Three plant-inspired pharmaceuticals: aspirin, L-DOPA and metformin

Today’s drug supply chain is a miracle of modern technology, with intricate and complex scientific processes involved in identifying, synthesizing and formulating medicines for a range of health conditions. Yet the roots of many of today’s most well known drugs – from general purpose aspirin to the diabetes medication metformin – are found in nature, with over 40% of all drugs sourced from nature.

While our ties to natural medicines are more abstract than they were in the past, modern medicine still relies on the natural world for inspiration. The following three molecules were first sourced from nature, and while they are now produced through synthetic chemistry, they owe their existence to the natural world.

Aspirin

The medicine we know today as aspirin is one of the oldest general purpose medications in the world. A derivative of salicylic acid (the molecule’s biologically active form), aspirin converts to salicylic acid upon ingestion.

Used to provide relief from pain, fevers and inflammation for millennia, aspirin’s most ancient ancestor – a molecule called salicin, which also converts to salicylic acid in the body – can be found in the leaves and bark of willow trees. Ancient civilizations like the Sumerians and Egyptians used willow as a medicine, but it wasn’t until 1828 that Joseph Buchner, a professor of pharmacy at Munich University in Germany, succeeded in extracting the active ingredient from willow and naming it salicin (derived from salix, the Latin word for willow).

Over the next seventy years, salicin was the subject of countless clinical trials and scientific experiments. In 1897, aiming to create a “better” salicylic acid with less GI irritation, German chemist Felix Hoffman created the synthetic version of salicylic acid – acetylsalicylic acid – that came to be known as “aspirin.” Today, the drug accounts for annual global sales of $2.6 billion, with 7,700 metric tons of volume produced and sold in 2019 alone.

Levodopa (L-DOPA) 

Levodopa is a molecule found in broad beans (Vicia faba), and is currently used to treat Parkinson’s disease. Upon crossing the blood-brain barrier into our brain, L-DOPA is converted to dopamine (its biologically active form).

The study of L-DOPA as a Parkinson’s treatment in many ways happened by accident. The molecule was first isolated in 1913, but was seen as dangerously toxic until Swedish pharmacologist Arvid Carlsson began experimenting with it again in the 1950s. Carlsson was attempting to minimize the side effects of a new schizophrenia drug called reserpine (another natural product), which caused catatonia by depleting stores of serotonin, noradrenaline and adrenaline. 

Carlsson discovered that L-DOPA could mitigate these side effects when converted to dopamine. Clinical trials confirmed this effect, and since L-DOPA’s approval by the FDA in 1970, it has been the mainstay of Parkinson’s disease therapy, with 2019 global production reaching 680 metric tons and global sales totaling $1.5 billion. In a demonstration of the drug’s unique staying power, no more effective Parkinson’s drug has yet been developed in the last half century.

In a nod to the enduring importance of L-DOPA, Carlsson was awarded the 2000 Nobel Prize in Physiology or Medicine. As a signal of the difficulty of synthesizing this molecule through synthetic chemistry, the 2001 Nobel Prize Chemistry was awarded for L-DOPA synthesis at industrial scale. 

Metformin

Metformin, the world’s most prescribed anti-diabetic drug, is the modern form of a medicine first used in medieval Europe. Doctors used the wild legume Galega officinalis as an herbal treatment for the plague and snake bites. The first recorded use of the plant – known by various names including goat’s rue, French lilac and Italian fitch – for diabetes was in 17th Century England.

It wasn’t until 1914 that French pharmacist and plant biochemist Georges Tanret isolated an alkaloid called galegine from seeds of G. officinalis; in 1927, Tanret published his study showing galegine’s hypoglycemic effect in rabbits and dogs. In the 1950s, French chemist Jean Sterne conducted studies of the antidiabetic properties of several compounds related to galegine, one of which was metformin, and the results were so striking that he filed a patent in 1957.

Over the next few years, interest in metformin grew steadily, and the drug soon became the standard treatment for type-2 diabetes. Yet in the US, openness to the drug was delayed for decades, until the FDA approved the drug for sale in 1994. Today, metformin accounts for $10 billion in global sales, with 54,000 metric tons of the drug produced annually.

From Farm to Pharmacy

Aspirin, L-DOPA and metformin today account for over $14 billion in annual sales. While these medications are now produced via chemical synthesis in tightly controlled lab settings, they all began their journeys as humble plants. Learn more about the journey behind plant-inspired drugs in our blog, and reach out to info@antheia.bio if you’d like to connect directly. *Drug sales and volume insights are provided by Cortellis Generics Intelligence™ (formerly Newport), ©Clarivate