Cilantro leaf harbors a potent potassium channel–activating anticonvulsant. Issue 10 (16th July 2019)

• Record Type: Journal Article
• Authors: Manville, Rían W.; Abbott, Geoffrey W.
• Is Part Of: FASEB journal. Volume 33:Issue 10(2019)
• Page Start: 11349
• Page End: 11363
• Publication Date: 2019-07-16
• Subjects: herbal medicine -- epilepsy -- KCNQ1 -- KCNQ2 -- KCNQ3; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.201900485R
• Languages: English
• ISSNs: 0892-6638

Abstract

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. FASEB J. 33, 11349–11363 (2019). www.fasebj.org