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Contact dermatitis as an adverse reaction to some topically used European herbal medicinal products – Part 2: Echinacea purpurea–Lavandula angustifolia

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Contact dermatitis as an adverse reaction to some topically used European herbal medicinal products – Part 2: Echinacea purpurea–Lavandula angustifolia

Abstract

This review focuses on contact dermatitis as an adverse effect of a selection of topically used herbal medicinal products for which the European Medicines Agency has completed an evaluation up to the end of November 2013 and for which a Community herbal monograph has been produced. Part 2: Echinacea purpurea Moench–Lavandula angustifolia Mill.
Contact Dermatitis Review Article COD
Contact Dermatitis
Contact dermatitis as an adverse reaction to some topically used
European herbal medicinal products Part 2: Echinacea
purpureaLavandula angustifolia*
Sebastiano Gangemi1,2,3, Paola L. Minciullo1,2, Marco Miroddi1, Ioanna Chinou4, Gioacchino Calapai1
and Richard J. Schmidt5
1Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria, 98125 Messina, Italy, 2Operative Unit of Allergy and Clinical
Immunology, Azienda Ospedaliera Universitaria Policlinico ‘G. Martino’, Via Consolare Valeria, 98125 Messina, Italy, 3Institute of Clinical Physiology, IFC CNR,
Messina Unit, Via Consolare Valeria, 98125 Messina, Italy, 4Division of Pharmacognosy & Chemistry of Natural Products, Department of Pharmacy, University
of Athens, 157 71 Zografou Athens, Greece, and 5BoDD - Botanical Dermatology Database, Penarth, UK
doi:10.1111/cod.12328
Summary This review focuses on contact dermatitis as an adverse effect of a selection of topically
used herbal medicinal products for which the European Medicines Agency has completed
an evaluation up to the end of November 2013 and for which a Community herbal
monograph has been produced. Part 2: Echinacea purpurea Moench– Lavandula angustifolia
Mill.
Key words: adverse drug reaction; contact dermatitis; Echinacea purpurea;Hamamelis
virginiana;Hedera helix; herbal medicine; Humulus lupulus;Hypericum perforatum;
Juniperus communis;Lavandula angustifolia; phytodermatitis.
Plant Sources of Some European Herbal
Medicinal Products and the Adverse Skin
Reactions They May Elicit – Part 2: Echinacea
purpurea–Lavandula angustifolia
Echinacea purpurea Moench (syn. Rudbeckia purpurea
L.); family Compositae (or Asteraceae)
Known commonly as purple coneower, the owering
aerial parts of this plant are the source of the crude drug
Echinaceae Purpureae Herba. However, in Europe, the
Correspondence: Paola L. Minciullo, UOC Allergologia e Immunologia Clinica
Policlinico Universitario, Via Consolare Valeria, 98125 Messina, Italy. Tel: +39
090 2212049; Fax: +39 090 694773. E-mail: pminciullo@unime.it
Conflicts of interest: Gioacchino Calapai and Ioanna Chinou are both mem-
bers of the Committee on Herbal Medicinal Products (HMPC) of the Euro-
pean Medicines Agency (EMA). In accordance with EMA policy on scientific
publications, the following disclaimer is added: ‘The views expressed in this
article are the personal views of the authors and may not be understood or
quoted as being made on behalf of or reflecting the position of the European
Medicines Agency or one of its committees or working parties.’ There are no
other conflicts of interests to declare for the other authors.
[For Part 1, see Contact Dermatitis 71(1): 1– 12 (2014);
doi: 10.1111/cod.12222]
Accepted for publication 16 November 2014
crude drug itself is not normally encountered, but rather
ethanolic extracts of the herb or root (‘tinctures’), and
products prepared from the dried expressed juice (1). His-
torically, at least two other species of Echinacea may have
been collected and mislabelled as E. purpurea,namely
Echinacea angustifolia DC. and Echinacea pallida Nutt, and
much of the early research reported for E. angustifolia and
E. purpurea was probably actually conducted on E. pallida
(2). Furthermore, some authorities now believe E. angus-
tifolia to be a variety of E. pallida, naming these two taxa
as E. pallida Nutt. var. angustifolia Cronquist and E. pallida
Nutt. var. pallida, respectively (3). Notwithstanding this
confusion, these three taxa are now individually recog-
nized as sources of crude drugs in Europe, providing Echi-
naceae Angustifoliae Radix, Echinaceae Pallidae Radix,
Echinaceae Purpureae Herba, and Echinaceae Purpureae
Radix, which have accordingly been made the subjects of
individual Community herbal monographs (4).
Although indigenous to the United States and south
central Canada, these plants, and E. purpurea in partic-
ular, are widely cultivated for medicinal use, as garden
ornamentals, and for cut owers. They were tradition-
ally used as herbal remedies by the Great Plains Indian
tribes of North America. Later, settlers from Europe also
recognized Echinacea species as useful remedies both when
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Contact Dermatitis 72(4): 193-205 (2015) [ISSN 0105-1873]
CONTACT DERMATITIS CAUSED BY HERBAL MEDICINES GANGEMI ET AL.
taken internally and when applied externally for a variety
of conditions, including rattlesnake bites and other ven-
omous bites and stings, septic wounds, burns, abscesses,
colds, catarrh, tonsillitis, pyorrhoea (periodontitis), and
many other conditions (2, 5, 6). The Community herbal
monographs now recognize the use of orally administered
preparations only for the short-term supportive treatment
of the common cold. However, it should be noted that the
value of echinacea preparations in the treatment of colds
has not been unequivocally established (7).
The Community herbal monograph on Echinaceae
Purpureae Herba additionally recognizes a traditional use
for the external treatment of small supercial wounds
(1). Specically, the monograph recognizes the use for no
more than 1 week of an ointment containing the dried
juice expressed from the fresh herb.
The Community herbal monograph (1) acknowledges
that contact dermatitis may occur following cutaneous
use of E. purpurea preparations. However, published case
reports appear to be lacking. In a study of 1032 consec-
utive or randomly chosen patients in Dutch patch test
clinics in 1988–1989, 2 patients reacted to a proprietary
ointment containing ‘Echinacea tincture 10%’, report-
edly prepared from E. angustifolia (8).The signicance of
this observation is diminished because proper authentica-
tion of the patch test material was seemingly not carried
out, and nor were tests carried out with the Echinacea
tincture alone.
In view of the claimed immune stimulant activity of
echinacea products (2, 9), it is perhaps surprising that
reports of allergic side-effects are not more commonly
encountered either following topical exposure or follow-
ing oral administration. A case of echinacea-associated
anaphylaxis in an atopic woman in Australia was
reported in 1998 (10). In a later report, 5 cases of
adverse reactions to echinacea products in Australia
were evaluated comparatively. Three of the patients had
positive prick test results. A further 51 Australian adverse
drug reports implicating echinacea were then reviewed.
Observed reactions included cases of anaphylaxis, acute
asthma, and urticaria/angioedema. Four patients were
hospitalized, 4 reacted after their rst known exposure,
and 1 suffered multiple progressive systemic reactions.
In a follow-on study, 20 of 100 atopic subjects who had
never taken echinacea products also had positive prick
test reactions. Atopic subjects were over-represented
in those experiencing adverse reactions. Accordingly, it
was concluded that atopic patients should be advised
of the risks associated with oral exposure to echinacea
products (11). In 2001, a case of recurrent erythema
nodosum that was temporally and perhaps causally asso-
ciated with the oral use of echinacea as a herbal therapy
was reported from Canada (12); and in 2004, a are of
pemphigus vulgaris in a 55-year-old male was correlated
with ingestion of a herbal supplement containing echi-
nacea that he began taking after he developed an upper
respiratory tract infection (13).
