A Peek Inside Mother Nature’s Medicine Cabinet

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Fall is, traditionally, the best season for hiking (although this year has been stifling!).

Nonetheless, getting out to enjoy the fall colours will no doubt be a focus for many in the coming months. While out enjoying the vibrant flora and diversity of nature, consider that approximately 80% of medications in use today are derived from plants and trees.

For example, the bark of apple trees provided the foundation for a class of recently approved type 2 diabetes medications, called SLGT2 inhibitors. The original substance, called phlorizin, was isolated from apple trees in 1835 by a French chemist. Modifications to improve efficacy and reduce side effects were made and approval for use in Canada came in 2014. These drugs derived from apple trees work by restricting the amount of glucose taken up by the kidney. Therefore, instead of entering the bloodstream, glucose is carried to the bladder and then excreted. A patient with type 2 diabetes may excrete upwards of 200-300 calories worth of glucose while taking these pharmaceuticals. Importantly, cardiovascular disease is also improved by these compounds.

The most commonly prescribed anti-diabetic medication, metformin, was originally derived from French lilac. Another name for this plant is goat’s rue, a name imparted because of the observed toxicity to grazing animals. Interestingly, using low doses, physicians of the Middle Ages would use this plant to treat diabetes. Following these initial observations, the first piece of scientific literature describing metformin was published in 1922. Approval for this drug to treat diabetes in Canada came in 1972. This pharmaceutical works to reduce blood glucose by compromising the cell’s ability to generate energy. This mechanism is related to the idea that a small challenge to cellular homeostasis can provide health benefits.

Perhaps the most famous plant-derived medicine in today’s society is a compound isolated from willow trees known as salicylate. The medicinal properties of salicylate were noted in The Ebers papyrus, an ancient Egyptian medical text from 1550 BCE, which points out that willow bark has anti-inflammatory and pain relieving properties. In 400 BCE, the father of modern medicine Hippocrates, would brew up willow-leaf tea for mothers about to give birth. At the turn of the 19th century, salicylate was modified into what would become aspirin (acetylsalicylic acid), a mainstay for pain relief. More recently, clinical trials are underway investigating another modified version of salicylate as an anti-diabetic agent. For diabetes, the mechanism by which salicylate works is likely similar to metformin, that is, salicylate compromises the ability of the cell to generate energy.

Over a century ago cholesterol build-up within arterial walls was observed in people who had died from heart attacks. Researchers have now concluded that circulating cholesterol is a critical risk factor for cardiovascular disease. In the early 1970s, scientist were attempting to identify medicines that would reduce cholesterol. Derived from fungus, statins fit the bill. Scientists initially isolated statins from two different species of fungi and published the data in 1976. The pharmaceutical giant, Merck, recognizing the value of this work, isolated their own statin in 1978. In 1987, the product of a fungus called Aspergillus terreus hit the open market. Statins work to reduce cholesterol by inhibiting the body’s ability to synthesize cholesterol and are a life-saving, multi-billion dollar industry.

But why would plants produce such compounds in the first place? How would these chemicals benefit a tree, plant, or fungus? One hypothesis is that these compounds are defense mechanisms, akin to the quills of a porcupine, or the poison of a poison-arrow dart frog. They are anti-predator adaptations. With SGLT2 inhibitors (from apple trees) it would be detrimental to predators to have compromised glucose absorption and lose precious calories. With metformin (French lilac) and salicylate (willow trees), compromising cellular energy production would likely have a negative impact on predator health. Finally, considering cholesterol is a vital component of cellular integrity, reducing a predator’s cholesterol synthesis via statins (fungi) would definitely be toxic.

So enjoy the scenery on your fall hike and who knows, you may find yourself looking at the source of life-saving medication.

By Brennan Smith, PhD.

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