Evaluation of Pacific
Northwest Native Plants For
the Presence of ACE
Inhibitors
Andrea M Garcia
Working with Dr. Joe Karchesy
What is ACE


ACE, Angiotensin
Converting Enzyme
An exopeptidase
that catalyses the
conversion of
Angiotensin I to
Angiotensin II, in the
Renin- Angiotensin
pathway
Renin- Angiotensin pathway
http://www.hypertensiononline.org
What is the Renin- Angiotensin
pathway
Angiotensinogen
Renin
Angiotensin I
ACE
Angiotensin II
Hypertension
High blood pressure is considered
to be a silent killer.
Nearly one in three U.S. adults have high
blood pressure.
 Uncontrolled high blood pressure can lead
to stroke, heart attack, heart failure or
kidney failure.
 Once high blood pressure develops, it
usually lasts a lifetime and it can be
prevented and controlled by taking action.

Preventive measures
Synthetic drugs
 Exercise and good
eating habits.
 Use of natural
products, teas or
supplements.
 Plant products that
exhibit ACE
inhibition.


hawthornberries
What are ACE inhibitors?
A group of
pharmaceuticals or
compounds that slow
or inhibit the activity
of ACE.
 Based on research
from the venom of a
Brazilian pit viper that
led to the
development of the
first ACE inhibitor drug
to treat hypertension.

Ace inhibitors in plants
There are various secondary metabolites
with inhibitory activity towards ACE.
 Found in flavonoids, proanthocyanidins
and small peptides.
 There are well known plant extracts that
have been used by indigenous peoples.

Reason for investigating ACE
inhibition in plants
Herb drug interactions.
 Low cost compared to synthetic drugs.
 They have a wide range of therapeutic use
and are suitable for chronic treatments
 Find better and more selective
compounds.
 Possibility of indicating new molecular
structure with ACE activity.

List of plants under study that we think
may contain ACE inhibition
Black Cohosh
Cimicifuga elata
Baneberry
Actea Rubra
Prince Pine
Pipsisewa
Ocean Spray
Holodiscis discolor
Red Alder
Alnus Rubra
Devil’s Club
Oplopanax Horridum
Soapberry
Shepherdia canadenis
Buckbrush
Amelanchier Alnifolia
In Vitro Screening of Inhibitors
Collect specimens of plants to be studied.
Isolate compounds.
React plant ACE inhibitors with rabbit lung
enzyme assay.
 Test for ACE activity, using the HPLC
method (Hansen et al. 1995).
 Further testing for the plants that exhibit
ACE compounds will be done for us
through the college of pharmacy.



Reaction

Use a Titer plate
– Rabbit lung ACE
enzyme
– Plant solution
– Dansyltriglycine
substrate
Incubate
 Stop the reaction and
analyze with HPLC.

ACE – Catalyzed Cleavage of
Dansylytriglycine.

Dansyltriglycine (dansylGly-Gly-Gly), UV labeled
tripeptide.

Presence of ACE

Dansylglycine (dansylGly)

Diglycine (Gly-Gly)
From Elbl and Wagner, 1991
High Performance Liquid
Chromatography




Dansyl-L-glutamine: the
internal standard
Dansylglycine, product of
enzyme reaction
Dansyltriglycine,
substrate of enzyme
reaction.
Ratio of the two is the
measurement of
inhibition.
From Hansen etal, 1995
Status
Analysis currently underway for ACE
inhibition
 Promising compounds will be forwarded to
Pharmacy for further characterization.

Acknowledgements
 Jaworski Scholarship, HHMI, Garden Club
of America
Joe Karchesy, Kevin Ahern, Debbie Maynard
