Table Of ContentARTEMISIA
Medicinal and Aromatic Plants - Industrial Profiles
Individual volumes in this series provide both industry and academia with in-depth coverage
of one major medicinal or aromatic plant of industrial importance.
Edited by Dr Roland Hardman
Volume 1
Valerian
edited by Peter J. Houghton
Volume 2
Perilla
edited by He-Ci Yu, Kenichi Kosuna and Megumi Haga
Volume 3
POPPY
edited by Jeno Bernith
Volume 4
Cannabis
edited by David T. Brown
Volume 5
Neem
H.S. Puri
Volume 6
Ergot
edited by Vladimir Kren and Ladislav Cvak
Volume 7
Caraway
edited by fiva NCmeth
Volume 8
Saffron
edited by Moshe Negbi
Volume 9
Tea Tree
edited by Ian Southwall
Volume 10
Basil
edited by Hiltunen and Holm
Volume 11
Fenugreek
edited by Georgios Petropoulos
Volume 12
Ginkgo biloba
edited by Teris A. Van Beek
Volume 13
Black Pepper Piper Nigrum
edited by P.N. Ravindran
Volume 14
Sage
edited by Spriadon E. Kintzios
Volume 15
Ginseng
edited by W.E. Court
Volume 16
Mistletoe - The Genus Viscum
edited by A. Biissing
Volume 17
Tea - Bioactivity and Therapeutic Potential
edited by Yong-su Zhen
Volume 18
Artemisia
edited by Colin W. Wright
ARTEMISIA
Edited by
Colin W. Wright
The School of Pharmacy
University of Bradford
UK
London and New York
First published 2002 by Taylor & Francis
11 New Fetter Lane, London EC4P 4EE
Simultaneously published in the USA and Canada
by Taylor & Francis Inc,
29 West 35th Street, New York, NY 10001
Taylor & Francis is an imprint of the Taylor & Francis Group
O 2002 Taylor & Francis
All rights reserved. No part of this book may be reprinted or reproduced or utilised
in any form or by any electronic, mechanical, or other means, now known or
hereafter invented, including photocopying and recording, or in any information
storage or retrieval system, without permission in writing from the publishers.
Every effort has been made to ensure that the advice and information in this book
is true and accurate at the time of going to press. However, neither the publisher
nor the authors can accept any legal responsibility or liability for any errors or
omissions that may be made. In the case of drug administration, any medical
procedure or the use of technical equipment mentioned within this book, you are
strongly advised to consult the manufacturer's guidelines.
British Library Cataloguing in Publication Data
A catalogue record for this book is available from the British Library
Library of Congress Cataloging in Publication Data
A catalog record for this book has been requested
ISBN 0-415-27212-2
CONTENTS
Preface to the series
Preface
Contributors
1. Introduction to the Genus
Marco Mucciarelli and Massimo Maffei
2. Analysis and Quality Control of Commerical Artemisia Species
H.J. Woerdenbag and N. Pras
3. Artemisia absinthium
Stanley G. Deans and Alan I. Kennedy
4. Artemisia dracunculus
Stanley G. Deans and Elisabeth ].M. Simpson
5. Artemisia herba-alba
Peter Proksch
6. Ethnobothany, Phytochemistry and BiologicalPPharmacological Activities
of Artemisia ludoviciana ssp. Mexicana (Estafiate)
Michael Heinrich
7. Artemisia pallens
R. N. Kulkarni
8. Artemisia vulgaris
Peter A. Linley
9. Artemisia Species in Traditional Chinese Medicine and the Discovery of
Artemisinin
Hongwen Yu and Shouming Zhong
10. Cultivation of Artemisia annua L.
John C. Laughlin, G.N. Heazlewood and B.M. Beattie
11. Variation and Heritability of Artemisinin Content in Artemisia annua L.
Nicholas Delabays, Charly Darbellay and Nicole Galland
12. Phytochemistry of Artemisia annua and the Development of
Artemisinin-Derived Antimalarial Agents
Rajendra S. Bhakuni, Dharam C. Jain and Ram P. Sharma
vii
ix
xi
1
vi
CONTENTS
13. The Mode of Action of Artemisinin and its Derivatives
Colin W; Wright and David C. Warhurst
14. The Clinical Use of Artemisinin and its Derivatives in the Treatment
289
of Malaria
Polrat Wilairatana and Sornchai Looareesuwan
15. Regulation of the Quality and Use of Artemisinin and its Derivatives
309
Penelope Phillips-Howard
Index
323
PREFACE TO THE SERIES
There is increasing interest in industry, academia and the health sciences in medici-
nal and aromatic plants. In passing from plant production to the eventual product
used by the public, many sciences are involved. This series brings together informa-
tion which is currently scattered through an ever increasing number of journals.
Each volume gives an in-depth look at one plant genus, about which an area special-
ist has assembled information ranging from the production of the plant to market
trends and quality control.
Many industries are involved such as forestry, agriculture, chemical, food, flavour,
beverage, pharmaceutical, cosmetic and fragrance. The plant raw materials are
roots, rhizomes, bulbs, leaves, stems, barks, wood, flowers, fruits and seeds. These
yield gums, resins, essential (volatile) oils, fixed oils, waxes, juices, extracts and
spices for medicinal and aromatic purposes. All these commodities are traded world-
wide. A dealer's market report for an item may say "Drought in the country of
origin has forced up prices".
