Thyme The Genus Thymus - 1st Edition

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First published 2002
by Taylor & Francis
1 1 New Fetter Lane, London EC4P 4EE
Simultaneously published rn the USA and Canada
by Taylor & Francis Inc,
2 9 West 35th Street, New York, N Y 10001
Taylor & Frnnczr is an zlizpllnt of the Taylor & Fran~.ijGrozp
O 2002 Taylor & Francis

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neither the publisher nor the authors can accept any legal responsibility
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ISBN 0 4 1 5-28488-0
For Rainer, Inma, Natalia, Angel and RubCn
Contents

Prefdce to the series

Preface
List of contributors

The history, botany and taxonomy of the genus Thymus

RAMON MORALES

Population structure and the spatial dynamics of genetic

polymorphism in thyme
J O H N D THOMPSON

Essential oil chemistry of the genus Thymus - a global view

ELISABETH STAHL-BISKUP

Essential oil polymorphism in the genus Thymzls

FRANCISCO SAEZ A N D ELISABETH STAHL-BISKUP

Flavonoids and further polyphenols in the genus Thymzls

ROSER VILA

Field culture, in vitro culture and selection of Thymus

CHARLES REY AND FRANCISCO SAEZ

Harvesting and post-harvest handling in the genus Thymus

PETRAS R. VENSKUTONIS

Thyme - processing of raw plant material

PETRAS R. VENSKUTONIS

The Genus Thymus as a source of commercial products

BRIAN M LAWRENCE A N D A R T H U R 0 . TUCKER
10 The medicinal and non-medicinal uses of thyme
A N T O N I O ZARZUELO A N D ESPERANZA CRESPO

11 Thyme as a herbal drug - pharmacopoeias and other product

characteristics
ELISABETH STAHL-BISKUP

Index
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 infor-
mation 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 mlay 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, aflatoxic, 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 fertilization, 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 European 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 anti-malarials derived from species of Cinchona and Artenzisia.
The methods of detection of pharmacological activity have become increasingly reliable
and specific, frequently involving enzymes in bioassays and avoiding the use of labora-
tory animals. By using bioassay linked fractionation of crude plant juices or extracts,
x Preface to the seriej

compounds can be specifically targeted which, for example, inhibit blood platelet
aggregation, or have anti-tumour, or anti-viral, or any other required activity. W i t h
the assistance of robone 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 armamenoaria of plants in their pharmacopoeias which are used through-
out 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 competi-
tion from 'me too' compounds from rival companies often discourage the attempt Inde-
pendent 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 dictary 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 effi-
cacy, of each ingredient of each plans, was not required. This was a major step forward
towards more sensible regulations in regard to phytomedicines.
My thanks are due to the staffs of Harwood Academic Publishers and Taylor & Francis
who have made this series possible and especially to the volume editors and their chapter
contributors for the authoritative information.

Roland Hardman
Preface

When Roland Hardman asked us to edit the book "The Genus Thymas" within his
remarkable series "Medicinal and Aromatic Plants - Industrial Profiles" it was a big
challenge for us because the amount of material concerning the genus Thymw has
increased continuously and immensely up to the present. W e knew that it would not
be an easy job to compile all the results revealed by more than 2000 scientific publica-
tions. Nevertheless, from the beginning we were enthusiastically dedicated to this
task - as editors and authors - always convinced that we were doing a very valuable job
discussing Thymw under different aspects. W e both spent several years with scientific
studies on the botany, chemistry and systematology of Thynzw always being aware of
the urgent need of a compilatory work as a fundamental basis for further research
projects. Therefore with the publication of this book not only the wish of the series
editor but also our own wish for a comprehensive report on the status quo of the genus
Thymus came true.
Everyone who has ever dealt with the genus Thymus knows that Thynzw vulgavzs L.
deserves close attention. Its pleasant aroma and flavour as well as its potent pharmaco-
logical activities give him the predicate of one of the most popular plants widely used
as flavouring agent, culinary herb, herbal medicine, and it is used in perfumes as well as
being a commercial source of the monoterpene thymol. Therefore Thynzus vulgarzs L.
became the central species in quite a few contributions to the book, especially in those
dealing with thyme as a source of commercial products and as an herbal drug on the
one hand and on the other hand in those articles discussing field culture, harvesting,
post-harvest handling and processing of thyme. Nevertheless for us the presentation of
the material covering the whole genus Thymus has been an aim of prime importance.
Therefore we made every endeavour to find authors who were willing- to elucidate the
scientific achievements of the whole genus and discuss the problems of this species-rich
plant genus, of a taxonomically complex group present in all temperate regions of the
northern hemisphere. The result is a review of the history, the botany, and the taxonomy
of the genus Thymus including several aspects of the population structure in thyme as
well as the complete essential oil and flavonoid chemistry of the genus. Following our
own scientific inclinations a separate chapter was dedicated to the problem of essential
oil polymorphism in the genus Thymus.
W e hope we have succeeded in presenting an informative overview of the information
presently available on the genus Thymus: botany, taxonomy, chemistry, and pharmacology
xii Prefdce

which also takes into account several applied aspects such as field culture, harvesting
and processing of thyme. The readers may consider this book to be a reliable basis and
feel stimulated to invest further efforts into the research of this promising genus which
still shows many gaps which are worth filling during the coming decades.

