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Discovery: Caper Berry’s Quercetin Activates KCNQ Potassium Channel

For many years now, Amanda Archibald, RD, culinary genomics expert and author of The Genomic Kitchen, puts the caper berries at the top of her superfood list because of high levels of quercetin. It is well known that quercetin has been shown to decrease decrease the transcriptional activity of the nuclear factor of transcription kappa B (NF-kB), which reduces risk of chronic systemic inflammation. New research shows that quercetin found specifically in pickled capers activates proteins required for normal human brain and heart activity, and may even lead to future therapies for the treatment of epilepsy and abnormal heart rhythms.

capers and quercitin

Researchers from the University of California, Irvine School of Medicine have discovered that quercetin, commonly consumed when eating capers, can directly regulate proteins required for bodily processes such as the heartbeat, thought, muscular contraction, and normal functioning of the thyroid, pancreas and gastrointestinal tract.

Published in Communications Biology, the discovery was made by the laboratory of Geoffrey Abbott, PhD, a professor in the Department of Physiology and Biophysics at the University of California, Irvine School of Medicine. Kaitlyn Redford, a graduate student in the Abbott Lab, was first author of the study titled, “The ubiquitous flavonoid quercetin is an atypical KCNQ potassium channel activator.”

The Abbott Lab found that quercetin, a plant-derived bioflavonoid, modulates potassium ion channels in the KCNQ gene family. These channels are highly influential in human health and their dysfunction is linked to several common human diseases, including diabetes, cardiac arrhythmia, and epilepsy.

The study revealed that quercetin modulates the KCNQ channels by directly regulating how they sense electrical activity in the cell, suggesting a previously unexpected mechanism for the therapeutic properties of capers. The mechanism may extend to other quercetin-rich foods in our diet, and quercetin-based nutritional supplements.

“Now that we understand how quercetin controls KCNQ channels,” said Abbott, “future medicinal chemistry studies can be pursued to create and optimize quercetin-related small molecules for potential use as therapeutic drugs.”

The Abbott Lab screened plant extracts for the ability to alter activity of KCNQ channels and found that one percent extract of pickled capers activated channels important for normal human brain and heart activity. Further studies revealed the molecular mechanism – quercetin from the caper extract binds to a region of the KCNQ channel required for responding to electrical activity, and in doing so, tricks the channel into opening when it would normally be closed.

The researchers discovered that 1% extract of capers, which are the immature flower buds of the caper bush (Capparis spinosa), KCNQ-dependently hyperpolarizes cells. The molecular basis for this effect involves KCNQ activation by a ubiquitous flavonoid, quercetin, via an atypical mechanism and binding site and discuss implications for medicinal and food use of quercetin and the foods that contain it.

“Increasing the activity of KCNQ channels in different parts of the body is potentially highly beneficial,” said Abbott. “Synthetic drugs that do this have been used to treat epilepsy and show promise in preventing abnormal heart rhythms.”

The researchers note that pickling promotes conversion of rutin (flavonoid compound also called rutoside in capers) to quercetin, the ingredient that they found to be an efficacious KCNQ channel activator. This makes pickled capers as the richest known “natural” source of quercetin, with a maximum reported concentration of 520 mg/100 g for canned capers, compared to a maximum of 323 mg/100 g quercetin for raw capers. Though, mean reported quercetin values are more similar between the two forms, suggesting variations in the pickling or canning process could affect content. They also point out that quercetin was much less potent than other plant-derived KCNQ channel activators, such as E-2-dodecenal from other plants such as cilantro (Coriandrum sativum), a plant that also contains quercetin.

Archaeological evidence for human caper consumption dates back as far as 10,000 years, according to archaeological findings from Mesolithic soil deposits in Syria and late Stone Age cave dwellings in the Greece and Israel. Capers have traditional been used as folk medicine for hundreds if not thousands of years and are in current use or study for their potential as anti-cancer, anti-diabetic and anti-inflammatory properties, and their possible circulatory and gastrointestinal benefits.

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Source: Redford, K.E., Abbott, G.W. The ubiquitous flavonoid quercetin is an atypical KCNQ potassium channel activator. Commun Biol. 2020; 3, 356.


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