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FASEB J. 2019 Oct;33(10):11349-11363. doi: 10.1096/fj.201900485R. Epub 2019 Jul 16.

Cilantro leaf harbors a potent potassium channel-activating anticonvulsant.

Author information

1
Bioelectricity Laboratory, Department of Physiology and Biophysics, School of Medicine, University of California-Irvine, Irvine, California, USA.

Abstract

Herbs have a long history of use as folk medicine anticonvulsants, yet the underlying mechanisms often remain unknown. Neuronal voltage-gated potassium channel subfamily Q (KCNQ) dysfunction can cause severe epileptic encephalopathies that are resistant to modern anticonvulsants. Here we report that cilantro (Coriandrum sativum), a widely used culinary herb that also exhibits antiepileptic and other therapeutic activities, is a highly potent KCNQ channel activator. Screening of cilantro leaf metabolites revealed that one, the long-chain fatty aldehyde (E)-2-dodecenal, activates multiple KCNQs, including the predominant neuronal isoform, KCNQ2/KCNQ3 [half maximal effective concentration (EC50), 60 ± 20 nM], and the predominant cardiac isoform, KCNQ1 in complexes with the type I transmembrane ancillary subunit (KCNE1) (EC50, 260 ± 100 nM). (E)-2-dodecenal also recapitulated the anticonvulsant action of cilantro, delaying pentylene tetrazole-induced seizures. In silico docking and mutagenesis studies identified the (E)-2-dodecenal binding site, juxtaposed between residues on the KCNQ S5 transmembrane segment and S4-5 linker. The results provide a molecular basis for the therapeutic actions of cilantro and indicate that this ubiquitous culinary herb is surprisingly influential upon clinically important KCNQ channels.-Manville, R. W., Abbott, G. W. Cilantro leaf harbors a potent potassium channel-activating anticonvulsant.

KEYWORDS:

KCNQ1; KCNQ2; KCNQ3; epilepsy; herbal medicine

PMID:
31311306
PMCID:
PMC6766653
[Available on 2020-07-16]
DOI:
10.1096/fj.201900485R

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