A Reverse Pharmacology approach for evaluating traditional medicines

A Reverse Pharmacology approach for evaluating traditional medicines

A Reverse Pharmacology approach for evaluating traditional
medicines
in the Republic of Palau
to improve the management of obesity-linked diabetes

Jolle Houriet1, Christopher Kitalong2, Renata Campos Nogueira3, Carla Rudigier4, Jeanne Benichou5, Victor Yano2, Vanessa
Espangel2, Pearl L. Marumoto 2, Josepha Tiobech2, Christian Wolfrum4, Jean-Luc Wolfender1, Bertrand Graz2, 3

Contact

School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Rue Michel-Servet 1, 1206 Geneva,
Switzerland
2
Pacific Academic Institute for Research, 822 Ernguul Rd., Koror, Palau
3
Antenna Foundation, Avenue de la Grenade 24, 1207 Geneva, Switzerland
4
Institute of Food, Nutrition and Health, ETH Zurich, Schorenstrasse 16, CH-8603 Schwerzenbach, Switzerland .
5
ENSAT-National Institute of Agronomy and Environment of Toulouse, Avenue de lAgrobiopole, BP 32607 AuzevilleTolosane, France
1

Aim

Jolle Houriet
[email protected]
h

Republic of Palau (Micronesia, Pacific ocean)

An important recommendation of the World
Health Organization is the evaluation of
traditional medicines.
Reverse
Pharmacology
is
an
ethnopharmacological methodology which aims
precisely to evaluate traditional practices [1].
It includes three main stages:
1. Selection of medicinal herbs
2. Clinical evaluation
3. Laboratory studies
A
reverse
pharmacology
approach
was
implemented in the Republic of Palau to improve
the
management
of
Non-Communicable
Diseases.

Prevalence
of
overweight and obese
adults of around 80 %,
according to WHO data.

STATE OF
EMERGENCY
Declaration of State of Emergency on
Non-Communicable Diseases in 2011
(obesity-linked diseases, i.e. diabetes and
hypertension).

1. Selection of medicinal herbs
Selection
method

Selected
herb

Selection by a Retrospective Treatment
Outcome
(RTO)
method.
RTO
statistically identified the remedies
correlating with the best clinical
outcomes [2].

The drink of the leaves of Phaleria
nisidai
(thymelaeaceae)
positively
correlated with the lower blood sugar
criterion.
This drink is also called by the Palauan
population Delal A Kar, the Mother of
medicine [3].

2. Clinical evaluation
Study design

Key results

This first clinical study ever organized
in Palau was designed as a pilot
randomized, double-blind, crossover
clinical study.
The drink of Phaleria nisidai was
evaluated as an an adjuvant therapy
for patients with insufficient diabetes
control [4].

Patients with insufficient diabetes
control improved their glycemia during
the clinical study (reduction of HbA1C).
Decreased blood pressure and weight
reduction were also observed [4].

Material Transfer
Agreement
A
Material
Transfer
Agreement
(MTA)
was
established between the
Pacific Academic Institute of
Research (PAIR) and both
universities.

Future steps
Clinical study on nontreated diabetic patients,
compared to the
standard first-line
treatment.
Identification of the
bioactive components to
select markers for
standardization and
quality control.
Reference
s

3. Laboratory
studies
Bioactivi
ty

Mice fed a high fat diet with
the
freeze-dried
drink
showed:
Greater
sensitivity
to
insulin
Improved
glucose
tolerance
Higher insulin secretion

HO
OH
HO
HO
HO

O
H

O

OH
OH

OH

O

Phytochemist
ry

The freeze-dried drink is
characterized by a high
amount of the C-glycoside
xanthone mangiferin and
other
minor
related
xanthones [5].

Advantages of the Reverse
Pharmacology

This study succeeded in identifying a promising herbal
medicine to improve diabetes control.
Valorization of traditional medicine made by the
population.
Prioritization of the clinical evaluation of the selected
medicinal herb at the beginning of the drug development
process [1].
Highly valuable post-clinical laboratory studies thanks to
the preliminary clinical evaluation.
Low cost compared to the
classic drug development
Acknowledgmen
approach [1].
ts

1.Willcox M., et al., A "reverse pharmacology" approach for developing an anti-malarial phytomedicine. Malar J, 2011. 10 Suppl 1: p.
S8.
2.Graz B., et al., Screening of traditional herbal medicine: First, do a retrospective study, with correlation between diverse treatments
used and reported patient outcome. J Ethnopharmacol, 2005. 101(13): p. 338-339.
3.Graz B., et al., Traditional local medicines in the republic of Palau and non-communicable diseases (NCD), signs of effectiveness. J
Ethnopharmacol, 2015. 161: p. 233-7.
4.Kitalong C., et al., "DAK", a traditional decoction in Palau, as adjuvant for patients with insufficient control of diabetes mellitus type
II. J Ethnopharmacol, 2017. 205: p. 116-122.
5.Kitalong C., et al., Phenolics from Phaleria nisidai with Estrogenic Activity. Records of Natural Products, 2012. 6(3): p. 296-300.

Icons from Noun Project:
Gan Khoon Lay (overweight humans), Corpus
delicti (Choose pharmacy), Eucalyp (diabetes),
Wilson Joseph (population), Juan Manueal Corredor
(human), Dinosoft Labs (agreement), Alina Oleynik
(mouse), Juraj Sedlka (molecule), Meaghan
Hendricks (future), Gan Khoon Lay (advantages).

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