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Developmental Biology - Botanical Medicines

How Folk Medicines Affect Hypertension

Lavender, fennel and chamomile act upon a potassium channel target in blood vessels...

Published in Proceedings of the National Academy of Sciences (PNAS), a new study illustrates how many of the known traditional botanical plants used to lower blood pressure activate a specific potassium channel (KCNQ5) in blood vessels. KCNQ5, together with other potassium channels including KCNQ1 and KCNQ4, functions in vascular smooth muscle. When activated, KCNQ5 relaxes blood vessel walls.

Herbs such as lavender, fennel and chamomile, have a long history of use as folk medicines used to lower blood pressure. In a new study, University of California, Irvine researchers explain the molecular mechanisms that make them work.
Interestingly, the KCNQ5-selective potassium channel activation feature found in these botanicals is missing in modern synthetic drug-making.

Until now, it seems to have eluded conventional screening methods utilizing chemical libraries, which may account for why it is not a recognized feature of synthetic blood pressure medications.
Documented use of botanical folk medicines stretches back as far as recorded human history. There is DNA evidence, dating back 48,000 years, that suggests consumption of plants for medicinal use by Homo neanderthalensis. Archaeological evidence, dating back 800,000 years, even suggests non-food usage of plants by Homo erectus or similar species. Today, evidence of the intended results of botanical folk medicine ranges from anecdotal to clinical trials. However, the underlying molecular mechanisms often remain elusive.
"We found KCNQ5 activation to be a unifying molecular mechanism shared by a diverse range of botanical hypotensive folk medicines. Lavandula angustifolia, commonly called lavender, was among those we studied.

"We found it to be among the best at producing the maximum in KCNQ5 potassium channel activators — along with fennel seed extract and chamomile.

"Our discovery of these botanical KCNQ5-selective potassium channel openers may enable development of future targeted therapies for diseases including hypertension and KCNQ5 loss-of-function from brain damage."

Geoff Abbott PhD, Professor of Physiology and Biophysics, University of California, Irvine (UCI) School of Medicine, and senior investigator on the study.
Abstract
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.

Highlights
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.

Authors
Rían W. Manville, Jennifer van der Horst, Kaitlyn E. Redford, Benjamin B. Katz, Thomas A. Jepps and Geoffrey W. Abbott.

Acknowledgements This study was supported by the National Institutes of Health, National Institute of General Medical Sciences and the National Institute of Neurological Disorders and Stroke. Also involved in the study were UCI's Rían Manville, PhD, PhD student Kaitlyn Redford and Benjamin Katz, PhD, and from the University of Copenhagen, Denmark, PhD student Jennifer van der Horst and Thomas Jepps, PhD.

About the UCI School of Medicine: Each year, the UCI School of Medicine educates more than 400 medical students, as well as 200 doctoral and master's students. More than 600 residents and fellows are trained at UC Irvine Medical Center and affiliated institutions. The School of Medicine offers an MD; a dual MD/PhD medical scientist training program; and PhDs and master's degrees in anatomy and neurobiology, biomedical sciences, genetic counseling, epidemiology, environmental health sciences, pathology, pharmacology, physiology and biophysics, and translational sciences. Medical students also may pursue an MD/MBA, an MD/master's in public health, or an MD/master's degree through one of three mission-based programs: the Health Education to Advance Leaders in Integrative Medicine (HEAL-IM), the Leadership Education to Advance Diversity-African, Black and Caribbean (LEAD-ABC), and the Program in Medical Education for the Latino Community (PRIME-LC). The UCI School of Medicine is accredited by the Liaison Committee on Medical Accreditation and ranks among the top 50 nationwide for research. For more information, visit som.uci.edu.

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Oct 3 2019   Fetal Timeline   Maternal Timeline   News  




Lavender (Lavandula angustifolia), a plant widely used in herbal teas, essential oils, soaps and
lotions, was discovered to be among the most efficacious KCNQ5 potassium channel activators.
CREDIT Bo Abbott
Phospholid by Wikipedia