Buzz
Medical students are required to study an extensive array of pharmaceuticals during their education, with a deep understanding of each being crucial. It may come as a surprise to learn how many of these medications have their roots in natural sources. While many are aware that aspirin originates from willow bark, fewer realize the vast number of other drugs derived from plants.
Many widely used and effective medications today have remarkably intriguing backstories and were originally sourced from nature. As a medical student, I find the origins of these drugs incredibly captivating and hope you share the same fascination.
10. Cannabis Sativa And Dronabinol
The Cannabis sativa plant has recently been at the center of debates surrounding the legalization of marijuana. Although marijuana is the most well-known product of this plant, it has also given rise to another highly beneficial pharmaceutical compound.
The signs of marijuana intoxication are widely recognized, such as red eyes, enlarged pupils, dry mouth, heightened appetite, delayed reflexes, feelings of euphoria, lightheadedness, shallow breathing, and an elevated heart rate. While some of these effects may seem undesirable, the medical field has identified certain symptoms that can be beneficial for treating specific patient groups.
Dronabinol, a synthetic version of THC, has been developed to harness some of marijuana's effects. This drug serves multiple purposes, but it is primarily employed to stimulate appetite in AIDS patients and to prevent nausea in those undergoing chemotherapy.
Despite some debate surrounding dronabinol, studies indicate that it poses minimal risks and has a low likelihood of abuse. It’s fascinating to think that inducing hunger could have such therapeutic value.
9. Podophyllum Peltatum And Etoposide
For centuries, Native Americans utilized the Podophyllum peltatum plant as a purgative, antiparasitic, and cathartic, long before its medicinal value was formally acknowledged. Notably, the Penobscot tribe of Maine reportedly used it to address “cancer,” while the Iroquois applied it for snakebite treatment and as a means of suicide. However, the medical application of P. peltatum wasn’t officially recognized in the United States until 1820 and in Europe until 1861.
Hartmann Stahelin, a Swiss pharmacologist, made significant strides in the field of cancer therapy. With a strong inclination toward biomedical sciences, he was appointed to head the pharmacology department in Basel in 1955, focusing on research in cancer and immunology.
During his tenure in Basel, Stahelin spearheaded the discovery of several antitumor agents derived from P. peltatum, commonly known as mayapple. Initially dismissed by chemists as “dirt,” Stahelin identified a unique extract from the Podophyllum plant with remarkable properties. Upon purification, this compound was revealed to belong to a novel class of antitumor drugs.
The drug, named etoposide, functions by inhibiting the division of tumor cells. It targets a specific enzyme essential for cell replication, thereby significantly impacting rapidly dividing cells like cancer cells. Today, etoposide is widely used to treat various cancers, particularly lung cancer, and has played a crucial role in saving countless lives.
8. The Calabar Bean And Physostigmine
The Efik people of Akwa Ibom State, now part of Southeast Nigeria, were the first to encounter physostigmine from the calabar bean (Physostigma venenosum). In Efik culture, the calabar bean was frequently used as a trial poison for individuals accused of witchcraft. The accused were given the milky extract of the bean; death confirmed guilt, while survival, often due to vomiting the poison, led to their acquittal and release.
Missionaries documented the Efik’s use of the calabar bean, and some beans were brought back to Scotland. In 1855, toxicologist Robert Christison experimented with the poison by ingesting a bean himself, surviving to record his observations.
Throughout the 1860s, the calabar bean was extensively studied, particularly by Douglas Argyll Robertson, who pioneered its medical application and noted its effects on the pupil. Thomas Fraser later isolated the most potent component, naming it physostigmine. In 1867, Ludwig Laqueur tested the extract on himself, successfully using it to treat his glaucoma. By the 1920s, Otto Loewi identified the neurotransmitter acetylcholine and discovered that the calabar bean extract enhanced its activity, significantly impacting the parasympathetic nervous system.
Medically, physostigmine boosts acetylcholine levels by inhibiting the enzyme acetylcholinesterase, which degrades it. It is particularly effective in treating myasthenia gravis and has recently been explored for Alzheimer’s treatment due to its ability to cross the blood-brain barrier.
7. Meadow Saffron And Colchicine
The medicinal use of Colchicum autumnale, commonly known as meadow saffron, dates back to 1500 BC, as documented in the ancient Egyptian Ebers Papyrus for treating rheumatism and swelling. Over time, C. autumnale has been employed to address conditions like gout, familial Mediterranean fever, Behcet’s disease, and pericarditis. Its mechanism of action resembles that of Taxol, as it inhibits microtubule formation.
As early as the first century AD, Pedanius Dioscorides described C. autumnale as a remedy for gout, a form of arthritis marked by needle-like crystal deposits in joints, leading to sudden pain, swelling, and redness. Other notable figures, including Alexander of Tralles, Persian physician Avicenna, and Ambroise Pare, also advocated for its use in gout treatment. Colchicine was first isolated from C. autumnale in 1820 by French chemists P.S. Pelletier and J.B. Caventou, with further purification by P.L. Geiger in 1833.