It is generally thought that no single constituent or
group of constituents is responsible for the activities of
echinacea. Rather, several groups of constituents (the
alkamides, caffeic acid derivatives, polysaccharides, and
alkenes/polyenes) appear to contribute to activity (6).
Similarly, the constituent(s) responsible for the adverse
effects remain unidentied.
Hamamelis virginiana L.; family Hamamelidaceae
This species, commonly known as witch hazel, forms a
deciduous shrub or small tree. It is native to eastern North
America from Nova Scotia to Florida and as far west
as Texas, but is cultivated in Europe and elsewhere as
a garden ornamental. The leaves and the bark are the
source of the crude drugs Hamamelidis Folium (14) and
Hamamelidis Cortex (15), respectively. A herbal prepara-
tion known as Aqua (or Liquor) Hamamelidis, hamamelis
water, distilled witch hazel or just ‘witch hazel’, which is
an aqueous ethanolic distillate prepared from the fresh
leaves and bark or from the dried twigs, is also the sub-
ject of a Community herbal monograph (16). The plant
material used commercially to prepare the crude drugs
and herbal preparations is obtained mainly from the east-
ern United States and Canada (17).
The leaves contains 3–10% tannins (catechins
and gallotannins, plus cyanidin and delphinidin-type
proanthocyanidins), avonoid galactosides and glu-
curonides, avonoids including kaempferol, quercetin,
quercitrin, and isoquercitrin, and 0.01–0.5% volatile oil.
The bark contains 8–12% tannins, small amounts
of avonols, and 0.1% volatile oil. It is richer in
hydrolysable tannins, whereas the leaves mainly con-
tain condensed tannins. Hamamelis water is a clear,
colourless liquid containing 13–15% ethanol, and
has the characteristic odour of the volatile oil distilled
from the plant material. Thus, in addition to water and
alcohol, hamamelis water contains steam-volatile sub-
stances, including 𝛼-ionones,𝛽-ionones, hexen-2-al, and
6-methyl-3,5-heptadiene-2-one (18), which are known
collectively as ‘hamamelis ketone’. It contains no tannins
(17), and therefore lacks the astringent properties of leaf
and bark preparations.
Historically, decoctions prepared from hamamelis
bark were used by North American Indians to prepare
poultices for use on ‘swellings and tumours of a painful
character’, as well as for ‘external inammations’. The
decoction of the bark is astringent (because of the tannins
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194 Contact Dermatitis,72, 193– 205
CONTACT DERMATITIS CAUSED BY HERBAL MEDICINES GANGEMI ET AL.
it contains), and has been used to treat ‘haemoptysis,
haematemesis and other haemorrhages’, as well as
‘diarrhoea, dysentery and excessive mucous discharges’,
haemorrhoids, ‘old, abby, fetid ulcers’, ‘sore mouth’, and
other such conditions (19).
It would appear that the supposed virtues of dis-
tilled witch hazel were invented by the pharmaceutical
industry in the late 1800s, when a proprietary prepa-
ration was originally introduced (20). Subsequently, a
non-proprietary preparation was made the subject of
pharmacopoeial monographs in the United States and
the United Kingdom (i.e. Liquor Hamamelidis), but then
seemingly fell out of favour. The preparation appeared
in a list of suggested deletions from the British Pharma-
copoeia (21), because it was considered to be ‘little more
than a weak solution of alcohol’. Shortly thereafter, in
1918, the United States Dispensatory (22), in describing
its uses, noted that ‘This water was probably introduced
into the British Pharmacopoeia and US Pharmacopoeia
IX on account of the large demand for it which has
grown out of the wide advertisements of a certain pro-
prietary medicine, and the universally recognized need
in American families for an embrocation which appeals
to the psychic inuence of faith. As the tannic acid of
hamamelis bark does not come over into the distillate the
water is therapeutically a mixture of water and alcohol,
the volatile oil being found in too minute a proportion to
possess any therapeutic value.’ Nevertheless, this prepa-
ration continues to be widely recommended as a soothing,
astringent application for sprains and bruises, as a
haemostat for small supercial wounds, and as an appli-
cation for minor skin irritation, authors [see, for example
(18, 23)] inadvertently perpetuating the notion that dis-
tilled witch hazel is endowed with the healing properties
associated with the tannin-containing preparations.
The Community herbal monograph (16) recognizes
the traditional use of distilled witch hazel for relief of
minor skin inammation and dryness of the skin, and
for the temporary relief of eye discomfort resulting from
dryness of the eye or exposure to wind or sun. In both
applications, the distillate is diluted before use, to a
strength corresponding to 5–30% in a semi-solid prepa-
ration for cutaneous use, and 1:10 in eye drops for ocular
use. In addition, the Community herbal monograph
recognizes the traditional use of herbal preparations
(variously: tinctures, decoctions, dry extracts, and liquid
extracts) of hamamelis leaf (14) and hamamelis bark
(15) for relief of minor skin inammation and dryness of
the skin, for symptomatic relief of itching and burning
associated with haemorrhoids, and as a mouthwash
and gargle for relief of minor inammation of mucous
membranes of the oral cavity.
‘Hamamelis’ has been described (24) as being one of
the less common causes of allergic contact dermato-
conjunctivitis. No positive patch test reactions to
‘Hamamelis virg. 10% in petrolatum’ were observed
in a series of 280 consecutive eczema patients (25). In a
series of 1032 consecutive or randomly chosen patients
in Dutch patch test clinics in 1988–1989, 2 patients
reacted on patch testing with Hamametum, a propri-
etary ointment containing ‘Hamamelis extract 25%’ used
for treating haemorrhoids. A further 2 patients reacting
to this ointment may have been reacting to the wool
fat in the ointment base (8). A non-atopic woman who
developed contact allergy to an unspecied proprietary
‘eye gel’ reacted when patch tested with the ‘witch hazel
distillate’ that it contained. Five control subjects did not
react to the eye gel (26). The identity of the sensitizer(s)
in witch hazel preparations remains unknown.
Hedera helix L.; family Araliaceae
This well-known plant is the common ivy, an evergreen
ground covering and climbing woody vine. It is native
to most of Europe and western Asia, but is found world-
wide, becoming a noxious weed where conditions suit its
growth (27). Selected cultivars are also widely grown as
house plants and as garden ornamentals.
The leaves are the source of the crude drug Hederae
Helicis Folium, otherwise known as Herba Hederae
Helicis. Historically in the United States, the leaves and
the berries have been used medicinally, applications
of the leaves having been recommended for ‘sanious
ulcers’ (i.e. those yielding a thin, fetid discharge of pus
mixed with serum or blood), ‘cutaneous eruptions’,
‘tetters’, and itch, and the berries were said to be purga-
tive and even emetic (22). In Europe, the internal use
of the leaves has been deprecated, whereas the utility
of a decoction prepared from the leaves for washing
and in poultices against vermin, scabies, skin diseases,
ulcers and abscesses has been acknowledged (28). More
recently, however, the leaves and the berries have become
recognized as a stimulating medicine for chronic catarrh,
bronchitis, and, especially, whooping cough (29) Applied
externally, ivy preparations are said to moderate the
sensitivity of the peripheral nerves, thus nding a use
in the external treatment of rheumatism, neuritis, neu-
ralgia and particular ‘cellulagias’ (i.e. neurotrophic
manifestations that include subcutaneous tenderness
and thickening) (29).
