Preprint / Version 1

KCNQ5 activation is a unifying molecular mechanism shared by genetically and culturally diverse botanical hypotensive folk medicines

Authors

  • Rían Manville aBioelectricity Laboratory, Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, CA 92697;
  • Jennifer Horst bVascular Biology Group, Department of Biomedical Science, University of Copenhagen, 2200 Copenhagen, Denmark;
  • Kaitlyn Redford aBioelectricity Laboratory, Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, CA 92697;
  • Benjamin Katz cDepartment of Chemistry, University of California, Irvine, CA 92697
  • Thomas Jepps bVascular Biology Group, Department of Biomedical Science, University of Copenhagen, 2200 Copenhagen, Denmark;
  • Geoffrey Abbott aBioelectricity Laboratory, Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, CA 92697;

Keywords:

potassium channel, hypertension, herbal medicine

Abstract

Significance Botanical folk medicines have been used by diverse human populations and cultures for several millennia. Many are still in use today, but the underlying molecular mechanisms often remain elusive. Here we report the discovery of a molecular mechanism linking diverse plant extracts used traditionally to lower blood pressure (hypotensives). All of the hypotensive plants tested activated the KCNQ5 vascular-expressed potassium channel, whereas nonhypotensives did not. For one hypotensive plant, we describe discovery of the active small molecule (aloperine) and demonstrate that it KCNQ-dependently relaxes blood vessels. The discovery opens up a new source of potential therapeutic drugs and explains the mechanism behind folk hypotensive medicines used by diverse populations for thousands of years. Keywords: potassium channel, hypertension, herbal medicine

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