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Researchers discover molecular mechanisms of African folk medicine



UCI researchers discover molecular mechanisms of African folk medicine

UCI researchers reveal that the two components of Mallotus leaf tissue link to the previously unrecognized binding site on KCNK1, a potassium channel necessary to control electrical activity in many human organs, including the heart, kidneys, gastrointestinal tract, thyroid glands and pancreas. This computer model illustrates the new plant component, CPT1, isovaleric acid molecule (green), occupying a new bond (R243, red) to activate KCNK1. Credit: UCI Medical School / Geoff Abbott

Researchers at the Department of Physiology and Biophysics at the University of California, Irvine Medical School have discovered a molecular basis for the therapeutic action of an African folk remedy used to treat various illnesses and disorders, including diabetes, pain, headaches, paralysis and epilepsy.


Herbal remedy, a leaf from the Mallotus oppositifolius shrub, has been used throughout Africa for centuries. So far, the molecular mechanism has not been fully understood. Revelation, published in Science progress, revealed that the two components of the leafy Mallotus link to the previously unrecognized binding site on KCNK1, the potassium channel necessary for the control of electrical activity in many human organs, including the heart, kidneys, gastrointestinal tract, thyroid glands and pancreas.

"The plants are a rich source of compounds that modulate the ion channels. We found that the compounds of African folklore medicine are actually tied to a new location, positioned between the channel pores and its voltage sensor. In addition, one of the compounds was found chemical class that was previously not recognized as the KCNK Channel Opener. These double discoveries can facilitate future development of safer and more effective drugs. "

The UCI research team, comprised of Angele De Silva, BS, PhD, Dr. Rian Manville, Ph.D., and Geoffrei Abbott, Ph.D., mastered individual compounds from the leaf extract Mallotus for the activity of opening KCNK1, confirming one previously known channel activator and detecting a completely new activator . They then used computer modeling to identify the binding site for these drugs at KCNK1 and verify these previously unrecognized sites using functional studies of mutated KCNK1 channels. The UCI team also found that the new location of drug binding they discovered were present on another channel type, KCNK2 / 3, found in the brain and associated with epilepsy and encephalopathy. Discovering this new site might indicate the way to improved anti-epileptic drugs.

"The genetic disorder of KCNK1 causes deadly cardiac arrhythmias and is associated with stomach cancer, type II diabetes, and thyroid dysfunction and pituitary gland. KCNK2 / 3 disorder causes epilepsy and serious delay in development, and new strategies for therapeutically activating these potassium channels and overcoming the effects of genetic disorders revealing new botanical species that could help in KCNK drug development strategies highlights the importance of protecting plant species that can produce new therapies. Factors involving loss of an apartment anything, too much collection and climate change are endangering this priceless resource, "said Abot.


Explore further:
Researchers discover molecular mechanisms of old herbal medicines

More information:
"The deconstruction of African folk remedy reveals a new molecular strategy for therapeutic activation of potassium channel" Science progress (2018). advances.sciencemag.org / content / 4/11 / eaav0824

Reference of the journal:
Science progress

Provides:
University of California, Irvine


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