The most important constituents of H. helix are
bidesmosidic triterpene saponins based on hederagenin,
2𝛽-hydroxyhederagenin (also known as bayogenin), and
oleanolic acid. The main saponin is hederasaponin C
(also known as hederacoside C). Monodesmosides such as
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CONTACT DERMATITIS CAUSED BY HERBAL MEDICINES GANGEMI ET AL.
𝛼-hederin can develop by hydrolytic cleavage when fresh
leaves are dried. In addition, H. helix leaves have been
reported to contain avonoids (quercetin, kaempferol,
etc.), caffeic acid derivatives and other phenolics, such
as caffeic acid and dihydroxy-benzoic acid, the coumarin
glycoside scopolin, phytosterols (stigmasterol, sitosterol,
cholesterol, campesterol, and 𝛼-spinasterol), and poly-
acetylenes, including falcarinone, falcarinol, dihydrofal-
carinol, and didehydrofalcarinol (29–32).
The Community herbal monograph (33) recognizes a
well-established and traditional use of various aqueous
ethanolic extracts/preparations of the leaf of H. helix as
expectorants ‘in case of productive cough’ and ‘in cough
associated with cold’. No external/dermatological uses
are recognized, and listed undesirable effects include
allergic skin reactions, that is, skin rashes and urticaria,
and couperoses (i.e. broken capillaries and telangiecta-
sia). Interestingly, various leaf and stem extracts of H.
helix (CAS no. 84082-54-2) are recognized in Europe as
cosmetic product ingredients with a skin-conditioning,
hair-conditioning, astringent and/or antidandruff func-
tion (34). It follows that, in Europe, cosmetic products
are more likely to be the cause of adverse reactions to H.
helix-derived materials than herbal medicines. However,
the dermatological literature describes almost exclusively
reactions in gardeners, tree surgeons, horticulturalists
and the like following contact with freshly damaged plant
material (27, 35).
Leaves of the common ivy already had a reputation as a
remedy for treating corns when a case was reported from
Australia at the end of the 19th century of intense skin
irritation developing after application of ivy leaves soaked
in vinegar to a patient’s toes each night for a week. Three
further attacks of dermatitis occurred after she handled
wet ivy leaves (36). The skin-irritating properties of com-
mon ivy were, at that time, already known to gardeners
in England (37). Further reports quickly appeared in the
Australian, French and German literature (38–41), and
then sporadically over the next 40 years from the United
States (42–44) and Spain (45). More recent patch test
studies have shown sensitivity to H. helix in Australia
(46), South Africa (47), and England (48, 49). Individual
cases have been reported from Italy (50), England (51,
52), Switzerland (53), Denmark (54, 55), Spain (56,
57), and Germany (58). It has also been recognized that
patients sensitized to Algerian ivy (Hedera algeriensis Hib-
berd) react similarly to H. helix (59, 60), and that patients
sensitized to H. helix may react to several other plants
in the family Araliaceae (56, 61, 62) and also to carrots
(Daucus carota L., family Umbelliferae) (56, 63).
The contact allergens of H. helix have been identied
in guinea-pigs (64) as the polyacetylenes falcarinol and
didehydrofalcarinol. Irritancy at higher concentrations
was observed. The isolated substances elicited reactions in
patients being investigated for sensitivity to H. helix. The
allergenicity of falcarinol has also been shown in human
volunteers (32). A number of patch test studies in patients
being investigated for sensitivity to H. helix (32, 48, 56,
57, 64, 65) have now shown reactivity to falcarinol and
to didehydrofalcarinol.
Rarely, urticarial reactions following skin contact with
H. helix leaf extracts (54, 66) and anaphylaxis follow-
ing ingestion of a commercial ivy syrup product (67)
have also been reported, but the identity of the respon-
sible agent(s) remains to be established. An intense scar-
latiniform rash associated with hallucinations, and with
delirium and clonic convulsions alternating with stupor,
occurred in a 3.5-year-old boy who had eaten a quantity
of ivy leaves (68).
It may be deduced from the literature that sensitization
to H. helix is predominantly a hazard for gardeners, horti-
culturists, and those involved in similar such occupations
who come into contact with damaged plant material (35,
49, 51, 52, 65). However, falcarinol has been detected in a
H. helix extract-containing cosmetic product, so it is possi-
ble that individuals who have become sensitized through
contact with damaged H. helix (knowingly or unknow-
ingly) could react to such products (64).
Humulus lupulus L.; family Cannabaceae
This plant is the common hop, botanically a climbing
bine, which is best known for its fragrant green-coloured
ower cones (hop ‘strobili’ or ‘strobiles’) used in the brew-
ing industry for making beers. The dried ower cones
also provide the crude drug Lupuli Flos or Flores Humuli
Lupuli (69). The Community herbal monograph (70) rec-
ognizes the traditional use of Lupuli Flos, administered
orally, for the relief of mild symptoms of mental stress and
to aid sleep. Historically, hops have also been applied top-
ically in the form of a fomentation or poultice to treat
‘painful swellings and tumours’ (71, 22). Although no
dermatological uses are recognized in the Community
herbal monograph (70), various extracts and oils from
H. lupulus (CAS no. 8060– 28-4; CAS no. 8007-04-3)
are recognized in Europe as cosmetic product ingredi-
ents with skin-conditioning, hair-conditioning, perfum-
ing, masking and other functions (34). It follows that, in
Europe, cosmetic products are more likely to be the cause
of adverse skin reactions to H. lupulus-derived materials
than herbal medicines.
The sedative properties of hops have been recognized
for at least 180 years. An early report (72) described
a case of a 14-year-old girl who had been engaged in
hop-picking for a week. Because her hands were cold and
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196 Contact Dermatitis,72, 193– 205
CONTACT DERMATITIS CAUSED BY HERBAL MEDICINES GANGEMI ET AL.
chapped, she placed them in the hop-bin to warm them.
Shortly afterwards, she felt tingling and smarting on the
hands. The afiction was spread to her face because of her
habit of passing her hand over her forehead to arrange
her hair. She became somnolescent and had visual dis-
turbances. Her face became deeply erythematous and
swollen. By the next evening, her hands and face were
covered with vesicles. Since that time, dermatoses associ-
ated with hop-picking have been described in many other
reports. Systematic studies of occupational hop-related
skin diseases have been carried out in the United Kingdom
(73) and in eastern Europe (74, 75).
A case has been described of airborne dermatitis caused
by hops in a 57-year-old female farmer (76) who also
experienced acute dermatitis of the hands. Prick tests with
saline and glycerol extracts of hop leaves and cones gave
positive results, and a glycerol extract of the hop cones
produced positive patch test reactions at 48 and 72hr.
Relapses of her dermatitis occurred upon connubial expo-
sure to hop allergens on her husband, and to hop extract
present in an externally applied beauty cream and in an
orally administered herbal sedative.
A further case has been described (77) of a patient who
complained of urticaria on both hands while working
with ripe dried hops, although not with fresh ones. Type
1 allergy was conrmed by prick test and specic IgE.
The patiens also had a history of urticaria–angioedema
immediately after oral peanut (Arachis hypogaea L., family
Leguminosae), banana (probably a triploid, so-called
AAA group cultivar of Musa acuminata Colla, fam-
ily Musaceae) and chestnut (Castanea sativa L., family
Fagaceae) intake.
