ArticlePDF Available

Yarrow (Achillea millefolium L.): A Neglected Panacea? A Review of Ethnobotany, Bioactivity, and Biomedical Research1

Abstract and Figures

Yarrow ( Achillea millefolium L.): A Neglected Panacea? A Review of Ethnobotany, Bioactivity, and Biomedical Research. Yarrow (Achillea millefolium L.) is one of the most widely used medicinal plants in the world, primarily for wounds, digestive problems, respiratory infections, and skin conditions, and secondarily, among other uses, for liver disease and as a mild sedative. Preclinical studies indicate that it may have anti-inflammatory, anti-ulcer, hepatoprotective, anxiolytic, and perhaps antipathogenic activities. Animal studies have also shown that yarrow is generally safe and well tolerated. The claim that yarrow has been shown to be specifically contraindicated during pregnancy is based on a single low-quality rat study the results of which were incorrectly interpreted. The combination of human use data from multiple cultures, independently reporting similar activities for yarrow, and the discovery of potentially relevant bioactivities by in vitro and animal studies represent meaningful evidence of the plant’s efficacy. We therefore argue that human clinical trials should be funded and conducted.
Content may be subject to copyright.
Yarrow (Achillea millefolium L.): A Neglected Panacea? A Review
of Ethnobotany, Bioactivity, and Biomedical Research
Missouri Botanical Garden, P. O. Box 299( St. Louis, MO 631660299, USA
University of MichiganDearborn, 6515 Cherry Hill Rd., Ypsilanti, MI 48198, USA
*Corresponding author; e-mail:
Yarrow (Achillea millefolium L.): A Neglected Panacea? A Review of Ethnobotany, Bioact-
ivity, and Biomedical Research. Yarrow (Achillea millefolium L.) is one of the most widely
used medicinal plants in the world, primarily for wounds, digestive problems, respiratory
infections, and skin conditions, and secondarily, among other uses, for liver disease and as a
mild sedative. Preclinical studies indicate that it may have anti-inammatory, anti-ulcer, he-
patoprotective, anxiolytic, and perhaps antipathogenic activities. Animal studies have also
shown that yarrow is generally safe and well tolerated. The claim that yarrow has been
shown to be specically contraindicated during pregnancy is based on a single low-quality rat
study the results of which were incorrectly interpreted. The combination of human use data
from multiple cultures, independently reporting similar activities for yarrow, and the discovery
of potentially relevant bioactivities by in vitro and animal studies represent meaningful evi-
dence of the plantsefcacy. We therefore argue that human clinical trials should be funded
and conducted.
Key Words: Achillea millefolium; ethnobotany; medicinal plants; toxicology; yarrow.
Yarrow (Achillea millefo lium L., Asteraceae) is
among the most widespread and widely used
medicinal plants in the world. It has been popular
for millennia as a treatment for wounds and
infectious diseases, as well as many other con-
ditions. Chandler et al. (1982) reviewed the
ethnobotany and phytochemistry of yarrow in
this journa l. At that time, the exten t of human
use data was already enormous, and chemical
research had discovered enough constituents
having known bioactivity that Chandler et al.
(1982) were able to conclude Many of the
plants other uses can also be explained by the
types of constituents present ..., adding further
that their review had showed that ...atleast
some of the traditional medicinal herbs were
effective. In the intervening quarter-centu ry,
more direct evidence regarding yarrows bioactiv-
ities has been generated by bioassays and animal
studies. Nonetheless, no human clinical trial of a
single-herb yarrow product for its traditional uses
has yet been conducted. The purpose of the
present review is to argue that the weight of
evidence from preclinical research and human use
data, in the absence of such trials, is sufcient to
warrant the presumption that yarrow, used in
tradition al fashion, is likely to possess useful
activity, and that the medical research community
ought to initiate more thorough studies of this
promising botanical as expeditiously as possible.
The genus Achillea, which includes ca. 110
140 species as presently dened (Ehrendorfer and
Guo 2006), is largely native to Eurasia, with a few
species native to northern Africa and North
America. Hybridization and infraspecic variabil-
ity have complicated the taxonomy, so until
recently there was no single broadly accepted
classication of the A. millefolium species com-
plex. According to the narrowest circumscription,
A. millefolium is native to Europe and includes
Received 6 January 2010; accepted 08 November
2010; published online 14 April 2011.
Economic Botany, 65(2), 2011, pp. 209225
© 2011, by The New York Botanical Garden Press, Bronx, NY 10458-5126 U.S.A.
three subspecies: subsp. millefolium and the pink-
owered subsp. alpestris (Wimm. & G rab.)
Gremli are widespread, while subsp. ceretanum
Sennen (whose owers are white, as normal for
wild subsp. millefolium, but relatively large) is
conned to Spain and southern France. Several
closely related species or microspecies belong to
an A. millefolium species complex, with A. collina
J. Becker ex Reichenb. and A. pannonica Scheele
most frequently treated as subspecies of A.
millefolium, though usually excluded today (cf.
Richardson 1976). ITS and trnL-trnF sequence
data (Guo et al. 2004) and AFLP data (Guo et al.
2005) conrm that A. millefolium and related
species form a me ssy, frequently hybridizing
polyploid complex (including diploids through
octoploids), with some species that had tradition-
ally been placed in other sections being hybrids
with some A. millefolium comple x ancestry .
Ploidy level is informative in the recog nition of
species; for example, A. millefolium sensu stricto is
hexaploid, while A. collina is tetraploid and A.
pannonica are usually reported to be octoploid.
Additionally, the common native North Amer-
ican yarrow has been recognized at the species
level as A. lanulosa Nutt. (itself sometimes divided
into multiple species) or at the subsp ecic level as
A. millefolium subsp. lanulosa (Nutt.) Piper.
As narr owly dened, this taxon is tetraploid
(Ehrendorfer 1973; Gervais 1977), while North
American populations recognized by some
authorities as A. borealis Bong. may be tetraploid
or hexaploid (Ehrendorfer 1973; Ramsey 2007).
Guo et al. (2005) concluded from AFLP data that
the North American polyploids were genetically
distinct from A. millefolium, havin g a closer or
more direct relationship to diploid A. asiatica
Serg. Pentaploid hybrids between native tetra-
ploids and escaped purple-owered hexaploid
millefolium cultivars were at one point common
in Quebec (Gervais 1977), although the extent of
their long-term persistence is unknown.
This review does not take a position on
whether this North American yarrow should be
treated taxonomically as being conspecic with A.
millefolium. However, the two have been used
interchangeably, and most older American ethno-
botanical literature refers to A. millefolium with-
out making it clear whether the introduced or
indigenous taxon was meant. Traditional Native
American uses would always have involved the
native taxon in the pre-Columbian era, but would
later likely have included the introduced taxon
wherever the latter became common. For con-
venience, the few references referring specically
to use of A. lanulosa are here taken as applying
to a broadly dened A. millefolium.
Ethnobotany and History of Use
Yarrow is one of the oldest known botanicals
used by humans (sensu lato): it is among the six
medicinal plants whose pollen was found in a
Homo neanderthalensis grave at Shanidar, dated to
65,000 B.P. (Leroi-Gourhan 1975, 1998; Solecki
1975). Though it is impossible to know whether
usage since then has been continuous, it has
certainly been persistent, as yarrow has been
broadly accepted as a medicine by many recent
cultures within its range. Duke has repeatedly
argued (e.g., Duke 1986; Duke and Ayensu
1985) that plants used by unrelated groups for
similar purposes are especially likely to be
effective: given the statistical unlikelihood that
multiple cultures would randomly adopt and
retain the same use for an inert plant (Moerman
adopted and retained by multiple cultures has a
increased likelihood of being genuinely bioactive.
The plant is named Achillea after Achilles, a
powerful warrior in Greek mythology (Fig. 1).
The oldest surviving texts to record the use of
yarrow in the European classical medical tradition
are by Pliny the Elder and Dioscorides, both
during the rst century C.E. These texts set a
lower limit on the age of yarrowsuseby
Western cultures, although, as for most bota-
nicals, folk use in an oral tradition may have long
preceded the plants appearance in scholarly
medicine. A necessary caveat is that, though most
authorities have interpreted these references as
being to A. millefolium, the traditional assign-
ments of Linnean names to plants in classical
texts are seldom certain: if, for example, a classical
common name were later used for another species
with similar appearance, range, and uses, errors
would result. Dioscorides (4:36) described the
herb achilleios,ormillefolium (among other
names), as being useful to stop bleeding, includ-
ing from wounds and abnormal menstrual bleed-
ing, and reduce inammation; a decoction could
be used as a douche for menstrual bleeding and
be drunk for dysentery (Osbaldeston and Wood
2000). Plinys Natural History (25:4244) indi-
cated that a plant probably identiable as yarrow
was known by names including achilleos, sideritis,
and millefolia, and that some people also used the
former two names for several other species, some
quite different in description, with all being
considered valuable for wounds (Jones 1956). Pliny
also reported achillea to be useful for looseness of
the bowels (26:51), bleeding (26:131), excessive
menstruation (sometimes given as a sitz bath;
26:151), and earache (25:164).
