Researchers at the University of California, Irvine (UCI) have identified a molecule in extracts from plants with a long history of use by Native Americans as topical analgesics also doubles as a gastrointestinal aid. The study “shines a light on the incredible ingenuity and medicinal wisdom of Californian Native American tribes,” said Geoffrey Abbott, lead author and a professor in the Department of Physiology and Biophysics at the UCI School of Medicine.

Stopping both pain and diarrhea

Before the advent of modern pharmacology, humans have had to rely on nature for ailments. Specifically, they would look for plants that could heal wounds, cure some diseases, and ease troubled minds. The oldest evidence of medicinal plants dates from 60,000 years ago, the age of a burial site of a Neanderthal man who had been buried alongside eight species of plants, some of which have medicinal properties. Even in today’s age of synthetic drugs, about 40% of the most common drugs found in a pharmacist’s counter are derived from plants that people have used for centuries.

Native Americans are one of the cultures renowned for their medicinal plant knowledge. According to one myth, the earliest use of medicinal plants among the Native American tribes started after they watched animals eat certain plants when they were sick. Some of their favorite medicinal herbs include red clover (treats inflammation and respiratory conditions), black gum bark (relieves chest pains), hummingbird blossom (treats mouth and throat conditions), wild ginger (treats earache and ear infections), slippery elm (treats skin conditions, sore throats, and even spider bites), and lavender (a remedy for insomnia, anxiety, and depression).

Such plants were so important and cherished that medicine men would take steps to protect them from over-harvesting. For instance, they would only pick every third plant they found.

In a new study, researchers analyzed the molecular makeup of an extract of plants collected in Muir Woods National Monument, a region in California known for its coastal redwood forests. These plants have a long history of use in Native American traditional medicine as topical analgesics for insect bites, stings, sores, and burns. Overall, the researchers analyzed 40 plants from Californian coastal redwood forest plants.

The scientists found that the plants activated the KCNQ2/3 potassium channel, which passes electrical impulses between the brain and other tissues. KCNQ2/3 is present in nerve cells that sense pain, and its activation soothes pain by lowering the strength of the pain signal.  The team found that extracts from 9 of the 40 plant species increased KCNQ2/3 current significantly — and all 9 were used as traditional medicine by Native Americans.

But the same plant extracts that activate KCNQ2/3 have the opposite effect on KCNQ1-KCNE3, an intestinal potassium channel. The inhibiting effects on the ion protein channel KCNQ1-KCNE3 can prevent diarrhea, the researchers found. Diarrhea is no joke — it is responsible for 1 in 9 child deaths worldwide, more than AIDS, malaria, and measles combined. The fact that we could have a drug that doubles as both a painkiller and diarrhea inhibitor may prove mighty useful in the future.

“Done in collaboration with the US National Parks Service, this study illustrates how much there is still to learn from the medicinal practices of Native Americans, and how, by applying molecular mechanistic approaches we can highlight their ingenuity, provide molecular rationalizations for their specific uses of plants, and potentially uncover new medicines from plants,” Abbott said.

Inspired by these findings, Abbott and colleagues are now undertaking a broader screen of plants native to North America, on the lookout for new molecules that could be used to treat a range of conditions. They’ve already found that quercetin, tannic, and gallic acids present in several of the plants studied are responsible for the medicinal properties of these plants.

Of particular interest are potentially novel non-opioid painkillers. According to 2018 data, up to 30% of patients prescribed opioids for chronic pain misuse them and 10% develop an opioid use disorder.

The findings appeared in the journal Frontiers in Physiology.