Inside the pharmaceutical greenhouse

For centuries, millions of people around the world have turned to the plants and trees around them to develop herbal and traditional remedies. Chamomile to help you relax, ginger to support the immune system, aloe vera to soothe burns – these practices have been handed down from generation to generation, with mixed results.

Oddly enough, the majority of these plants are also highly toxic if incorrectly used, but within their leaves, flowers, and bark is a world of medical wonders that can be used to cure and treat a plethora of modern ailments.

While not all of these ‘treatments’ have the same level of scientific backing, today approximately 11% of drugs deemed essential by the World Health Organization have roots in botanicals. In fact, many of these plants get their names from the doctors that studied them, as botany and medicine were intrinsically linked up until the 17th century.

Here, we take a look at some of the most influential examples of plants in medicine.

Willow bark (Salix alba)

For centuries, willow bark has held a place of honour in traditional medicine as a source of pain relief. However, it is unlikely that the ancient Sumerians and Egyptians could have known that the bark they were advised to chew on, contained an ingredient that would become of one of the most used drugs in the world – aspirin.

It wasn’t until 1828 that the active ingredient in willow bark was finally discovered, when German pharmacologist Johann Buchner refined the bark into yellow crystals, which he subsequently named Salicin, after the Salix genus of the plant. This process was taken a step further in 1838, when Italian chemist Raffaele Piria used these yellow crystals to develop salicylic acid.

Building on the work of Buchner and Piria, French chemist Charles Gerhardt became the first to modify salicylic acid with an acetyl group, resulting in an early claim to the discovery of aspirin. However, as the compound lacked stability, Gerhardt opted not to develop it further.

The breakthrough for aspirin eventually came in 1890, when the German dye manufacturer Bayer established a pharmaceutical division. While there is ongoing controversy over how each individual should be credited for the discovery of aspirin at Bayer, we do know that there were three key figures involved: Arthur Eichengrün, Felix Hoffmann, and Heinrich Dreser.

Opium poppy (Papaver somniferum)

Perhaps the most well-known plant in medicine, the opium poppy is also one of the oldest in recorded history. The specific date and location of discovery of the plant has been lost to history. However, the tale of the opium poppy can be found in prominent texts, including a believed reference to the plant on the Sumerian clay tablet. Dated around 2100 BCE, this is considered to be the world’s oldest recorded list of medical prescriptions.

The milky latex sap found within the unripe poppy seed pod contains upwards of 80 alkaloids that can be used to target the opioid receptors that regulate pain and temperature control. German pharmacist and pioneer of alkaloid chemistry Friedrich Sertürner became the first to isolate morphine from opium (as well as the first person to isolate the active ingredient associated with a medicinal plant or herb).

Following this, in 1832, French chemist Pierre Jean Robiquet isolated codeine from opium’s several active components while working to refine morphine extraction processes.

A similar compound, diamorphine, was synthesised by the chemist C.R Alder Wright in 1874. Better known by its other name – heroin – this compound remained relatively unchanged for the next 23 years, until a re-synthesised version developed by aspirin-creator Felix Hoffmann caught the attention of Bayer Pharmaceuticals and was transformed into a pain management drug.

Until the early 19th century, a mixture of raw opium and ethanol, known as laudanum, was used to treat a wide array of ailments. Given the dangers associated with misuse of opioids, heroin has since been banned in most countries, while other opium derived medications are now heavily regulated.

Snowdrop (Galanthus nivalis)

Despite its dainty stature, the snowdrop, Galanthus nivalis, has carved out a substantial place in pharmaceutical history. Early descriptions of the mind-altering properties of ingesting an extract from snowdrops can be found as far back as ancient Greece, with references to an herb with “a black root, but milklike flower” seen in Homer’s Odyssey, widely attributed to the snowdrop.

Although the plant has been extensively used in traditional medicines, it wasn’t until the 1950s that researchers began to explore its potential in pharmaceuticals.

The official story behind the discovery of snowdrops’ medical properties remains uncertain, but a leading theory links traditional uses with the development of the compound, galantamine. Having observed how villagers would rub the bulbs and leaves of snowdrops on their foreheads to ease nerve pain, Bulgarian chemist Dr Dimitar Paskov and his team isolated and extracted the alkaloid galantamine, a competitive, reversible, acetylcholinesterase inhibitor, as part of efforts to treat poliomyelitis.

