PHYTOTHERAPY RESEARCH

Phytother. Res. 20, 519–530 (2006)

Published online 20 AprilBIOACTIVITY
2006 in Wiley InterScience
OF CHAMOMILE (MATRICARIA RECUTITA L.) 519
(www.interscience.wiley.com) DOI: 10.1002/ptr.1900

REVIEW ARTICLE
A Review of the Bioactivity and Potential
Health Benefits of Chamomile Tea (Matricaria
recutita L.)

Diane L. McKay* and Jeffrey B. Blumberg

USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA

Chamomile (Matricaria recutita L., Chamomilla recutita L., Matricaria chamomilla) is one of the most
popular single ingredient herbal teas, or tisanes. Chamomile tea, brewed from dried flower heads, has been
used traditionally for medicinal purposes. Evidence-based information regarding the bioactivity of this herb is
presented. The main constituents of the flowers include several phenolic compounds, primarily the flavonoids
apigenin, quercetin, patuletin, luteolin and their glucosides. The principal components of the essential oil
extracted from the flowers are the terpenoids α -bisabolol and its oxides and azulenes, including chamazulene.
Chamomile has moderate antioxidant and antimicrobial activities, and significant antiplatelet activity in vitro.
Animal model studies indicate potent antiinflammatory action, some antimutagenic and cholesterol-lowering
activities, as well as antispasmotic and anxiolytic effects. However, human studies are limited, and clinical
trials examining the purported sedative properties of chamomile tea are absent. Adverse reactions to chamo-
mile, consumed as a tisane or applied topically, have been reported among those with allergies to other plants
in the daisy family, i.e. Asteraceae or Compositae. Copyright © 2006 John Wiley & Sons, Ltd.

Keywords: Matricaria recutita; Chamomilla recutita; chamomile; herbal tea; tisane; apigenin.

INTRODUCTION NOMENCLATURE

While there is an extensive literature suggesting health
benefits associated with drinking teas prepared with
Camilla sinensis (i.e. black, green and oolong teas)
(McKay and Blumberg, 2002), evidence-based infor-
mation regarding the effects of most herbal teas, or
tisanes, is quite limited. One of the most commonly
consumed single ingredient herbal teas is chamomile,
prepared with dried flowers from Matricaria recutita L.
This is a review of the available scientific literature re-
lated closely or directly to the bioactivity and potential
health benefits of chamomile tea. Like many other
herbal preparations used in traditional cultures, the
therapeutic uses and purported health benefits of
chamomile are based largely on folklore rather than on
scientific substantiation. Information regarding the
phytochemical content, in vitro experiments, animal
models and human studies available in the recent sci-
entific literature is presented.
Chamomilla recutita L. (synonymous with Matricaria
recutita L. Rauschert, and Matricaria chamomilla) is an
annual herbaceous plant indigenous to Europe and
Western Asia that has been naturalized in Australia,
Britain and the USA. Also known as German chamo-
mile, Hungarian chamomile, mayweed, sweet false
chamomile or wild chamomile, the plant is cultivated in
Germany, Hungary, Russia and other southern and
eastern European countries for the flower heads. Infu-
sions and essential oils from fresh or dried flower heads
have aromatic, flavoring and coloring properties. Both
are used in a number of commercial products including
soaps, detergents, perfumes, lotions, ointments, hair
products, baked goods, confections, alcoholic beverages
and herbal teas.
NUTRIENT AND PHYTOCHEMICAL
CONSTITUTENTS

