Mistletoe The Genus Viscum 1st Edition
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Dedicated to my parents,
my wife Claudia,
and our children, Oliver and Annika,
for their attendance.
Copyright © 2000 OPA (Overseas Publishers Association) N.V. Published by license under the
Harwood Academic Publishers imprint, part of The Gordon and Breach Publishing Group.
CONTENTS
Preface to the Series ix
Preface xi
Contributors xiii
1. Introduction: History of Mistletoe Uses 1
Arndt Büssing
2. Viscum in the Context of its Family, Viscaceae, and its Diversity in Africa 7
Donald W.Kirkup, Roger M.Polhill and Delbert Wiens
3. European Mistletoe: Taxonomy, Host Trees, Parts Used, Physiology 31
Hans Becker
4. Korean Mistletoes and Other East-Asian Populations 45
Won-Bong Park
5. Mistletoes from Argentina. Ligaria cuneifolia var. cuneifolia as a
Substitute for the European Mistletoe (Viscum album L.) 61
Teresa B.Fernández, Beatriz G.Varela, Carlos A.Taira, Rafael A.Ricco,
Alberto A.Gurni, Silvia E.Hajos, Elida M.C.Alvarez and Marcelo
L.Wagner
6. Cultivation and Development of Viscum album L. 75
Hartmut Ramm, Konrad Urech, Markus Scheibler and
Gianfranco Grazi
7. The Biotechnology of Viscum album L.: Tissue Culture, Somatic
Embryogenesis and Protoplast Isolation 95
Spiridon Kintzios and Maria Barberaki
8. Chemical Constituents of European Mistletoe (Viscum album L.)
Isolation and Characterisation of the Main Relevant Ingredients:
Lectins, Viscotoxins, Oligo-/polysaccharides, Flavonoides, Alkaloids 101
Uwe Pfüller
9. Biological and Pharmacological Properties of Viscum album L.
From Tissue flask to Man 123
Arndt Büssing
10. Toxicology of Mistletoe and their Components 183
Gerburg M.Stein
11. Adverse Effects during Therapy with Mistletoe Extracts 195
Gerburg M.Stein and Peter A.Berg
vii
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viii CONTENTS
12. Overview on Viscum album L. Products 209
Arndt Büssing
13. Pharmaceutical Quality Control of Mistletoe Preparations 223
Elmar Lorch and Wilfried Tröger
14. Natural Versus Recombinant Mistletoe Lectin-1. Market Trends 237
Josef Beuth
15. The Magic Potion becomes Serious: Whole Plant Extracts vs. Defined
Components 247
Gerburg M.Stein and Michael Schietzel
Copyright © 2000 OPA (Overseas Publishers Association) N.V. Published by license under the
Harwood Academic Publishers imprint, part of The Gordon and Breach Publishing Group.
PREFACE TO THE SERIES
There is increasing interest in industry, academia and the health sciences in medicinal
and aromatic plants. In passing from plant production to the eventual product used
by the public, many sciences are involved. This series brings together information
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 specialist 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 worldwide. 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
(CVO/EU No 2092/91) 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
example, inhibit blood platelet aggregation, or have antitumour, or antiviral, or any
ix
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x PREFACE TO THE SERIES
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 authenticated
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 aromatic
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 multinational
pharmaceutical firms, acknowledging the lay public’s growing demand for
phytomedicines in the Western World.
The business of dietary supplements 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 preparation
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 Harwodd Academic Publishers who have made
this series possible and especially to the volume editors and their chapter contributors
for the authoritative information.
Roland Hardman
Copyright © 2000 OPA (Overseas Publishers Association) N.V. Published by license under the
Harwood Academic Publishers imprint, part of The Gordon and Breach Publishing Group.
PREFACE
Mistletoe is still a controversial plant. Growing between heaven and earth, never
touching the ground, and not accepting the seasons. Even discussing its clinical impact
results in polarisation: Rejected by clinical oncologists but used by practitioners and
cancer patients. It is applied as a remedy to treat a broad spectrum of different diseases,
such as epilepsy, diabetes, hypertension, arthrosis, hepatitis, HIV infection, labour
pains, and cancer.