This literary record has recently been sup-
ported by marine archaeology. Yarrow is among
plants reported, using DNA analysis, to be
present in two pressed tablets of plant material
recovered in the 1980s from a collection of
medical supplies in a Roman ship that sank off
the coast of Tuscany, sometime between 140 and
120 B.C.E. The DNA analysis, organized by
Alain Touwaide and Emanuela Appetiti of the
Institute for the Preservation of Me dical Tradi-
tions and performed by Robert Fleischer at the
Smithsonian Institution, is the rst of its type.
Their investigation tentatively identied several of
the tablets ingredients, all considered in writings
of the time to be medicinal; in addition to
yarrow, the study found DNA evidence of carrot,
radish, parsley, celery, wild onion, and cabbage
(Touaide and Appetiti, pers. comm. 10 February
2011; see also Anon. 2011).
Three major surviving Old English medical
texts from ca. 9501000 C.E. were primarily
translations of earlier Latin works, though includ-
ing some inuence from pre-Christian Northern
European traditions; all recommend yarrow,
usually as a component in multispecies recipes
(Pollington 2000). Uses included the treatment
of wounds, inammation and swellings, diarrhea,
intestinal pain, heartburn, lung disease, tooth-
ache, headache, difcult urination, and snake and
dog bites.
Similar uses of yarrow survive to the present day:
common European folk uses are for gastrointestinal
disorders and loss of appetite, for menstrual prob-
lems, and as a diaphoretic, and topically as a
poultice, wash, or bath for skin inammations,
wounds, and external bleeding (Wichtl 2004).
However, Germany s Commission E ofcially
approved oral yarrow medications only for mild
gastrointestinal disturbances, dyspepsia, and loss of
appetite (Blumenthal et al. 1998). In Italy, yarrow
is used for a variety of conditions, but primarily for
gastrointestinal conditions (Guarrera 2006); other
relatively frequent uses are for menstrual problems,
as a diuretic or for urinary problems, for toothache,
and as a sedative. In Hungary, the plant is known
Fig. 1. The Education of Achilles. Left, wall painting from the Greek city of Herculaneum (Italy), ca 200 BCE;
right, Chiron and Achilles by James Barry, ca 1772. This scene was a favorite theme of painters in the 17
centuries. In legend, Achilles was tutored by the centaur Chiron in the arts of war, music, and medicine. On
his rst military expedition to Troy, Achilles forces were dispersed by Telephus, king of the Mysians, although
Achilles wounded Telephus. Eight years later, the Greek eet was reassembled, though the route to Troy remained
a mystery, and Telephus injury had never healed. When Apollo told him that a cure could only come from the
one who wounded him, he made a deal with Achilles. Achilles poulticed the wound with the plant whose healing
virtues he had discovered, Achillea, and Telephus, cured, directed the eet to Troy. Chiron trained other young
men, including Asclepius, Actaeon, and Jason (of the Argonauts), all of whom have medicinal plants named after
them. Chiron himself has three: Centaurea, Centaurium, and Chironia. Such richly metaphorical and mythical
sources are a powerful way for cultures to maintain ethnobotanical knowledge.
as cickafark (kitten tail) and has been used for
internal ailments as well as for burns and wounds
(Kolos and Kolosné Pethés 1956); more recent
reports include use as a tea for treating bronchitis,
urinary and kidney problems, and for diarrhea and
vomiting (Sulyok and Siklos 1998).
Over a third of the 125 records of folk use of
yarrow in Britain and Ireland were for conditions
involving blood, such as bleeding wounds, nose-
bleeds, uterine hemorrhag e, and high blood
pressure; a similarly large percentage involved
respiratory infection s, fevers, and rheumatic com-
plaints (Allen and Hateld 2004). Use as a tonic
seems also to have been common, and scattered
uses for a broad variety of discomforts were
reported. Allen and Hateld (2004) argue that
the ethnobotanical tradition of illiterate Anglo-
Saxon and Germanic groups developed for the
most part independently of the classical botanical
tradition as represented in popular herbals, which
emphasized Mediterranean species often not
available in the British Isles. This explains
plausibly why, although yarrow is frequently used
for gastrointestinal problems such as diarrhea and
rarely for respiratory infections in the classical
tradition, folkloric tradition in the British Isles
used it often to treat respiratory infections but
rarely to treat digestive disease s. Thus, within
Europe alone, uses of yarrow for bleeding and for
infectious diseases are likely to have been inde-
pendently derived at least twice. Alternatively,
uses by well-distinguished European cultures
could have descended from commo n cultural
ancestors; if so, persistence in multiple groups
for a great many generations might also support
an hypothesis of observable benet.
In China, yarrow has been used to stop
bleeding and to treat sores, snakebite, wounds,
hemorrhoids, varicose veins, dysmenor rhea, and
tuberculosis, among others (Duke and Ayensu
1985). Although China, of course, has a very
distinct medical tradition, the independence of
these uses from European inuence is perhaps
Chandler et al. (1982) compiled from 15
references a list of 30 medical uses for yarrow by
at least 22 Native American tribes. Uses were
diverse, but most fell into about four broad
categories: wounds, bruises, skin damage or
disorders, and bleeding conditions; colds, fever,
and sore throat; digestive problems; and general
tonic use. Moermans authoritative (1998) com-
pilation identied 377 distinct medicinal use
reports for yarrow by Native American groups,
the most for any plan t. Yarrow wa s used
medicinally by no fewer than 76 tribes. The most
widespread uses identied by Moerman (1998)
included uses for skin problems and injuries,
respiratory illnesses and digestive problems,
toothaches, and eye problems (Table 1). As in
Europe, topical preparations such as washes and
poultices were usually preferred for dermatolog-
ical problems. Other relatively common uses were
for liver and kidney problems and as a tonic or
panacea, used apparently for almost any ail-
ment. The common uses in North America again
overlap strongly with those in European tradi-
tions, but are undoubtedly independently
derived, and perhaps repeatedly (as there are
more major cultural/linguistic groups in North
America than in Europe, with the North Amer-
ican groups being at least as divergent from one
another as are the European groups).
The extraordinarily widespread use of this
plant in North America highligh ted its apparent
absence of use by the Hopi; none of the standard
sources on the Hopi report its use (e.g., Fewkes
1896; Vestal 1940; Whiting
1939). Yet yarrow is
used by many neighbors of the Hopi, including
the Apache, Navajo, Ute, Papago, Paiute, and
Zuni. In particular, the Zuni had a ceremonial
societ y called the Yayat which, among other
Skin Conditions, Wounds, Bleeding,
Blood Problems
Dermatological aids 54
Eye treatments 9
Blood medicine 5
Burn dressing 6
Antihemorrhagic 2
Hemostat 2
Hemorrhoid treatment 1
Potentially Infectious Conditions 80
Cold remedy 27
Febrifuge 16
Antidiarrheal 11
Throat aid 9
Misc. disease remedy 7
Cough remedy 5
Diaphoretic 5
Toothache 14
Liver Disease 5
All Others 199
things, practiced dramatic conjuring with re;
one authority said they juggled re like confetti,
and others said they ate it, rst washing them-
selves with the cooling juice of the chewed
blossoms and roots of yarrow (Stevenson 1915).
In consultation with Hopi ofcials and with the
ofcial Hopi ethnobotanical consultant, I (DM)
learned that the Yayat society was made up of
both the Hopi and Zuni, and, indeed, my
consultants great-grandfather had been a member
of this society (Lomaomvaya, pers. comm.).
Yarrow may have been considered such an
important plant to the Hopi that knowledge of
its use was kept to small circles of initiates, and
not shared with researchers.