Despite its long-standing efficacy, colchicine lacked FDA-approved prescribing guidelines, dosage recommendations, or drug interaction warnings until as recently as 2009.
6. Indian Snakeroot And Reserpine
Rauwolfia serpentina, known as Indian snakeroot or sarpagandha, has been used medicinally in India for centuries before its introduction to the Western world. Botanist Georg Rumpf, associated with the Dutch East India Trading Company, first documented the plant in 1755, noting its use in South Asia to treat insanity. Marketplaces across India sold extracts from its roots as pagalon ki dawa, or “medicine for the mad.” Additionally, mothers in Eastern India used it to soothe crying infants, as well as to address labor pains, snakebites, fever, and digestive issues. Mahatma Gandhi reportedly consumed root extracts for their calming effects.
In the early 20th century, India initiated efforts to standardize and study the pharmacological properties of sarpagandha. Professor Salimuzzaman Siddiqu began systematic research on its active components in 1927. Dr. Kartick Chandra Bose and Gananath Sen, prominent physicians from Calcutta (now Kolkata), independently observed its effectiveness in treating high blood pressure and mental disorders. Dr. Rustom Vakil, regarded as the father of modern cardiology in India, played a key role in popularizing its use for hypertension.
Reserpine, isolated in 1952 from the dried root of R. serpentina, gained rapid popularity in Western medicine. It was the first drug to demonstrate antidepressant properties in a randomized placebo-controlled trial. Although its use has declined due to significant side effects, it was instrumental in advancing our understanding of neurotransmitters' role in depression and blood pressure regulation.
5. Indian Hemp And Pilocarpine
When settlers arrived in the New World during the early 1600s, they observed that indigenous Brazilian tribes possessed extensive knowledge of local medicinal plants. Among these, Pilocarpus jaborandi (Indian hemp) stood out for its use in treating various ailments, particularly fever. The leaves were known to induce heavy sweating, salivation, and urination, helping to expel toxins from the body. The name jaborandi originates from the Tupi word meaning “what causes slobbering.”
By the 1870s, P. jaborandi had been integrated into Western medicine, gaining popularity in Europe for treating intestinal and lung disorders, fever, skin conditions, kidney disease, and edema. Remarkably, it was also discovered to counteract deadly nightshade poisoning. In 1875, pilocarpine, the active compound responsible for its effects, was isolated from the plant. This breakthrough was achieved independently by researchers in France and England.
Pilocarpine quickly became a highly effective treatment for glaucoma by reducing intraocular pressure. Today, it remains a widely used remedy for glaucoma and is also employed to induce sweating in cystic fibrosis diagnosis. Despite advancements, laboratories have yet to fully replicate or synthesize the pilocarpine found in P. jaborandi, making this plant one of Brazil’s most significant exports.
4. The Pacific Yew Tree And Paclitaxel
Scientists are constantly exploring novel methods to combat cancer, often discovering that potential treatments are closer than they think. In 1955, the National Cancer Institute established the Cancer Chemotherapy National Service Center (CCNSC) to identify new cancer therapies. During the 1960s, the CCNSC collaborated with the US Department of Agriculture to search for these cures in nature. Over two decades, they tested approximately 30,000 natural plant and animal products.
Among the 30,000 samples, one proved to be a breakthrough in cancer treatment. Researchers Dr. Monroe Wall and Mansukh Wani identified that extracts from the bark of the Pacific yew tree (Taxus brevifolia), native to the Pacific Northwest, were toxic to tumor cells. Further studies revealed that the toxic compound was synthesized by a fungus within the bark, leading to the development of the chemotherapy drug paclitaxel.
Paclitaxel, marketed as Taxol, is widely used to treat breast and ovarian cancers. It functions by inhibiting microtubules, effectively preventing cancer cells from dividing and growing. Since its discovery, paclitaxel has become a cornerstone of cancer therapy, saving countless lives worldwide.
3. Foxglove And Digoxin
Digoxin was once a cornerstone in treating heart failure and arrhythmias. It functions by reducing the heart rate while enhancing the force of each contraction. However, the drug has a very narrow therapeutic window, making overdose a significant risk with severe consequences.
The discovery of digoxin by Scottish physician William Withering occurred in 1775. While practicing medicine, Withering encountered a patient with a severe heart condition for which no effective treatment existed at the time. Believing his condition fatal, the patient sought help from a local gypsy, who administered an herbal remedy that led to a miraculous recovery.
Intrigued, Dr. Withering tracked down the gypsy and persuaded her to reveal the remedy's ingredients. Among them, Digitalis purpurea, or foxglove, was identified as the primary component. Foxglove's potency was already recognized, having been used as a poison in medieval trials by ordeal and topically to treat wounds.
Withering promptly began experimenting with different forms of foxglove extract on 163 patients. He discovered that dried, powdered leaves yielded the best outcomes, and the treatment was first officially administered in 1785. Although less commonly used today, digoxin was groundbreaking in its ability to aid those suffering from heart failure.
