Pickled capers are commonly used as a condiment added to lox sandwiches, pasta, and salad dressings, and now most recently are tied to activating proteins for brain and heart health. Researchers from the University of California, Irvine (UCI), School of Medicine have discovered that the compound quercetin, commonly consumed when eating capers, regulates proteins required for bodily processes such as thought, muscular contraction, thyroid, pancreas, and gastrointestinal function.

Their study, “The ubiquitous flavonoid quercetin is an atypical KCNQ potassium channel activator,” is published in Communications Biology and led by Geoffrey Abbott, PhD, a professor of physiology & biophysics at UCI School of Medicine and senior associate dean, academic personnel, School of Medicine.

Quercetin, a flavonoid found in fruits and vegetables, has previously been linked to improving mental/physical performance and reduce infection risk. The researchers found that quercetin regulates potassium ion channels in the KCNQ gene family, which are highly influential in human health and their dysfunction is linked to several common human diseases, including diabetes, cardiac arrhythmia, and epilepsy.

“Recent studies uncovered the ubiquitous and influential KCNQ family of voltage-gated potassium (Kv) channels as a therapeutic target for several medicinal plant compounds. Capers—immature flower buds of Capparis spinosa—have been consumed for food and medicinal purposes for millennia. Here, we show that caper extract hyperpolarizes cells expressing KCNQ1 or KCNQ2/3 Kv channels. Capers are the richest known natural source of quercetin, the most consumed dietary flavonoid,” explained the researchers.

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

“We discovered that 1% extract of capers, which are the immature flower buds of the caper bush (Capparis spinosa), KCNQ-dependently hyperpolarizes cells. 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.”

Abbott noted that increasing the activity of KCNQ channels in different parts of the body is potentially highly beneficial. KCNQ channels consist of four subunits that encircle a central pore, which enables the selective passage of potassium ions across the cell membrane. Neural KCNQ channels are drug targets for the treatments of epilepsy and a variety of neurological disorders, including chronic and neuropathic pain, deafness, and mental illness.

“Quercetin potentiated KCNQ1/KCNE1, KCNQ2/3, and KCNQ4 currents but, unusually, not KCNQ5. Strikingly, quercetin augmented both activation and inactivation of KCNQ1, via a unique KCNQ activation mechanism involving sites atop the voltage sensor and in the pore. The findings uncover a novel potential molecular basis for therapeutic effects of quercetin-rich foods and a new chemical space for atypical modes of KCNQ channel modulation.”

“Synthetic drugs that do this have been used to treat epilepsy and show promise in preventing abnormal heart rhythms.”

Capers have traditionally been used as folk medicine for thousands of years and have been studied for their potential as anticancer, antidiabetic, and anti-inflammatory properties, and their possible circulatory and gastrointestinal benefits.

Their findings may lead to future therapies for the treatment of epilepsy and abnormal heart rhythms.

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