Over 120 constituents have been identified in chamo-

mile flowers (Mann and Staba, 1986). Amino acids,
polysaccharides and fatty acids are present in the muci-
* Correspondence to: Diane L. McKay, Antioxidants Research Labora- lage, which makes up approximately 10% of the flower
tory, Jean Mayer USDA Human Nutrition Research Center on Aging at head. The yield of the volatile or essential oil from the
Tufts University, 711 Washington Street, Boston, MA 02111, USA. flowers is 0.4–2.0%. The main constituents of the oil
E-mail: diane.mckay@tufts.edu
Contract/grant sponsor: U.S. Department of Agriculture (USDA) Agri-
include the terpenoids α-bisabolol and its oxides (≤ 78%)
cultural Research Service; contract/grant number: 58-1950-001 and azulenes, including chamazulene (1–15%) (Matos
Contract/grant sponsor: Hain Celestial Group (Boulder, CO). et al., 1993; Mimica-Dukic et al., 1993; Stanev et al.,
Copyright © 2006 John Wiley & Sons, Ltd. Received
Phytother. 15519–530
Res. 20, February(2006)
2006
Accepted 23 February
DOI: 2006
10.1002/ptr
Copyright © 2006 John Wiley & Sons, Ltd.
520 D. L. MCKAY AND J. B. BLUMBERG
1996; Pino et al., 2000; Pino et al., 2002). Chamazulene
is an artifactual component, formed under high tem-
perature and/or acidic conditions from matricin
(prochamazulene), which is present in fresh flower
heads. The formation of chamzulene can be minimized
with CO2 extraction (Reverchon and Senatore, 1994).
Farnesene (12–28%), spathulenol and spiroethers, in-
cluding the cis/trans-en-yn-dicycloethers (8 – 20%), are
also present in the volatile oil (Lis-Balchin et al., 1998;
Maday et al., 1999; Weglarz and Roslon, 2002). Teas
brewed from chamomile contain 10 –15% of the essen-
tial oil available in the flower. Qualitative and quanti-
tative differences in the essential oil of chamomile
are not markedly affected by growing conditions (e.g.
fertilizer rate, irrigation, pesticide application), but
can vary significantly between growing regions, in cul-
tivated versus wild plant populations, and with differ-
ent processing conditions (Salamon and Honcariv, 1994;
Povh et al., 2001; Szoke et al., 2003).
Wild and cultivated populations of chamomile also
differ with respect to mineral content. Wild growing
chamomile contains a wider variety of mineral elements,
while cultivated types have higher ratios of K/Na and
Ca/Mg (Maday et al., 2000). Whole plants contain about
36 µg/g Mn (Laila, 1988). The dissolution of most min-
erals present in chamomile tea is in the range 10–26%,
with K, Ca, and Mg present in the highest concentra-
tions (Maday et al., 2000).
Several flavonoids and other phenolic compounds
have been identified in various parts of the chamo-
mile flower head, i.e. ligulate flowers, tubular flowers
and receptacles. Apigenin (16.8%), quercetin (9.9%),
patuletin (6.5%), luteolin (1.9%) and their glucosides
are the major flavonoids present in the total flower,
although their relative concentrations vary within the
different flower parts (Mann and Staba, 1986; Mulinacci
et al., 2000; Barene et al., 2003). For example, apigenin
is more highly concentrated in the ligulate flowers (68%)
than in the tubular flowers (0.9%) or receptacles (0.8%),
while quercetin is lowest in the ligulate flowers (2.1%)
and higher tubular flowers (12.4%) and receptacles
(10.0%). Mulinacci et al. (2000) reported the presence
of large amounts (39.1%) of the cinnamic acid deriva-
tives ferulic and caffeic acid, as well as other unidenti-
fied phenolic derivatives (25.8% of the total flower).
The coumarins herniarin and umbelliferone (in a ratio
of 1:5) make up approximately 0.1% of the total
constituents (Kotov et al., 1991; Ahmad and Misra,
1997). These compounds, as well as the flavonoids and
phenolics, are soluble in hot water, and the amounts
obtained from frequent consumption of infusions or
teas are not negligible (Ceska et al., 1992; Mulinacci
et al., 2000).
IN VITRO STUDIES
Antioxidant capacity. Several laboratories have exam-
ined the antioxidant potential of chamomile. With
the ferric reducing ability of plasma (FRAP) assay,
Dragland et al. (2003) determined that the antioxidant
capacity of chamomile was relatively low (<18 mmol/
100 g) in comparison with a selection of other medici-
nal and culinary herbs. The mean value of the chamo-
mile varieties tested (17.7 mmol/100 g) was higher than
Copyright © 2006 John Wiley & Sons, Ltd.
coriander (3.3 mmol/100 g), but much lower than pep-
permint (78.5 mmol/100 g) and oregano (137.5 mmol/
100 g, the highest value obtained). Lee and Shibamoto
(2002) reported the activity of a dichloromethane
extract of a steam-distilled solution of dried chamomile
(20 g/L water) using two different assay systems. In
the aldehyde/carboxylic acid assay, with BHT and α-
tocopherol as the standards, the highest dose (500 µg/
mL) of the chamomile extract inhibited hexanal
oxidation by 50% over a 40 day period. All the herb
and spice plant extracts examined in this experiment
exhibited dose-dependent inhibitory activity between
concentration (10–500 µg/mL) and antioxidant activity.
Compared with chamomile, the inhibition activities of
thyme and basil were higher (100%), lavender and
cinnamon were lower (5–6%) and rosemary was com-
parable (59%) in this assay system. In a conjugated
diene assay measuring the inhibition of hydroperoxide
formation from methyl linoleate (without initiators
or metal catalysts), the trend of inhibition for all
herbs and spices was similar to that of the hexanal
oxidation. At the highest concentration (200 µg/mL),
chamomile exhibited 31% inhibition of conjugated diene
formation.
Several commercially available essential oils of
chamomile were tested by Lis-Balchin et al. (1998) with
an agar plate-based method where the essential oils
were added to plates containing β-carotene and linoleic
acid, then incubated at 45 °C until the background color
was bleached. The antioxidant values were reported as
the intensity of retained color, and the diameter of the
color retention zone. Although not an ideal assay for
the assessment of antioxidant activity due to its intra-
assay variability, a small difference between the activi-
ties of the two German oils (diameter: 10.5 vs 13.6; color
intensity: very modest vs. modest) and a greater differ-
ence between German and Roman oils (diameter: 0)
were observed. Al-Ismail and Talal (2003) studied
the antioxidant effect of water and alcohol extracts of
chamomile flowers on long-term storage of anhydrous
butter fat. Both extracts showed a moderate effect in
controlling hydrolytic rancidity, measured by peroxide
value and free fatty acids, but the antioxidant effect of
the water extract was reported to be significantly higher
than the alcohol extract. No other studies measuring
the direct antioxidant potential of aqueous chamomile
infusions have been reported.
Chamazulene extracted from chamomile was shown
to inhibit Fe2+/ascorbate-induced lipid peroxidation,
measured with the thiobarbituric acid reactive sub-
stances (TBARS) assay, in a concentration and time-