2. The Cinchona Tree And Quinine
Quinine, derived from the bark of the South American cinchona tree, was originally used by the Quechua people as a muscle relaxant. The Jesuits introduced it to Europe, and by 1570, the Spanish recognized its medicinal value. Nicolas Monardes and Juan Fragoso documented its effectiveness in treating diarrhea. While quinine had various ancient applications, its most significant discovery came in the early 17th century.
In the early 17th century, the marshes and swamps near Rome were infested with malaria-carrying mosquitoes. Malaria, caused by parasitic protozoans, leads to symptoms like fever, fatigue, vomiting, headaches, jaundice, seizures, and death. The disease claimed the lives of many popes, cardinals, and citizens. Agostino Salumbrino, a Jesuit apothecary, observed the use of cinchona bark for malaria's shivering phase. Unaware that its effect on malaria was unrelated to its impact on rigors, he brought the bark to Rome.
Over time, cinchona bark became one of Peru's most prized exports, even healing King Charles II. In 1737, Charles Marie de La Condamine identified the most potent component of the bark, which was later isolated by Pierre Joseph Pelletier and Joseph Caventou in 1820. The extract was named quinine, derived from the Incan word quina, meaning “bark” or “holy bark.”
Large-scale malaria prevention using quinine began around 1850. The drug played a crucial role in European colonization of Africa. In the early 19th century, Peru attempted to ban the export of cinchona bark, seeds, and saplings to maintain its monopoly. However, the Dutch successfully cultivated the tree in their Indonesian plantations, eventually becoming the primary global supplier.
During World War II, the Allies lost access to quinine when Germany occupied the Netherlands and Japan controlled Indonesia and the Philippines. The United States managed to secure four million seeds from the Philippines, but not before thousands of Allied soldiers succumbed to malaria in Africa and the South Pacific. Similarly, thousands of Japanese troops died due to ineffective quinine production despite their control.
Since its discovery, quinine has saved millions of lives and significantly influenced wars, colonization, and history. In 2006, the World Health Organization replaced it as the first-line treatment for malaria with newer drugs. Quinine is also used to treat conditions like babesiosis, restless leg syndrome, lupus, and arthritis.
1. Deadly Nightshade And Atropine
Atropa belladonna, also known as belladonna or deadly nightshade, is an herb with centuries of use in treating various ailments. Native to Europe, North Africa, and West Asia, it has since been introduced to Canada and the United States. Before the Middle Ages, it served as an anesthetic for surgeries. Its potent toxicity also made it a favored poison for political adversaries and a weapon on arrow tips in ancient Rome.
During the Middle Ages, deadly nightshade gained popularity for cosmetic purposes. Venetian women used it to redden their skin as a form of blush. It was also employed to dilate pupils, enhancing a woman’s allure and attractiveness. This practice earned the herb the name belladonna, meaning “beautiful lady.” However, its lethal potential was soon recognized, and it became a tool for assassins, criminals, and witches to create poison.
Despite its historical use as a poison and cosmetic, A. belladonna was later discovered to have significant medicinal benefits. It could alleviate pain, relax muscles, reduce inflammation, and treat whooping cough and hay fever. In the 1930s, atropine, the therapeutic compound in belladonna, was isolated. While belladonna itself lacks approved medical uses, atropine has become a vital medication in modern medicine.
Atropine is classified as an anticholinergic, meaning it inhibits the neurotransmitter acetylcholine. Its effects are essentially the opposite of physostigmine. Atropine can dilate pupils, increase heart rate, and reduce secretions. Beyond its use in raising heart rate and reducing saliva before surgery, it also counters certain overdoses. Derivatives like tiotropium and ipratropium bromide are used to treat various lung conditions.
+ Chondrodendron Tomentosum Vine And Tubocurarine
For centuries, South American indigenous tribes used poison from the Chondrodendron tomentosum vine for hunting. Spanish conquistadors returning from the New World recounted tales of a mysterious “flying death.” In 1516, chronicler Peter Martyr d’Anghera documented these stories in his book De Orbe Novo for King Ferdinand and Queen Isabella. Sir Walter Raleigh, during his 1594 visit to Venezuela, also described the use of poisoned arrows in his book Discovery of the Large, Rich and Beautiful Empire of Guiana. One of Raleigh’s lieutenants called the poison ourari, which evolved into various European names, including “curare.”
Exploration of South America paused until the 18th century due to conflicts. Physician Edward Bancroft spent five years in South America and returned with curare samples. Sir Benjamin Brodie experimented with these samples on small animals, keeping them alive using bellows to inflate their lungs. Charles Waterton, who moved to South America in 1804, obtained ourari from a local tribe. In 1814, he demonstrated its effects on three donkeys to an audience including Sir Benjamin Brodie. The first donkey died instantly after a shoulder injection, the second survived until a leg tourniquet was removed, and the third was revived with bellows and lived.
Claude Bernard’s experiments on frogs revealed that curare acts at the nerve-muscle junction. Further studies highlighted its potential as a muscle relaxant for anesthetized patients. Synthetic curare-like compounds were developed, mimicking the original substance. Today, these compounds are essential in nearly all anesthesia procedures, inducing complete skeletal muscle relaxation during surgery or mechanical ventilation as part of general anesthesia.
