Topic 4.3
Medicinal Plants

Plants as Medicines

The vast majority of the world's population still rely on plants as their primary source of medicines. In Canada and other industrialized countries, there has been a resurgence in public interest in plant-based medicines and therapeutic agents. Nevertheless, the majority of commonly used medications are produced synthetically, thanks to modern chemistry.

Identifying the one active ingredient responsible for symptom relief or treatment in a medicinal plant does not always meet with success and therein lies the challenge. Plant-derived medicines can have a number of different active ingredients and, in combination, may achieve better outcomes, especially for chronic diseases that have a spectrum of symptoms (for example, AIDS or diabetes). Not all conditions are treatable using a single compound. However, a mixture of active ingredients can also cause problems such as unwanted drug interactions or harmful side effects. If plants are misidentified and used to make herbal medicines, the consequences can be deadly.

Plants Are Master Biochemists

Plants use a vast array of secondary compounds/metabolites to aid in their survival. Plant secondary metabolites are not essential for the maintenance of plant cellular function but nevertheless, serve plants in many different and important ways. These metabolites are restricted in their distribution and typically occur in specific organs, tissues or cell types at different stages of growth and development.

Secondary metabolites can serve as defence compounds, as signalling molecules or as protection from harmful solar radiation. They can act as antifreeze or may aid in pollen and seed dispersal. These metabolites can alter the local environment, modifying the forest air, for example, or the soil surrounding the roots. Plant secondary metabolites can alter the physiology of organisms that ingest them, act as anti-nutritional agents, as browsing deterrents or function as poisons. Some of the most toxic compounds found on the planet are produced by plants.

Cancer Drugs

Many of the most effective cancer drugs used today are directly obtained from plant extracts. Two very effective drugs, vinblastine and vincristine, are extracted from periwinkle plants, ornamental plants commonly found in gardens. Although biochemical pathways used for vinblastine synthesis in plants have recently been elucidated (Caputi et al., 2018), chemical synthesis remains a major challenge. Currently, periwinkle plants remain the only source of these chemotherapeutic agents.

Vincristine is used in the treatment of certain types of leukemia and lymphomas while vinblastine is more broadly effective as an anti-cancer drug. Why is vinblastine such an effective cancer drug? Cancer cells tend to divide rapidly which is why they make tumours.  Eventually, these cancerous cells break away from the original or primary tumour and invade other body tissues producing tumours in new locations. This process is known as metastasis. Vinblastine blocks key components of the cell division machinery leading to cell death. Therefore, rapidly dividing cells, like cancer cells, die when exposed to vinblastine. Of course, so do rapidly dividing healthy cells which is why proper dosing is critical when cancer patients receive treatment.

 

 

Bark: Home to Potions and Poisons

The next time you walk by a mature tree, take a good look at the bark. It is truly a thing of beauty. The outermost bark, which is made up mostly of dead cells, protects the living cells beneath that conduct water, minerals and organic compounds between the roots and canopy of the tree. The fact that the outermost bark is mostly made up of dead cells can be used to the tree's advantage. Why? It makes an ideal place for storing potions and poisons! Tree bark has been the source for a number of important drugs like aspirin (used for pain relief, fever and inflammation), paclitaxel (also known as the anti-cancer drug Taxol) and quinine (for treating malaria).

The African Cherry Tree

The pharmacologically active substances contained in extracts from the bark of the African Cherry tree are used to treat non-cancerous enlargement of the prostate gland. The active compounds in the bark extract work together and have few undesirable side effects. No single active ingredient with the same benefits has been successfully identified. As a result, the bark is highly valued, motivating the illegal harvest of bark from wild trees. Overharvesting has put African Cherry trees at risk for becoming endangered. Cultivating these trees using sustainable harvesting methods are being implemented and benefit both the trees and the local communities.

 

 

Willow, Yew and Cinchona Bark

Aspirin is the most widely used drug in the world. It is used to reduce pain, fever and inflammation. It is also used as a preventative medication for people with coronary disease.  Aspirin is a modified form of salicylic acid that can be isolated from willow bark. It was the historical association between willow bark and pain relief that led to aspirin's discovery. As is the case with a number of the compounds we have discussed, plants use salicylic acid as a defence compound.