dependent manner (50% inhibition with 18 µM after
45 min incubation) (Rekka et al., 1996). In the same
study, chamazulene (25 mM) was also shown to inhibit
the autoxidation of dimethyl sulfoxide (DMSO) (33 mM)
by 76%, and had a weak capacity to interact with
1,1-diphenyl-2-picrylhydrazyl (DPPH). In a different
study of chamomile extracts, McAnlis et al. (1997)
tested quercetin and apigenin, along with kaempferol,
myricetin and rutin for their effects on the oxidative
modification of LDL using both Cu2+- and 2, 2′-azobis(2-
amindinopropane) dihydrochloride (AAPH)-induced
oxidation. Quercetin was the most potent inhibitor
of Cu2+-mediated LDL oxidation, and apigenin was
the least. At 0.5 µmol/L, quercetin increased the
Cu2+-induced oxidation lag time by 64.3 ± 5.6 min.
Phytother. Res. 20, 519–530 (2006)
DOI: 10.1002/ptr
 BIOACTIVITY OF CHAMOMILE (MATRICARIA RECUTITA L.)
At the same concentration, quercetin increased
the AAPH-induced lag phase by 58.3 ± 3.1 min and
decreased the rate of propagation from 1.2 ± 0.1 to
0.8 ± 0.1 abs units/min. Conversely, apigenin (0.1–
5.0 µmol/L) added to LDL reduced lag time and
increased the rate of propagation in response to AAPH,
suggesting a possible pro-oxidant effect. The stati-
stical significance of the changes described in this study
was not reported.
Antimicrobial activity. Essential oils extracted from
chamomile have exhibited some antimicrobial activity
against certain species of bacteria, fungi and viruses in
vitro. German chamomile oils (Matricaria chamomilla)
were slightly more effective against 25 different gram-
positive and gram-negative bacteria and 20 strains of
Listeria monocytogenes than oil from Roman ‘chamo-
mile’ (Chamaemelum nobile), but neither was as effec-
tive as Moroccan ‘chamomile’ (Ormensis multicaulis)
(Lis-Balchin et al., 1998). At best, the efficacy of these
oils (10 µL) was low (8–56%) when compared with other
plant essential oils used in this experiment, e.g. bay
leaf (100%), clove (96%), cinnamon (96%), thyme
(56 –100%). However, the antifungal activities of the
German chamomile oils against Aspergillus niger, A.
ochraceus and Fusarium culmorum were, on average,
higher than the other two ‘chamomile’ oils (63–
75% inhibition). Soliman and Badeaa (2002) also re-
ported the antifungal activities of M. chamomilla oil
against two additional Aspergillus strains (A. flavus, A.
parasiticus) and F. moniliforme. In this experiment, the
highest concentration of chamomile oil used (3000 ppm)
exhibited the highest inhibition against these micro-
organisms (91–95%); however, the oils of thyme and
cinnamon were more effective at lower concentrations
(≤500 ppm). Esters and lactones from German chamo-
mile showed activity against Mycobacterium tuberculo-
sis and M. avium (Lu et al., 1998), and an ethanol
extract of German chamomile inhibited the growth
of both herpes and polio virus (Aggag and Yousef,
1972; Vilagines et al., 1985). Al-Ismail and Talal (2003)
reported that, in general, aqueous extracts of chamo-
mile were more effective against molds and yeast,
while alcohol extracts showed higher activities against
bacteria.
Anti-platelet activity. Chamomile was reported by Pierre
et al. (2005) to be one of only three herbs (of the
28 aqueous extracts tested) to exhibit significant anti-
platelet activity in vitro. Nettle and alfalfa were the
other two. Chamomile inhibited platelet aggregation
induced by ADP (60%) and collagen (84%), as well as
whole blood aggregation induced by collagen (30%)
compared with controls (p < 0.05). Although none of
the three herbs were able to inhibit arachidonic acid or
thrombin-induced platelet aggregation, chamomile and
alfalfa strongly inhibited thromboxane B2 synthesis
induced by either ADP or collagen. However, unlike
alfalfa and nettle, chamomile did not significantly in-
crease cGMP levels in platelets.
Apigenin – chemopreventive potential. Chamomile is
one of the richest natural sources of apigenin (840 mg/
100 g in contrast to 9 mg/100 g present in peppermint),
a flavone that is extracted from the ligules for commer-
cial use. Apigenin has an effect on a number of cellular
Copyright © 2006 John Wiley & Sons, Ltd.
521
processes including cell cycle progression (Sato et al.,
1994; Lepley et al., 1996; Lepley and Pelling, 1997;
Reiners et al., 1999), cell signaling enzymes, pathways
and gene expression (Kuo et al., 1994; Huang et al.,
1996; Lin et al., 1997; Uda et al., 1997; Kanda et al.,
1998), the regulation of cell membrane transport
(Morita et al., 1990; Illek and Fischer, 1998; Lenne-
Gouverneur et al., 1999; Niisato et al., 1999; Avallone
et al., 2000), gap junctional intracellular communica-
tion (Chaumontet et al., 1994; Chaumontet et al., 1997),
cytokine production and the inflammatory response
(Gerritsen et al., 1995; Smolinski and Pestka, 2003).
Evidence supporting the potential mechanisms involved
in these processes supports a potential role of chamo-
mile in chemoprevention (as an inhibitor of cell prolif-
eration and oncogene expression), on neuronal activity
and as an antiinflammatory agent.
In studies of cell cycle progression, flow-cytometric
analyses showed that apigenin was able to arrest rat
neuronal cells (Sato et al., 1994), mouse skin cells
(Lepley et al., 1996), human HL-60 cells (Lepley et al.,
1996) and human diploid fibroblasts (HDF) (Lepley
and Pelling, 1997) in the G2/M phase in a dose-
dependent and reversible (when apigenin was removed
from the culture) fashion. Lepley and Pelling (1997)
were also able to demonstrate an apigenin-induced
arrest of HDF in the G0/G1 phase using cells syn-
chronized in G0 and replated in medium containing
10–70 µM apigenin; at the lowest concentration, apigenin
reduced the percentage of cells in the S phase by
20% compared with control cultures.
Apigenin can inhibit selected enzymes involved in
intracellular signaling cascades and suppress the expres-
sion of proto-oncogenes, actions which suggest its
potential as a potential anti-cancer agent. Apigenin is
an effective mitogen-activated protein (MAP) kinase
inhibitor (Kuo and Yang, 1995; Kanda et al., 1998). In
mouse hepatoma cells apigenin was a more effective
inducer of quinone reductase activity (50% increase at
20 µM) than catechin and epicatechin (0% increase at
0–100 µM) but not quercetin (100% increase at 13 µM)
(Uda et al., 1997). Human cytochrome P450 3A4 was
inhibited 50% (IC50) with a commercially available
ethanol extract of chamomile diluted to 1–2% of
full strength (Budzinski et al., 2000). In a more recent
experiment, Ganzera et al. (2006) found that crude
chamomile essential oil (4.97 µg/mL), and its compo-
nents cis-spiroether (6.13 µM), trans-spiroether (7.14 µM)
and chamazulene (7.58 µM), were also potent inhibitors
of the 3A4 isoform. At 10 µM apigenin was able to in-
hibit protein kinase C activity (50%) in mouse fibroblast
cells by competing with adenosine triphosphate (ATP)
(Huang et al., 1996). It also reduced the level of 12-
O-tetradecanoyl-phorbol-13-acetate (TPA)-stimulated
