of nutrient is lacking in the soil. In fact, the research done around it involves experimentally manipulating nutrient supply, leading to the discovery that levels of secondary metabolites vary according to the resources available to the plant. Two deficiencies in specific that trigger a stress response are a lack of carbon and nitrogen in the soil. This is based upon the carbon/nitrogen balance hypothesis, which explains concentration of secondary metabolites in terms of the abundance of plant resources, specifically in carbon and nitrogen. Keep in mind that a proper carbon to nitrogen ratio is essential for plant life, explaining why this is an effective trigger. The hypothesis rests upon an assumed foundation that the plant prioritizes growth (primary metabolism) over secondary metabolism. Therefore, carbon and nitrogen are used in secondary metabolite production only after the requirements for growth are fulfilled.

But, in the event that growth is limited by nitrogen deficiency (or carbon excess), the theory predicts a sort of balancing act done by the plant in order to prioritize growth. When there is a lack of nitrogen, there will be an increased synthesis of carbon-based secondary metabolites due to carbon being more accessible to the plant. It is only able to use compounds containing carbon, hydrogen, and oxygen to photosynthesize. Therefore, this manner of nutrient deficiency leads to a negative effect on the production of secondary metabolites with nitrogen, but can have a positive effect on the production of secondary metabolites with carbon. This is definitely a factor that demonstrates the careful coordination that is involved in the creation of secondary metabolites. However, this wouldn’t exactly be beneficial to the plant per say, as nitrogen deficiencies in general lead to stunted growth in plants despite the production of secondary metabolites that attempt to keep it alive.

There was an experiment done on the plant Rhodiola sachalinensis, which is a Chinese medicinal herb, that involved manipulating soil nutrient factors– not just involving carbon and nitrogen. This plant produces a secondary metabolite called salidroside, shown to have therapeutic effects on depression, Alzhiemer’s, and tumors. Like flavonoids, it’s an antioxidant, and is shown to have therapeutic effects in cardiovascular diseases as well. Research showed that when soil was low in pH and high in nitrogen, there was a high level of salidroside production. However, excesses in phosphorus and potassium in the soil greatly reduced salidroside production. Since each medicinal plant will have varying deficiencies, nutrients, and compounds that affect secondary metabolite concentration, manipulating the soil through experiments such as this one can provide a framework for how to most efficiently select soil for the cultivation of medicinal plants.

Conclusion