Natural products do not mean safe products and account of this has to be taken
by the above industries, which are subject to regulation. For example, a number of
plants which are approved for use in medicine must not be used in cosmetic
products.
The assessment of "safe" to use starts with the harvested plant material which has
to comply with an official monograph. This may require absence of, or prescribed
limits of, radioactive material, heavy metals, aflatoxin, pesticide residue, as well as
the required level of active principle. This analytical control is costly and tends to
exclude small batches of plant material. Large scale contracted mechanised
cultivation with designated seed or plantlets is now preferable.
Today, plant selection is not only for the yield of active principle, but for the
plant's ability to overcome disease, climatic stress and the hazards caused by
mankind. Such methods as in vitro fertilisation, meristem cultures, and somatic
embryogenesis are used. The transfer of sections of DNA is giving rise to
controversy in the case of some end-uses of the plant material.
Some suppliers of plant raw material are now able to certify that they are
supplying organically-farmed medicinal plants, herbs and spices. The Economic
Union directive (CVOIEU No 2092191) details the specifications for the obligatory
quality controls to be carried out at all stages of production and processing of
organic products.
Fascinating plant folklore and ethnopharmacology leads to medicinal potential.
Examples are the muscle relaxants based on the arrow poison, curare, from species
of Chondrodendron, and the antimalarials derived from species of Cinchona and
Artemisia. The methods of detection of pharmacological activity have become
increasingly reliable and specific, frequently involving enzymes in bioassays and
avoiding the use of laboratory animals. By using bioassay linked fractionation of
crude plant juices or extracts, compounds can be specifically targeted which, for
vii
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v111
PREFACE TO THE SERIES
example, inhibit blood platelet aggregation, or have antitumour, or antiviral, or any
other required activity. With the assistance of robotic devices, all the members of a
genus may be readily screened. However, the plant material must be fully authenti-
cated by a specialist.
The medicinal traditions of ancient civilisations such as those of China and India
have a large armamentarium of plants in their pharmacopoeias which are used
throughout South East Asia. A similar situation exists in Africa and South America.
Thus, a very high percentage of the World's population relies on medicinal and aro-
matic plants for their medicine. Western medicine is also responding. Already in
Germany all medical practitioners have to pass an examination in phytotherapy
before being allowed to practise. It is noticeable that throughout Europe and the
USA, medical, pharmacy and health related schools are increasingly offering training
in phytotherapy.
Multinational pharmaceutical companies have become less enamoured of the
single compound magic bullet cure. The high costs of such ventures and the endless
competition from me too compounds from rival companies often discourage the
attempt. Independent phytomedicine companies have been very strong in Germany.
However, by the end of 1995, eleven (almost all) had been acquired by the multina-
tional pharmaceutical firms, acknowledging the lay public's growing demand for
phytomedicines in the Western World.
The business of dietary supplement in the Western World has expanded from the
Health Store to the pharmacy. Alternative medicine includes plant based products.
Appropriate measures to ensure the quality, safety and efficacy of these either
already exist or are being answered by greater legislative control by such bodies as
the Food and Drug Administration of the USA and the recently created European
Agency for the Evaluation of Medicinal Products, based in London.
In the USA, the Dietary Supplement and Health Education Act of 1994 recognised
the class of phytotherapeutic agents derived from medicinal and aromatic plants.
Furthermore, under public pressure, the US Congress set up an Office of Alternative
Medicine and this office in 1994 assisted the filing of several Investigational
New Drug (IND) applications, required for clinical trials of some Chinese herbal
preparations. The significance of these applications was that each Chinese prepara-
tion involved several plants and yet was handled as a single IND. A demonstration
of the contribution to efficacy, of each ingredient of each plant, was not required.
This was a major step forward towards more sensible regulations in regard to
phytomedicines.
My thanks are due to the staff of Harwood Academic Publishers who have made
this series possible and especially to the volume editors and their chapter contribu-
tors for the authoritative information.
Roland Hardman
PREFACE
The genus Artemisia comprises some 400 species including a number which are
important for their medicinal properties. Chief among these is A. annua, the source
of the antimalarial drug artemisinin. According to a legend, in the 5th century B.C.
the city of Selinus in Sicily was delivered from a plague thought to be malaria and
this event was commemorated by the minting of a coin. The obverse of the Selinus
coin (figure la), shows a chariot driven by Artemis representing the women of the
city who suffered severely from the fever accompanied by her brother Apollo, who,
as the god of healing is firing arrows to destroy the plague (McGregor, 1996). The
reverse of the Selinus coin (figure lb), also includes Artemis and Apollo represented
as a cockerel and a bull respectively while the central figure is the river god Selinus
representing Empedocles, a student of Pythagoras who is reputed to have delivered
the city from the fever by cleansing the surrounding marshes. Although this interpre-
tation of the reverse of the coin is not generally accepted by modern scholars, the
association of Artemis with Artemisia (= plant sacred to Artemis) and with the deliv-
erance of Selinus from malaria is fascinating.
The herb A. annua has been used in China for thousands of years to treat fevers
and the isolation of artemisinin in 1971, a highly potent antimalarial agent has
proved to be of considerable importance as malaria parasites are increasingly devel-
oping resistance to established antimalarial drugs. Artemisinin is unusual in that the
molecule contains a peroxide group which is rarely found in nature although
another example is the explosive compound ascaridole, the major constituent of
l a
Figure 1 The Selinus coin. The British Museum