phosphorylation of cellular proteins, and could suppress
TPA-induced expression of the oncogenes C-JUN and
C-FOS (Huang et al., 1996; Lin et al., 1997). Other stud-
ies have shown that apigenin could inhibit tyrosine
kinases (Kuo et al., 1994) and, in the case of prostate
cancer cells, it could reduce hyperphosphorylation (Lee
et al., 1998; Gupta et al., 2002), downregulate NF-kappa
B/p65, AR protein expression and decrease both intra-
cellular and secreted forms of PSA (Gupta et al., 2002).
In estrogen-dependent MCF-7 cells, 10 µM apigenin
inhibited estradiol (E2)-induced DNA synthesis (Wang
and Kurzer, 1998) and, in a different strain of steroid
Phytother. Res. 20, 519–530 (2006)
DOI: 10.1002/ptr
522 D. L. MCKAY AND J. B. BLUMBERG
hormone receptor-positive breast carcinoma cells,
acted as a weak progestin (Rosenberg et al., 1998). In a
subsequent experiment, Rosenberg Zand et al. (2001)
found that a 200 ng/mL ethanol extract of commerci-
ally available chamomile gel capsules exhibited both
weak estrogenic and progestational activity, but not
androgenic activity in their tissue culture screening
assay.
The effects of apigenin on nuclear receptor levels
were demonstrated by Seagart et al. (2000). Using
human keratinocytes, apigenin potently inhibited vita-
min D receptor (VDR) mRNA and protein expression
without changing the half-life of VDR mRNA. Con-
currently, retinoid X receptor (RXR) α was down-
regulated, p21(WAFI) was upregulated and c-myc
mRNA decreased dramatically.
The antimutagenic activity of apigenin has been as-
certained with the Salmonella typhimurium assay and
in Chinese hamster ovary cells. Mutagenesis induced
with 2-aminoanthracene, benzo[a]pyrene, 1-nitropyrene
(1-NP) or 1,6-dinitropyrene (1,6-DNP) were effectively
inhibited 43–62% in the presence of apigenin (Birt
et al., 1986; Kuo et al., 1992). Kuo et al. (1992) also
observed a significant and dose-dependent reduction in
the frequency of sister chromatid exchanges (SCE).
At 0–100 µM, apigenin did not prevent the in vitro
production of photoproducts in salmon sperm DNA,
suggesting that it is not effective in preventing DNA
damage due to ultraviolet light (UVA/B) (Birt et al.,
1997).
The biological effects of many flavonoids are due
to their interaction with the cellular plasma membrane
(Lenne-Gouverneur et al., 1999). In cultured bovine
adrenal chromaffin cells, apigenin had a moderate ef-
fect on stimulating tyrosine uptake, whereas quercetin
had no significant effect (Morita et al., 1990). Apigenin
also had a stimulatory effect on a bumetanide-sensitive
Na+/K+/2Cl− cotransporter in a renal epithelial cell
line (Niisato et al., 1999). Apigenin and quercetin both
stimulated Cl− currents in a dose-dependent manner in
transepithelial experiments using Calu-3 cells (Illek
and Fischer, 1998). In cultured rat cerebellar granule
cells, apigenin reduced γ-aminobutyric acid (GABA)-
activated Cl− currents in a dose dependent manner
(Avallone et al., 2000). In rat epithelial cells, 10–25 µM
apigenin enhanced gap junction (GJ) intercellular com-
munication and prevented the inhibition induced by a
tumor promoter, whereas other flavonoids such as
catechin (present in green and black tea) at 50 µM did
not (Chaumontet et al., 1994; Chaumontet et al., 1997).
In tumor cell lines, apigenin upregulated GJ function
and dye transfer in tumors expressing GJ nearly 4-fold,
but was inactive in a GJ-negative tumor cell line
(Touraine et al., 1998).
Apigenin – antiinflammatory actions. The therapeutic
potential for apigenin as an antiinflammatory agent
was demonstrated in vitro with its ability to interfere
with leukocyte adhesion and adhesion protein upregula-
tion in human endothelial cells (Gerritsen et al., 1995).
It also inhibited interleukin-1 (IL-1) α-induced pro-
staglandin synthesis, tumor necrosis factor (TNF)-
α-induced IL-6 and IL-8 production, and blocked
adhesion of leukocytes to cytokine-treated endothelial
cells. In murine macrophage cells, 3.7 and 37 µM
apigenin significantly inhibited LPS-induced IL-6 pro-
Copyright © 2006 John Wiley & Sons, Ltd.
duction in a dose-dependent manner, but not TNF-α
(Smolinski and Pestka, 2003). Other studies using
apigenin in cell culture models have also shown
that this flavonoid has inhibitory effects on adhesion
molecule expression (Panes et al., 1996; Wolle et al.,
1996), prostaglandin (PG) E2, cyclooxygenase (COX)-
2 and nitric oxide production (Liang et al., 1999). A
different component of chamomile oil chamazulene,
but not its precursor matricine, has also been shown
to inhibit the inflammatory process in vitro (Safayhi
et al., 1994). At 15 µM, chamazulene inhibited the
synthesis of leukotriene B4 in stimulated rat peritoneal
nucleophilic granulocytes by 50%, whereas matricine
had no effect up to the highest concentration tested
(200 µM). Additionally, 2 µM chamazulene blocked the
chemical peroxidation of arachidonic acid in a cell-free
system, while 200 µM matricine exhibited a moderate,
but non-significant, inhibition. In an experiment exam-
ining histamine release from rat mast cells, another
chamomile essential oil component, en-yne dicycloether,
partly inhibited a protamine sulphate-provoked de-
granulation at concentrations >100 µM, whereas neither
chamzulene nor α-bisabolol had any distinct effects
(Miller et al., 1996). The potential anti-allergenic
activity of chamomile has been demonstrated in vitro
in human basophils (Middleton and Drzewiecki,
1982). Quercetin and apigenin were the most effective
inhibitors of antigen-induced histamine release from
basophils among the 22 naturally occurring flavo-
noids tested. At 50 µM, quercetin inhibited histamine
release by 95.8% and apigenin by 89.4%; by com-
parison, the inhibition activity exhibited by catechin
was only 5.7%.
ANIMAL MODEL STUDIES
Antiinflammatory actions. A freeze-dried extract of
chamomile given to Wistar albino rats suppressed both
the inflammatory effect and leukocyte infiltration in-
duced by a simultaneous injection of carrageenan and
prostaglandin E1 (Shipochliev et al., 1981). In mice fed
a diet containing 1.2% w/w of an ethyl acetate extract
of dried M. recutita flowers for 11 days, scratching
behavior induced by the compound 48/80 was sup-
pressed in a dose-dependent manner (Kobayashi et al.,
2003). In addition, both the ethyl acetate fraction of an
ethanol extract and the ethanol extract of a hot water
infusion of the German chamomile flower also showed
strong inhibition towards 48/80-induced scratching.
The inhibitory effects of these chamomile extracts
were comparable to the effect elicited with 10 mg/kg
of the anti-allergenic agent, oxatomide. In a later
experiment, Kobayashi et al. (2005) determined that
the antipruritic effects of the ethyl acetate extract, as
well as chamomile essential oil, were dose-dependent.
The ethyl acetate preparation (300 mg/kg) was also
shown to enhance the effects of either antihistamic
agent oxatomide or fexofenadine (10 mg/kg) with com-
bined administration. In rats pretreated with apigenin