Yarrow is somewhat weedy; subsp. millefolium
is now widely distribu ted in the New World, and
it has become a valued medicinal plant in Central
and South America. In Veracruz, it is used for
diarrhea and colic, for latido (pulse), and to
calm the nerves (Cano Asseleih 1997). Bussmann
and Sharon (2007) report that A. millefolium is
used in Peru, under the names of milenrama and
chonc hón, for gastritis, diabetes, blood ,and
cholesterol, and topically for skin infections and
to dispel bad spells. Likewise, it is used in
Brazil, under the names of mil-folhas and erva de
cortadura, to treat wounds and skin problems,
diarrhea, and other gastrointestinal problems
(Cruz 1979; Hatsuko Baggio et al. 2008; Silva
and SantAna 19 95 ). In the northern A mazon,
Achillea millefolium wasemployedasananti-
hemorrhoidal, emmenagogue, and stimulant
(Bennett, pers. comm.; García Barriga 19 75.)
The species was also dispersed to the Pacic, and
is now used as an antimalarial i n Indonesia
(Murnigsih et al. 2005). It is a lso re por tedly in
use in South Africa and Botswana, where it is
naturalized (Arnold 2002;Eloff,pers.comm.
2009). Medicinal uses adopted by people in
colonized areas where yarrow did not previously
exist, of course, will often have been inuenced
by European practices and beliefs rather than
being independently derived.
It is fashionable to assume that a plant used for
too many different indications is ineffective for
all of them. A lengthy laundry list of uses could
arise in part from the fact that a substance with a
desirable observed risk-benet ratio may be occa-
sionally used to treat practically any condition,
including some for which it is not active, just as
the genuine activity of antibiotics against bacterial
diseases has led many to use them for viral
infections. On the other hand, a single bioactivity
could benet multiple conditions, just as one
antibiotic may treat diverse infectious diseases. To
discuss efcacy meaningfully, one must focus on a
few key uses best supported by ethnobotanical
data. For y arrow, these include wounds and
bleeding, miscellaneous skin conditions, respira-
tory infections, and gastrointestinal ailments. A
limited suite of bioactivities, including antihe-
morrhagic, anti-inammatory, and/or directly or
indirectly antipathogenic activities, would be
adequate to make yarrow active against all of
those conditions. Given yarrows chemical com-
plexity and the previous ly reported activities of its
chemical constituents or related compounds, it
is not unreasonable to suspect that all of those
bioactivities could be present. Indeed, the plant has
already been demonstrated to possess several relevant
activities. The traditional use of yarrow for liver
disease, though less frequent, is also of particular
interest, be cause animal studies demonstrati ng
hepatoprotective effect have been performed.
Chandler et al. (1982) reviewed the ethno-
botany and phytochemistry of yarrow; the present
review therefore will not attempt to present a
thorough summary of chemical content. Both in
publications reviewed therein, and in later pub-
lications (notably, Orav et al. 2006), consi derable
variation of chemotypes within A. millefolium is
reported. In older literature, chemists generally
did not provide adequate taxonomic information
or cite voucher specimens that would allow the
exact nature of study materials to be independ-
ently determined; therefore, some of the reported
infrataxon variability in che mical content and
bioactivity was probably due to the failure to
distinguish between subspecies or species of the
A. millefo lium complex (Chandler et al. 1982;
Guédon et al. 1993). Furthermore, essential oil
composition is altered during maturation and
extraction methods signicantly affect product
composition (Ro hloff et al. 2000); these and
similar factors may have contributed to the
complexity of the situation.
Some recent chemical studies have fully iden-
tied A. millefolium samples (e.g., Candan et al.
2003; Guédon et al. 1993; Kokkalou et al. 1992)
although some still fail to clearly distinguish
between subspecies (e.g., Bélanger and Dextraze
1993; Stojanović et al. 2005) or even species (e.g.,
Glasl et al. 2002; Hofmann and Fritz 1993).
Guédon et al. (1993), using only French samples,
found that subsp. millefolium and subsp. cereta-
num had similar avonoid content, while subsp.
alpestris was distinctive. As subsp. ceretanum also
morphologically resembles su bsp. millefolium
(except for its somewhat larger owers), its
separation from that subspecies may be question-
able. Proazulenes, blue compounds found as a
component of the essential oil, are common in
Achillea sect. Millefolium.Thepink-owered
subsp. alpestris is supposedly the only European
subspecies of A. millefolium that contains chama-
zulene (Lamaison and Carnat 1988), which is one
of the known active compounds in Matricaria
chamomilla L. (e.g., McKay and Blumberg 2006),
though it is reported from related species, such as
A. collina (e.g., Bozin et al. 2008; Cernaj et al.
1983; Verzár-Petri et al. 1979). However, it is not
clear whether subsp. millefolium has been
adequately surveyed for chamaz ulene content .
Detailed study of populations from North Bavaria
found high proazulene levels in rare hexaploid
individuals that had been identied as subsp .
millefolium (Michler and Arnold 1999; Preit-
schopf et al. 1989); the authors suggested that
proazulene content in the taxa surveyed could be
correlated with habitat type. Studies show ing high
levels of chemical variation in surveyed popula-
tions of A. millefolium continue to report that
some populations have high levels of chamazulene
(Gudaitytė and Venskutonis 2007), although it is
not clear that such populations have been
denitively identied as subsp. millefolium.
Few chemical studies have included the Amer-
ican yarrow. Greger and Werner (1990) reported
that alkamides in A. lanulosa and A. asiatica were
different from those in ve species of the Euro-
pean A. millefolium complex, providing an inde-
pendent line of evidence for a relationship
between the former two taxa. Bélanger and
Dextraze (1993) reported dramatic variation in
chamazulene content in A. millefolium from
Quebec. Though they considered A. lanulosa to
be a distinct species, it is conceivablegiven the
difculty of identication of these taxathat their
high-chamazulene accessions could have been the
tetraploid subsp. lanulosa or hybrids thereof.
Considerable recent chemic al research has also
been done on other species in the A. millefolium
complex (e.g., Benedek et al. 2007a; Greger and
Werner 1990; Marchart and Kopp 2003; Orth et
al. 2000; Todorova et al. 2007; Trendalova et al.
2006; Unlü et al. 2002; Werner et al. 2003,
2006). These studies have demonstr ated that
quantitative and qualitative variations in chemical
content are useful to distinguish species, partic-
ularly the diploid species (Benedek et al. 2007a),
which is unsurprising if higher-ploidy taxa are
usually of allopolyploid origin. Species outside the
A. millefolium complex, though chemically dis-
tinctive, may have antimicrobial activity compa-
rable to that of A. millefolium (e.g., Dokhani et al.
2005; Stojanović et al. 2005; Unlü et al. 2002). If
taxa with very different chemical compositions are
bioactive, bioactivity in these taxa is unlikely to
be due to any single mol ecule.
Information on bioactivities can be derived
from in vitro assays, which may use isolated cells
or living tissues, and from in vivo studie s in
animals or humans. Most research studies are of
the former type, which are much cheaper. Bio-
assays provide useful preliminary indication that a
substance might have certain bioactivities. How-
ever, results are of little or no direct relevance to
consumers, especially when the studied substan-
ces are isolated compounds given in unnatural
doses or nonpolar extracts that differ greatly from
traditional products. False positive results, false
negative results, and evidence of nonexistent
safety risks are all regularly generated. Not all
human uses of a plant can be explored through
bioassays; there seems to be no in vitro assay that
reasonably reects a plants value for wound healing
or menstrual bleeding, for example. Likewise,
though antiviral bioassays exist, no studies utilizing
yarrow in these assays have been published. Bio-
assays that appear most relevant to traditional uses
for dermatological, gastrointestinal, and respiratory
ailments are those that screen for anti-inammatory
and antipathogenic activity; antispasmodic activity
may be relevant for gastrointestinal problems.
Studies that have screened yarrow for other activities,
such as antioxidant, estrogenic, and anticancer
activities, are reviewed more briey.
Bioassay Results
Hexane-ether-methanol extracts of A. millefolium
and three other Achillea species (which may bear
little resemblance to traditional aqueous or aque-
ous-ethanolic extracts) displayed antimicrobial
activity against all tested bacteria, including Staph-
ylococcus aureus, Escherichia coli, Klebsiella pneumo-
niae, Pseudomonas aeruginosa,andSalmonella enter-
itidis (Stojanović et al. 2005). However, another
study screening Brazilian medicinal plants against
four pathogenic bacteria reported no signicant
activity in a 90% ethanol-10% water extract of A.
millefolium (Holetz et al. 2002). Yarrow essential
oil is reportedly active against Streptococcus pneumo-
niae, Clostridium perfringens, and Acetinobacter
lwofi,aswellasMycobacterium smegmatis (Can-
dan et al. 2003;Unlüetal.2002). Since yarrow is
used for gastrointestinal disorders, it is notable that a
methanol extract of yarrow is active against Heli-
cobacter pylori, which can cause stomach ulcer and
gastritis, at a minimum inhibitory concentration of
50 μg/ml (Mahady et al. 2005), which would be
easily obtained in the stomach after oral dosing.