The bark of the Pacific Yew tree was the original source of the anti-cancer drug, paclitaxel. As noted by Susan Horwitz, one of the scientists who figured out why paclitaxel is toxic to animal cells, "It's the kind of structure that only a tree would make" (Horwitz, 2003). Like vinblastine, paclitaxel is effective because it blocks normal cell division. Cancer cells die when unable to divide.

The malaria drug, quinine is extracted from the bark of Cinchona calisaya, also known as the fever bark tree. This bark is still used to make quinine today because it is too expensive to synthesize chemically. Historically, quinine was key to empire building and expansion in the 19th century. It allowed Europeans to live in areas with malaria by reducing the mortality rates caused by the disease. Although another effective plant-derived anti-malaria drug is also used today, called artimesinin, malaria is still a significant global health problem (WHO, 2020b).

 

 

Plants: Dressed to Kill?

How do plants manage to prevent self-harm when armed with an arsenal of highly toxic compounds? The trick is to control the timing of manufacture, make only small amounts, limit the tissues and cells that make it or to store them on the outside. This is exactly why bark is an ideal place to store something like paclitaxel. By doing so the tree dresses itself in chemical deterrents, keeping pests at bay. Knowing that yew bark contains paclitaxel shouldn't keep you from hugging a yew tree, however, because it takes 2, 700 kilograms of dried bark to yield just 3 grams.

On the surface of leaves, stems and flowers many plants have hairs. Like bark, these hairs offer great locations for producing and/or storing noxious chemicals. Think about the last time you brushed up against a stinging nettle. Remember that nasty rash? That reaction happened because your skin was pierced by sharp, needle-like hairs filled with histamines (and other chemicals). Hairs also serve as repositories for the psychoactive cannabinoids found in marijuana plants. When you inhale marijuana vapours, you are actually inhaling tetrahydrocannabinol that was stored in the plant's secretory hairs!

 

 

Plant Extract or Purified Compound: Which Is Better?

Plant extracts, which fall under the umbrella of herbal medicines, can be made a number of different ways. In the context of this discussion, a plant extract refers to a preparation that concentrates pharmacologically active substances present in a medicinal plant or plants. A single pharmacologically active compound containing no contaminants (pure), is equivalent to a purified compound. Purified pharmacologically active substances are often synthesized chemically.

From a medicinal perspective, are plant extracts better than purified pharmacologically active substances? The answer to this question is not straight forward because both have advantages and disadvantages. 

Things to consider:

• cost
• supply
• consumer safety
• batch-to-batch variation
• ecological impacts

Extracts from single plants or obtained from different plants and combined, as practiced in Ayurvedic and Traditional Chinese Medicine, can be superior to a single purified compound in medicinal effect. Plant extracts tend to be affordable while synthetic compounds can be prohibitively expensive. Many people consider plant extracts safer because they are ‘natural’ but there can be a lot of batch-to-batch variation impacting efficacy.

Government regulatory requirements differ considerably for herbal medicines, affording little to no consumer protection whereas regulatory oversight for purified chemically synthesized compounds is very strict. No quality assurance exists for many herbal medicines because they are considered dietary supplements and not drugs. For medicinal plants, overharvesting can result in supply shortages, and as discussed in the case of the African Cherry tree, can be very problematic from societal, ecological and sustainability perspectives.

The Best of Both Worlds

Combining knowledge from traditional medicines with modern science can lead to new drug discoveries, standardization of traditional medicine formulations and could have many other direct and indirect benefits. For example, combining the best of both worlds might lead to more options for medical treatments globally, to cost reductions, to the increased efficacy and safety of herbal medicines and to economic benefits for the communities that grow and manage medicinal plants. Understanding the value of medicinal plant species could help protect them and aid in the conservation of other plant species and the ecosystems in which they live.

Interestingly, a study comparing plant origins of well over 20,000 drugs and bioactive natural products revealed that certain plant families, for example, periwinkle, nightshade and poppy relatives, tend to be sources for drugs and medicinal compounds (Zhu et al., 2011). Armed with this information, the task of identifying bioactive plant compounds and drug discovery (bioprospecting) is likely to meet with greater success.