(50 mg/kg, p.o.), the upregulation of TNFα-induced
intercellular adhesion molecule-1 (ICAM-1) was effec-
tively blocked 5 h after treatment with rTNF (Panes
et al., 1996). The mechanism involved in this blocking
action was suggested to be unrelated to free radical
Phytother. Res. 20, 519–530 (2006)
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 BIOACTIVITY OF CHAMOMILE (MATRICARIA RECUTITA L.)
scavenging or leukocyte function. Pro-inflammatory
cytokine production was inhibited in mice pretreated
with 50 mg/kg apigenin for 1 h then injected with stimul-
ant lipopolysaccharide (LPS) (Smolinski and Pestka,
2003). Analysis of serum collected 90 min later showed
lower levels of LPS-induced IL-6 (65%) and TNF-α
(76%) in apigenin-treated animals (n = 12) compared
with those treated with LPS alone (n = 6). Apigenin
also demonstrated delayed type hypersensitivity in the
mouse (Gerritsen et al., 1995) and potent antiinfl-
ammatory activity in carrageenan-induced rat paw
edema (Al-Hindawi et al., 1989; Gerritsen et al.,
1995).
A lyophilized ethanol extract of dried chamomile
administered to Wistar rats (n = 10), at 1.6 g fresh plant/
kg bw (equivalent to 1% of the estimated lethal dose),
inhibited paw edema by 41.1% compared with control
rats (n = 35) receiving only carrageenan (Al-Hindawi
et al., 1989). By comparison, the edema in rats treated
with 100 mg/kg acetylsalicylic acid was inhibited by
32.4%. In Swiss mice, the topical application of a chamo-
mile extract to the inner surface of the ear reduced
edema induced by the application of a 2.5% emulsion
of croton oil (Tubaro et al., 1984). In this experiment,
an ethanol extract of chamomile containing 0.05 mg/
mL α-bisabolol, 0.45 mg/mL bisabolol oxides, 0.4 mg/
mL apigenin and its glucosides, 0.8 mg/mL en in
dicycloethers, and 0.02 mg/mL azulenes was applied to
test animals in doses equivalent to 0.75, 0.25 and 0.08 mg
of dried flowers per animal (n = 40/group). Compared
with control animals (n = 104), mice treated with 0.25 mg
of chamomile extract had an 8.5% reduction in edema
and those treated with 0.75 mg had a 23.4% reduction.
No significant changes were observed in mice treated
with the lowest dose used (0.08 mg). The 0.75 mg dose
of chamomile extract induced a reduction similar to
that obtained with 0.45 mg benzydamine (26.6%), a non-
steroidal antiinflammatory agent used as a reference;
however, neither treatment reached the level of reduc-
tion attained with 0.15 mg hydrocortisone (56.4%).
Della Loggia et al. (1990) found that topical treatment
with an extract of fresh chamomile containing 51.8 mg/
100 g bisabolol, 29.6 mg/100 g matricine and 5.3 mg/100 g
apigenin at a dose equivalent to 750 µg of dry product
(n = 25) was as effective as the reference drug, 0.60 mg
benzydamine (n = 25) in preventing inflammation
in mice subjected to croton oil induced edema. The
benzydamine, fresh chamomile extract and dried chamo-
mile extract (54.6 mg/100 g bisabolol, 16.4 mg/100 g
matricine, 6.3 mg/100 g apigenin; n = 26) inhibited
the inflammatory response in this model by 31.6%,
31.6% and 23.7%, respectively, compared with the
control group (n = 41); however, chamomile essential
oil containing 55.6 mg/100 g bisabolol, 4.7 mg/100 g
chamazulene, but no matricine or apigenin at a dose
equivalent to 30 µg essential oil was ineffective (6.6%
inhibition; n = 25).
Tumorigenesis. The topical application of chamomile
was also tested for its effectiveness on skin tumori-
genesis in mice. Tumorigenesis initiated by 7,12-
dimethylbenz(a)anthracene (DMBA) and promoted by
TPA in SENCAR mice was attenuated by the applica-
tion of 20 µM apigenin (Wei et al., 1990). In this experi-
ment, no carcinomas occurred 33 weeks after DMBA
initiation in apigenin-treated animals, while 48% of
Copyright © 2006 John Wiley & Sons, Ltd.
523
those not treated with apigenin developed tumors. A
second experiment showed that apigenin also decreased
the incidence of DMBA-induced skin papillomas. The
papilloma incidence 26 weeks post-DMBA for mice
treated with 0, 5 and 20 µM apigenin was 93.3%, 58.0%,
and 39.3%, respectively. A tendency to decrease
the conversion of papillomas to carcinomas was also
observed with apigenin treatment, although there were
no significant differences between the three groups. In
a different study, the pretreatment of mouse epidermis
with apigenin for 30 min prior to the application of 17 nM
TPA inhibited the induction of ornithine decarboxylase
(ODC) activity by 6 h (Birt et al., 1986) and, in a dose
response test, 30–90% inhibition of TPA-induced ODC
was observed in mice pretreated with 12.5–100 µM
apigenin. ODC activity induced with 0.45 J/cm2 ultra-
violet A and B (UVA/B) light was inhibited 25–45%
in mice treated with 5 µM apigenin for 12 h prior to and
1 h following UVA/B exposure (Birt et al., 1997). Mouse
skin carcinogenesis induced by exposure to 40 J/cm2
UVB alone over 11 weeks was also attenuated by
treatment with 10 µM apigenin. Cancer incidence was
also reduced (52%), and a significant increase in tumor-
free survival was observed in apigenin-treated animals.
DMSO and DMSO/acetone were found to be appro-
priate and effective vehicles for topical delivery of
apigenin in mouse skin (Li and Birt, 1996; Li et al.,
1996); these beneficial effects against skin cancer
were not achieved via systemic circulation (Li et al.,
1996). Injections of apigenin in mice bearing tumors
from a mixture of 90% wild type and 10% herpes
simplex virus-thymidine kinase gene-modified MCA38
adenocarcinoma cells did have an antitumor effect
(Touraine et al., 1998) with a remission in apigenin-
treated animals of 60–70% compared with 30% in
mice treated with the antiviral agent ganciclovir
alone.
Antigenotoxic actions. Chamomile essential oil attenu-
ated the genotoxic effects of the mutagenic agents
daunorubicin and methyl methane sulfonate (MMS) in
mouse bone marrow (Hernandez-Ceruelos et al., 2002).
Mice injected with 5, 50 or 500 mg/kg chamomile oil
plus 10 mg/kg daunorubicin (n = 5/group) had 25.8%,
75.6% and 75.6% fewer sister chromatid exchanges
(SCE) than mice treated with daunorubicin alone. A
similar effect was found in mice treated with 250, 500
or 1000 mg/kg chamomile oil plus 25 mg/kg MMS with
inhibition of SCE at 24.8%, 45.9% and 62.5%, respec-
tively, when compared with the control group treated
with MMS alone. No changes in either cellular prolif-
eration kinetics or mitotic indices were observed in the
chamomile oil/MMS groups; however, a lack of cytotoxic
protection against daunorubicin with chamomile oil at
the two highest doses was reported.
Hypocholesterolemic effects. An aqueous extract of
chamomile was reported to have an effect on serum
cholesterol levels in hyperlipidemic Wistar rats (Al-
Jubouri et al., 1990). After 10 days, the hyperlipidemic
mice treated orally with a 6% aqueous extract of chamo-
mile (4 mg/kg) had significantly reduced serum choles-
terol compared with control rats; no changes were
observed in serum triglyceride levels. The chamomile
