23 Jul Why Cilantro Extract May One Day Be Used to Treat Epilepsy
MedicalResearch.com Interview with:
Geoffrey W. Abbott PhD
Department of Physiology and Biophysics,
Bioelectricity Laboratory, School of Medicine,
University of California
MedicalResearch.com: What is the background for this study?
Response: The main focus of my laboratory is the study of potassium ion channels – proteins that coordinate electrical activity in all organisms. When human potassium channels do not function properly, it can result in pathologically discordant electrical activity, and diseases such as cardiac arrhythmia, myotonia, and epilepsy – depending on whether the affected potassium channel is in the heart, skeletal muscle or brain, for example. T
here are existing drugs that directly regulate ion channels for therapeutic benefits, including one – retigabine – that opens neuronal potassium channels in the KCNQ family, to treat epilepsy. Retigabine causes side effects including turning the skin blue, and was withdrawn from clinical use in 2017. Retigabine may make a comeback because a form of epilepsy was recently discovered, arising from mutations in the KCNQ2 gene, that is associated with severe developmental delay and seizures. In my lab, we are interested in discovering new therapeutic agents that might more safely fix dysfunction in KCNQ2 and other potassium channels.
We turned to plants as a possible source of compounds. We are interested both in explaining the underlying mechanism of traditional botanical medicines, and also discovering unanticipated therapeutic chemicals synthesized naturally by plants.
Response: The main findings of our latest study are that cilantro extract, which has long been used as a folk medicine to treat epilepsy, among other disorders, can activate potassium channels in the KCNQ family. In addition, we isolated the specific compound from cilantro that shows channel-opening activity: the fatty aldehyde, E-2-dodecenal. Finally, we showed that E-2-dodecenal delays chemically-induced seizures in mice to a similar extent to that shown by other groups studying whole cilantro extract, and that the effect was blocked when we added another compound that inhibits neuronal KCNQ channels. E-2-dodecenal activation of KCNQ channels in the brain is therefore an important molecular mechanism underlying the anticonvulsant effects of cilantro.
MedicalResearch.com: Why do so many people dislike the taste of cilantro?
Response: Some people do not like consuming cilantro because it tastes soapy to them. This is in fact down to aldehydes, similar to E-2-dodecenal, which we found to activate KCNQ channels. However, the effect of aldehydes on taste is thought to be transmitted by aldehydes binding to olfactory receptors, another type of protein unrelated to KCNQ channels. Some people carry genetic sequence variants in specific olfactory receptors that make cilantro taste soapy to them, while the majority of people (including myself) do not carry these variants, and they instead enjoy cilantro.
MedicalResearch.com: What should readers take away from your report?
Response: There is much misinformation available regarding herbal remedies, and unfortunately this can lead to general mistrust of this important area of medicine. Our latest research and also similar research by other labs in this field show that it is possible to identify quantitative therapeutic effects and underlying molecular mechanisms for some folk remedies. Although many plant medicines used on the basis of anecdotal evidence may indeed be ineffective or even dangerous in some cases, this should not hide the fact that many folk medicines are both safe and effective. Before and since the advent of modern western medicine, folk medicines derived from plants have been used in many cases highly effectively across the globe. In some cultures this continues vigorously to the present day, with Asian countries including China and Korea being obvious examples.
Native Americans also have a rich history of medicinal plant usage, and my lab is currently studying these traditions as well. Culantro, also known as chadon beni, is related to cilantro and also contains high levels of E-2-dodecenal, and has been used medicinally across Central America and the Caribbean. It is essential that we learn from cultures older than our own, and one way to do this is to apply modern approaches to explore folk medicines. It is also important to remember that many medicinally useful plants are endangered because of habitat destruction, climate change, and over-collecting. By learning more about the cultural, medicinal and possible commercial significance of these plants, we can help to protect them or even identify the active components so they can be synthesized rather than extracted at the expense of the plant and its habitat.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: Aside from testing the efficacy and discovering the mechanisms behind folk medicines, we might in the future also identify compounds that can either become medicines themselves, or can be the lead compounds for further medicinal chemistry optimization to improve potency, efficacy, pharmacokinetic profile and/or safety. E-2-dodecenal, for instance, is orders of magnitude more potent that retigabine but is not as efficacious, and we do not yet know the safety profile for E-2-dodecenal (although we know that cilantro is tolerated by most people).
It is interesting to note that E-2-dodecenal is widely used as a food flavoring and also as a scent in many soaps, shampoos, cosmetics and household cleaning products. This suggests that millions of people are exposed to potentially significant concentrations of E-2-dodecenal on a regular basis. It would be interesting to discover what, if any, are the public health effects (positive or negative).
Finally, KCNQ channels are not just expressed in the brain. There are five genes in the family, and the various subtypes are expressed in the heart, gastrointestinal tract, pancreas, vasculature, lungs, pituitary gland, thyroid, etc. Our study also demonstrated that E-2-dodecenal can open the KCNQ subtypes present outside the brain, with possibly therapeutic actions on KCNQ1 channels in the heart, for example. We believe that the widespread expression of KCNQ channels, combined with their sensitivity to a variety of small molecules, could make them targets for compounds in folk medicines that have been used historically for a wide range of disorders. My lab is currently intensively studying this possibility.
MedicalResearch.com: Is there anything else you would like to add? Any disclosures?
Response: One potential area for therapeutic possibilities is to combine herbal medicines and/or modern medicines to improve efficacy or reduce the concentrations required to achieve therapeutic activity, to improve safety. My lab, with the help of University of California, Irvine, recently submitted a patent application in which we describe that by combining different herbal and modern compounds to leverage the heteromeric composition of the most common neuronal KCNQ channel (KCNQ2-KCNQ3 complexes), we can synergistically activate the channels and reduce the dose required for activity.
Research in this area in my lab has been financially supported by funding from the US National Institutes of Health.
Cilantro leaf harbors a potent potassium channel–activating anticonvulsant
Rían W. ManvilleandGeoffrey W. Abbott FASEB 16 Jul 2019 https://doi.org/10.1096/fj.201900485R
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