Today, galantamine is commonly used to slow the progression of Alzheimer’s disease and mitigate its symptoms, such as memory loss, although it cannot cure the disease.

While the alkaloid was initially isolated from the snowdrop (most notably G. woronowii), nowadays, galantamine is obtained from daffodils (Narcissus) and snowflakes (Leucojum), as well as synthetically.

Madagascar periwinkle (Catharanthus roseus)

The aptly named Madagascar periwinkle is native to the island nation of Madagascar. It’s delicate pink and white flowers have made it a popular decorative plant in gardens around the world. However, traditionally, infusions made from the leaves of the Madagascar periwinkle were used by the indigenous people of the island to treat a variety of conditions, most notably diabetes.

Frederick Banting and Charles Best’s discovery of insulin in 1921, and its subsequent commercialisation by Eli Lilly, marked a significant turning point in the treatment of diabetes. However, as some receiving the treatment began to develop resistance, researchers set out to find alternative lead compounds.

In the 1950s, this search brought researchers to the Madagascar periwinkle. Two research teams from Eli Lilly and the University of Western Ontario independently began to investigate the potential of chemicals derived from the plant in the fight against diabetes.

While the plant extracts proved to be less effective in lowering blood sugar in mice subjects, researchers noticed a significant decrease in white blood cells. As such, the chemicals found within the Madagascar periwinkle could be highly effective in fighting some types of cancer, specifically those involving a proliferation of white blood cells.

The two research teams decided to join forces to investigate further. Through this collaboration, they identified two key alkaloids: vinblastine, a potent inhibitor of cell division, and vincristine, which inhibits leukocyte production and maturation.

These alkaloids work by preventing cells from dividing by blocking tubulin.

Following FDA approval of vincristine in 1963, the drug has since been successfully used for treatment of childhood acute lymphoblastic leukaemia and non-Hodgkin lymphomas.

Meanwhile, vinblastine is used in combination with other chemotherapy drugs to combat lymphomas, as well as testicular, ovarian, breast, bladder, and lung cancers.

Sweet wormwood (Artemisia annua)

Stories of using traditional medicine to combat malaria exist throughout history. But as is often the case, it was necessity that fuelled interest in exploring how traditional applications could inform pharmaceutical developments. In 1967, at the height of the cultural revolution, then-Chairman of the Communist Party of China, Mao Zedong launched a covert military operation, code named Project 532, to find antimalarial medications.

At the time, China’s forces were heavily embroiled in the Vietnam war, where the emergence of drug resistant malaria created an urgent need for new treatments. Project 532 was split into three main branches, one for developing synthetic compounds, one for clinical studies, and another for investigating traditional Chinese medicine. It was headed by the famed Chinese pharmaceutical chemist and malariologist Tu Youyou.

Biomedical interest in Traditional Chinese Medicine was not a new concept, however, Tu’s embrace of Chinese meteria medica, notably The Handbook of Prescriptions for Emergency Treatments, written in 340 by Ge Hong, is a more recent example of efforts to investigate the ‘clinical’ potential of substances. From an initial list of 2,000 traditional herbal preparations, Tu and her team of phytochemical researchers identified possible antimalarial activities in 640 candidates.

Of the more than 380 extracts obtained from Chinese herbs, the Artemisinin (or qinghaosu, as it is known in China) derived from extracts of sweet wormwood was demonstrated as a strong potential for treatment of intermittent fevers, a key symptom of malaria.

As head of the research group, Tu volunteered to be the first human subject. Once the product was deemed safe, clinical trials were then conducted in human subjects. Artemisinin-based combination therapies are now standard treatment worldwide for P. falciparum malaria, as well as malaria.

For her work in malaria research, Tu was awarded the Nobel Prize in Medicine in 2015.

Oceancetaceen – Alice Chodura, Public domain, via Wikimedia Commons

About the author

Eloise McLennan is the editor for pharmaphorum’s Deep Dive magazine. She has been a journalist and editor in the healthcare field for more than five years and has worked at several leading publications in the UK.

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