Past and Present Uses of Toxic Medicinal Plants: The World Tour

Introduction

Historically, poisonous plants have been used for medicine, decoration, and religious rituals, and even as a source of immortality. They have inspired, protected, and threatened us, and surprisingly, saved our lives. Recently, there has been a push to turn to more plant-based medicine—especially for cancer treatments—in the hopes of decreasing drug side effects while still maintaining their effectiveness [1].

While this paper originally aimed to discuss seven toxic, medicinal plants—one from each of the Earth’s seven continents—the reality is that most plants have spread across continental borders, completely opposing my wishes. Therefore, the location chosen for each plant is not absolute, and only indicates the continent which the plant has the most significant history with. So, get ready for a journey through the past and present medicinal uses of some of the world’s most dangerous plants.

Asia

Starting our tour in Asia, we have the Rosary Pea—also called the jequirity bean—or Abrus precatorius. This plant has a long, diverse history which includes being a treatment for seizures, a tea ingredient, and an easy suicide method [2]. At first glance, the rosary pea is rather inconspicuous, described as having pink and white petals, annual fruit production, and colorful seeds that lend themselves nicely to jewelry [3]. It has been used in Christian countries to make necklaces, ornaments, and wreaths, and in the seventies, was involved in recall scandals when people sold this toxic accessory [3].

The rosary pea has been used to treat a variety of conditions worldwide, due to its well-known medicinal properties. In West Africa, the roots were chewed to treat snake bites, whereas in Brazil, people used the water extract from dried leaves as a nerve tonic. In many countries, it was used both as an aphrodisiac and an abortive agent [4]. The list of historical uses for the rosary pea is excessively long and covers almost every condition known to humankind, including treatment for tumors, diarrhea, fractures, vomiting, gray hair, paralysis, tuberculosis, alopecia, and tetanus, to name a few [2, 4, 5, 6]. The plant's seeds, leaves, and roots have been dried, boiled in milk, chewed, powdered, macerated, taken with honey, crushed, extracted, and juiced [4]. While some of its medicinal uses have proved ineffective, the rosary pea is a medicinal plant with antibacterial, antidiarrheal, antifertility, antifungal, anti-inflammatory, and antitumor properties [4]. Luckily, the poison only lives inside the seeds, protected by a hard, thick coat that can’t be digested, so swallowing the seeds whole causes no ill effects. This isn’t to advocate for swallowing the seeds of the rosary pea, but if the situation suddenly arose, you would be alright (and maybe even impress your would-be poisoner!) Because the poison is not concentrated in the rest of the plant, historical use of the leaves and roots for their antibacterial properties would have been safe and beneficial. On the other hand, using the seeds for treatments would have been incredibly dangerous, as even small doses can cause death. Outside of its medicinal uses, it has also been used as a tea ingredient in China [5] and as a substitute for licorice in India and Indonesia, because the roots, stem, and leaves of the plant contain glycyrrhizin, the major component in licorice root [5, 6, 7].

Today, many different compounds isolated from the roots, leaves, and seeds of the rosary pea are being studied for their potential in treating cancer. Not all compounds are equally effective, however. While root and leaf extracts have shown positive results, they are notably worse at killing cancer cells compared to the seed extracts Abrin P2 and Abrus Agglutinin (AGG). AGG in particular has shown notable promise for decreasing tumor sizes and killing cancerous cells by inactivating their ribosomes, or protein factories, and creating an abundance of harmful molecules called reactive oxygen species. Although as of 2023, AGG has not made it to human trials, there have been numerous tests on mice that support its unique ability to selectively target tumor cells and leave the animal unharmed [8, 9, 10]; an incredible feat for such a deadly chemical!