Hexane-ether-methanol extra cts of Achillea
millefolium and three other spe cies inhibited
Aspergillus niger and Candida albicans (Stojanović
et al. 2005), and essential oil of yarrow (both A.
millefolium subsp. millefolium and A. setacea)
also inhibits Candida species (Unlü et al. 2002).
Anticandidal activity was not observed by Holetz
et al. (2002). Conicting results could be due to
differences in raw material quality, extract type, or
methodology. (Holetz et al. screened 13 plants
traditionally used for infectious diseases versus 8
pathogens; most tests showed no activity, and
only 11 of the 104 combinations of plant and
pathogen displayed a good minimal inhibitory
concentration of less than 100 μg/ml. This would
seem to be a surprisingly low hit rate.)
Murnigsih et al. (2005)screened24aqueous
extracts of plan ts traditionally used for malaria in
Java for antimalarial and antibabesial activity
(Babesia gibsoni is a tick-transmitted canine proto-
zoan parasite that destroys red blood cells). Yarrow
was one of six species found to display strong
inhibitory activity (over 80% inhibition at a 1 mg/
ml concentration) in both assays. Yarrow essential
oil at high concentrations may have some activity
against Trypanosoma cruzi, although clove oil is
much more active (Santoro et al. 2007).
Yarrow inhibits inammation-related pro-
teases, including human neutrophil elastase
(HNE) and matrix metalloproteinases (MMPs)
in vitro (Benedek and Kopp 2007; Benedek et
al. 2007b). Both crude extracts (20% methanol,
evaporated under low pressure and the aqueous
solution lyophilisated) and a avonoid-enriched
fraction inhibited HNE at IC
values of about
20 μg/ml, while a dicaffeoylquinic acids
(DCQA)-enriched fraction inhibited HNE at an
value of about 72 μg/ml (Benedek et al.
2007b); concentrations required to inhibit MMP-
2 and MMP-9 were an order of magnitude
higher, and the DCQA fraction was more potent.
Both total extracts and multiple fractions of
yarrow inhibited human neutrophil respiratory
burst activity (Choudhary et al. 2007); several
fractions had activity similar to or greater than that
of indomethacin, a nonsteroidal anti-inammatory
pharmaceutical drug (NSAID). Proazulenic sesqui-
terpene lactones, including matricin, are degraded
into chamazulene carboxylic acid, which has been
shown to be a COX-2 inhibitor (Ramadan et al.
2006, see discussion below); in fact, Ramadan et
al. began to study this compound because of its
observed similarity to synthetic COX-2 inhibitors.
Thus, at least three different compound classes
contribute to anti-inammatory activity.
Sellerberg and Glasl (2000) tested the effect of
several hot-water yarrow extracts on blood coag-
ulation via an in vitro assay using human blood
plasma. Yarrow signicantly shortened the recal-
cication time, which is an indication of possible
hemostyptic activity in vivo. Flowering material
was most potent; at 5% concentration, a whole
herb extract was signicantly more potent than
leaf or ower extracts and nonsignicantly more
potent than stem extracts, and the authors surmised
that much of the activity was contained in the stem.
Though variation in the activities of a relatively wide
range of concentrations was not statistically signi-
cant, whole-herb concentrations from 1.0% to
5.0% appeared superior, reducing the recalcication
time to less than 50% of the control. The highest
concentrations used for some parts (12.5% for
whole herb, 5% for leaf) were entirely or nearly
ineffective, possibly indicating the presence of
compounds in the leaf with contradictory activities
that become inuential at high concentrations.
Crude yarrow extract showed an antispasmodic
effect in isolated rat jejunum (Yaeesh et al. 2006).
A avonoid-enriched fraction of yarrow showed
an antispasmodic effect in isolated guinea pig
ileum (Lemmens-Gruber et al. 2006). Several
avonoid agycones, including quercetin, luteolin,
and apigenin, had potent individual antispas-
modic activities in the same test, and concen-
trations of these avonoids in yarrow tea would
be high enough to produce this effect in vivo
(Lemmens-Gruber et al. 2006). The mechanism
of this activity has been attributed in part to a
calcium-channel blocking activity and in part to
mediator-antagonistic effects.
Konyalioglu and Karamenderes (2005)
screened 15 species of Achillea for antioxidant
activity using several different in vitro measures of
activity in human erythrocytes and leucocytes,
and found that all were active.
Yarrow showed modest estrogenic activity in an
assay using recombinant MCF-7 cells (Innocenti
et al. 2007). The authors reported that [a]fter
fractionation, estrogenic activity was found in the
methanol/water fraction, although the reported
minimum concentration that display ed any activ-
ity was 8.75×10
g/L for the crude extract,
versus 2.8×10
g/L for the methanol/water
fraction, suggesting that compounds not present
in that fraction contribute synergistically to
activity. Innocenti et al. (2007) likewise reported
that avonoids including apigenin and luteolin
were the primary active compounds, although in
isolation apigenin activated estrogen receptor α
(ERα) only at a minimum concentration of
g/L, while luteolin was inactive;
apigenin and luteolin respectively activated ERβ
at minimum concentrations of 3.70×10
and 2.20×10
g/L. The se compounds, which
occur in many other plants, have weak estrogenic
activity in vitro (e.g., Breinholt and Larsen 1998;
Zand et al. 2000), but are 4,000 to 4 million
times less potent than an active pharmaceutical
control, 17β-estradiol (Breinholt and Larsen
1998). The relevance to human consumers is
therefore questionable.
Lin et al. (2002)testedfteen selected
botanicals against ve hum an liver-cancer cell
lines. A boiling water extract of yarrow, at a
concentration of 2,000 μg/ml, ca used an average
of 55.3% inhibition in three cell lines that were
negative for hepatitis B virus. For the two cell
lines that experienced over 50% inhibition at
that dose, the IC
values were 1,422 μg/ml and
430.4 μg/ml;forthethird,inhibitionof40.7%
at 2,000 μg/ml was the strongest shown by any
tested plant. Yarrow extract was much less active
against two cell lines positive for hepa titis B ;
however, it was one of only two plants tested
that inhibited one of those (Hep3B) at all
without being strongly cytotoxic. Tozyo et al.
(1994) reported that three sesquiterpenoids from
yarrow (achimillic acids A, B, and C) were active
against mouse leukem ia c ells. This does not, of
course, imply that whole yarrow would have
antileukemic activity.
In Vivo Bioactivity Studies
Animal studies directly show a substances
effect on a whole organ or organism, which canat
bestbe guessed at from a bioassay. Such studies
make it possible for researchers to document
health-related endpoints, such as increased wound
healing, that cannot be elucidated at all by in
vitro studies. Conduct of such studies is limited
by their expense. For example, though animal
models of wound healing, antipathogenic, and
antiplasmodial activity are available, no such
studies have been performed using yarrow.
Relevant studies to date have explored anti-
inamma tory activity and protective effects
against gastric and liver damage.
In the most relevant study, a gel containing 6%
yarrow extract was equal to a diclofenac sodium
gel in reducing carrageenan-induced paw edema
(by nearly 50%) in albino rats (Maswadeh et al.
2006). Most animal studies have used isolated
molecules from yarrow, which may be relevant to
drug discovery efforts but do not effectively test
the traditional use. Rupicolin B and 11,13-
dehydrodeacetylmatricarin, both sesquiterpene
lactones isolated from A. setacea, are anti-
inammatory in the croton oil ear test (Zitterl-
Eglseer et al. 1991). Chamazulene carboxylic acid
is anti-inammatory in mouse ear lobe edema
models, in one experiment reducing inamma-
tion by 38% compared to 45% for naproxen at
the same dosage (Ramadan et al. 2006); however,
the same molecule has little effect in a carrageenan
paw edema model (Ramadan et al. 2006)the
same type of test for which a whole yarrow extract
was quite effective (Maswadeh et al. 2006).
A lipophilic fraction from an extract of A.
collina ower heads (part of the A. millefolium
complex, though excluded from the species in the
favored treatment), given to mice at 250 mg/kg,
reduced pain responses by almost half in an acetic
acid-induced writhing test (Gherase et al. 2002),
which was suggested to demonstrate an analgesic
effect; a very high dose (500 mg/kg) of a
hydrophilic extract was also reported to amelio-
rate the increase in periton eal vascular perme-
ability caused by administratio n of acetic acid.