The causative agents of hop-induced contact skin reac-
tions remain to be established. However, it is evident that
both irritant and allergic effects have been described. In
hop pickers, the dermatitis has been attributed (78, 79)
to mechanical abrasion by the rough hairs on the climb-
ing stem. It has also been suggested (78) that lupulin, a
yellow powdery secretion of the glandular hairs on the
scales of the hop cones, may be responsible for the irrita-
tion. From a study carried out in a hop pickers’ hospital, it
was concluded that at least three distinct conditions were
associated with hop-picking, namely ‘hop rash’, ‘hop eye’,
and ‘hop gout’ (80). Hop rash was believed to arise from
the inevitable inoculation into the innumerable scratches
on the skin of hop pickers of proteins in hop juices and
hop pollen. A study carried out in Herefordshire (United
Kingdom) (73) obtained positive patch test reactions to
fresh hop oil (in 6 of 18 tests), aged hop oil (in 1/18),
hop cones (in 6/18), humulone (in 2/18), and lupulone
(in 2/18). Fresh hop oil contains 40% 𝛽-myrcene, but
this compound disappears from aged hop oil (81). It is on
the basis of these observations that 𝛽-myrcene, humulone
and lupulone have been assumed to be the low molecular
weight allergens in hop oil.
Hypericum perforatum L.; family Hypericaceae
This plant is commonly known as St John’s wort, this
name referring to the day, St John’s day (i.e. midsummer
day, June 24), on which the plant is normally seen to be
owering. It is a perennial herb with yellow owers, and
is indigenous to Europe and West Asia (82). The owering
tops of the plant, dried, provide the crude drug Hyperici
Herba (83).
Both well-established and traditional uses of herbal
substances/herbal preparations derived from St John’s
wort are recognized in Community herbal monographs.
Thus, the oral use of herbal preparations of St John’s
wort for the treatment of mild to moderate depressive
episodes is considered to be well established (84). In addi-
tion, three traditional uses are recognized, namely oral
use of herbal preparations for the relief of temporary men-
tal exhaustion, oral use for the symptomatic relief of mild
gastrointestinal discomfort, and cutaneous use for the
symptomatic treatment of minor inammations of the
skin (such as sunburn) and as an aid in healing of minor
wounds (85). Interestingly, it is believed that use of St
John’s wort on wounds might have a basis in the doctrine
of signatures, which suggested that a ‘wounded’ (perfo-
rated: H. perforatum) plant is intended by nature to cure
wounds (86). Uses of externally applied St John’s wort
preparations for several other conditions, with a basis in
folk tradition and medical experience, have been described
in the popular and medico-scientic literature (83, 87).
These other conditions include bruises, ulcers, varicoses,
haemorrhoids, myalgia, sciatica, rheumatism, lumbago,
cramps, and keloid scars.
The phytochemistry of St John’s wort is well docu-
mented. With reference to the dried drug, phloroglucinol
derivatives, principally hyperforin, adhyperforin, and
furanohyperforin, account for 0.2–4% by weight; naph-
thodianthrones, mainly pseudohypericin and hypericin,
protohypericin, protopseudohypericin, cyclopseudohy-
pericin, and skyrin derivatives, account for 0.06– 0.4%;
avonoids, mainly quercetin glycosides, account for
2–4%; and procyanidines and tannins account for
6–15%. Also present are small quantities of caf-
feoylquinic and p-coumaroylquinic acids, and an essen-
tial oil containing, among other volatiles, 2-methyloctane
and 𝛼-pinene (82, 83).
‘Hypericum oil’, otherwise known as Hyperici Oleum,
is not the essential oil but a liquid extract of the crude
drug prepared by using a vegetable oil such as olive
oil, sunower oil, linseed oil or wheat germ oil as a
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Contact Dermatitis,72, 193– 205 197
CONTACT DERMATITIS CAUSED BY HERBAL MEDICINES GANGEMI ET AL.
solvent. The liquid extract is then allowed to ferment
during storage in a warm sunny place for 6 weeks until
the oil is bright red. It has been reported that Hyper-
ici Oleum does not contain hypericin, the red colour
being ascribed to breakdown products of hypericin (88).
Hypericum Perforatum Extract (CAS no. 84082-80-4)
and Hypericum Perforatum Oil (CAS no. 68917-49-7;
CAS 84082-80-4) are recognized in Europe as cosmetic
product ingredients with ‘astringent/soothing/skin pro-
tecting/tonic/antimicrobial/masking’ and emollient
functions, respectively (34). However, there is much
confusion regarding the nature of various extracts and
preparations described in the literature. Infusions of the
herb or owers in a bland xed oil such as olive oil are
sometimes described as Hypericum Perforatum Extract
and sometimes as Hypericum Perforatum Oil. Further-
more, a xed oil can be extracted or expressed from the
seeds of the plant and, as noted above, a volatile oil can
be distilled from the whole plant, each of these also being
described as Hypericum Perforatum Oil. The term Hyper-
icum Perforatum Extract may also refer to a product
prepared by solvent (e.g. methanol or ethanol) extraction
of the capsules, leaves, and stem heads, followed by evap-
oration of the solvent. Therefore, care has to be taken to
determine exactly how extracts have been prepared when
interpreting the literature on this subject.
The potential of St John’s wort preparations to cause
adverse skin reactions in humans has to be viewed in
the context of the well-known propensity of several
Hypericum species to, on ingestion by animals, produce
primary photosensitization – a condition known as
hypericism – following absorption of hypericin (89– 92).
Presumably because St John’s wort is not eaten as a culi-
nary herb, photosensitivity resulting from ingestion of the
plants has not been observed in humans. Photosensitivity
was also not observed in a prospective randomized study
of patients taking H. perforatum extract at doses used
for the treatment of depressive disorders (93). However,
photosensitivity/skin reddening/erythroderma/itching
has very occasionally been reported in patients taking St
John’s wort extracts medicinally (94–99).
In a report on the safety of Hypericum Perforatum
Extract and Hypericum Perforatum Oil, produced for
review by a self-styled Cosmetic Ingredient Review
Expert Panel in the United States (100), the results of
dermal irritation, sensitization and photosensitization
tests were reported. The materials tested were described
(unfortunately, rather inadequately) as ‘a mixture of
Hypericum Perforatum Extract (1–5%), olive (Olea
Europaea) oil (>50%), and tocopherol (<0.1%)’ and ‘a
mixture containing Hypericum Perforatum Oil, butylene
glycol, and water (percentages not specied)’. These
preparations were found variously to be non-irritating,
non-sensitizing and not phototoxic when applied to rabbit
or guinea-pig skin. However, it was reported that Awassi
sheep fed the owers for 14 days did show signs of dermal
and generalized toxicity.
A case of contact dermatitis has been reported in a trap-
per in Australia (101), who complained of extensive der-
matitis of the exposed parts, which he suspected had been
caused by (a botanically unidentied) St John’s wort. He
showed a blister-like reaction when patch tested with the
plant. The reaction was very severe, and took several days
to subside when the patch was removed. Contact photo-
toxicity of a 1% dispersion of hypericin has been shown on
mouse ears; the activity of the hexa-acetate ester of hyper-
icin was also investigated, this substance being found to be
similarly active at 60-fold greater dilution (102).