Europe

Traveling west, one might come across the yew tree—more uncommonly known as Taxus baccata—which looks like an amalgamation of many smaller trees glued together. This British evergreen is recognized by its thick reddish-brown trunks, rounded canopy, and shallow root systems [11]. It has an ancient, haunting, yet protective presence, and has been deliberately planted next to churches across Britain and Ireland for hundreds of years. For example, in the west of Britain, Church Preen lies tucked away underneath a yew tree estimated to be over 1,000 years old. It is believed that some such trees were planted as early as the 5th century [12]. In Wales, churches were encircled with yew trees planted over centuries, indicating their lasting cultural significance. Its recurrent presence near churches is most likely because its large canopy protects graves and buildings in the churchyard from moisture, wind, and rot, and because early Christian missionaries venerated it as a sign of immortality, due to its long lifespan. When the yew tree “chooses” where to live, however, it is found on the steep limestone cliffs of Britain and the tops of mountains in Ireland [12]. It has been featured in many Irish folklore tales, dating back almost one thousand years, where it represented beauty, safety, immortality, magic, royalty, and religion [12].

The yew tree is associated with immortality not only because the tree itself is immortal, but also because animals who eat it become immortal too. Okay, maybe not, but the yew tree has indeed been used to treat various medical conditions and prolong life. The leaves, bark, and flowers are all toxic, but have been used in small doses to treat asthma, bronchitis, epilepsy, headaches, and heart disorders [13]. Part of the reason it has medicinal properties is that the yew tree produces low concentrations of a chemotherapeutic drug called Paclitaxel, which has antimitotic properties. The plant also possesses other beneficial chemicals, such as alkaloids, flavonoids, and essential oils which have antibacterial, anti-inflammatory, antifungal, and antioxidant properties [13]. The leaves, bark, and flowers have been taken as tea or juice, added to honey for coughs, and put in steam baths to relieve rheumatism [13, 14].

Interestingly, Paclitaxel is currently on the market as a chemotherapeutic agent against breast, ovarian, and lung cancer under the brand name Taxol. It functions by binding to microtubules and stabilizing them so cell division cannot occur [14]. Paclitaxel is not a miracle drug, however, and can cause adverse side effects, as well as chemoresistance in breast cancer patients, so it generally works better when paired with other chemotherapeutic drugs [15]. Still, the fact that the yew tree is regularly used in medicine today is an homage to the incredible ability of toxic plants.

Africa

For our next stop, we head south to Africa to find the castor bean plant—scientifically known as Ricinus communis. This plant is the culprit behind castor oil, and if that level of fame wasn’t enough, its beans also contain ricin, one of the most toxic compounds to ever exist. The plant can grow up to 10 meters tall and live for many years. The red flowers resemble starfish, and the toxic brown seeds sport a mottled pattern similar to that of a frog [16]. The castor bean, like the rosary pea, produces a ribosome-inactivating protein that kills cells by stopping their ability to make proteins. This deadly property makes ricin the perfect weapon for people looking to murder politicians in the United States (there have been three attempted assassinations of US politicians using ricin).

With its roots in Eastern Africa, the castor bean is mentioned in the Papyrus Ebers, an Egyptian medical script well over three thousand years old. It categorizes the bean as a remedy that could be used to treat constipation, fix a “diseased head,” increase the length of women’s hair, and cure abscesses. The remedies consisted of swallowing the berries with beer, rubbing the stalk or seed oil to the site of infection, or working the crushed berries in like shampoo. Castor oil was such an effective treatment for abscesses that the Papyrus Ebers even exclaimed, “Lo, the Evil will fly as though he had never suffered nothing!” when describing its effect [17]. Outside of the Papyrus Ebers, the castor bean has been used in rituals and sacrifices, and as an oral contraceptive, a nutritional supplement, and an emetic [16].

There are modern medical benefits to the castor bean plant, despite the high toxicity of the seeds. The processed, refined vegetable oil isolated from  the seeds has anti-inflammatory, antimicrobial, and antioxidant properties, and has shown antiproliferative effects on breast cancer cells [21]. Castor oil is also easy to access as it is produced in India, China, and Brazil, and over 7,000 tons of castor oil is consumed globally every year [18]. On the other hand, the seed toxin ricin is globally consumed nowhere but could be a promising chemical in cancer treatment. Now, I know what you are thinking: If ricin is so promising, then what is its effect on in-vitro CXCR4+ cancer cells and in-vivo acute myeloid leukemia? Well, when ricin was modified in a recent experiment, it selectively and effectively targeted the cancer cells that expressed the CXCR4 cancer receptor. Since the selectivity of a drug is important to reduce toxic side effects, this study was incredibly encouraging [19]. However, ricin had to be modified so it would not attack every cell it came in contact with. Additionally, ricin has a bad habit of being degraded by lysosomes in our cells, so it has had to be further modified in order to exist long enough in our bodies to have any real benefit [20]. Therefore, while there is potential for ricin in cancer treatment, currently, it is too toxic and inconsistent to be used outside of laboratory experiments. Castor oil, on the other hand, might be a more viable alternative due to its antimicrobial and antiproliferative effects on cancer cells, and because castor oil is inherently less deadly than ricin [21].