What is fact and what is fiction in the mistletoe story? The following chapters may
give a glimpse that the book is still open, and that the last and final chapter of mistletoe
research remains to be written.
Thirty spokes join together in the hub.
It is because of what is not there that the cart is useful.
Clay is formed into a vessel.
It is because of its emptiness that the vessel is useful.
Cut doors and windows to make a room.
It is because of its emptiness that the room is useful.
Therefore, what is present is used for profit.
But it is in absence that there is usefulness.
Lao Tzu, The Tao Te Ching
Copyright © 2000 OPA (Overseas Publishers Association) N.V. Published by license under the
Harwood Academic Publishers imprint, part of The Gordon and Breach Publishing Group.
CONTRIBUTORS
Elida M.C.Alvarez Arndt Büssing
Member of the Research Career Krebsforschung Herdecke
CONICET Department of Applied Immunology
Cátedra de Inmunología-IDEHU University Witten/Herdecke
Facultad de Farmacia y Bioquímica Communal Hospital
Universidad de Buenos Aires 58313 Herdecke
Junín 956 (1113), Buenos Aires Germany
Argentina
Maria Barberaki Teresa B.Fernández
Department of Plant Physiology Faculty Cátedra de Inmunología-IDEHU
of Agricultural Biotechnology Facultad de Farmacia y Bioquímica
Agricultural University of Athens Universidad de Buenos Aires
Iera Odos 75 Junín 956 (1113), Buenos Aires
11855 Athens Argentina
Greece
Gianfranco Grazi
Hans Becker
Institut Hiscia
Institute of Pharmacognosy and
Verein für Krebsforschung
Analytical Phytochemistry
Kirschweg 9
University of the Saarland
4144 Arlesheim
P.O. Box 151150
Switzerland
66041 Saarbrücken
Germany
Alberto A.Gurni
Peter A.Berg Cátedra de Farmacobotánica
Medical Clinic Facultad de Farmacia y Bioquímica
Department of Internal Medicine II Universidad de Buenos Aires
University of Tübingen Junín 956 (1113), Buenos Aires
Otfried-Müller-Strasse 10 Argentina
72076 Tübingen
Germany
Silvia E.Hajos
Josef Beuth Member of the Research Career
Institute for Scientific Evaluation for CONICET
Naturopathy Cátedra de Inmunología-IDEHU
University of Cologne Facultad de Farmacia y Bioquímica
Robert-Koch Strasse 10 Universidad de Buenos Aires
50931 Cologne Junín 956 (1113), Buenos Aires
Germany Argentina
xiii
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Harwood Academic Publishers imprint, part of The Gordon and Breach Publishing Group.
xiv CONTRIBUTORS
Spiridon Kintzios Rafael A.Ricco
Department of Plant Physiology Cátedra de Farmacobotánica
Faculty of Agricultural Biotechnology Facultad de Farmacia y Bioquímica
Agricultural University of Athens Universidad de Buenos Aires
Iera Odos 75 Junín 956 (1113), Buenos Aires
11855 Athens Argentina
Greece
Donald W.Kirkup Markus Scheibler
Herbarium, Royal Botanic Gardens Institut Hiscia
Kew, Richmond Verein für Krebsforschung
Surrey TW10 3AE Kirschweg 9
England 4144 Arlesheim
Switzerland
Elmar Lorch
Helixor Heilmittel
Michael Schietzel
Hofgut Fischermühle
Krebsforschung Herdecke
P.O. Box 8
Communal Hospital
72344 Rosenfeld
University Witten/Herdecke
Germany
58313 Herdecke
Won-Bong Park Germany
College of Natural Science
Seoul Women’s University Gerburg M.Stein
Seoul, 139–774 Krebsforschung Herdecke
Korea Communal Hospital
University Witten/Herdecke
Uwe Pfüller 58313 Herdecke
Institute of Phytochemistry Germany
University Witten/Herdecke
Stockumer Strasse 10
Carlos A.Taira
58453 Witten
Member of the Research Career
Germany
CONICET
Cátedra de Farmacología
Roger M.Polhill
Facultad de Farmacia y Bioquímica
Herbarium, Royal Botanic Gardens
Universidad de Buenos Aires
Kew, Richmond
Junín 956 (1113), Buenos Aires
Surrey TW10 3AE
Argentina
England
Hartmut Ramm Wilfried Tröger
Institut Hiscia Helixor Heilmittel
Verein für Krebsforschung Hofgut Fischermühle
Kirschweg 9 P.O. Box 8
4144 Arlesheim 7234 Rosenfeld
Switzerland Germany
Copyright © 2000 OPA (Overseas Publishers Association) N.V. Published by license under the
Harwood Academic Publishers imprint, part of The Gordon and Breach Publishing Group.