A patient with multiple solar keratoses, after undergo-
ing laser treatment with a Q-switched frequency doubled
Nd:YAG laser at 532nm, developed a severe phototoxic
reaction to the laser light. She was also treated for facial
telangiectasia by use of a pulsed dye laser emitting at
585 nm, to which she also developed an exaggerated
and unexpectedly severe response. It transpired that the
patient was taking St John’s wort at the time of the laser
treatment. Medication with St John’s wort was stopped,
and treatment with the same energy uence and wave-
length was carried out a month later, with no untoward
effects. Also, potential problems with the copper vapour
laser (578 nm) and with the krypton ion laser (532 and
568 nm) were considered to be likely in patients taking
St John’s wort (103). Similarly, orally administered St
John’s wort extract containing hypericin has been found
to lower the erythemal threshold to ultraviolet (UV) A
(104) and UVB (105) irradiation. Finally, some success in
the photochemotherapy of vitiligo by oral administration
and topical application of St John’s wort extracts has been
claimed (106, 107). As photodynamic therapy is used
as a treatment for psoriasis, a combination of photother-
apy with St John’s wort or puried/synthetic hypericin
rather than psoralens might be an option, but clinical
evidence for such the efcacy of such use is still missing
(87). However, a study of the clinical effect of topical
H. perforatum ointment without light exposure in 10
patients with plaque-type psoriasis has been undertaken.
Erythema, scaling and thickness were evaluated; all were
signicantly lower where the formulated ointment had
been applied (108).
Juniperus communis L.; family Cupressaceae
This plant is the common juniper, an evergreen shrub
or small tree that is widely distributed in the northern
hemisphere, from Arctic to Mediterranean latitudes. It
© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
198 Contact Dermatitis,72, 193– 205
CONTACT DERMATITIS CAUSED BY HERBAL MEDICINES GANGEMI ET AL.
has needle-like leaves and bears berry-like cones com-
monly known as juniper berries. These cones, dried,
provide the crude drug Juniperi Pseudo-fructus. The
essential oil obtained by steam distillation of the ripe cones
is known as Juniperi Aetheroleum, Juniperus Communis
Oil, juniper berry oil, or, simply, juniper oil (109). Both
Juniperi Pseudo-fructus (110) and Juniperi Aetheroleum
(111) are the subjects of Community herbal monographs.
In the eld of cosmetics, Juniperus Communis Extract
(otherwise known as Juniperus Fruit Extract; CAS no.
84603-69-0) and Juniperus Communis Oil [other-
wise known as Juniperus Communis Fruit Oil (CAS no.
73049-62-4) and Juniper Communis Berry Oil (CAS no.
8002-68-4)] are recognized as cosmetic product ingre-
dients with ‘tonic/deodorant/masking’ functions (34).
Confusingly, in the context that wood and leaf oils are very
different in Juniperus species (112), CAS no. 84603-69-0
also refers to other kinds of extracts from other parts of
the J. communis plant, for example Juniperus Communis
Wood Oil and Juniperus Communis Branch/Fruit/Leaf
Extract. Therefore, CAS numbers cannot be relied upon as
indicators of the chemical composition of these cosmetic
products.
No well-established uses, but only traditional uses,
of herbal substances/herbal preparations derived from J.
communis are recognized in Community herbal mono-
graphs. As regards cutaneous use, the only indication rec-
ognized refers to the use of the essential oil (juniper berry
oil) as an adjuvant in the relief of minor muscular and
articular pain. For this indication, 1–1.5 g of juniper oil
is used as a bath additive three or four times weekly in a
full bath for 10–20 min at 35– 38C (111).
The composition of the essential oil is well documented.
Over 100 constituents have been reported. As with all
essential oils, the composition can vary with geographical
source, but, typically, the oil comprises 58% monoter-
penes, these being mainly the monoterpene hydrocarbons
𝛼-pinene, 𝛽-pinene, 𝛽-myrcene, sabinene, and limonene.
Monoterpene alcohols, including terpinene-4-ol and ter-
pineol, are also present in the oil, together with various
sesquiterpene hydrocarbons, including 𝛽-caryophyllene,
𝛼-muurolene, and 𝛾-muurolene (109). Because these
volatile oil constituents are found in a multitude of other
plant-derived volatile oils/fragrances, the possibility of
cross-reaction with juniper berry oil in patients who are
contact-sensitive to one or other of those oils has to be
expected.
Undiluted juniper berry oil applied to the backs of hair-
less mice and swine was not irritating, but was moder-
ately irritating when applied to intact or abraded skin of
rabbits for 24hr under occlusion. No phototoxic effects
were reported for undiluted juniper berry oil on hairless
mice and swine (113, 114). Juniper Extract (undiluted
leaf extract) applied to the dorsal skin of 25 human vol-
unteers in photopatch tests did not induce irritation, pho-
toaggravation, or phototoxicity (115).
Skin irritation was observed in 2 of 20 subjects patch
tested (24 hr of application) with an aged sample of
juniper berry oil (116). Juniper berry oil (8% in petro-
latum) produced no skin irritation after a 48-hr closed
patch test on human subjects (113, 114).
In a human maximization test, no evidence of sensitiza-
tion was observed in any of the 25 subjects tested with 8%
juniper berry oil in pet. (113). In a more recent study, 86
of 299 patients with allergic reactions to an International
Contact Dermatitis Research Group perfume mixture con-
taining one essential oil and seven other fragrance sub-
stances were tested with juniper berry oil and 34 other
essential oils. Six of the 86 subjects were found to be sen-
sitive to juniper berry oil (117). The identity of the aller-
gen(s) was not determined.
A 53-year-old aromatherapist with an acute bilateral
hand eczema was patch tested with working dilutions of
essential oils. ‘Juniper essential oil’ (which may or may
not have been juniper berry oil) at a concentration of
1% in grape seed oil did not elicit any reactions at 48 or
96 hr (118). A 47-year-old patient who, over a period of
25 years, had to enter a smokehouse repeatedly during
the transportation of meat and sausage products devel-
oped both eczema of the face and hands and occupational
asthma in response to a spice used in the production of
sausages (containing juniper berry oil) and to a smoking
powder used in the smoking of sausages (containing
juniper). No further skin reactions or respiratory prob-
lems were observed after the patient began working in an
ofce (119).
Lavandula angustifolia Mill. ssp. angustifolia (syn.
Lavandula officinalis Chaix); family Labiatae (or
Lamiaceae)
Lavender, also known as English lavender, garden laven-
der, or true lavender, is a low-growing shrub that is native
to southern Europe but is extensively cultivated world-
wide as an ornamental plant and for the production of
its essential oil (lavender oil), which is used mainly as a
fragrance in cosmetic, domestic and professional products
(120), but is also in aromatherapy (121, 122). Both the
owering tops of the plant and the essential oil obtained
by steam distillation from the owering tops are also used
as traditional herbal remedies in Europe for the treatment
of anxious restlessness, agitation, insomnia, and similar
such conditions. Furthermore, lavender oil has been used
for local massage in cases of rheumatism, gout, neuralgia,
sciatica, and scabies (122).
© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Contact Dermatitis,72, 193– 205 199
CONTACT DERMATITIS CAUSED BY HERBAL MEDICINES GANGEMI ET AL.
The common name lavender is used loosely to refer
not only to the two currently recognized subspecies of
L. angustifolia but also to Lavandula latifolia Medik. (syn.
Lavandula spica var. latifolia L.; otherwise known as spike
lavender) and to numerous cultivars/hybrids between
these species, known as lavandins and referred to botan-
ically as Lavandula ×intermedia Emeric ex Loisel. Perhaps
understandably, the botanical name ‘Lavandula vera’is
commonly but unauthoritatively used for describing the
botanical source of ‘true’ lavender or lavender oil. How-
ever, true lavender is not L. vera DC., this name now being
considered to be a synonym of L. angustifolia ssp. pyre-
naica Guinea (123), otherwise known as the Pyrenean
lavender.