Australia

Hopping on a plane to Australia, let’s take a look at the most famous foxglove plant, also known as Digitalis purpurea. The foxglove plant is invasive to Australia, but because it’s the most interesting toxic plant that exists in Australia, I’m including it in this section. The name Digitalis does, in fact, mean digits, because (it’s hypothesized) the flowers can be worn on the fingers like a cap or thimble. This is also the (hypothesized) reason behind the “glove” part of the common name. The “fox” part, of course, refers to the fact that foxes famously love to wear gloves...or something [22]. Every part of this purple, flowering plant is toxic and can cause cardiac glycoside poisoning or even death when eaten. Even simply breathing its pollen or touching its leaves can cause irritation and allergic reactions.

It may explain how Digitalis purpurea does not have a varied history of medicinal uses. It has mostly been used to treat heart conditions, as it causes the heart muscles to contract forcefully to quickly combat low blood pressure. Foxglove has also been recommended as an ointment for wounds, as a sedative, to induce vomiting, and as a treatment for dropsy and tuberculosis. It’s worth noting that, as heart failure symptoms can look like tuberculosis, doctors in the 16th to 18th centuries tended to confuse the two, and believed they had cured tuberculosis with foxglove when in reality they had only treated a heart condition. It’s worth noting because foxglove plants cannot do anything for tuberculosis [23].

The molecule in foxglove responsible for increasing blood pressure is called digoxin and is currently in use today. It’s still dangerous, which can make finding the right dose difficult, but it’s being administered as a second-line treatment for atrial arrhythmia and heart failure [24]. Digoxin has been shown to reduce hospitalizations of people with these heart conditions but does not increase life expectancy, which is why it’s primarily used on the sickest patients after other treatments have failed [25].

North America

After ten days of hang-gliding our way over the Pacific Ocean, we’ll see the beautiful California coast and…what’s that?! What’s that innocent-looking flower growing in the marshlands? Why, it’s the water hemlock, of course! It also goes by the name poison hemlock, Cicuta maculata. This plant can grow up to eight feet tall and has small white flowers clustered at the ends of its branches. Like most toxic plants, the poison is mostly located in the seeds, which can cause grand mal seizures and death mere hours after being consumed. While toxic to humans, water hemlock poisoning is more commonly associated with livestock. The seeds and roots spread easily, and smell and taste deceptively “sweetish, aromatic, and warm,” which is unfortunate for farmers and their animals [26, 27].

Like the foxglove plant, water hemlock is invasive to North America, but has been around long enough to appear in records as a medicinal plant. For example, in the early 1800s, Cherokee Native Americans in the southeast United States may have used it as a contraceptive [28]. However, reports similar to these tend to be over two hundred years old, and are mentioned only briefly. So, although there may have been attempts to use water hemlock for medicinal purposes, it was not widespread.

The major toxin in water hemlock is cicutoxin, which causes convulsions and respiratory paralysis. In the past, people have toyed around with the idea of using cicutoxin to treat breast cancer and leukemia, but nothing concrete has come of it [29]. This is probably because cicutoxin is simply is too toxic and would cause more harm than good. Not only would it put the patient at an extremely high risk of death, but the long-term effects of eating just one rootstalk of the water hemlock include mental impairment and anxiety [30]. Therefore, unless a modified version of cicutoxin can be made for medicinal purposes, it will continue to be just an idea.

South America

Moseying down South to the Amazon rainforest, we might get to feast our eyes on the curare vine or Chondrodendron tomentosum. This tropical vine with heart-shaped leaves makes its home glued to trees, as it climbs up and weaves through the canopy. It can be recognized by its smooth, glossy leaves with fuzzy white undersides, giving it the nickname “velvet leaf.” Unlike most poisonous plants, curare is harmless when eaten and is only deadly when injected [31].

