South African Traditional Medicines Research Unit
Current projects 11 - 12
- Computerised
database of African medicinal plants (tramed iii)
The general
objectives of the traditional medicines database and information centre
are:
- To use ethno-epidemiological
techniques for collecting information on medicinal plants in Africa and
their traditional uses, and to record and codify this information in a comprehensive
database.
- To develop models for
the rational use and development of herbal remedies in Africa in order to
harmonise traditional practices with the present health care systems.
- To identify bioactive
compounds among the traditional remedies and to investigate them as potential
leads in drug development, with special reference to remedies being used
for malaria and tuberculosis.
- To develop and contribute
to the scientific basis of drug evaluation and control insofar as it has
bearing on the protection and rational use of medicinal plants in Southern
Africa.
The primary objective
is to produce a computerised and comprehensive database on African medicinal
plants, within a period of three years, which will apply to southern and east
Africa.
The database has already
been started by the MRC Traditional Medicines Research Group at the University
of Cape Town.
Data collected will be
further verified through field studies, the existing published and oral literature,
and the laboratory research component of this project.
The database will be made
widely available for use by policy makers, research workers, ministries of
health, drug regulatory authorities, traditional healers, the public and the
pharmaceutical industry.
The database contains
the following essential elements with subsets in each element to provide as
much detail as possible:
- Botanical/taxonomic
description: plant, family, genus, etc.
- Preparation, administration,
users and location;
- Reported chemical constituents;
and
- Reported pharmacological
and toxicological information of constituents.
Information will be gathered
from the literature; from institutions such as herbaria and botanical gardens;
from workshops with traditional healers with their proper consent as to how
the information being imparted by them will be used; and from already recorded
narrative accounts.
In addition, information
obtained from ethnomedical and ethnobotanical research, and from conservation
strategies for endemic and endangered medicinal plants, is being incorporated
in the database.
In each of the collaborating
institutions there will be a main computer for the database, connected to
terminals through a server. The computers will be linked for constant updating
of the database.
- A
study of the mode of action of a novel antimalarial drug, pyronaridine
Project
Leader: Prof. P. Folb
Primary Investigator: Chikumbusko Mtegha
Researchers: Prof. P. Folb, Dr P. Smith, Quinton Fivelman
Collaborator: Dr T. Egan, chemistry department
Chloroquine is the most
widely used antimalarial drug as it is cheap to synthesise and is well tolerated.
Its use – and that of related drugs - has unfortunately been limited
by the proliferation of Plasmodium falciparum strains (the parasite that causes
this life threatening disease) that are resistant to chloroquine, as well
as the emergence of multidrug resistant strains.
Chloroquine acts against
the blood stages of the malaria parasite which are responsible for the clinical
manifestations of the disease. The mechanism of action of chloroquine and
related compounds is not fully known. The mechanisms which cause resistance
in P falciparum are even less known, but it is clear that chloroquine action
is related to its accumulation in very high concentrations in the digestive
food vacuole of the parasite [1].
Pyronaridine is also a
blood schizontocidal drug that is structurally related to chloroquine, being
a substituted 1-aza-acridine and also a substituted 1,5-napthyridine [2].
It has been shown to have a high in vitro activity against chloroquine sensitive
and chloroquine resistant strains of Plasmodium falciparum and this high activity
has been validated in clinical trials in China, Thailand and Cameroon, in
which malarias resistant to chloroquine were cured [3].
Pyronaridine is a promising
drug and there are plans to release it for clinical use in Africa in the coming
years, but its mechanism of action is not yet understood.
Evidence suggests that
it acts in the same way as chloroquine and other 4-aminoquinolines, and reports
of cross-resistance with chloroquine could shorten its time in use [4,5].
The aim of the project
is to develop a Plasmodium falciparum strain(s) that is resistant to pyronaridine
by putting certain strains in culture under drug pressure. This developed
strain(s) will then be used, along with chloroquine resistant and chloroquine
sensitive strains, in drug uptake studies, drug sensitivity studies and drug
combination studies. Radiolabelled pyronaridine will be used to characterise
its accumulation into the malaria parasite and into digestive food vacuoles
isolated from the parasite.
Results from these studies
will give some insight into the mechanism of action of pyronaridine and the
mechanisms involved in the development of drug resistance. These insights
will assist researchers to develop ways of avoiding, or overcoming resistance,
in the clinical management of malaria.
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