Strictly, the term ‘lavender oil’ refers to the essential
oil obtained by steam distillation from the owering
tops of L. angustifolia ssp. angustifolia; ‘spike lavender oil’
refers to the oil distilled from L. latifolia; and ‘lavandin oil’
refers to oils distilled from Lavandula ×intermedia culti-
vars. Confusingly, the cosmetics industry has referred to
lavandin plants botanically as ‘Lavandula hybrida’ (124),
from which the cosmetics ingredients Lavandula Hybrida
Extract (CAS no. 91722-69-9) and Lavandula Hybrida
Oil (CAS no. 8022-15-9) are supposedly derived (34).
L. hybrida’ is not an accepted botanical name: L. hybrida
E.Rev. ex Briq. is now recognized as a synonym of L. angus-
tifolia Mill., that is, true lavender, not lavandin, whereas
Lavandula ×hybrida Balb. ex Ging. is a synonym of Lavan-
dula ×heterophylla Viv. (123), the sweet lavender, a hybrid
believed to be derived from crossing Lavandula dentata L.
with L. angustifolia Mill. (Plant List). Lavandula Interme-
dia Oil (CAS no. 92623-76-2), that is, lavandin oil, is also
a recognized cosmetics ingredient. Furthermore, (true)
lavender oil may be referred to as Lavandula Angustifolia
Oil (CAS no. 8000-28-0 or 90063-37-9) or as Lavandula
Ofcinalis Flower Oil (CAS no. 84776-65-8). Thus, care
has to be taken when interpreting the results of pub-
lished investigations, because the essential oils derived
from these various species and cultivars do differ in their
composition.
The principal components of lavender oil are monoter-
pene alcohols (60–65%) and esters, comprising mainly
(–)-linalool and (–)-linalyl acetate. Also present are cis-
ocimene (3–7%), terpinene-4-ol (3 –5%), limonene, cine-
ole, camphor, lavandulyl acetate, lavandulol, 𝛼-terpineol,
𝛽-caryophyllene, geraniol, and 𝛼-pinene. Non-terpenoid
aliphatic components include 3-octanone, 1-octen-3-ol
and its acetate, and 3-octanol (122).
Community herbal monographs recognize the tra-
ditional oral use of both lavender ower preparations,
namely Lavandulae Flos (125), and of lavender oil,
namely Lavandulae Aetheroleum (126). Dermatological
use is also recognized, but only for lavender oil used
as a bath additive (1–3 g of oil per full bath) for relief
of mild symptoms of mental stress and exhaustion
and to aid sleep, with a recommendation that the
temperature of the bath should be 35– 38Candits
duration 10– 20 min. Notwithstanding the extensive
skin contact with lavender oil that occurs during such
‘balneotherapy’, contact dermatitis appears not to have
been reported following such exposure. In a blind study
involving 635 women who used, variously, ‘pure lavender
oil’ (botanical source not specied), ‘synthetic lavender
oil’ (of unspecied composition) or ‘an inert substance’
(2-isobutyl-3-methylpyrazine) as a bath additive (six
drops per bath, daily for 10days) postnatally to inves-
tigate the effectiveness of balneotherapy as a means
of reducing perineal discomfort, no side-effects were
reported (127). However, 2 cases of facial dermatitis
have been described in patients who used lavender oil
to refresh a ‘lavender pillow’ being used to aid sleep
(128). Also, 3 cases of gynaecomastia in prepubertal boys
occurred after topical application of products containing
lavender and tea tree oils – a ‘healing balm’ containing
lavender oil, a styling gel containing lavender and tea
tree oils, and a lavender-scented soap. The boys were
aged between 4 and 10years. Gynaecomastia resolved
after use of the lavender-containing products was dis-
continued. Anti-androgenic activity of both lavender oil
and tea tree oil was demonstrated in vitro by the use of
MDA-kb2 human breast cancer cells stably transfected
with an androgen-inducible and glucocorticoid-inducible
mouse mammary tumour virus–luciferase reporter
plasmid (129).
Formal studies involving human test subjects suggest
that lavender oil is benign upon skin contact. At a con-
centration of 16% in pet., lavender oil did not produce any
irritation after 48 hr in a closed patch test and produced
no sensitization reactions in a human maximization test
(130). Similar negative results were obtained with 5%
lavandin oil (124), 10% lavender absolute (131), and
8% spike lavender oil (132), each in pet. In a series of
evaluations of linalool, linalyl acetate and a number
of other linalyl esters for skin irritation in male and
female volunteers, no irritation was observed in a 48-hr
closed patch test with 20% linalool in pet. or in a 48-hr
semi-occluded patch test with 32% linalyl acetate in
acetone. However, mild irritation was observed in a 48-hr
semi-occluded patch test with 32% linalool in acetone.
No reactions were observed in the human maximization
test with 20% linalool in pet. in 25 male volunteers, but
3 positive reactions were observed with some samples
of linalyl acetate (10% in pet.) tested in a total of 131
volunteers. It should also be noted that linalool and
© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
200 Contact Dermatitis,72, 193– 205
CONTACT DERMATITIS CAUSED BY HERBAL MEDICINES GANGEMI ET AL.
linalyl acetate (100% concentration) have both been
shown to be irritant on prolonged contact (20 hr) with
rabbit skin, but, inconsistently, some studies reported
no irritation, whereas others reported mild or severe
irritation (133).
Prospective testing with linalool, linalyl acetate and
lavandin oil (each at 1% and 5%) in cohorts of 100 con-
secutive patients attending European patch test clinics
failed to elicit any allergic reactions (134). However, in
other similar prospective studies of consecutive patients, 6
of 1147 showed positive patch test reactions to 1% laven-
der oil in pet. (135), and 4 of 200 showed positive patch
test reactions to 2% lavender oil in pet. (136). In investiga-
tions of patients presenting with cosmetic or medication
use-related or occupationally acquired allergic contact
dermatitis, lavender, spike lavender and lavandin oils and
their components linalool, linalyl acetate, geraniol, etc.
are often found to elicit positive patch test reactions in
patients who have been exposed to these oils (137– 150).
A recent systematic review of case reports and case series
of adverse effects associated with aromatherapy found
that the most common adverse effect was dermatitis, and
that lavender oil (and also peppermint, tea tree oil, and
ylang-ylang oils) was found to be among the most com-
mon essential oils responsible for adverse effects (151).
An epidemiological study conducted in Japan showed an
increasing incidence of positive patch test reactions to
lavender oil, with the incidence rising from 1% to 14%
over a period of 9years in patients being investigated for
cosmetic use-related allergic contact dermatitis, this rise
seemingly being associated with a similar rise in the use
of lavender oil in aromatherapy (152). In a 6-year study
of cosmetics product allergens in Japan (153), lavender
oil (and also ylang-ylang, cananga and geranium oils,
and jasmine absolute) was found to be among the most
common causative agents.
The inconsistency of ndings in formal studies of
irritancy and allergenicity and in multicentre prospec-
tive studies can now be explained in light of the nding
that lavender oil (154) and its components linalool
(155–158), linalyl acetate (159) and geraniol (160)
are susceptible to autoxidation in air to form peroxides
and hydroperoxides that have been shown to be potent
contact allergens. In a recent multicentre study (161)
involving 4731 consecutive patients in 13 UK derma-
tology departments who were patch tested with both
stabilized limonene and linalool and with the hydroper-
oxides of these terpenes, 12 patients (0.3%) showed
positive patch test reactions to stabilized linalool. In
contrast, 281 (6%) reacted to linalool hydroperoxides,
prompting the observation that non-oxidized linalool
and, by extension, good-quality fresh lavender oils are
liable to produce false-negative patch test reactions.
