KCNQ5 activation is a unifying molecular mechanism shared by genetically and culturally diverse botanical hypotensive folk medicines
Research output: Contribution to journal › Journal article › peer-review
Botanical folk medicines have been used throughout human history to treat common disorders such as hypertension, often with unknown underlying mechanisms. Here, we discovered that hypotensive folk medicines from a genetically diverse range of plant species each selectively activated the vascular-expressed KCNQ5 potassium channel, a feature lacking in the modern synthetic pharmacopeia, whereas nonhypotensive plant extracts did not. Analyzing constituents of the hypotensive Sophora flavescens root, we found that the quinolizidine alkaloid aloperine is a KCNQ-dependent vasorelaxant that potently and isoform-selectively activates KCNQ5 by binding near the foot of the channel voltage sensor. Our findings reveal that KCNQ5-selective activation is a defining molecular mechanistic signature of genetically diverse traditional botanical hypotensives, transcending plant genus and human cultural boundaries. Discovery of botanical KCNQ5-selective potassium channel openers may enable future targeted therapies for diseases including hypertension and KCNQ5 loss-of-function encephalopathy.
Original language | English |
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Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 116 |
Issue number | 42 |
Pages (from-to) | 21236-21245 |
ISSN | 0027-8424 |
DOIs | |
Publication status | Published - 2019 |
- potassium channel, hypertension, herbal medicine
Research areas
Links
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6800379/pdf/pnas.201907511.pdf
Final published version
ID: 229898449