Researchers did not make it clear, and the present
reviewers are not equipped to evaluate, whether
anti-inammatory activity, in the absence of
specically analgesic activity, could adequately
account for reduction in apparent animal suffer-
ing during a writhing test.
Aqueous yarrow e xtract effec tively heals
chronic ulcers previously induced by acetic acid
in rodents (Cavalcanti et al. 2006). Seven days of
treatment reduced mucosal damage by 75% at a
100 mg/kg/day dose and by 90% at a 300 mg/kg/
day dose; these results were superior to the
positive pharmaceutical control of ranitidine,
given at 60 mg/kg. The calc ulated ED
yarrow was 32 mg/kg, which translates to a
reasonable human dose. Addition ally, acute
administration of yarrow extract, concomitant to
ulcer-inducing treatment with 70% ethanol or
indomethacin, signicantly reduced mucosal
damage from those substances (Cavalcanti et al.
2006). Doses used included 125, 1,500, and
2,000 mg/kg; the higher doses were more
effective, especially in preventing damage due to
ethanol. A second rat study (Hatsuko Baggio et
al. 2008) likewise found that a hot-water aqueous
extract of yarrow reduced the formation of
ethanol- and indomethacin-induced ulcers,
although the calculated ID
of 900 mg/kg was
higher than that of two other medicinal plant
extracts traditionally used in Brazil for gastric
problems. (The authors found modest antioxi-
dant activity in vivo and modest, mostly non-
signicant organ-specic effects on glutathione
formation, which were suggested to have a
cytoprotective effect. A mouse study done simul-
taneously with the same yarrow extract found that
it had no effect on gastrointestinal motility.)
These two studies are of particular relevance to
human use for gastrointestinal problems because
an appropriate extract type was used.
Yaeesh et al. (2006 ) induced hepatitis in mice
by treatment with d-galactosamine and lipopoly-
saccharide, giving doses which killed all control
mice. Pretreatment of the mice with crude yarrow
extract at 300 mg/kg reduced mortality from
100% to 40%; yarrow also signicantly improved
liver enzyme levels and reduced histopath ology.
The test substance was a 70% aqueous-methanol
extract, extracted for three days and ltered , the
extraction repeated twice, and the combined
extract evaporated to paste and redissolved in an
aqueous solution. Benedek et al. (2006) reported
that yarrow extract had a choleretic effect two to
three times that of cynarin (1,3-dicaffeoylquinic
acid, a known choleretic) in isolated, perfused rat
livers. Their study produced a 20% methan olic
extract, then used solid phase extraction to
produce an enriched fraction containing 48.8%
dicaffeoylquinic acids and 3.4% luteolin-7-O-
beta-D-glucouronide. However, the authors
noted that those compounds are polar and thus
readily extracted by water and water-ethanol
preparations such as are traditionally used.
In female Wistar rats, an aqueous extract of
yarrow owers reduces conict behavior (Molina-
Hernandez et al. 2004), which is considered to be
an indication of anxiolytic activity. (Yarrow has
been used as a mild sedative or calmative, but is
not widely reputed for this purpose.) The effect
may vary in response to the animals hormone
levels; doses ranging from 8.0 to 12.0 mg/kg of
yarrow extract signicantly reduced conict
behavior during proestrus, while only the highest
dose had signicant effects during diestrus, a
period during which control rats display higher
levels of conict behavior (Molina-Hernandez et
al. 2004).
There has been limited research on yarrow in
chickens, apparently directed at nding botanicals
whose inclusion in commercial diets might
improve growth in factory-farmed chicks. Yarrow
herb at 1% of the diet was the best of several
herbs and essential oils tested in improving
performance of female broiler chicks, although
yarrow oil had little benet (Cross et al. 2007).
Yarrow impr oved weight gain, but did not affect
intestinal microora or sialic acid excretion.
Safety and Toxicology
One side effect of yarrow is well documented:
the plant causes allergic contact dermatitis in
some people. The sensitizing compound s are
guaianolides (a subcategory of sesquiterpenoid),
and especially alpha-peroxyachifolid, which in
fresh material is present at variable concentrations
of up to 0.6% in blossoms and 0.05% in leaves
(Hausen et al. 1991; Rücker et al. 1991; Rücker
et al. 1994). Concentration may diminish in
dried or processed material due to degradation of
the compound (Rücker et al. 1994).
Graf et al. (1994) reported yarrow tea to be
weakly genotoxic in the Drosophila wing-spot or
Somatic Mutation And Recombination Test
(SMART); they simultaneo usly reported, among
other results, that nettle tea, black tea, quercetin,
and rutin were weakly genotoxic. Although the
sensitivity of the SMART test depends upon
choice of fruit y strain, with extremely sensitive
genotypes being preferred (e.g., Aguirrezabalaga
et al. 1994; Rodriguez-Arnais et al. 1993), its
specicity has not been systematically investigated.
However, it is certainly short of 100%, as some of
the other substances reported upon by Graf et al. are
common dietary constituents whose consumption
is not linked to disease or impaired reproduction
although they have been the subjects of much more
study. Results of mammalian studies on the same
substances, wherever available, are unquestionably
of greater informative value.
In vivo rodent and avian studies have not
observed toxicity in yarrow, although most
studies have been short-term. Cavalcanti et al.
(2006) gave rats acute doses of aqueous yarrow
extract of up to 10 g/kg orallyand up to 3 g/kg
intraperitoneallywith no deaths. In longer-term
studies, they reported no signs of relevant
toxicity in Wistar rats treated with aqueous
yarrow extract at doses of up to 1.2 g/kg/day by
gavage for up to 90 days; slight changes in liver
weight and blood cholesterol and glucose levels,
not correlated with dose or period of exposure nor
suggestive of toxicity, were observed. That study
included biochemical and histopathological
examinations, as well as autopsies of sacriced
animals. A study of pregnant female rats (Boswell-
Ruys et al. 2003), discussed in detail below, gave
ethanolic extracts by gavage at 2.8 g/kg/day for a
week, with no signs of maternal toxicity.
As noted above, yarrow contains avonoids
that have weak estrogenic activity in vitro; van
Meeuwen et al. (2007) suggest that apigenin and
other avonoid food supplements may poten-
tiate the growth of breast cancer. These puried
compounds are not sold as dietary supplements,
and many commonly consumed plants contain
them. While this concern may merit investiga-
tion, most effects reported for plant compounds
in vitro prove, when pursued, not to occur in vivo
(the many reported potential drug interactions
being a good example). A 3-day treatment of
immature fema le Wistar rats with yarrow did not
result in any uterotrophic effects (Dalsenter et al.
2004); thus, there is to date no evidence that
yarrow has estrogenic activity in vivo. Genistein
was an order of magnitude more estrogenic, in terms
of causing proliferation of breast cancer cells, than
apigenin in van Meeuwen et al.s(2007)study,and
the quantity of genistein and other phytoestrogenic
isoavones in soy is substantial. Nevertheless,
though concern has been raised that soy could
stimulate growth of estrogen-sensitive tumors (e.g.,
Messina et al. 2006), in the overall human
population soy seems to have either no effect or a
protective effect on breast cancer risk (e.g., Kumar
et al. 2004; Qin et al. 2006). Unless some animal
study using yarrow extract nds a cancer-promoting
effect or signicant estrogenic activity, there is no
rationale for consumer concern.
In male rodents, yarrow has some effects on
spermatogenesis, at least at extreme dosages. In
mice, an ethanolic extract of yarrow, delivered
intraperitoneally at 200 mg/kg/day, and a hydro-
alcoholic extract delivered orally at 300 mg/kg/
day impaired spermatogenesis; morphological
changes observed include d germ cell necrosis
(Montanari et al. 1998). In male Wistar rats
given up to 1.2 g/kg/day of aqueous yarrow
extract for 90 days, those receiving the highest
dose showed a signicant increase in abnormal
sperm (Dalsenter et al. 2004 ); no other toxicity or
reduction in weight gain was seen.
Reproductive Toxicology
One study (Boswell-Ruys et al. 2003)of
reproductive toxicology, using ve rats per treat-
ment group, has been performed. While its
results were touted as alarming, they seem rather
in fact to support the safety of yarrow in
pregnancy, although such a small study cannot
be conclusive. Boswell-Ruys et al. (2003) found
neither contraceptive, abortifacient, nor terato-
genic activity in rats w hen ethanolic yarrow
extract was given at 2.8 g/kg/day on days 18or
815 of pregnancy, 56 times the allegedly
recommended daily human dose of 50 mg/kg
(of body weight). Boswell-Ruys et al. reported
that placental weights were increased in both
groups of yarrow-treated rats and that body
weight was reduced in fetuses exposed on days
815, the basis for their negative conclusion.