Elisabeth Stahl-Biskup
Francisco SBez
Contributors

Dr Esperanza Crespo Bundesstrasse 45

Departamento de Farmacologia D-20146 Hamburg, Germany
Facultad de Farmacia
Campus de La Cartuja Dr John D. Thompson
Universidad de Granada Centre d'Ecologie Fonctionelle
1807 1-Granada, Spain et Evolutive
CNRS
Dr Brian M. Lawrence 1919 Route de Mende
c/o R.J. Reynolds Tobacco Company 34293 Montpellier Cedex 5
Research and Development France
Bowman Gray Technical Center
950 Reynolds Boulevard Dr Arthur 0.Tucker
Winston-Salem, NC 27 105, USA Department of Agriculture and Natural
Resources
Dr Ram6n Morales Delaware State University
Real Jardin Botinico de Madrid, CSIC Dover DE 19901-2277, USA
Plaza de Murillo, 2
28014-Madrid, Spain Dr Petras R. Venskutonis
Department of Food Technology
Charles Rey Kaunas University of Technology
Station fgdgrale de recherches en Radvilenu pl. 19
production vggetale de Changins Kaunas
Centre des Fougkres LT-3028, Lithuania
CH-1964 Conthey, Switzerland
Dr Roser Vila
Dr Francisco SBez Unitat de Farmacologia i
Departamento de Biologia Vegetal Farmacognhsia
(Botinica) Facultat de Farmacia
Facultad de Biologia Avda. Diagonal, 643
Universidad de Murcia 08028 Barcelona, Spain
30100-Espinardo, Murcia, Spain
Dr Antonio Zarzuelo
Prof. Dr Elisabeth Stahl-Biskup Departamento de Farmacologia
Institut fiir Pharmazie Facultad de Farmacia
Universitat Hamburg Campus de La Cartuja
Abteilung Pharmazeutische Universidad de Granada
Biologie and Mikrobiologie 1807 1-Granada, Spain
1 The history, botany and taxonomy
of the genus Thymus

INTRODUCTION

Within the Labiate family, with about 220 genera, the genus Thymus is one of the
eight most important genera with regard to the number of species included, although
this number varies depending on the taxonomical point of view. If we choose criteria
to minimise variability, available data report 215 species for the genus, a number
on1y exceeded by the genera Salvia, Hyptis, Scatellaria, Stachys, Teucrium, Nepeta, and
Plectranthus.
The common English word 'thyme' has traditionally been used to name both the genus
and its most commercially used species, Thymus vulgaris, sometimes leading to misun-
derstandings. Generally speaking, thyme is an aromatic plant used for medicinal and spice
purposes almost everywhere in the world. The genus Thymw is very frequent in the
Mediterranean region, where some species form a special type of bushy vegetation not
more than 50cm high, well adapted to hot and dry summer weather. The Spanish
name for these vegetation communities, 'tomillares', include other Labiate species such
as Sideritis, Satureja, Salvia or Lavandz~la,with similar climatic and edaphic patterns.
A common feature of these and many orher aromatic plants is the presence of countless
glandular hairs of different forms which contain volatile essential oils that evaporate
when the glandular hairs are damaged. This way they produce an intensive fragrance
that embraces the plant. It is probably due to the strong scent that humans have always
been attracted to these plants and have exploited their essential oils for popular and
industrial purposes.

