Cilantro leaf harbors a potent potassium channel-activating anticonvulsant

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

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Anticonvulsants / pharmacology*
  • Binding Sites / drug effects
  • Coriandrum / chemistry*
  • KCNQ Potassium Channels / metabolism*
  • Mutagenesis / drug effects
  • Neurons / drug effects
  • Neurons / metabolism
  • Plant Leaves / chemistry*
  • Xenopus laevis / metabolism

Substances

  • Anticonvulsants
  • KCNQ Potassium Channels