extract had no effect on the control rats with respect to
either cholesterol or triglycerides.
Phytother. Res. 20, 519–530 (2006)
DOI: 10.1002/ptr
524 D. L. MCKAY AND J. B. BLUMBERG
Cardiac effects. In spontaneously beating isolated rat
atria, exposure to apigenin had a positive chronotropic
effect (Lorenzo et al., 1996). At 0.01–30 µM apigenin
increased the atrial rate in a dose-dependent manner
and reduced the uptake of radiolabeled noradrenaline.
Gastrointestinal effects. The antispasmodic effects of
different chamomile preparations have been examined
in isolated guinea-pig ileum. According to Achterrath-
Tuckermann et al. (1980), compounds contained in
both aqueous and oil extracts of the plant are effective
antispasmodics in isolated guinea-pig ileum. Compared
with papaverine, a smooth muscle relaxing drug, α-
bisabolol was 91% as effective on spasms induced
with barium chloride, while bisabolol oxides A and
B were 46–50% as effective. Among the flavonoids
tested, apigenin was 3.3 times more potent than
papaverine, followed by quercetin, which was 72% as
active, patuletin (68%) and luteolin (44%). Using the
same model, Forster et al. (1980) demonstrated the
effectiveness of an ethanol extract of chamomile on
spasms induced by acetylcholine and histamine. At doses
of 2.5 and 10 mL/L (of a 31% w/w solution), the chamo-
mile extract shifted the dose response curves of both
acetylcholine and histamine to the right, reflecting an
increase in their median effective dose, when compared
with an ethanol control solution. Atropine (7 µg/L)
similarly shifted the dose response curves but, unlike
chamomile, this antispasmodic drug was unable to de-
crease the maximal contraction in response to either
acetylcholine or histamine.
In rats, both apigenin and α-bisabolol inhibited the
development of gastric ulcers induced by indomethacin,
stress and alcohol (Szelenyi et al., 1979). In this study,
α-bisabolol was also shown to reduce healing times in
ulcers induced by either chemical stress or heat coagu-
lation. Apigenin, at 12.5–50 mg/kg administered i.p.
reduced both small and large intestinal transit time in
mice with castor oil-induced diarrhea (Di Carlo et al.,
1993). In contrast, catechin, the principal flavonoid in
green tea, administered at doses up to 200 mg/kg, had
no effect in this experiment.
Hepatic effects. Like green and black teas, chamomile
tea can modulate the activity of hepatic cytochrome
P450. Maliakal and Wanwimolruk (2001) provided
Wistar rats (n = 5) free access to a 2% chamomile tea
solution for 4 weeks and found the CYP1A2 isoform
activity was 39% lower than a control group given water
alone.
In a study by Babenko and Shakhova (2006), a prepa-
ration containing the chamomile flavonoids apigenin,
luteolin, apigenin-7-glucoside, luteolin-7-glucoside, isor-
hamnetin and quercetin reduced ceramide levels in the
liver of older rats. Ceramide accumulates in several
tissues and cells during the aging process, and regulates
the biochemical and genetic events that occur with time.
The administration of chamomile flavonoids (160 mg/
kg/day) for 7 days reduced the liver ceramide mass
and sphingomyelinase activity of older rats (age 27–28
months) down to the levels found in adult rats (24
months).
Central nervous system effects. Della Loggia et al. (1982)
employed a lyophilized aqueous extract of chamomile
prepared with 50 g flowers infused for 5 min with 1 L
Copyright © 2006 John Wiley & Sons, Ltd.
boiling water to study basal motility, exploratory and
motor activities of Swiss-NOS mice. Long-term motil-
ity was reduced 57.1% within 10 min of treatment
with 360 mg/kg chamomile i.p. (n = 15) and reached a
maximum inhibition of 92.1–97.5%, compared with
controls (n = 15) 1.5–2.5 h later; motor coordination
was not affected. Short-term motor activity was reduced
90% with a dose of 180 mg/kg i.p. (n = 24). Locomotor
activity was reduced by 46.0% and 56.5% and the
number of head-dippings reduced by 34.4% and 39.4%
with doses of 180 and 320 mg/kg, respectively. Chamo-
mile administered at 160 and 320 mg/kg i.p. (n = 16/
group) potentiated hexobarbital-induced sleep in mice
by 37.1% and 62.7%, respectively, compared with
controls given 100 mg/kg of the barbituate alone. In
mice, Viola et al. (1995) tested a purified fraction of an
aqueous chamomile extract containing apigenin admin-
istered i.p. to examine its effect on anxiolytic, sedative,
locomotor, myorelaxant and anticonvulsive activities.
At 3 mg/kg, a dose similar to those used for benzodia-
zepines (BDZ), apigenin significantly increased the
percentage of entries and time spent in the open
arms of an elevated plus maze, behaviors indicative of
an anxiolytic effect. Doses up to 10 mg/kg produced
no changes in spontaneous ambulatory locomotor
activity; at 30 and 100 kg/mL, there was a 26% and
46% reduction in activity, respectively, and a moderate
decrease in the head-dipping behaviors indicating a
mild sedative effect. At 100 mg/kg apigenin had no
myorelaxant effect, in contrast to 3 mg/kg of the
BDZ diazepam.
In mice treated with doses up to 80 mg/kg apigenin,
Viola et al. (1995) found no significant anticonvulsant
activity after challenge with 50–80 mg/kg of the seizure-
inducing pentylenetetrazole (PTZ); however, at 20, 40
and 80 mg/kg apigenin increased the onset time of con-
vulsions by approximately 2-fold compared with mice
given PTZ alone. Testing doses much lower than em-
ployed by Viola et al. (1995), Avallone et al. (2000)
found that apigenin did not have a significant anxiolytic
effect at 0.5–10 mg/kg. At 1.0 mg/kg the number of
entries and time spent in the open arms of an elevated
plus maze were higher than the control group, but did
not reach statistical significance. Similarly, Avallone
et al. (2000) reported that apigenin had no myorelaxant
effect up to 50 mg/kg and no effect on picrotoxin- (6
and 8 mg/kg) induced convulsions at 25 and 50 mg/kg,
but did significantly reduce the time of latency in the
onset of convulsions. Open field tests showed signifi-
cant reductions in locomotor activities compared with
controls at apigenin doses of 25 and 50 mg/kg, but not
at 12.5 mg/kg, indicating a sedative effect at the higher
doses, similar to Viola et al. (1995). The lack of effect
with the addition of a BDZ agonist to apigenin-treated
animals suggests that the sedative properties of apigenin
may not be due to a direct effect on BDZ receptors,
but to other neurotransmission systems.
Salgueiro et al. (1997) observed that 10 mg/kg
apigenin administered to Wistar rats either pre- or post-
training had no effect on training or test session per-
formance of inhibitory avoidance, active avoidance or
habituation to an open field, unlike diazepam which
had an amnestic effect on animals subjected to the same
tests. Also in contrast to diazepam, apigenin had no
effect on the tail-flick test, indicating the lack of an
analgesic effect. These results also suggest that apigenin
Phytother. Res. 20, 519–530 (2006)
DOI: 10.1002/ptr
 BIOACTIVITY OF CHAMOMILE (MATRICARIA RECUTITA L.) 525

