While catnip is a common herb that is often used in cat toys and treats—due to its euphoric and hallucinogenic effects on our domesticated felines—it has also long been known for its powerful repellent action on insects, and mosquitoes in particular. An international team of scientists at Northwestern University and at Lund University has now identified a receptor that is responsible for the aversive effect that catnip and its nepetalactone ingredient, has on these insects. The studies, reported in Current Biology, showed that catnip and nepetalactone activate the insect TRPA1 receptor to trigger this aversion, but have no effect on the human TRPA1 receptor.
The team says that as well as supporting the use of catnip compounds as a natural mosquito repellent, their findings could help develop even more effective, and selective compounds. In the meantime, they suggest, the findings may just encourage people to gather catnip from their gardens at the start of the next mosquito season, rather than rely on synthetic chemical mosquito repellents.
“We discovered that catnip and its active ingredient nepetalactone activate the irritant receptor TRPA1, an ancient pain receptor found in animals as diverse as flatworms, fruit flies and humans,” said Marco Gallio, PhD, an associate professor of neurobiology in the Weinberg College of Arts and Sciences. “We now think catnip is so aversive to so many insect species because it activates this widespread irritant receptor. What is particularly interesting is that, unlike wasabi or garlic compounds that also activate these receptors in humans, catnip appears to selectively activate the insect receptor. This explains why humans are indifferent to it, and provides a serious advantage for its use as a repellent.”
Gallio and colleagues describe their studies in a paper titled, “The irritant receptor TRPA1 mediates the mosquito repellent effect of catnip,” in which they concluded, “Our results support the use of catnip and nepetalactone as insect-selective irritants and suggest that, despite TRPA1’s broad conservation, insect TRPA1 can be targeted for the development of safe repellents.”
Traditional approaches to mosquito control have commonly involved the use of insecticides, but these chemicals can also kill off other insect species as collateral damage. Modern formulations of insect repellents such as N,N-diethyl-3-methylbenzamide (DEET), target mosquito odor and taste receptors, rendering the insect incapable of recognizing the chemical cues that signal a human prey.
Catnip (Nepeta cataria)—a member of the mint family—is a common garden herb that is well known for its heady effects on domestic cats, but also has a long history of use both in herbal medicine, and as a powerful insect repellent. The very different effects of catnip on cats and on insects have been attributed to a class of structurally closely related iridoids, and in particular to two isomers of nepetalactone, which typically make up to 80% of catnip extracts.
While recent research suggests that catnip compounds may be at least as effective at warding off mosquitos as synthetic insect repellents such as DEET, just how catnip triggers aversion in insects hasn’t been understood. And why cats are so attracted to catnip is an entirely different story and one that is also not entirely understood. Research indicates that this may be due to an unusual interaction between one of catnip’s active ingredients and a molecular component present in the reward system of the cat brain.
“Although likely in use for millennia to ward off troublesome invertebrates, catnip has only more recently been systematically explored as a potential insect repellant, heralded as a natural alternative to the synthetic chemicals dominating the market,” the authors noted. “The catnip iridoids have been suggested to activate the cat μ-opioid pathway, thereby triggering the brain reward systems; in contrast, why insects are strongly repelled by catnip remains unknown.”
“Catnip and its active ingredient, nepetalactone, have been used for millennia to ward off insect pests, at least since the time of Pliny the Elder,” added Marcus C. Stensmyr, associate professor at Lund University and co-corresponding author. “But why Catnip is so potent on such a broad range of insect species has remained unknown.”
The Gallio lab at Northwestern studies the sensory systems of the fruit fly Drosophila, including the mechanisms that control responses to external temperature and pain. The Stensmyr lab at Lund mainly focuses on mosquitoes and other insect vectors of human disease. In previous work, the Gallio Lab and others had demonstrated that humans, insects and many other animal species possess a version of the transient receptor potential ankyrin 1 (TRPA1) ion channel, a protein best known as the “wasabi receptor” that senses environmental irritants like pain and itch.
For their newly reported research, the collaborators studied insect species to better understand how catnip and its active ingredient working to repel a broad range of insects, while having no irritant effect on humans. They carried out a range of tests, including offering mosquitoes a blood meal in a dish covered with a nylon sock doused in catnip, experiments involving a wind tunnel, and tests in which volunteers place their hand in a cage with live mosquitos, with or without the protection of a catnip oil rub. They also carried out experiments using Drosophila melanogaster fruit flies and Aedes aegypti mosquitoes that carried different variants of TRPA1, including the human version the gene TRPA1.
“In vitro, both catnip extract and its active ingredient nepetalactone can directly activate fly and mosquito TRPA1,” the scientists wrote. But they also found that even within the same insect species, TRPA1s seem to have diversified into “catnip-sensitive and catnip-insensitive variants.” The experimental results suggested that some, but not all of the fly and mosquito TRPA1 variants act as catnip targets. Interestingly, their studies also demonstrated that TRPA1-deficient mosquitoes and flies showed no aversion to catnip. “In vivo, D. melanogaster and Ae. aegypti TRPA1 mutants are no longer repelled by catnip and nepetalactone,” they added.
“Our work demonstrates how catnip iridoids function as powerful natural insect repellents because they activate the insect TRPA1, an ancient receptor for noxious and irritant chemicals—explaining at once catnip’s powerful aversive effect and its road spectrum of insect targets,” the team concluded.
Gallio believes that the newly discovered mechanism also provides proof of concept for the development of next-generation mosquito repellents that exploit the same logic— selectively targeting the mosquito irritant receptor. “This is an entry point to study how this molecule works on the receptor,” he said. “Once we understand its chemistry and how it interacts with the receptor, we could design even more powerful and selectively targeted molecules.”
The authors stated, “… the fact that catnip activates a number of insect TRPA1 variants, combined with the observation that catnip appears ineffective toward vertebrate TRPA1 (and human in particular), supports the notion that this property may be further exploited to design class- or even group-selective insect repellents.”
“Mosquitos, in particular those that act as vector for disease, are becoming a bigger problem as climate change creates attractive conditions for them farther north and south of the equator,” Stensmyr noted. “Plant-derived compounds represent a new emerging approach to developing insect repellents, as plants have long known how to protect themselves from insect pests.”
Gallio further pointed out that plant-derived repellents are often available at a much lower cost and are easier to obtain. Catnip’s accessibility could have major implications in developing countries where mosquito-borne diseases are a huge problem.