South Americans in and around the Amazon rainforest utilized this unique property of curare to hunt animals with poisoned arrows. It’s a useful poison because it causes paralysis, convulsions, tremors, low blood pressure, sensory issues, and difficulty breathing. Once shot, hunters could easily collect birds high in treetops before they flew away. Medicinally, curare was brought to France in the 1800s and was used experimentally to cure tetanus, epilepsy, chorea, and hydrophobia. Because curare causes paralysis, it was primarily used as a muscle relaxant for people with chronic muscle cramps and spasms, but the effects were short-lasting and ineffective [32].

In early 1939, researchers at Bristol Myers Squibb purified curare into a drug called Intocostrin, which could be used as a light anesthetic to avoid the unpleasant side effects of stronger anesthesia [33]. This was considered quite a breakthrough at the time. Today, curare is no longer widely used for anesthesia, because although it causes paralysis, it doesn’t stop pain [34], and there are much safer drug options available. However, it can still be used today to reduce patients’ shivering [35].

Antarctica

The last plant on our journey is unique, because it’s not medicinal and not a plant at all. This is because Antarctica, for some reason, has very few plants. This fungus goes by the gruesome name “funeral bell” or Galerina marginata and colonized Antarctica between two million and ten thousand years ago [36]. The funeral bell consists of a smooth, orange-brown cap and grows only one to three inches off the ground on the Antarctic coasts. The main toxins in the mushroom are amatoxins, which are heat tolerant, and therefore not destroyed by cooking, a unique property compared to most  other  toxins.  Amatoxins inhibit protein synthesis and cause vomiting, diarrhea, and liver damage within a few days [37]. Because the funeral bell also grows in North America, amateur foragers have unfortunately mistaken it for an edible or hallucinogenic mushroom and died [37]. In the poetic words of Chatgpt, “In the desolate expanse of Antarctica, where life struggles to endure, the funeral bell stands as a chilling testament to the dangers lurking in even the most remote corners of our world”. How ominous!

Conclusion

Toxic plants have been intertwined with human health since their discovery, and have had both life-saving and deadly consequences. They’ve been used traditionally in folk medicine, as drugs in hospitals, and have held religious symbolism. While some are too dangerous to be regularly used medicinally, others can be. However, the line between deadly poison and life-saving medication is an ancient, fraying tightrope. Aside from the interesting botanical purposes, it’s important to be safe when considering these plants for healthcare. The sheer variety in toxicity, history, and uses of toxic plants is immense and would take ten times as many words to describe. So, I hope this brief introduction has sparked your curiosity for the power of nature, and encouraged admiration for toxic plants; because, while deadly, they have the potential to save lives.

About the Author: Mia Karlsson

Mia Karlsson is a class of 2024 undergraduate student majoring in Molecular and Medical Microbiology. She chose microbiology to dive deep into the details of disease, viruses, and the immune system and explore how everything we can’t see works. She chose to write this paper because of the fascinating relationship people have had with toxic plants throughout time. In her spare time, she makes surreal, eccentric art and helps run an art fundraising club on campus called Cherry Tea Collective that raises money for a different charity each year. She hopes people come away from reading the paper with a broader understanding of the unique capabilities of poisonous plants.

Author's Note

This piece was inspired by a podcast I listened to called This Podcast Will Kill You where every episode outlines the biology, history, and current news of famous diseases. I always found the history section to be the most interesting because people have interacted with diseases in quite dramatic and fascinating ways. Some diseases, like gout, have been seen as a symbol of wealth and prosperity while other diseases were seen as consequences of bad air or of living an impure lifestyle. As I was writing another paper on the more molecular effects of the toxic plant, the rosary pea, I felt like I was missing part of the story: The history. This paper on toxic plants and diseases fills in this gap and gives insight into our current relationship with these plants. It also shines a light on the complicated and ancient relationship that we have with a variety of toxic plants. I hope this piece entertains readers and inspires gratitude for the fascinating, toxic plants occupying our planet today.

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