Cilantro leaf harbors a potent potassium channel-activating anticonvulsant.

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.

• Authors: Rían W Manville, Geoffrey W Abbott
• Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J) Vol. 33 Issue 10 Pg. 11349-11363 (10 2019) ISSN: 1530-6860 [Electronic] United States
• PMID: 31311306 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Anticonvulsants
• KCNQ Potassium Channels

Topics

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