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Phytochemical Pharmacy: The Healing Potential of Plants

The views expressed are those of the author and are not necessarily those of Scientific American.


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Plants are often seen as the static background components of the landscape. They grow and get bigger, maybe change color in the fall, but to the casual observer they are no livelier than the surrounding rocks. It is a shame that so many people hold this common model, because plants can be every bit as vibrant and dynamic as animal life.

Fascinatingly, plants have developed a variety of biochemical defences to cope with the constraint of their sessile existence. When an animal is attacked, it can fight or run away, and when a plant is attacked it fights back too, just on a whole new level.

The types of molecules most often employed by plants in their defences are called secondary metabolites, because they are made using supplementary reactions, which are usually the continuation of a pathway. During metabolism, the photosynthesis reactions allow the plant to retrieve energy stored chemically in the form of glucose. The glucose is then broken down during respiration, when the plant requires energy for cell growth, development, and repair.

The chemical compounds generated from the complex metabolism reactions can also be further modified into adapted variations, often unique to a species. For example, the substance aconitine, a potent neurotoxin produced by the monkshood plant Aconitum napellus, is derived from terpene, a metabolic product that functions as a precursor for many other compounds (Stewart 2009).

Of course many of the compounds, secondary or otherwise, produced by plants can remain quite beneficial when they are taken out of their plant system context. We are always reminded to eat plenty of fruits and vegetables because they are rich in essential vitamins. Well, the plants don’t care at all that these molecules happen to keep us healthy. For them, the vitamin K group is produced as a crucial component of the photosynthetic machinery. The vitamin C group works in the chloroplasts as a powerful reducing agent to help repair the oxidative strain caused by photosynthesis. This oxidative capacity is usurped by animals that consume the plant, and it is used in similar repair situations (citation).

Another familiar molecule, beta carotene, is a major light harvesting compound which helps the plant capture solar energy, and yet prevents too much energy from harming the cells. Once eaten, this plant molecule can be split apart and used to help synthesize Vitamin A, which is required for proper sight (Cazzonelli 2011).

Like basic photosynthetic machinery, other metabolites that have become ubiquitous in our culture may have a completely different role for a plant. Both caffeine and nicotine are produced because they are lethal to insects and parasites, as I’m sure a plant would have no reason to stay up all night.

Of course this report would not be complete without paying due tribute to the poster child of medicinal plant success: aspirin, or salicylic acid. Produced by members of the Salix genus, the group that includes willow trees, salicylic acid is actually a hormone employed by the tree to induce a systemic resistance against pathogens. This means that the whole tree becomes resistant even if it’s only attacked in one specific area (Taiz and Zeiger 2010).

So plants can create many substances that go way beyond their objective to produce sugar/take care of photosynthetic machinery, and these compounds could yield an array of possibilities for manipulating the human body’s biochemistry. This means that there is a potential gold mine of chemical therapies just waiting to be harvested from nature. A compound isolated from plants could be subsequently modified to increase its effectiveness, as was the case with aspirin.

When compared to other methods of drug development, there are several reasons why naturally produced compounds could make better therapeutic candidates. The first has to do with the developmental process. One way to go about manufacturing a new drug is to modify an existing compound that is already in the market, say to improve its ability to target specific tissues, or lessen current side effects. Although easier than starting from scratch, this method is still inherently limiting.

However, with no previous knowledge of where to begin, a trial and error approach may be discouraging and expensive. This is where plants come in, because human civilizations have been using herbal remedies for centuries; we have already discovered, perhaps by accident, the physiological effects that different botanical species create. A simple look into our history could inspire drug developers into the next step of cancer research.

Another advantage that natural compounds have over synthetic drug development is that there is often more data on the long term effects of the treatments. A brand new compound fresh out of the laboratory would be a complete mystery as to what exactly it does. That’s not to say it wouldn’t be thoroughly tested, for perhaps ten years or more, but how are we to know what effects the drug may have beyond that? Perhaps a medication that was used early in life would have adverse effects when the individual reaches his or her fifties, sixties, or more. On the contrary, for a drug development project rooted in the manufacture of a substance used historically by a previous civilization, we may already have the long term effects documented. The ancient Inca peoples of the Andes Mountains were known to chew coca leaves to protect against altitude sickness; this could be a potential anti-nausea therapy.

Despite these benefits, it is difficult to go about plant research in the same way that one would study therapeutic chemistry, because after all, these are living organisms. In the past, a research project investigating the potential of a certain natural compound could have all its funding withdrawn when it was determined that the chemical was impossible to isolate from the plant species. As disappointing as this concept is, it makes sense for several reasons.

