Cilantro leaf harbors a potent potassium channel-activating anticonvulsant

Rian Manville, Geoffrey Abbott

Research output: Contribution to journalArticleResearchpeer-review

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.
Original languageEnglish
Pages (from-to)11349-11363
Number of pages15
JournalThe FASEB Journal
Volume33
Issue number10
DOIs
Publication statusPublished - 1 Oct 2019

Fingerprint

Coriandrum
Potassium Channels
Anticonvulsants
Protein Isoforms
Voltage-Gated Potassium Channels
Brain Diseases
Traditional Medicine
Mutagenesis
Computer Simulation
Seizures
Binding Sites
Therapeutics

Keywords

  • KCNQ1
  • KCNQ2
  • KCNQ3
  • epilepsy
  • herbal medicine

Cite this

Manville, Rian ; Abbott, Geoffrey. / Cilantro leaf harbors a potent potassium channel-activating anticonvulsant. In: The FASEB Journal. 2019 ; Vol. 33, No. 10. pp. 11349-11363.
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Cilantro leaf harbors a potent potassium channel-activating anticonvulsant. / Manville, Rian; Abbott, Geoffrey.

In: The FASEB Journal, Vol. 33, No. 10, 01.10.2019, p. 11349-11363.

Research output: Contribution to journalArticleResearchpeer-review

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