HISTORICAL BACKGROUND

T h e history of Thymus before Linnk

Several explanations exist concerning the origin of the name 'Thymus'. Some authors assume
that the Latin name Thymus comes from the Greek word thyo (perfume). Another inter-
pretation of its etymology considers the Greek word thymos (courage, strength). Originally
'thymus' described a group of aromatic plants with similar aspects which were used as
stimulants of vital functions. Many popular names in the Romance languages are
derived from the Latin name. The same occurs with the English name.
In his work about medicinal plants and poisons, Dioscorides (First century, translation
of Laguna, 1555) writes about 'Thymo'. Laguna however did not find there any Thymus
species, but a plant corresponding to the genus Satureja. O n page 294 Laguna describes
the Serpol, presenting two varieties, a cultivated and a wild one. The latter, Zygis, resembles
a Thymus species. It is presented as an erect plant, whereas the former shows a creeping
habit.
In his Natural History, Book 21, Chapter 10 (translation of Huerta, 1629), Plinio (First
century) reports on T. vz~lgarisas follows: 'in the Narbonne province, the stony fields
are full of thyme, and thousands of sheep come from very far provinces to feed on it'.
Later (page 289) he speaks about two different varieties of thyme, a white and a black
one, and he comments on their therapeutic attributes. In Chapter 62 of his first book,
Clusius (1576) refers to T . vulgaris with his Thymum durius sive Plinii. The subsequent
chapter 'De Serpyllo silvestri Zygi' includes a description of T . zygis, which is one of
the most common species in Spain; and in Chapter 64 entitled 'De Tragorigano' he
writes: 'Multis Hispaniae locis provenit solo arido petroso cum Stoechade permista',
refering to T . nzastichina, whose Spanish name is 'sarilla'. Some years later, in the book
of icons of Lobelius (1581) five drawings of thyme are presented all being very difficult
to identify.
In the beginning of the seventeenth century, like preceding authors, Dodonaeus
(1616) also described two varieties saying: 'Thymo: unum cephaloton dictum, alterum
durius'. Today we can be sure that with the first he refers to Thynzbra capitata and with
the second to Thymus vulgaris. His Serpyllo vulgari seems to be a Thymus species of the
section Serpyllzlm. Furthermore, in his chapter 'De Serpyllo ex Dioscoride, Theophrasto
et aliis', he comments on the different ideas about Serpyllunz expressed by several
authors. H e describes T . mastichina, the first plant which he treats in his Chapter 1 8
on Tragoriganu?iz,applying the criteria of Dioscorides. W e can find in the work of
Bauhin (1623) a few years later, that he divides Thynzw into four parts: the first
( T . vulgaris folio tenzliore), as well as the second ( T . vulgaris folio latiore) seems to be
T . vulgaris; the third is called Thynzw capitatus (today Thynzbra capitata), and the fourth is
Thyvzum inodorunz. Within his Serpyllum nine different varieties are considered; the
last one, 'Serpyllum folio Thymi', has turned out to be identical with the Zygis of
Dioscorides.
In the eighteenth century Barrelier (1714) presents a book of icons. Icon number 788
represents T . nzorodevi (Martinez, 1936) from 'the kingdom of Valencia'; icon number
780 shows T . hyenzalis (Figure 1. l ) and number 694, entitled Marum hispanicurn, contains
a drawing of T . piperella. In his list of names with short explanations Tournefort (1719)
described six varieties of T . lusitanicus, four of them are T . lotocephalus and another is
T. mwohi (Figure 1.2). Within Thymbra he considers 'ThyvzLva hispanica', with T. mastichina
and T . zygis.

The Linnean Thymus

It is very interesting to observe the changes made by LinnC in his different works
about the Thymus species. Most of his knowledge is based on experiences of former
authors. In Hortus Cliffortianus (1737, pp. 305-306) he describes six species.
Nowadays we know that two of them, the latter ones, do not refer to Thynzw but to
Saturejd and Acinos. His No. 1, T , erectus turned out to be T . vulgaris (Figure 1.3), No. 2
T . repens is a species within the section Serpyllum, No. 3 is Thymbra capitata, and No. 4
T . mastichina (Figure 1.4). In his Hortus Upsalielzsis (1748, pp. 160-161) only
T . vulgaris and T . mastichina are mentioned. The reference work for the binomial
 The hi~tory,botany and taxonomy oftbe genus Thymus 3

Fzgz~re 1.1 Drawings from Barrelier (1714)work, number 780 corresponds to T. hye7zaIis.

system of nomenclature in Botany 'Species Pluntarunz 1st edition' (1753) includes the
following eight species in Thynzus: 1. T. serpyllanz, 2. T , vulgaris, 3. T . zygis, 4. T . acinos
(today Acinos urvensis),5 . T. alpinus (today Acinos a&inus),6. T. cephdlotos (today T. lotocephulus),
7 . T. villosas, and 8. T. pzlegioides (Figure 1.5). Within Saturejd we find 4. Sdt~~reja
nzastichina (today T . ~nastichina).
In Genera Plantarum (1754, p. 257) Linnaeus lists in 646. Thymas: Serpyllzm, Acinos,
and Mustirhina. Species Pluntarz~nz2nd edirion (1762, pp. 825-827) transferred T. nzustichina,
former Sutureju nzastichina, as number 8 into Thynzas. In the 1st edition this number was
 Figure 1.2 Drawings from Barrelier (1714) work, number 788 corresponds to T. moroderi.

established for T. pulegioides. This transfer Linnaeus commented on literally: 'Ambigit

media inter Saturejam et Thymum, sed cum stamina delirescant in fundo corollae,
et stylus corolla longior ad Thymum refero'. In Systema Nutarae 2 (12th edition, 1767,
P. 400) for the first time T. piperella appears.
 The history, botany and taxonomy of the genus Thymus 5

Ftgure 1.3 Typus of T. vulgaris in Linn6 (1737)Hortus Cliffortianus

After Linnaeus
Brotero (1804) described a new species, T. caespititiu~.Also Hoffmannsegg and Link
(1809), in their magnificent and big work about the Flora of Portugal, described
some new species: T. albicans, T. capitellatus, T. camphoratus, and T. sylvestris. It was
Bentham (1834) who, for the first time, divided the genus Thynzw into sections:
Matichina, with T. mastichina and T . tomentosuJ;Serpyllzkm with T, vulgaris, T. piperella,