However, the yarrow product given w as an
ethanolic extract. Thus, each treatment group
had two control groups, one receiving only water
and the second receiving a dose of ethanol
equivalent to that in the yarrow preparation.
The only signicant difference between either
yarrow group and the corresponding eth anol
control group was in placental weight for rats
exposed on days 815.
A close examination of this st udys results
suggests the failure of Boswell-Ruys et al. to
correctly interpret their own data (partly repro-
duced in Table 2). For rats treated on days 815,
they claimed that Yarrow treatment . . . caused a
reduction in fetal weight. This reduction was not
signicant in comparison to the ethanol control
group, which like the yarrow group had received
1.98 g/kg/day of ethanol, a quantity admittedly
chosen because of previous reports that a dose of
2 g/kg/day signicantly reduced fetal weight!
They further asserted: This decrease in fetal
weight cannot be accounted for by an increased
litter size, as the yarrow treated group litter size
was no different from the control groups. The
total weight of fetuses, excluding a few very small
outliers that were not counted, in each group
can be calculated by multiplying the reported
average fetal weight by the reported number of
counted fetuses (Table 2). For the day 815 water
group, the total fetal weight should have been
3.79 g/fetus × 28 fetuses, or 106.12 g. For the
comparable ethanol group, the total fetal weight
should have been 89.04 g, and for the comparable
yarrow group, 116.48 gmore total fetal bio-
mass than in the water control group! The
difference between 28, 24, and 32 fetuses per
group ma y not have been statistically signicant,
but the assertion that those numbers are therefore
no different was at best an embarrassing over-
sight. There was, in short, no evidence that
yarrow had any independent effect whatsoever
on fetal development.
Boswell-Ruys et al. concluded that, because
they had not seen a no observable effect level,
yarrow should be considered contraindicated
during pregnancy, although it was of course their
choice to use only a sin gle very hi gh dose.
Minimizing use of medicinal products during
pregnancy is certainly wise. However, this study
suggests that yarrow is not a potent teratogen, at
least in rats. It is also unlikely to be an effective
abortifacient, as folklore occasionally claims it to
be, which is unsurprising given its lack of toxicity.
As has been the case for other plants, th e folklore
may have arisen from confusion between emmen-
agogic and abortifacient activities (and perhaps
because it is relatively easy for an ineffective plant
to gain a reputation as an emmenagogue).
Clinical Trials
No controlled human trials of single-compo-
nent yarrow products for their traditional uses
have been conducted. Ramadan et al. (2006 )
reported that when healthy human volunteers
were giv en 500 mg of matricin (one of the
proazulenic sesquiterpene lactone prodrugs in
yarrow) orally, micromolar levels of its anti-
inammatory metabolite, chamazulene carboxylic
acid, were found in their plasma. Another human
Treatment group # fetuses Avg. fetal weight, g Avg. placenta weight, g
Water, days 1 8 29 3.81±.32 0.60±.11
Ethanol, days 18 34 3.81±.31 0.63±.11
Yarrow, days 18 44 3.74±.28 0.64±.09
Water, days 8 15 28 3.79±.26 0.55±.10
Ethanol, days 815 24 3.71±.27 0.54±.10
Yarrow, days 815 32 3.64±.35
p<0.05 versus days 18 water group only;
p<0.01 versus days 815 water group only;
p<0.01 versus days 815
water and ethanol groups
study has found that use of yarrow leaf extract
signicantly reduces biting by Aedes mosquitoes
(Jaenson et al. 2006). Limited research has been
conducted on combination products that include
yarrow among their ingredients. Huseini et al.
(2005) tested a seven-species product called Liv-
52 in cirrhosis patients and found signi cant
benet; however, the small number of patients
involved in the trial (a total of 36 in both arms)
means that results cannot be taken as conclusive.
Likewise, Binić et al. (2010), also in a pilot study
with few patients, reported that a three-herb
topical preparation including yarrow healed sur-
face and ve nous leg ulcers, outperforming a
topical antibiotic.
Achillea millefolium (yarro w) is traditionally
and widely believed to be a benecial medicine
for respiratory infections, digestive ailments, and
injuries and inammatory conditions. Anti-
inammatory and possibly antipathogenic activ-
ities could indeed make it useful for these
purposes, and hemostyptic activity would inde-
pendently benet conditions such as skin injuries
and hemorrhoids. Demonstrated hepatoprotective
activity is also consistent with its less common use
for liver disease. Moreover, animal studies and
extensive human experience indicate that, for
those who are not allergic to it, yarrow is safe
and well tolerate d. Yarrow can be easily cultivated
on a domestic or industrial scale, permitting a
sustainable supply for production of affordable
dietary supplements. It therefore has signicant
potential to benet the public through use in
complementary medicine and self-care of minor
ailments. However, the fact that human trials
have not been conducted limits public knowledge
and use of the plant. Favorable clinical trial results
affect consumer preference, and the currently
more popular dietary supplements for similar uses
enjoy support from multiple clinical trials.
We argue that this species should be seen as a
very high priority for research funding, and clinical
trials of yarrow should be planned to validate uses
most strongly supported by ethnobotanical data.
The widely reputed wound-healing activity of
yarrow merits study, especially given favorable in
vitro assay results; however, animal research might
be more readily accepted. Given the chemical
variation within the Achillea millefolium complex,
an ideal rst step would be to determine whether
chemical content can be correlated with activity in
relevant bioassays, so that if potency appears to
vary with chemotype, the most potent chemotypes
can be chosen for future animal and human
studies. Given the great variability in chemical
composition and quality of available yarrow
products (Benedek et al. 2008), it is essential that
all studies of yarrow provide information on the
source of test materials and on their chemical
composition, via the publication of chemical
ngerprints or the quantication of specicbio-
active marker compounds from multiple com-
pound classes. The time has come for this ancient
medicine to take its place in the modern pharma-
copoeia, and science must rise to the challenge.
The authors wish to thank Brad Bennett, Alain
Touwaide, Emanuela Appettiti, and several sharp-
eyed anonymous reviewers; all helped with impor-
tant elements of the paper. Bob Voeks, editor of
Economic Botany, modied the production sched-
ule to help us add late-breaking issues.
DM adds For Mike.
Literature Cited
Aguirrezabalaga, I., I. Santamaría, and M. A.
Comendador. 1994. The w/w+ SMART is a
useful tool for the evaluation of pesticides.
Mutagenesis 9:341346.
Allen, D. E. and G. Hateld. 2004. Medicinal
plants in folk tradition. Timber Press, Port-
land, Oregon.
Anon. 2011. Research breakthrough. http://
medicine-revealed (February 2011).
Arnold, T. H. 2002. Medicinal and magical plants
of Southern Africa: An annotated checklist.
National Botanical Institute, Pretoria.
Bélanger, A. and L. Dextraze. 1993. Variability of
chamazulene within Achillea millefolium. Acta
Horticulturae (ISHS) 330:141146.
Benedek, B. and B. Kopp. 2007. Achillea
millefolium L. s.l. revisited: Recent ndings
conrm the traditional use. Wiener Medizini-
sche Wochenschrift 157:312314.
———, N. Geisz, W. Jäger, T. Thalhammer,
and B. Kopp. 2006. Choleretic effects of
yarrow (Achillea millefolium s.l.) in the isolated
perfused rat liver. Phytomedicine 13:702706.
———, N. Gjoncaj, J. Saukel, and B. Kopp.
2007a. Distribution of phenolic compounds
in Middleeuropean taxa of the Achillea mil-
lefolium L. aggregate. Chemistry and Biodiver-
sity 4:849857.
———, B. Kopp, and M. F. Melzig. 2007b. Achillea
millefolium L. s.l.Is the anti-inammatory
activity mediated by protease inhibitors? Journal
of Ethnopharmacology 113:31231 7.
———, K. Rothwangl-Wiltschnigg, E. Rozema,
N. Gjoncaj, G. Reznicek, J. Jurenitsch, B.
Kopp, and S. Giasl. 2008. Yarrow (Achillea
millefolium L. s.l.): Pharmaceutical quality of
commercial samples. Pharmazie 63:2326.
