Following a functional screen of extracts from US plants researchers found that plants with a long history of use by Native Americans as topical analgesics were often also used as gastrointestinal aids.
The study, published today in Frontiers in Physiology, found forest plants that activated the KCNQ2/3 potassium channel, a protein that passes electrical impulses in the brain and other tissues, showed a long history of use by Native Americans as topical analgesics, to treat conditions such as insect bites, stings, sores and burns. Less intuitively, the same plants that activated KCNQ2/3 and were used as traditional painkillers were often also used as gastrointestinal aids, especially for preventing diarrhoea.
“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,” said UCI School of Medicine professor Geoffrey Abbott, PhD.
KCNQ2/3 is present in nerve cells that sense pain, and activating it would relieve pain by reducing pain signal transmission. The breakthrough \came when the team discovered that the same plant extracts that activate KCNQ2/3 have an opposite effect on the related intestinal potassium channel, KCNQ1-KCNE3. Previous studies on modern medicines showed that KCNQ1-KCNE3 inhibitors can prevent diarrhoea.
The Abbott Lab is currently screening native US plants, having shown already that quercetin and tannic and gallic acids explained many of the beneficial effects of the plants. The team also identified binding sites on the channel proteins that produce the effects.
Knowing that these compounds activate versus inhibit closely related human ion channel proteins, drug specificity and safety can be improved and therefore safety. More specifically, the plant compounds can be further optimised with the goal of treating pain and secretory diarrhoea.
“I personally am very excited about the paper; it was my lab’s first published collaboration with the National Park Service, and it shines a light on the incredible ingenuity and medicinal wisdom of Californian Native American tribes,” said Prof Abbott.
New analgesics are being sought to fight the opioid crisis. In addition, according to the CDC, diarrhoeal diseases account for 1 in 9 child deaths worldwide; incredibly, diarrhoea kills over 2000 children every day worldwide – more than AIDS, malaria and measles combined.