affects BDZ receptors differently than classical BDZ

Decreased heart rate and ratings of sadness

Significant decrease in mean brachial artery

Significantly reduced crying time compared

Diarrhea ended sooner in treatment group

colic in 57% of treatment group vs 26% in

receptor ligands such as diazepam.

with placebo. 85% reduction in treatment

score compared with placebo. Eliminated

(85%) than placebo (58%). Duration was

Significantly higher colic improvement

In a study of ovarectomized rats, Yamada et al. (1996)
found that inhaling the vapor of chamomile oil reduced

and depression after drinking tea

a stress-induced increase in plasma adrenocorticotropic

group vs 49% in placebo group

hormone (ACTH) levels. Diazepam, co-administered
with the chamomile oil vapor, further reduced ACTH
levels, while flumazenile, a BDZ antagonist blocked

pressure from baseline

the effect of chamomile oil vapor on ACTH. Accord-
ing to Medina et al. (1998), the separation index (ratio
between the maximal anxiolytic dose and the minimal

also attenuated

placebo group
sedative dose) for diazepam is 3 while for apigenin it is
10. Compounds, other than apigenin, present in extracts

Outcome
of chamomile can also bind BDZ and GABA receptors
in the brain and are thought to be responsible for some
of the sedative effect; however, many of these com-
pounds are as yet unidentified (Avallone et al., 1996).

Duration

1 time

1 time
1 wk

1 wk
3d
HUMAN STUDIES AND POTENTIAL HEALTH/
THERAPEUTIC APPLICATIONS

Standardized herbal mixture (including

71.1 mg/kg/d chamomile) or placebo

Chamomile/apple pectin preparation

1 serving chamomile tea or placebo
In Germany, the chamomile flower is licensed as a

150 mL herbal mixture including

standard medicinal tea (infusion) for oral ingestion, for
topical application as a rinse or gargle, cream or oint-
ment, as a vapor inhalant, and as an additive for sitz or

chamomile or placebo
vapor baths. The German E Commission has approved

2 cups chamomile tea

chamomile for internal use to treat GI spasms and
Table 1. Summary of human studies examining the effects of orally ingested chamomile (Matricaria recutita)

inflammatory diseases of the GI tract, and external

use for inflammation of the skin, mucous membranes

(hot water)
and ano-genital area, bacterial skin diseases (including

or placebo
those of the oral cavity and gums) and respiratory
tract inflammation (Blumenthal et al., 1998). The list
Dose

of the purported benefits and uses of chamomile as a

folk remedy or as a complementary and alternative
medicine (CAM) therapy include: anodyne, antiallergy,

12 heart disease patients hospitalized

88 healthy breastfed infants (21–60

antiinflammatory, anxiolytic, antiseptic, carminative,

acute, non-complicated diarrhea

dermatitis, diuretic, poultice, sedative, spasmolytic, tonic

79 children (0.5–5.5 years) with

68 healthy infants (2–8 weeks)

and vulnerary. Studies providing evidence to either

support or refute the applicability of chamomile as a
treatment for many of these conditions in humans is for cardiac catheterization
Young Japanese males

quite limited (Table 1).