Binić, I., A. Janković, D. Janković, I. Janković,
and Z. Vručinić. 2010. Evaluation of healing
and antimicrobiological effects of herbal ther-
apy on venous leg ulcer: Pilot study. Phyto-
therapy Research 24:277282.
Blumenthal, M., W. R. Busse, A. Goldberg, J.
Gruenwald, T. Hall, S. Klein, C. W. Riggins,
and R. S. Rister, eds. 1998. The complete
German commission E monographs: Thera-
peutic guide to herbal medicines. American
Botanical Council, Austin, Texas.
Boswell-Ruys, C. L., H. E. Ritchie, and P. D.
Brown-Woodman. 2003. Preliminary screen-
ing study of reproductive outcomes after
exposure to yarrow in the pregnant rat. Birth
Defects Research Part B, Developmental and
Reproductive Toxicology 68:416420.
Bozin, B., N. Mimica-Dukic, M. Bogavac, L.
Suvajdzic, N. Simin, I. Samojlik, and M.
Couladis. 2008. Chemical composition, anti-
oxidant and antibacterial properties of Achillea
collina Becker ex Heimerl s.l. and A. pannonica
Scheele essential oils. Molecules 13:2058
Breinholt, V. and J. C. Larsen. 1998. Detection
of weak estrogenic avonoids using a recombi-
nant years strain and a modied MCF7 cell
proliferation assay. Chemical Research in
Toxicology 11:622629.
Bussmann, R. W. and D. Sharon. 2007. Plants of
the four winds: The magic and medicinal ora
of Peru. Gracart, Trujillo, Peru.
Candan, F., M. Unlü, B. Tepe, D. Daferera, M.
Polissiou, A. Sökmen, and H. A. Akpulat.
2003. Antioxidant and antimicrobial activity
of the essential oil and methanol extracts of
Achillea millefolium subsp. millefolium Afan.
(Asteraceae). Journal of Ethnopharmacology
Cano Asseleih, L. M. 1997. Flora medicinal de
Veracruz. I. Inventario etnobotánico. Univer-
sidad Veracruzana, Xalapa, Mexico.
Cavalcanti, A. M., C. H. Baggio, C. S. Freitas, L.
Rieck, R. S. de Sousa, J. E. Da Silva-Santos, S.
Mesia-Vela, and M. C. Marques. 2006. Safety
and antiulcer efcacy studies of Achillea
millefolium L. after chronic treatment in
Wistar rats. Journal of Ethnopharmacology
Cernaj, P., P. M. Repcak, K. Tesarik, and R.
Honcariv. 1983. Terpenoid compounds from
different parts of Achillea c ollina Becker
inorescences. Biologia P lantarum (Praha)
Chandle r, R. F., S. N. Hooper, and M. J.
Harvey. 1982. Ethnobotany and phytochem-
istry of yarrow, Achillea millefolium, Composi-
tae. Economic Botany 36:203223.
Choudhary, M. I., S. Jalil, M. Todorova, A.
Trendalova, B. Mikhova, H. Duddeck, and
Atta-ur-Rahman. 2007. Inhibitory effect of
lactone fractions and individual components
from three species of the Achillea millefolium
complex of Bulgarian origin on the human
neutrophils respiratory burst activity. Natural
Products Research 21:10321036.
Cross, D. E., R. M. McDevitt, K. Hillman, and
T. Acamovic. 2007. The effect of herbs and
their associated essential oils on performance,
dietary digestibility and gut microora in
chickens from 7 to 28 days of age. British
Poultry Science 48:496506.
Cruz, C. N. 1979. Dicionário de plantas úteis do
Brazil. Civilização Brasiliera, Rio de Janeiro.
Dalsenter, P. R., A. M. Cavalcanti, A. J. Andrade,
S. L. Araújo, and M. C. Marques. 2004.
Reproductive evaluation of aqueous crude
extract of Achillea millefolium L. (Asteraceae)
in Wistar rats . Reproductive Toxicology
Dokhani, S., T. Cottrell, J. Khajeddin, and G.
Mazza. 2005. Analysis of aroma and phenolic
components of selected Achillea species. Plant
Foods for Human Nutrition 60:5562.
Duke, J. A. 1986. Isthmian ethnobotanical dic-
tionary. Scientic Publishers, Jodhpur, India.
——— and E. S. Ayensu. 1985. Medi cinal
Plants of China. Reference Publications,
Algonac, Michigan.
Ehrendorfer, F. 1973. New chromosome numbers
and remarks on the Achillea millefolium polyploid
complex in North America. Österreichische
Botanische Zeitschrift 122:133143.
——— and Y.-P. Guo. 2006. Multidisciplinary
studies on Achillea sensu lato (Compositae
Anthemidae): New data on systematics and
phylogeography. Willdenowia 36:6987.
Fewkes, J. W. 1896. A contribution to ethno-
botany. American Anthropologist 9:1421.
García Barriga, H. 1975. Flora medicinal de
Colombia. Imprenta Nacional, Bogotá, D.E.
Gervais, C. 1977. Cytological investigation of the
Achillea millefolium complex (Compositae)in
Quebec. Canadian Journal of Botany 55:796
Gherase, F., M. D. Pavelescu, U. Stănescu, and
E. Grigorescu. 2002. Evaluarea experimentalia
privind activitatea analgezica a unor extracte
izolate din specia Achillea collina J. Becker ex
Reichenb. Revista Medico-Chiruricala A Soci-
etatii de Medici si Naturalisti Din Iasi
Glasl, S., P. Mucaji, I. Werner, A. Press er, and J.
Jurenitsch. 2002. Sesquiterpenes and avo-
noid aglycones from a Hungarian taxon of the
Achillea millefolium group. Zeitschrift für
Naturforschung [C] 57:976982.
Graf, U., A. A. Moraga, R. Castro, and E. Diaz
Carrillo. 1994. Genotoxicity testing of differ-
ent types of beverages in the Drosophila wing
Somatic Mutation And Recombination Test.
Food and Chemical Toxicology 32:423430.
Greger, H. and A. Werner. 1990. Comparative
HPLC analyses of alkamides within the Achillea
millefolium group. Planta Medica 56:482486.
Guarrera, P. M. 2006. Usi e tradizioni della ora
Italiana. Medicina Popolare ed Etnobotanica.
Aracne, Rome.
Gudaitytė, O. and P. R. Venskutonis. 2007.
Chemotypes of Achillea millefolium transferred
from 14 different locations in Lithuania to the
controlled environment. Biochemical System-
atics and Ecology 35:582592.
Guédon, D., P. Ab be, and J. L. Lamaison. 1993.
Leaf and ower head avonoids of Achillea
millefolium L. subspecies. Biochemical System-
atics and Ecology 21:607611.
Guo, Y.-P., F. Ehrendorfer, and R. Samuel.
2004. Phylogeny and systematics of Achillea
(AsteraceaeAnthemidae) inferred from nrITS
and plastid trnL-F DNA sequences. Taxon
Ehrendorfer. 2005. AFLP analyses demon-
strate genetic divergence, hybridization, and
multiple polyploidization in the evolution of
Achillea (AsteraceaeAnthemidae). New Phy-
tologist 166:273
Hatsuko Baggio, C., G. De Martini Okofuji, C.
Setim Freitas, L. M. Brandão Torres, M. C.
Andrade Marques, and S. Mesia-Vela. 2008.
Brazilian medicinal plants in gastrointestinal
therapy. Pages 4651 in R. R. Watson and V.
R. Preedy, eds., Botanical medicine in clinical
practice. CABI, Oxon, United Kingdom.
Hausen, B. M., J. Breuer, J. Weglewski, and G.
Rücker. 1991. α-Peroxyachifolid and other
new sensitizing sesquiterpene lactones from
yarrow (Achillea millefolium L., Compositae).
Contact Dermatitis 24:274280.
Hofmann, L. and D. Fritz. 1993. Genetical,
ontogenetical and environmental caused vari-
ability of the essential oil of different types of
the Achillea millefolium complex. Acta Horti-
culturae (ISHS) 330:147157.
Holetz, F. B., G. L. Pessini, N. R. Sanches, D. A.
Cortez, C. V. Nakamura, and B. P. Filho.
2002. Screening of some plants used in the
Brazilian folk medicine for the treatment of
infectious diseases. Memorias do Instituto
Oswaldo Cruz 97:10271031.
Huseini, H. F., S. M. Alavian, R. Hesmat, M. R.
Heydari, and K. Abolmaali. 2005. The ef-
cacy of Liv-52 on liver cirrhotic patients: A
randomized, double-blind, placebo-controlled
rst approach. Phytomedicine 12:619624.