CONTRIBUTORS xv
Konrad Urech Marcelo L.Wagner
Institut Hiscia Cátedra de Farmacobotánica and
Verein für Krebsforschung Museo de Farmacobotánica “Juan A.
Kirschweg 9 Domínguez”
4144 Arlesheim Facultad de Farmacia y Bioquímica
Switzerland Universidad de Buenos Aires
Junín 956 (1113), Buenos Aires
Beatriz G.Varela Argentina
Cátedra de Farmacobotánica
Delbert Wiens
Facultad de Farmacia y Bioquímica
Department of Biology
Universidad de Buenos Aires
University of Utah
Junín 956 (1113), Buenos Aires
Salt Lake City, Utah 84112
Argentina
USA
Copyright © 2000 OPA (Overseas Publishers Association) N.V. Published by license under the
Harwood Academic Publishers imprint, part of The Gordon and Breach Publishing Group.
1. INTRODUCTION: HISTORY OF MISTLETOE USES
ARNDT BÜSSING
Krebsforschung Herdecke, Department of Applied Immunology,
University Witten/Herdecke, Communal Hospital,
58313 Herdecke, Germany
MISTLETOE: THE MYTHICAL PLANT
Mistletoes belong to the families Loranthaceae and Viscaceae, which both are
taxonomically related to each other, and share the order Santalales. The family of
Viscaceae has seven genera (Arceuthobium, Dendrophthora, Ginalloa, Korthalsella,
Notothixos, Phoradendron, Viscum) and several hundred species world-wide. The
European white-berry mistletoe (Viscum album L.) is an evergreen, dioecious plant
growing half-parasitically on its host. V. album is a small shrub with linear lanceolate
leathery leaves which persist for several seasons. The yellowish-green flowers grow in
the sprout axil and develop the translucent, whitish berries in the late fall and early
winter. Theophrastos (371–286 BC) described mistletoe as an evergreen plant growing
on pine and fir trees, fed to animals. He recognised that mistletoe does not grow on
the earth, but is spread to trees by birds whose excretions contain “seeds” from the
berries.
Unlike other plants, mistletoe does not follow a 12 month vegetation period,
never touches the earth, and blooms during winter (see Ramm et al., this book).
The plant was considered sacred by the Celtic Druids, because in the dead of winter,
when branches of the oak tree were bare, the mistletoe is still green and flourished
without having roots on the earth. To them, the plant represented ever-lasting life.
Plinius G.P.Secundus (23–79 AC) reported the Druids to ceremoniously remove
mistletoe from oak trees with a golden sickle on the 6th day after new moon. They
believed the plant was an antidote for poisons and ensured fertility, and to possess
miraculous properties to cure each illness as an omnia sanans (Historia naturalis,
liber XVI, 95).