Gastrointestinal effects. No clinical trials have exam-

ined the gastrointestinal effects of chamomile alone,
although three trials have examined its efficacy in com-
Subjects

weeks)

bination with other components. Weizman et al. (1993)

tested the effects of a powdered herbal tea prepara-
tion containing extracts of M. chamomilla, vervain (Ver-
bena officinalis), licorice (Glycyrrhiza glabra), fennel
Delivery method

(Foeniculum vulgare) and balm-mint (Melissa officinalis)

as a treatment for infantile colic. In this randomized,
double-blind, placebo-controlled trial, 68 healthy term
Beverage

Beverage

Beverage

Beverage

infants (age 2–8 weeks) with colic were given either

Liquid

150 mL of the herbal tea preparation or a placebo bev-

erage containing no herbs for a period of 1 week. For
inclusion in the study, colic was defined as unexplained
De la Motte et al., 1997

irritability, agitation, fussiness or crying lasting more

Nakamura et al., 2002

Weizman et al., 1993

than 3 h/day, for at least 3 days/week, and continuing

Savino et al., 2005

Gould et al., 1973

for 3 weeks. Exclusion criteria included prematurity,

weight gain of <150 g/week, acute or chronic illness,
and drug therapy. Parents were instructed to adminis-
Reference

ter the assigned beverage with each colic episode, but

no more than 3 times daily, and to rate any improve-
ments observed in their own child. After 7 days, the
Copyright © 2006 John Wiley & Sons, Ltd. Phytother. Res. 20, 519–530 (2006)
DOI: 10.1002/ptr
526 D. L. MCKAY AND J. B. BLUMBERG
colic improvement score was significantly higher in the
herbal tea group than in the placebo group (1.7 ± 0.3 vs
0.7 ± 0.5). Among the 33 infants given the herbal tea,
colic was eliminated in 19 (57%) compared with 9 of
the 35 infants (26%) in the placebo group, although no
significant differences with regard to the number of
nighttime awakenings were observed. In a randomized,
double-blind, placebo-controlled trial, Savino et al.
(2005) determined that a standardized herbal prepara-
tion containing chamomile (71.1 mg/kg/day), fennel
(65.7 mg/kg/day) and balm-mint (38.8 mg/kg/day) ad-
ministered daily for 1 week reduced crying time among
breastfed colicky infants (n = 41) compared with a
placebo (n = 47, p < 0.005). Significant results were
attained within 4 days of treatment, and no side
effects were observed with this dosage. De la Motte
et al. (1997) examined the effects of a chamomile
extract and apple pectin preparation in 79 children
(age 0.5–5.5 y) with acute, non-complicated diarrhea.
In addition to the usual prescription of rehydration
and a realimentation diet, the children received either
the chamomile/pectin preparation (n = 39) or a placebo
(n = 40) for 3 days. The diarrhea ended sooner for
more children in the group treated with chamomile
and pectin (85%), than in the placebo group (58%).
The duration of the diarrhea was also significantly
attenuated with the chamomile and pectin treatment
by ≥5.2 h.
The effects of a chamomile-containing oral rinse on
oral mucositis or stomatitis induced by cancer thera-
pies have been examined in one case series and one
clinical trial. Carl and Emrich (1991) observed both the
prophylactic (n = 66) and therapeutic (n = 32) effects of
a chamomile mouthwash in a case series of 98 head
and neck cancer patients treated with either radiation
or systemic chemotherapy. In the prophylactic group,
one of the 20 radiation therapy patients developed
grade 3 mucositis in the final week of treatment, while
13 developed intermediate-grade and 6 developed
low-grade mucositis. Only 10 of the 46 chemotherapy
patients in the prophylactic group developed clini-
cally significant mucositis. Of the 32 patients in the
therapeutic treatment group (16 radiation, 16 chemo-
therapy), all experienced immediate relief from mouth
discomfort, and within 1 week nearly all patients
had no clinical signs of mucositis. In a double-blind,
placebo-controlled clinical trial of 164 chemotherapy
patients on their first cycle of 5-fluorouracil (5-FU), in
bolus form, Fidler et al. (1996) tested the efficacy of a
chamomile mouthwash administered 3 times daily for 2
weeks. In addition, all patients received oral cryotherapy
for 30 min with each dose of 5-FU. No differences in
stomatitis between the chamomile and placebo mouth-
wash groups were detected at the end of the study
period. In a review of commonly used medicinal herbs,
however, O’Hara et al. (1998) contend that 2 weeks
was too short a period to detect discernible differences
since mucositis, which is largely a result of immuno-
supression, takes weeks to develop.
Topical effects. Several studies have tested the effects
of topically applied chamomile preparations on inflam-
mation of the skin associated with atopic dermatitis
or eczema, radiation therapy and erythema. Aertgeerts
et al. (1985) compared the effects of a chamomile-
containing cream versus either 0.25% hydrocortisone,
Copyright © 2006 John Wiley & Sons, Ltd.
0.75% fluocortin butyl ester (a glucocorticoid) or 5%
bufexamac (a non-steroidal antiinflammatory) in 161
patients presenting with eczema on their hands, fore-
arms and lower legs who had been treated initially with
0.1% difluocortolone. During the 3–4 week mainte-
nance period, the chamomile cream was reported to be
as effective as 0.25% hydrocortisone and more effective
than both the glucocorticoid and non-steroidal antiflam-
matory agents. In a 2 week trial, Patzelt-Wenczler and
Ponce-Poschl (2000) compared the effects of chamo-
mile cream to 0.5% hydrocortisone and a placebo (the
vehicle cream) in patients with a medium degree of
atopic eczema. The chamomile-treated group showed
approximately 50% improvement in pruritis, erythema
and desquamation. While the degree of improvement
in the hydrocortisone group was mild in comparison,
the difference between the effects of the placebo and
the chamomile cream were only marginal, making the
study inconclusive. Hempel (1999) reported that 1%
hydrocortisone was more effective than a chamomile
ointment containing 1% CO2 extract (with no chama-
zulene and presumably more matricine) in a study of
80 patients with subacute eczema who were pretreated
with steroids. The difference in the global clinical im-
pression rating between the two treatments was, how-
ever, smaller in patients pretreated with potent steroids
than in those treated with weak steroids. Anderson
et al. (2000) found that massage with blended aro-
matherapeutic essential oils, some containing chamo-
mile, significantly improved night time disturbance
scores and day time irritation scores in 8 children (age
3–7 years) with atopic eczema which was non-respon-
sive to conventional therapy. Similar differences were
also observed in the control group (n = 8) receiving
massage without the essential oils, however, no signifi-
cant between-group differences were detected.
Chamomile cream proved less effective than 1%
hydrocortisone or witch hazel 24 h after inflammation
was induced by UV radiation (n = 24) in a study by
Korting et al. (1993) where subjects served as their own
control. In the same study, erythema induced with
cellophane tape stripping of the skin (n = 24) was sig-
nificantly reduced with hydrocortisone, but was only
less pronounced following chamomile treatment. In a
single blind, randomized, placebo-controlled trial of
50 women receiving radiation therapy for breast can-
cer, Maiche et al. (1991) tested the effects of a topical
chamomile cream versus an almond oil placebo on
the degree of radiation skin reaction. Each patient
served as their own control and both treatments
were applied twice daily, once 30 min prior to irradia-
tion and again before bed. No significant differences
were observed between the two treatments; however,
radiation-induced skin reactions in the chamomile-
treated areas were less frequent and appeared later.
The incidence of severe skin reactions due to radiation
in both groups was <10%.
Topically applied chamomile preparations have also
been examined for their effectiveness in wound care.
In a double-blind study of 14 patients with weeping
wounds following dermabrasion for tattoo removal, a
compress containing chamomile extract significantly
decreased the wound area and increased drying of the
wound (Glowania et al., 1987). Patients with chronic
wounds (n = 5) given a combination of chamomile and
lavender essential oils prepared in a grapeseed oil base
Phytother. Res. 20, 519–530 (2006)
DOI: 10.1002/ptr
 BIOACTIVITY OF CHAMOMILE (MATRICARIA RECUTITA L.)
did better than those receiving conventional therapy
(n = 3) in a study by Hartman and Coetzee (2002).
However, a chamomile-extract spray was not effective
in relieving post-operative sore throat and hoarseness
in a randomized double-blind, placebo-controlled study
of 161 elective surgical patients by Kyokong et al. (2002).
Among the 80 patients who received 111 mg of
chamomile extract spray before intubation, 42 (52.5%)
experienced no post-operative sore throat, compared
with 41 (50.6%) of the 81 patients who received a
saline spray. No significant differences were observed
24 h after the operation in either group.
Inhalation treatments. A hospital-based observational
study of 8058 women who gave birth between 1990 and
1998 found that chamomile oil administered via the
skin and/or inhalation was effective in alleviating pain
during labor and delivery (Burns et al., 2000), although
no specific endpoint measurements or statistics regard-
ing chamomile were reported. In a study examining
the effects of inhaling essential oils on electroencepha-
logram (EEG) activity and sensory evaluation in 13
healthy females by Masago et al. (2000), chamomile
significantly reduced alpha 1 activity, measured at the
parietal and posterior temporal lobes and contributed
to reports of a ‘comfortable feeling’. Roberts and
Williams (1992) reported on 22 subjects who were asked
to visualize positive and negative phrases following in-
halation of either chamomile oil or a placebo (crushed
green peppers) on two separate occasions. The chamo-
mile oil did not affect vividness ratings, but did signifi-
cantly increase the time taken for subjects to visualize
both positive and negative phrases (latency). The mean
response time increased from 3.2 to 3.6 s for the
positive images, and from 3.1 to 3.6 s for the negative
images. Negative mood ratings following the presenta-
tion of negative images were less extreme with chamo-
mile exposure compared with placebo (−3.0 vs. −3.5 s
respectively), and overall mood ratings were shifted in
a positive direction. The frequency of judgements was
similarly affected, i.e. subjects tended to think more
positive than negative images were presented following
exposure to chamomile.
Autonomic nervous system effects. Clinical trials on
the sedative and anxiolytic properties of chamomile have
not been conducted, although the effects of chamomile
tea on autonomic nervous system parameters including
heart rate, peripheral skin temperature, EEG and mood
were examined in young Japanese males. Nakamura
et al. (2002) observed a greater heart rate decrease and
skin temperature increase after 45 min of ‘calculation
work’ when subjects consumed chamomile tea versus a
control beverage of hot water. ‘Sadness and depres-
sion’, calculated from EEG data using the emotion spec-
tral analysis (ESA-16) system, also decreased more after
drinking chamomile tea, however, relaxation scores
increased after drinking either beverage.
Hemodynamic effects. The hemodynamic effects of
chamomile tea were examined in an open study of 12
heart disease patients hospitalized for cardiac catheteri-
zation. Gould et al. (1973) observed that patients had a
small but significant increase in mean brachial artery
pressure (91 to 98 mmHg) 30 min after drinking two
cups of chamomile tea (prepared as 2 tea bags in 6 oz
Copyright © 2006 John Wiley & Sons, Ltd.
527
water). No other significant changes in cardiac function
were observed, although 10 of the 12 patients fell into
a deep sleep within 10 min of consuming the tea.
Epidemiological studies have reported the intake of
flavonoids, particularly those present in chamomile
(apigenin, quercetin and luteolin), is inversely associ-
ated with heart disease risk (Hertog et al., 1993; Hertog
et al., 1995; Knekt et al., 1996). However, a 7 day inter-
vention study of 18 healthy men and women (mean age
25 ± 8 years) examining the effects of a daily dietary
supplement providing 377 ± 10 µmol quercetin (from
onions) and 84 ± 6 mg apigenin (from parsley) on plate-
let aggregation and other hemostatic variables in vivo
found no significant changes on collagen- or ADP-
induced platelet aggregation, thromboxane B2 produc-
tion, platelet number, factor VII, plasminogen, PAI-1
activity or fibrinogen concentrations (Janssen et al.,
1998).
ADVERSE REACTIONS/TOXICITY
Severe allergic reactions to chamomile have been re-
ported (Subiza et al., 1989; Reider et al., 2000), particu-
larly among those who also have allergies to other plants
in the daisy family (Asteraceae or Compositae) includ-
ing mugwort (Artemisia vulgaris) (De la Torre Morin
et al., 2001) and ragweed (Ambrosia trifida) (Subiza
et al., 1989). Both oral and topical uses have been re-
ported to cause contact dermatitis (Pereira et al., 1997;
Rodriguez-Serna et al., 1998; Rycroft, 2003), although
the risk of elicitation with Compositae-containing prod-
ucts in sensitive individuals is unknown (Paulsen, 2002).
Angioedema associated with contact urticaria (Foti
et al., 2000) and allergic conjunctivitis (Subiza et al.,
1990) has also been reported in patients who applied
chamomile tea, either as a compress or rinse, to their
eyes.
Potential drug interactions with chamomile have been
suggested, however, all are based on theoretical postu-
lates rather than empirical evidence. Coumarin, a con-
stituent of chamomile, may potentiate the effects of
warfarin therapy (Miller, 1998; Heck et al., 2000) by
acting as a vitamin K antagonist and interfering with
the blood coagulation processes. Similarly, coumarin
may provide additive blood thinning effects to the
antiplatelet or hypoprothrombinemic actions of aspi-
rin, other non-steroidal antiinflammatory drugs, and/or
acetaminophen when used concomitantly (Abebe, 2002).
Due to its mild sedative effect, chamomile also has the
potential to increase the CNS depressant effects of other
sedative drugs such as opioid analgesics, BDZ or alco-
hol and, therefore, a contraindication has been sug-
gested in conjunction with these agents (O’Hara et al.,
1998; Abebe, 2002; Larzelere and Wiseman, 2002).
Acknowledgements
Research support was provided by the U.S. Department of Agricul-
ture (USDA) Agricultural Research Service under Cooperative
Agreement No. 58-1950-001 and a grant from the Hain Celestial
Group (Boulder, CO). The contents of this publication do not neces-
sarily reflect the views or policies of the USDA nor does mention of
trade names, commercial products, or organizations imply endorse-
ment by the U.S. Government.
Phytother. Res. 20, 519–530 (2006)
DOI: 10.1002/ptr
528 D. L. MCKAY AND J. B. BLUMBERG
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