A slow growing plant, like a tree, may be impossible to propagate adequately enough to keep up with demand for the drug it produces. Suitable land area for ‘growing medicine’ may be scarce as the agricultural industry is struggling as it is with the food supply. There is also an issue of species conservation. An example is the case of paclitaxel, a potential anti-cancer agent produced by the yew tree, which could only be obtained by harvesting the bark. Fortunately the compound was isolated before the species was pruned into extinction.

Another complication with natural products is that plant compounds often act simultaneously with other bioactive chemicals within the organism. It is often found that certain active ingredients may require activators or complexes to have an effect. With this being said, it may not be enough to solely purify a single ingredient and test it out of its biological context. For the natural compounds that one can find on the shelves of a health store or local pharmacy, the tablets are often in the form of a ‘crude extract’. This means that the active ingredient was not completely purified from the surrounding plant matter. In terms of compounds requiring activators, this may be the better option, but it still complicates the goal of complete synthesis.

Nevertheless, modern medicine is beginning to turn to the potential of natural products, as researchers realize there is no reason to fish blindly. The controversy surrounding genetically modified organisms in Europe leads many countries to employ natural products as a substitute. However, even with all these distinctive advantages between phytochemical pharmaceuticals and fully synthetic drugs, it is important that we dispel the myth that natural compounds are somehow ‘safer’ than mainstream pharmaceuticals.

According to the historic concept of vitalism, all living things possess a sort of ‘vital force’ that is beyond scientific detection. This theory was long ago discounted through notable experiments that proved life is not produced by a vital force, but the concept survives and takes on a more indirect form when applied to natural products.

Often proponents believe that a naturally occurring compound is safer, has fewer side effects, or is in general always a more effective option than anything concocted in a laboratory. However, a chemical is a chemical, regardless of origin. That is to say, just because a vial of pure salicylic acid was biochemically extracted and purified from a sample of plant matter, it doesn’t make it any more superior or somehow different from salicylic acid that was artificially synthesized. The two compounds would have an identical effect on the human body. The misconception that natural products are safer is actually quite dangerous, because the active ingredients found in natural remedies can be toxic and must therefore be strictly regulated and tested just like any other drug.

The current inadequate regulation by the Food and Drug Administration (FDA) is abhorrent, which is a shame because it results in naturally derived products gaining a poor reputation in the medical field as ‘alternative medicine’. When thinking about government regulation, let’s take the headache medicine Tylanol, for example. This is a mainstream pain reliever that can be found in most homes and, with proper dosing, is generally safe.

However, what would happen if the production of Tylanol was not regulated, and a bottle purchased at one store could have zero active ingredients while another store’s stock could contain twice as much of the advertised amount? The consumer would never be sure of what he or she was getting, and taking a pill that is several times the proper dose could be fatal. Likewise, what if Tylanol was not thoroughly researched? The label may be inadequate in terms of side effects, proper dosage, or information concerning people with certain medical conditions.

If these hypothetical situations were the norm, Tylanol would not be deemed very safe at all according to mainstream medicine, and yet it actually can be an effective compound. I believe that the weak regulation behind the natural products industries is seriously limiting to the pharmaceutical industry.

Despite the current situation, there are actually quite a few medicinal plant products that were shown to be so effective that they melded into the progression of mainstream medicine. That is to say, the demeaning labels such as ‘alternative medicine’ and ‘homeopathic remedy’ that many doctors frown upon as some untested internet rumour have disassociated from them. On a medical industry level, the crux of the issue is that if medicinal plan research is done well, the resulting products should not end up being labelled as an ‘alternative medicine’. After all, nobody would consider aspirin to be an alternative home remedy.

Bibliography

Cazzonelli, Christopher I. “Carotenoids in nature: insights from plants and beyond.” Functional Plant Biology 38 (2011): 833-847.

Stewart, Amy. Wicked Plants. New York, New York: Workman Publishing, 2009.

Taiz, Lincoln, and Eduardo Zeiger. Plant Physiology. Fifth. Sunderland, Massachusetts : Sinauer Associates, Inc., 2010.

Jessica Fostvedt About the Author: Jessica Fostvedt is a Biological Sciences Masters student at Durham University, Durham England. She studies plant cellular biology and hopes to work for a PhD in plant biochemistry or secondary metabolites.

The views expressed are those of the author and are not necessarily those of Scientific American.






Comments 9 Comments

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  1. 1. iraspastor 11:00 am 04/15/2013

    Great Article.

    The issues surrounding topics like PK/PD of plant extracts is one of the confounding issues which why such beneficial heterogeneous plant substances are so hard for FDA to wrap their traditional “single compound mentality” around.

    Link to this
  2. 2. macgrant 5:58 pm 04/15/2013

    A Freudian slip?