Because of this nding that is the air oxidation products
of lavender oils that are mainly responsible for adverse
skin reactions to the oils, the International Fragrance
Association has, since 2009, recommended the addition
of an antioxidant 0.1% butylated hydroxytoluene or
𝛼-tocopherol – to lavender oil at the time of production
of the raw material to limit the formation of sensitizing
peroxides (162). Also, since the seventh Amendment to
the Cosmetics Directive 76/768/EEC made in 2003 (163),
and subsequently transposed into Regulation (EC) No.
1223/2009 (164), it has been mandatory in Europe to
declare the presence of linalool and geraniol in the lists
of ingredients on cosmetics products if their concentra-
tion exceeds 0.001% in leave-on products and 0.01% in
rinse-off products.
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European Parliament and of the Council
of 30 November 2009. Available at:
http://eur-lex.europa.eu/LexUriServ/
LexUriServ.do?uri=OJ:L:2009:342:0059:
0209:EN:PDF (last accessed 15 October
2014).
© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Contact Dermatitis,72, 193– 205 205
... [3] Moreover, preparations also vary owing to variations within the plant part used, the method used for the biochemical compound extraction, the geographic location. [4] Despite the variability among echinacea compounds, attempts have been made to standardize as well as to characterize the substance used in medical studies. [5] The properties of phytochemical constituents of echinacea roots have been analyzed for several oxidative stresses, including various types of cancers. ...
Preprint
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The information regarding the effect of the mycorrhizal inoculation on different Echinacea species is not available in detail. Therefore, here we determined the changes in the biochemical composition of echinacea as a result of mycorrhizal inoculation. This experiment was undertaken to assess the effect of the mycorrhizal association on biochemical properties of different echinacea species (E. angustifolia,E. purpurea, E. pallida). Here various echinacea species were inoculated with mycorrhiza to examine the species richness in different traits. The results established that biological traits (plant dry matter, chlorophyll content, carotenoid, N content, P content, K content) and physiological and mycorrhization characteristics (Root essential oil, ABTS Antioxidant, Ferric- Reducing Antioxidant, Total phenolic, AM Spore No., AM Root Colonization) both are higher under mycorrhizal association than the control plants of different echinacea species. E. purpurea showed greater results than the E. angustifolia and E. pallida. Among biochemical properties chlorophyll content, carotenoid and N, P, K were significantly higher underE. Purpurea than the E. angustifolia and E.pallida. Total dry matter was higher under E. angustifolia (49.23 g) and minimum dry matter was found under E. pallida (40.07 g). Physiological and mycorrhizal traits were significantly higher under E. purpurea than the other species. E. purpurea showed higher AM Spore No., AM Root Colonization 231.30, 78.70% respectively. Lowest physiological and mycorrhization characteristics were found under E. pallida. The result of mycorrhizal association was very effective for plant growth and increased bio-physicochemical properties than the control plants.
... Nonetheless, topically applied herbal medicinal preparations made of L. angustifolia may lead to such side-effects as contact dermatitis (Gangemi et al., 2015). Biological properties of linalool, namely sedative, anxiolytic, analgesic, anticonvulsant, anti-inflammatory, local anaesthetic, are discussed in the context of the molecule's chirality influence, the mechanisms of activity and type of study (in vitro, in vivo, clinical studies) (Aprotosoaie et al., 2014). ...
Article
Full-text available
Plant food additives are becoming more and more popular and broadly applied products, though the information on risks they poses to the organism is limited and contradictive. Obesity and overeating are some of the commonest health issues around the world, and people are increasingly consuming workability-enhancing preparations as a simple and fast method of weight control. The plant-based preparations are considered less harmful than the synthetic chemical ones. Lavandula angustifolia Mill., Melissa officinalis L. and Vitex angus-castus L. are broadly used as food additives and medicinal plants, despite the fact that their complex physiological assessment on model animals in the conditions of obesity has not yet been performed. We carried out a 30-day experiment on white male rats. All the animals were given high-fat diet, and the experimental animals, in addition to this diet, received 5% crumbled dry herbs of L. angustifolia, M. officinalis or V. angus-castus. Taking into account the overall amount of consumed food, the mean daily gain in body weight; at the end of the experiment, we determined the index of the weight of the internal organs, biochemical and morphological blood parameters. At the beginning and the end of the experiment, the rats were examined for motor and orienting activities, and emotional status. Rats on high-fat diet gained up to 112% body weight by the end of the experiment, while rats that had received V. angus-castus gained up to 119%, M. officinalis – 135%, L. angustifolia – 139%, compared with the initial body weight. Addition of medicinal plants to the diet led to increase in average daily weight increment, significantly and reliably after consuming lavender and lemon balm, less significantly and unreliably after eating Vitex. L. angustifolia and M. officinalis reduced the relative brain weight, and ingestion of L. angustifolia and M. officinalis caused notable decrease in the relative mass of the thymus (down to 58% and 47% of the relative weight of thymus in animals of the control group respectively). Also, these plants decreased the motor and orienting activities of the rats by the end of the experiment. As for the biochemical parameters of blood, the activity of alkaline phosphatase significantly increased to 406% following consumption of Melissa, to 350% after consuming lavender, and to 406% after Vitex, compared to the control group. Furthermore, all the groups were observed to have increased AST and ALT activities. Intake of lavender led to increases in cholesterol (to 125%) and LDL cholesterol (to 228%), whereas the groups that consumed lemon balm were observed to have decreases in urea nitrogen (to 79%), totalbilirubin (to 63%) and triglycerides (to 63%). Addition of Vitex led to increase in the index of aterogenecity against the background of notable fall in HDL cholesterol (to 52% of the control group). The medicinal plants also contributed to the normalization of the glucose level. Morphological analysis of blood revealed no significant changes, except heightened content of monocytes in blood, which is characteristic of all groups, including the control. Effects of L. angustifolia, M. officinalis and V. angus-castus on the organism of rats on excessive-fat diet require additional histological, histochemical and immunological surveys.
... Several reports have linked topical camphor application to allergic contact dermatitis, 80-82 but a review on contact dermatitis caused by topically used herbal medicines did not find an elevated risk for lavender, lavandin, and spike lavender oil. 83 Based on its established toxicity, 84 camphorcontaining ingredients should not be administered to toddlers and small children. 85 ...
Article
Full-text available
The main goal of this bulletin is to provide timely information and/or updates on issues of adulteration and mislabeling of essential oil (EO) of English lavender (Lavandula angustifolia Mill.) in particular with lavandin (Lavandula × intermedia Emeric ex Loisel, syn. Lavandula angustifolia Mill. × Lavandula latifolia Medik.), spike lavender (Lavandula latifolia Medik.), linalool and linalyl acetate-rich EOs, terpenes, and synthetic chemicals. This bulletin may serve as a guide for quality control personnel, the international herbal products, cosmetic, and essential oil industries, and the extended natural products community in general. It is also intended to present a summary of the scientific data and methods on the occurrence of species substitution, adulteration, the market situation, and economic and safety consequences for the consumer and the industry.
... Curcuma longa is a plant belonging to the family of Zingiberaceae whose rhizome, source of turmeric, has been used in cooking, cosmetics and medical treatments (Vaughn et al., 2016) from considerable time. The curcuminoids present in the rhizome are a mixture of curcumin, demethoxycurcumin, and bisdemethoxycurcumin (Gangemi et al., 2015). ...
