Bioactives in medicine

Objective: Explore the contribution of natural products to medicines.

Key learnings: Get to know a selection of medicines in clinical use that were discovered from plant sources.

Natural products have been used as medicine for humans and animals since ancient times in many cultures around the world.

Early civilizations in Egypt, Mesopotamia, India, China and Greece documented medicinal uses of plants and their preparation. In medieval Europe, monasteries kept herb gardens and produced texts on medicinal plant uses. The Age of Exploration brought new medicinal plants to Europe from the Americas, Africa and Asia.

One such medicine was prepared from the bark of the cinchona tree. Indigenous peoples of South America used the bark to treat fever, a symptom of malaria. Jesuit missionaries learned about its use and brought it to Europe in the early 17th century. The active component of cinchona bark, quinine, was isolated and became the primary treatment for malaria. Other medicines are now available but quinine is still used today in some circumstances.

Natural product derived medicines can have a wide range of effects in the body, or pharmacological effects, for the treatment and prevention of disease. Natural sources have provided a wealth of antimicrobial and anticancer agents. Other natural products can reduce inflammation, relieve pain or can modulate the immune system. Still others can have cardiovascular benefit or can regulate blood sugar and metabolism.

Many medicines derived from natural sources are essential medicines for humanity. Here are some examples:

Digoxin – medicine for the heart from a flower

The common purple foxglove (Digitalis purpurea) is native to Europe and grows widely in Ireland. A related species, Digitalis lanata or the woolly foxglove is native to Eastern European areas. They are poisonous plants and all parts of the plant are poisonous containing several toxic compounds called cardiac glycosides. The foxglove is sometimes called dead man’s bells. Ingestion of Digitalis can cause nausea, vomiting, severe headache, delirium and deadly disturbances of heart rhythm. Fatal poisonings have occurred where the plant was mistaken for comfrey which is used to make herbal teas or where children have drank water in a vase containing the flowers. 

One of the compounds it contains, however, has use as a medicine. Toxic in overdose, at therapeutic doses Digoxin is used for heart conditions such as heart failure and arrhythmias where its effect of increasing the strength of contraction of the heart is beneficial.  

The use of purple foxglove extract was first described in English speaking medical literature in 1785 but it was a century later before digoxin was identified in foxglove. Today it is still extracted from the plant because chemical synthesis is too difficult and expensive. Digoxin is commercially produced from Digitalis lanata. The plant is grown from seed for two years, harvested, dried and the leaves crushed into a powder and the compound is extracted and purified by chemical processes.

The chemical substance digoxin is isolated and must undergo a combination of specified quality tests before it can be deemed suitable for use in a medicinal product. These quality tests confirm that the drug substance is the desired substance and that it has adequately low levels of potential impurities. 

Galantamine – medicine for dementia from a flower

Galantamine is found in the bulbs and flowers of some species of snowdrop and daffodil including the common snowdrop (Galanthus nivalis). Galantamine is a treatment for mild to moderate Alzheimer’s disease. It works by increasing levels of a neurotransmitter in the brain. While not a cure, this improves cognitive function and slows the progression of Alzheimer’s disease.

Galantamine was used in traditional medicine in Eastern Europe for ailments such as nerve pain and muscle weakness. In the 1950s, a team of Bulgarian scientists investigating local plants isolated the compound galantamine and probed its biological effects. It became available as a licensed medicine for Alzheimer’s disease in the 2000s.

Initially, galantamine was extracted from botanical sources for pharmaceuticals. However, botanical sources contain very low amounts of galantamine and yields of the drug from the plant are low, approximately 0.1% by weight. The method is also limited by the availability of the plants. It is now possible to produce galantamine in a lab environment which ensures a stable and scalable supply of the drug for the pharmaceutical industry.

Morphine – powerful pain relief from a flower

Morphine is probably the most well-known medicine derived from a natural source. It is found in the opium poppy (Papaver somniferum). Morphine makes up approximately 10% of the dry weight of opium.

The medicinal use of opium dates back to ancient civilizations. Opium was harvested by cutting into the poppy capsules to release the milky latex which was collected and dried. The compound morphine was first isolated from raw opium in 1804 by Friedrich Sertürner, a German pharmacist. He named it “morphium” after Morpheus, the Greek god of dreams, due to its sleep-inducing effects. Morphine is a potent pain reliever used to manage acute and chronic pain that is moderate to severe in intensity.

It exerts its effects by reducing pain transmission in the central nervous system. It is also sedative and can induce a sense of euphoria. For these reasons and because tolerance develops with prolonged use, morphine has high potential for abuse and addiction.

Morphine is still primarily sourced from the poppy plant. While synthetic methods are possible and can ensure a stable supply not reliant on seasonal production, the process is not economically viable compared to poppy harvesting and extraction. Cultivation is strictly controlled. Legal producers in countries such as Turkey and India produce opium for medicinal purposes.

Digoxin, galantamine and morphine are three clinically used drugs discovered and extracted from flowering plants. These drugs are most appropriately used as single isolated compounds that are fully evaluated for purity. Clinical use requires careful dose levels of these agents. Testing for compliance to specifications in quality testing ensures safety and efficacy for patients.

Herbal medicines

Extracts from plant materials are sometimes suitable for medicinal purposes. In some cases, more than one extract component may contribute to the desired biological effect of the extract and sometimes components may act synergistically to produce the effect of the total extract. Here are some examples of herbal medicines that are authorised as medicinal products.

St. John’s Wort (extract of the herb Hypericum perforatum L.) is clinically used for the treatment of mild depressive symptoms. Peppermint oil is used to treat symptoms of irritable bowel syndrome.

Valerian root is a traditional herbal medicinal product for relief of symptoms of stress and to aid sleep. The extract of purple coneflower (Echinacea purpurea) herb and root is used to relieve common cold and flu-like symptoms.