    “…because a vile of pure salicylic acid…”

    Link to this
  3. 3. Humphrey2 6:05 am 04/16/2013

    I was enjoying this article until I got to the para starting “The current inadequate regulation by the Food and Drug Administration (FDA) is abhorrent”.

    Over regulation plays into the hands of those who would make serious money from pharmaceuticals. Agreed, there is a small risk from ‘natural’ products being sold as ‘alternative’ or ‘complementary’ supplements, however most if these would simply disappear if they became the subject of the type excessive knee jerk regulation seen suggested in the media recently.

    They would not become safe, they would become unavailable except from very dubious international sellers based in obscure countries.

    There are significant controls and usage guidance for ‘natural’ supplements currently in place, and the health problems associated with misuse are a very small fraction compared with health problems associated with misuse of on the shelf drugs, smoking and alcohol.

    The author presents the case for more research into ‘natural’ cures as an untapped resource, then states why this won’t happen, then attempts to create fear of natural supplements by suggesting they are unsafe.

    I worry that all this ‘nannying’ in the name of health and safety is becoming a danger to health itself and enables those with power and money to control and manipulate us further.

    We cannot protect everybody. There will always be someone who will unthinkingly walk out in front of a bus, just as there will always be someone who does not read the clear usage instructions and cautions on a ‘natural’ supplement.

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  4. 4. JessicaFostvedt 1:40 pm 04/16/2013

    Thank you all for your intelligent comments. However, I was not attempting to create a fear of natural supplements, instead I argue that they should be viewed in the same way as synthetic compounds.

    @macgrant Yes, it was supposed to be vial, please excuse the typo.

    Link to this
  5. 5. Anomalocaris 4:27 pm 04/16/2013

    As a student of Chemical Medicine and related new paths to Drug discovery I foud this article quiet interesting, in fact, plants are evolving just to proceed to keep their gene pool expresing itself, so I don’t think plants are antropocentrically generating compounds for us, any way, they use them or used to use the gene that code the enzymes and proteins that once produced those compounds or intervened in some way in the mechanisms those compounds took part. In fact, for instance, coffee plants started to deploy caffeine as a countermesure to avoid certain plagues in their habitat, and not only coffee plants and their related, but many groups.

    Link to this
  6. 6. Garganturat 11:47 pm 04/16/2013

    I think the article has some good ideas, but there are a couple of problems.

    The main issue with natural products is supply. In many cases, like the example of Taxol in the article, it can be difficult to generate enough of the compound to meet demand. The problem wasn’t solved by the “isolation” of the compound, but the semisynthesis of it from a precursor derived from the plant cell culture.
    Some other examples are artimisinin, although there has been some recent progress on making a precursor by rebuilding part of the metabolic pathway in yeast.

    Although some of the most well known secondary metabolites are drugs that have been around for thousands of years, they are not necessarily safe, such as morphinan alkaloids.

    As well, secondary metabolites have a wide range of other uses, such as flavours, fragrances and pigments.

    I do agree with the author that these natural products need to be better regulated, as there are many examples of natural products that are extremely toxic. Just because they’re from a plant it doesn’t make them safe.

    One thing I would be careful about is the “crude extracts” you mention. Even today, many of the complex mixtures from plants have not been thoroughly characterized. Our knowledge about these compounds and their biosynthesis is so fragmented. The presence of some compounds may pose a risk to the patient over time, or might change from batch to batch or plant to plant. It’s also possible a plant grown under certain stressors generates a toxic compound, while under laboratory conditions it doesn’t.

    One thing that is at the interface of secondary metabolism and chemistry is Sarah O’Connor’s work at the John Innes Centre, where they make “natural products” derived from altered precursors in vivo.

    Link to this
  7. 7. JessicaFostvedt 6:08 pm 04/17/2013

    @Garganturat You may be pleased to hear that I applied to the John Innes Centre for PhD studies.

    As for regulation, my main concern was in labeling and quality control. I believe there should be more consumer protection policies to ensure that if a bottle says Tablet X contains 200mg, then Tablet X is actually found to contain 200mg. Whether the actual ingredient X has been proven effective is a different type of regulation. (Both are important however)

    Link to this
  8. 8. Garganturat 10:36 pm 04/17/2013

    Sweet!
    I hope that works out well for you.

    I completely agree with you, but I also feel that’s impossible to do if you’re using crude extracts.

    Link to this
  9. 9. geshundtheit 12:43 pm 04/22/2013

    Keep your eyes on Solazyme. Their algae technology my de-couple plant-based compounds from traditional agriculture. Recent patents hint a cell-based terpene production. This is kind of a big deal.

    Link to this

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