One of the most difficult steps in developing a drug to treat an illness is finding a biological target for the compound to act on. In many cases, nature has solved this problem for us, and all it takes are a few astute observations from people to figure out how we can make use of our surroundings to improve and maintain our health. Once the effects of a certain plant or animal product on the human body are observed, the exact substance causing these effects must be extracted. Pharmaceutical chemists then synthesize these compounds or compounds closely related to them as a potential drug that undergoes further safety and effectiveness testing.
In areas of the world where malaria is endemic, quinine is one of the most effective treatments for this parasitic infection. Now reserved for the most severe cases of malaria, this drug has been used for centuries in South America and Europe to treat fever and shivering. Quinine is an alkaloid (compounds containing basic nitrogen atoms) derived from the bark of the cinchona tree, and possesses the characteristic bitter taste of this plant. Reserpine, another alkaloid, is a drug used to treat hypertension and psychosis. Although not commonly used nowadays, it remains an option for treating those with high blood pressure who are resistant to other medications. The compound was first isolated from the Indian snakeroot Rauvolfia serpentine. This plant also contains another chemical – yohimbine – which acts on the alpha 2 receptors of adrenaline and is used as a remedy for erectile dysfunction.
The willow tree (genus Salix) has provided humanity with one of the most important drugs we have ever used. The plant contains the active compound salicin, used for centuries to relieve pain and fever by Native Americans as well as the Ancient Egyptians. In fact, salicin was the drug at the centre of the first clinical trial in scientific history, conducted in 1763 [1]. In the late 1800s, it was used for the production of acetylsalicylic acid (Aspirin) - the most widely used drug in history, which single-handedly converted Friedrich Bayer’s company from a small dye manufacturer to a pharmaceutical titan. The cardiac glycoside digoxin is extracted from Digitalis lanata (foxglove). Early attempts at medicinal use of this plant were hindered by its toxicity and fatality in overdose. It currently has an important role in the treatment of heart failure as well as abnormal rhythmicity of the heart, yet requires stringent monitoring and careful dosage prescription to avoid its harmful effects.
The aptly named plant Atropa belladonna was once used by women in Italy to dilate their pupils and make them look more attractive. It contains a mixture of toxic alkaloids (known to cause hallucinations) that inhibit the action of the autonomic nervous system (the part of the nervous system devoted to controlling the automatic, unconscious functions of the body). Derived from this plant is the widely used anticholinergic drug atropine, which is used in ophthalmology to dilate the pupils, to treat cases of organophosphate (insecticide) poisoning, and to treat those with abnormally low heart rates. Another anticholinergic drug, curare, acts on a distinct set of receptors and was once widely used as a muscle relaxant during anaesthesia. Derived from the Strychnos toxifera plant, this paralyzing poison was historically used by South American tribes to cover the tips of their hunting arrows.
Angiotensin-converting enzyme (ACE) inhibitors were derived in the 1960s from the venom of the Brazilian pit viper, Bothrops jararaca. The venom kills by causing a severe drop in arterial pressure through blockage of the renin angiotensin aldosterone system, an essential physiological mechanism which controls blood pressure. ACE inhibitors such as lisinopril, captopril and enalapril have become first-line agents for high blood pressure, particularly in younger Caucasian patients, and have a good safety profile. It is noteworthy that their selective mechanism of action means that ACE inhibitors may not be effective for everyone in terms of lowering blood pressure. Despite this, the drugs have several other unique benefits including protecting the kidneys in diabetes and improving heart function in patients with heart failure [2].
A more recent drug yielded from nature’s gift basket is exenatide, an anti-diabetic agent licensed for use in 2005. This drug was isolated from lizard (Gila monster) saliva and has been shown to stimulate insulin release from the pancreas [3]. Unlike other anti-diabetic drugs, exenatide has an important feature – it only increases insulin secretion when glucose levels are high and therefore, does not lead to an abnormally low blood glucose (hypoglycaemia). It also has numerous other beneficial effects including promoting weight loss. Similarly, a new agent proposed for the treatment of stroke is also derived from saliva - that of the vampire bat Desmodus rotundus. This drug, called desmoteplase, is still in the testing phases of development (phase III trials), but has already shown great promise [4]. It stays in the body for a longer time than other thrombolytics (drugs which dissolve blood clots), is more selective in its action, and does not lead to neurotoxicity. It is possible that it may represent a breakthrough in the treatment of stroke, which is currently a highly debated and complicated issue.
People have been using natural resources for medicinal purposes for millennia
Nowadays, we are in possession of complex methods to design, test and use medicines. Despite this, it’s not uncommon that a drug crosses our path which reminds us that no matter how technologically advanced we are, our dependence on nature is eternal. People have been using the earth’s natural resources for medicinal purposes for millennia, and continue to do so. However, only a handful of these substances - which include both animal and plant products - have been scientifically deemed safe and effective enough for modern use.
[1] Stone, Philos Trans, 1763
[2] Pahor et al, Diabetes Care, 2000
[3] Gavin, Ethnic Dis, 2007
[4] Schleuning, Pathophysiol Haemos Thromb, 2001
by Ahmed Khalil
this article originally appeared 2013 in CNS Volume 6, Issue 4, Integrative Medicine
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