Study finds single molecule within a specific plant used by Native
Americans can treat both pain and diarrhea

Date:
November 16, 2021
Source:
University of California - Irvine
Summary:
Researchers have revealed a striking pattern following a functional
screen of extracts from plants collected in Muir Woods National
Monument, in coastal redwood forest land in California. They found
plants with a long history of use by Native Americans as topical
analgesics, were often also used as gastrointestinal aids.



FULL STORY ==========================================================================
In a University of California, Irvine-led study, researchers revealed
a striking pattern following a functional screen of extracts from
plants collected in Muir Woods National Monument, in coastal redwood
forest land in California. They found plants with a long history of
use by Native Americans as topical analgesics, were often also used as gastrointestinal aids.


==========================================================================
The study, published today in Frontiers in Physiology, found plants that activated the KCNQ2/3 potassium channel, a protein that passes electrical impulses in the brain and other tissues, showed a long history of use
by Native Americans as topical analgesics, to treat conditions such as
insect bites, stings, sores and burns. Less intuitively, the same plants
that activated KCNQ2/3 and were used as folk analgesics, were often also
used as gastrointestinal aids, especially for preventing diarrhea.

"Done in collaboration with the US National Parks Service, this study illustrates how much there is still to learn from the medicinal practices
of Native Americans, and how, by applying molecular mechanistic approaches
we can highlight their ingenuity, provide molecular rationalizations
for their specific uses of plants, and potentially uncover new medicines
from plants," said Geoffrey Abbott, PhD, a professor in the Department
of Physiology and Biophysics at the UCI School of Medicine.

KCNQ2/3 is present in nerve cells that sense pain, and its activation
would be expected to soothe pain by disfavoring transmission of the pain signal. The breakthrough finding came when the team discovered that the
same plant extracts that activate KCNQ2/3 have the opposite effect on
the related intestinal potassium channel, KCNQ1-KCNE3. This finding was striking as previous studies on modern medicines showed that KCNQ1-KCNE3 inhibitors can prevent diarrhea.

The Abbott Lab is currently undertaking a much broader screen of native
US plants toward these goals. Already they have shown that quercetin
and tannic and gallic acids, present in several of the plants studied, explained many of the beneficial effects of the plants. The team also identified binding sites on the channel proteins that produce the effects.

With this knowledge at the molecular level of compounds that can activate versus inhibit closely related human ion channel proteins, future work
can be directed at improving drug specificity and therefore safety, while retaining efficacy. More specifically, medicinal chemistry approaches
can be applied to further optimize the plant compounds with the goal of treating pain and secretory diarrhea.

"I personally am very excited about the paper; it was my lab's first
published collaboration with the National Park Service, and it shines
a light on the incredible ingenuity and medicinal wisdom of Californian
Native American tribes," said Abbott.

The public health implications for improved drugs in these areas are considerable. Novel, non-opioid analgesics are highly sought after as
we battle the twin public health concerns of chronic pain and opioid
addiction. In addition, according to the CDC, diarrheal diseases account
for 1 in 9 child deaths worldwide; incredibly, diarrhea kills over 2000 children every day worldwide -- more than AIDS, malaria and measles
combined.

========================================================================== Story Source: Materials provided by
University_of_California_-_Irvine. Note: Content may be edited for style
and length.


========================================================================== Journal Reference:
1. Geoffrey W. Abbott, Kaitlyn E. Redford, Ryan F. Yoshimura, Ri'an W.

Manville, Luiz Moreira, Kevin Tran, Grey Arena, Alexandra
Kookootsedes, Emma Lasky, Elliot Gunnison. KCNQ and
KCNE Isoform-Dependent Pharmacology Rationalizes Native
American Dual Use of Specific Plants as Both Analgesics and
Gastrointestinal Therapeutics. Frontiers in Physiology, 2021;
12 DOI: 10.3389/fphys.2021.777057 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/11/211116152353.htm

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