The mythical plant mistletoe was used in ancient times together with aromatic
substances as an incense (Rätsch, 1997; Fischer-Rizzi, 1999). Scenting of houses,
animals and man with the blend of these herbs was suggested to protect against
lightning, spells and bad dreams (Marzell, 1923), or to get in contact with “elementary
power of nature” and to find the “inner stability” (Fischer-Rizzi, 1999). Burning of
the “light-grown” mistletoe may release the “captured elementary power of light”
(F.Wollner, personal communication).
Even today, the evergreen mistletoe is a symbol of fertility and good luck, and
kissing under branches of mistletoe during the Christmas tide is popular in many
Copyright © 2000 OPA (Overseas Publishers Association) N.V. Published by license under the
Harwood Academic Publishers imprint, part of The Gordon and Breach Publishing Group.
2 ARNDT BÜSSING
European countries and North America. This exchange of kisses is interpreted as a
promise to marry and a prediction of happiness and long life. In the Middle ages and
later, branches of mistletoe were hung from ceilings to ward off evil spirits, and were
located over house and stable doors to prevent the entrance of witches and ghosts
(Tabernaemontanus, 1731; Marzell, 1923). In contrast, a Tanganyika species of
Loranthus was used to put spells on somebody (Watts and Breyer-Brandwisk, 1962).
According to Nordic mythology as described in the “Edda” (Snorri Shurlason,
1200 AC), which is a collection of ancient Viking poems, the god of shamans (Odin)
and the goddess of love and beauty (Free) bound all being of earth from ever harming
their son Balder. However, the tiny mistletoe did not take root in the earth, and
therefore, was not bound to the oath. Balder was killed at Loki’s instigation by a twig
of mistletoe (mistilteinn) shot by his blind brother Hödur. Interestingly, von Tubeuf
(1923) clearly stated that mistletoe is unknown in the northern parts of Scandinavia
and Island, and thus, the legend must be rooted in other areas of Europe, or probably
the Near East.
Mistletoe as a Remedy
The intentions of mistletoe uses were manifold and conflicting in several cases.
According to the Greek physician and author Dioskorides (15–85 AC), Hippocrates
(460–377 BC) used the mistletoe to treat diseases of the spleen and complaints
associated with menstruation. Plinius (23–79 AC) reported mistletoe from oak trees,
when applied as a chewed pulp, to be beneficial for epilepsy, infertility, and ulcers
(Historia naturalis, liber XXIV, 12). Around 150 AC, the Platonist Celsus reported
the use of mistletoe in the treatment of swellings or tumours (De Medicina, liber V, 18
and 23). Although the conditions have never been accurately defined, the use of
mistletoe in medicine was referred also by the Alexandrian physician and surgeon
Paulus Aegineta (625–690 AC), and the Persian philosopher and physician Avicenna
(Ibn-Sina, 980–1037 AC) (Foy, 1904). However, as suggested by Marzell (1923),
“oak mistletoes” described and used by most ancient scientists might not be identical
with the white-berry mistletoe (V. album), which is green even in winter, but might be
the yellow-berry Loranthus europaeus which in turns looses the leaves during winter.
It seems unlikely that also the Celtic druids may have used Loranthus, which is common
on oak trees, as the exceptional botanical properties of V. album predisposes its use as
a miraculous plant.
During the middle ages, mistletoe was recommended as a treatment for epilepsy
because it never fell to the ground. In fact, Paracelsus (Theophrastus Bombastus von
Hohenheim, 1493–1541) recommended that epileptics should wear oak mistletoe on
their right hand, and rosaries were made of mistletoe (mistlin paternoster) during the
15th century to prevent the disease (Marzell, 1923). In the 12th century, the abbess and
composer Hildegard von Bingen (1098–1179) wrote treaties about natural history
and medicinal uses of plants, animals and stones, and described mistletoe as a treatment
for diseases of spleen and liver. In the European herbals of the 16th century, mistletoe
was reported to warm, to soften, to astringent, and to be more sharp than bitter (von
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Harwood Academic Publishers imprint, part of The Gordon and Breach Publishing Group.