Article
Full-text available
Curcumin, primary component of the spice turmeric extracted from the rhizomes of Curcuma longa, represents the major anti-oxidant and anti-inflammatory substance found in turmeric, acting thought various mechanisms not completely understood. Curcumin modulates cytokines, growth factors, transcription factors, inflammatory molecules and cell signaling pathways. During restorative dentistry practice, free resin monomers of 2-hydroxyethyl methacrylate (HEMA) propagate through dentin micro-channel and pulp into the bloodstream affecting cellular integrity. The study highlights the significance of application of curcumin bioactive component into liposomal formulations (CurLIP) to restore the homeostasis of dental pulp stem cells (hDPSCs) in response to 3 and 5 mmol L-1 HEMA treatment. Cell proliferation in combination with changes of the morphological features, proinflammatory cytokines secretion as Interleukin (IL) 6, IL8, Monocyte Chemoattractant Protein-1 (MCP1) and Interferon-gamma (IFNγ) were assayed along with the nuclear factor (NF)-kB, an inducible transcription factor involved in the activation of several cell processes associated to extracellular signal-regulated kinases (ERK) and posphorylated (p-) ERK pathway. Our results showed a decreased cell proliferation, morphological changes and upregulation of IL6, IL8, MCP1 and IFNγ in presence of 3 and 5 mmol L-1 HEMA treatment. CurLIP therapy in hDPSCs provokes an increase in cell proliferation and the block of inflammatory cytokines secretion through the inhibitory regulation of NFkB/ERK and pERK signaling cascade. The natural nanocarrier CurLIP influences numerous biochemical and molecular cascades causing anti-inflammatory properties in response to HEMA treatment in human dental pulp stem cells, representing an innovative endodontic formulation able to improve the quality of dental care with a major human community impact.
Chapter
Plants are a significant cause of skin reactions worldwide. Because most affected individuals do not present to a dermatologist, it is likely that skin reactions to plants are under-reported. Plants may induce mechanical irritant reactions, e.g., due to spines or hairs. Trauma to the plant may release chemical irritants such as calcium oxalate crystals or phorbol esters. Skin contact with furocoumarins in some plants, notably members of the Apiaceae, followed by exposure to ultraviolet A, induces a characteristic streaky rash leading to hyperpigmentation (phototoxicity). A few plant species including nettles (Urtica spp.) inject toxins into unsuspecting predators, a form of chemical warfare. These toxins include histamine, inducing nettle rash (urticaria). Other nonprotein plant constituents such as cinnamic acid derivatives may induce urticaria by a pharmacological mechanism. However, some individuals may develop immunologically mediated urticaria and even anaphylaxis caused by immediate hypersensitivity to plants or plant products, including fruit, vegetables, and nuts. Finally, a few plant families have the potential to induce allergic contact dermatitis; these include the daisy family (Asteraceae/Compositae) and poison ivy family (Anacardiaceae).
Article
Background Lavender is commonly used in aromatherapy and in a broad range of personal and household products. It has been identified as a contact sensitizer and has been reported to cause allergic contact dermatitis (ACD). Objectives To report our experience with contact allergy and ACD to lavender and to raise awareness of lavender as a potential contact allergen. Method A retrospective database review was performed of patients attending patch testing clinics at the Skin and Cancer Foundation, Victoria, Australia, from January 1, 1993 to December 31, 2017. Results Among the 2178 patients patch tested to lavender over this period, a total of 58 positive reactions were recorded in 49 individuals, giving a positive patch test prevalence for patients tested to lavender of 2.2%. Twenty‐seven patients were diagnosed with ACD. The most common sources of exposure to lavender were personal care products and essential oils. Of the patients with ACD, 74% were tested to lavender absolute with a positive result in 90% of cases. Conclusion Lavender is an uncommon cause of ACD but is important to consider given the potential for exposure through the use of personal care items and essential oils. This article is protected by copyright. All rights reserved.
Article
Background: Natural ingredients have variable compositions, so their allergenic potencies may differ. Objectives: To retrospectively analyse subjects reacting to herbal remedies over the past 27 years, with the aim of (i) evaluating demographic characteristics and lesion locations, (ii) describing the frequencies of positive patch test reactions, (iii) identifing sensitization sources, and (iv) studying concomitant sensitivity. Patients and methods: In total, 15980 patients were patch tested between 1990 and 2016 with the European baseline series and/or other series, product(s) used, and, whenever possible, the respective ingredients. Results: Altogether, 8942 (56%) of 15 980 patients presented with at least one positive reaction. Reactions to topical herbal medicines, most often applied to treat an eczematous condition, leg ulcers, or other wounds, were seen in 125 (0.8%), that is, 1.4% of the contact-allergic subjects. Hands, legs and feet were the most frequently affected body sites. Twenty-one botanical allergens were identified, the commonest being Myroxylon pereirae (balsam of Peru), Compositae plants, and tincture of benzoin. Many patients presented with multiple positive test reactions, and some did not react to the commercial allergens but only to the products used. Conclusions: Topical herbal remedies should not be applied on damaged skin, as multiple sensitization may develop. Moreover, patch testing with the culprit products is important for the diagnosis.
Article
Full-text available
Common ivy is an ornamental plant, that is ubiquitous in Mexico. Its allergens can cause contact dermatitis, asthma and allergic rhinitis. We describe two cases of anaphylaxis related to common ivy syrup ingestion. We performed skin prick test with Hedera helix syrup, and using a dialized and ultrafiltered of common ivy syrup commercial presentation (dry common ivy extract: 7mg/ml), as well as using Hedera helix pollen extract. We describe two cases of anaphylaxis related to ingestion of Hedera helix syrup. Skin prick test with the commercial presentation and with the pollen extract were positive in both patients. In this study we confirmed the causal relationship of anaphylaxis due to the ingestión of ivy syrup in two patients through skin prick tests with ivy syrup and ivy pollen extract. Common ivy can cause contact dermatitis, asthma and allergic rhinitis, but we do not know the allergens that could be related to systemic and respiratory reactions, then, more studies in this topic are requiered.
Article
One hundred and five outpatients with mild depressions of short duration were treated in a double-blind study with either 3 x 300 mg hypericum extract or placebo. The therapy phase was 4 weeks. The effectiveness was judged according to the Hamilton Depression Scale after 2 and 4 weeks. The values of the mean basic score in these periods fell from 15.8 to 9.6 or 7.2 in the active group, and in the placebo group, from 15.8 to 12.3 and 11.3. The difference between active and placebo groups were statistically significant with P < .05 and P < .01 achieved after 2 and 4 weeks, respectively. In the active group, 28 of 42 patients (67%) and, in the placebo group, 13 of 47 Patients (28%) responded to treatment. Notable side effects were not found.
Chapter
Concurrent with the development of commercial gas chromatography in the late 1950’s and early 1960’s, botanists and chemists began to realize the value of a “new” suite of characters for the analysis and classification of plants — the terpenoids. Not only are the terpenoids under strong genetic control (Irving and Adams 1973), but the use of electronic digital integrators give quantitative characters amenable to multi-variate and geographic analyses (Adams 1970a; Adams 1972a). Given this “new” suite of quantitative chemical characters, the field of terpenoid chemosystematics rapidly expanded during the next two decades. The purpose of this chapter is to orient the novice to some of the basic procedures of analyses of terpenoids (particularly steam volatile components) and to show the utility of these compounds for the analyses of patterns of variation within and among forest tree taxa.