Innocenti, G., E. Vegeto, S. DallAcqua, P.
Ciana, M. Giorgetti, E. Agradi, A. Sozzi, G.
Fico, and F. Tomè. 2007. In vitro estrogenic
activity of Achillea millefolium L. Phytomedi-
cine 14:147152.
Jaenson, T. G., K. Pålsson, and A. K. Borg-
Karlson. 2006. Evaluation of extracts and oils
of mosquito (Diptera: Culicidae) repellent
plants from Sweden and Guinea-Bissau. Jour-
nal of Medical Entomology 43:113119.
Jones, W. H. S. 1956. [Pliny, the Elder]
Naturalis Historia. English and Latin. Harvard
University Press, Cambridge, Massachusetts.
Kokkalou, E., S. Kokkini, and E. Hanlidou.
1992. Volatile constituents of Achillea millefo-
lium in relation to their infraspecic variation.
Biochemical Systematics and Ecology 20:665
Kolos, E. and E. Kolosné Pethés. 1956. Hazai
gyogynövényeink, 2nd edition. Tudomanyos
es semeretterjeszto, Budapest.
Konyalioglu, S. and C. Karamenderes. 2005.
The protective effects of Achillea L. species
native in Turkey against H
-induced oxi-
dative damage in human erythrocytes and
leucocytes. Journal of Ethnopharmacology
Kumar, N., K. Allen, D. Riccardi, A. Kazi, and J.
Heine. 2004. Isoavones in breast cancer
chemoprevention: Where do we go from here?
Frontiers in Bioscience 9:29272934.
Recherche dazulène chez les trois sous-espèces
dAchillea millefolium L. Annales Pharmaceu-
tiques Françaises 46:139143.
Lemmens-Gruber, R., E. Marchart, P. Rawnduzi,
N. Engel, B. Benedek, and B. Kopp. 2006.
Investigation of the spasmolytic activity of the
avonoid fraction of Achillea millefolium s.l. on
isolated guinea-pig ilea. Arzneimittelforschung
Leroi-Gourhan, A. 1975. The owers found with
Shanidar IV, a Neanderthal burial in Iraq.
Science 190:562564.
——— 1998. Shanidar et ses eurs. Paléorie nt
Lin, L.-T., L.-T. Liu, L. -C. Chang, and C.-C.
Lin. 2002. In vitro anti-hepatoma activity of
fteen natural medicin es from Canada. Phy-
totherapy Research 16:440444.
Mahady, G. B., S. L. Pendland, A. Stoia, F. A.
Hamill, D. Fabricant, B. M. Dietz, and L. R.
Chadwick. 2005. In vitr o s usceptibility of
Helicobacter pylori to botanical extracts used
traditionally for the treatment of gastrointestinal
disorders. Phytotherapy Research 19:988991.
electrophoretic separation and quantication
of avone-O- and C-glycosides in Achillea
setacea W. et K. Journal of Chromatography
BAnalytical Technologies in the Biomedical
and Life Sciences 792:363368.
Maswadeh, H. M., M. H. Semreen, and A. R.
Naddaf. 2006. Anti-inammatory activity of
Achillea and Ruscus topical gel on carrageenan-
induced paw edema in rats. Acta Poloniae
Pharmaceutica 63:277280.
McKay, D. L. and J. B. Blumberg. 2006. A
review of the bioactivity and potential health
benets of chamomile tea (Matricaria chamo-
milla L.). Phytotherapy Res earch 20:519530.
Messina, M., W. McCaskill-Stevens, and J. W.
Lampe. 2006. Addressing the soy and breast
cancer relationship: review, commentary, and
workshop proceedings. Journal of the National
Cancer Institute 98:12751284.
Michler, B. and C.-G. Arnold. 1999. Predicting
presence of proazulenes in the Achillea mil-
lefolium group. Folia Geobotanica 34:143
Moerman, D. E. 1998. Native American ethno-
botany. Timber Press, Portland, Oregon.
——— 2007. Agreement and meaning: Rethink-
ing consensus analysis. Journal of Ethnophar-
macology 112:451460.
Molina-Hernandez, M., N. P. Tellez-Alcantara, M.
M. T. Jaramillo. 2004. Anticonic actions of
aqueousextractsofowers of Achillea millefolium
L. vary according to the estrous cycle phases in
Wistar rats. Phytotherapy Research 18:915920.
Montanari, T., J. E . de Carvalho, and H.
Dolder. 1998. Antispermatogenic effect of
Achillea millefolium L. in mice. Contraception
Murnigsih, T., Subeki, H. Matsuura, K. Takahashi,
M. Yamasaki, O. Yamato, Y. Maede, K.
Katakura, M. Suzuki, S. Kobayashi, Chairul,
and T. Yoshihara. 2005. Evaluation of the
inhibitory activities of the extracts of Indonesian
traditional medicinal plants against Plasmodium
falciparum and Babesia gibsoni. Journal of
Veterinary Medical Science 67:829831.
Orav, A., E. Arak, and A. Raal. 2006. Phyto-
chemical analysis of the essential oil of Achillea
millefolium L. from various European countries.
Natural Products Research 20:10821088.
Orth, M., D. Juchelka, A. Mosandl, and F. C.
Czygan. 2000. Enantiomere Monoterpene im
ätherischen Öl von Achillea millefolium s.l.:
Eine zusätzliche taxonomische Bestimmung-
shilfe? Pharmazie 55:456459.
Osbaldeston, T. A. and R. P. A. Wood, eds.
2000. Dioscorides: De materia medica. Ibidis
Press, Johannesburg.
Pollington, S. 2000. Leechcraft: Early English
charms, plant lore, and healing. Anglo-Saxon
Books, Norfolk, England.
Preitschopf, A., B. Michler, and C.-G. Arnold.
1989. Achillea millefolium: Occurrence, ploidal
level, and proazulene variation. Planta Medica
Qin, L.-Q., J.-Y. Xu, P.-Y. Wang, and K. Hoshi.
2006. Soyfood intake in the prevention of
breast cancer risk in women: A meta-analysis
of observational epidemiological studies. Jour-
nal of Nutrition Science and Vitaminology
(Tokyo) 52:428436.
Ramadan, M., S. Goeters, B. Watzer, E. Krause,
K. Lohmann, R. Bauer, B. Hempel, and P.
Imming. 2006. Chamazulene carboxylic acid
and matricin: A natural profen and its natura
prodrug, identied through similarity to syn-
thetic drug sub stances. Journal of Natural
Products 69:10411045.
Ramsey, J. 2007. Unreduced gametes and neo-
polyploids in natural populations of Achillea
borealis (Asteraceae). Heredity 98:143150.
Richardson, I. B. K. 1976. Achillea . Pages 159
165 in T. G. Tutin, V. H. Heywood, N. A.
Burgess, et al., eds., Flora Europaea, Vol. 4.
Cambridge University Press, Cambridge.
Rodriguez-Arnais , R., E. W. Vogel, and A.
Szakmary. 1993. Strong intra-species variabil-
ity in the metabolic conversion of six procarci-
nogens to somatic cell recombinagens in
Drosophila. Mutagenesis 8:543551.
Rohloff, J., E. B. Skagen, A. H. Steen, and T. H.
Iversen. 2000. Production of yarrow (Achillea
millefolium L.) in Norway: Essential oil con-
tent and quality. Journal of Agricultural and
Food Chemistry 48:62056209.
Rücker, G., D. Manns, and J. Breuer. 1991.
Peroxide als Panzeninhaltsstoffe. 8. Mitt.
Guaianolid-Peroxide aus der Schaf garbe, Achi l-
lea millefolium L., Ausloser der Schafgarben-
dermatitis. Archiv der Pharmazie (Weinheim)
———, M. Neugebauer, and A. Kiefer. 1994.
Quantitative Bestimmung von α-Peroxyachifolid
in der Schafgarbe durch HPLC mit amperome-
trischer Detektion. Pharmazie 49:167169 .
Santoro, G. F., M. G. Cardoso, L. G. Guimarães,
L. Z. Mendonça, and M. J. Soares. 2007.
Trypanosoma cruzi: Activity of essential oils
from Achillea millefolium L., Syzygium aroma-
ticum L. and Ocimum basilicum L. on epimas-
tigotes and tr ypomasti gotes. Exp erimental
Parasitology 116:283290.
Sellerberg, U. and H. Glasl. 2000. Pharmacog-
nostical examination concerning the hemos-
typtic effect of Achillea millefolium Aggregat.
Scientia Pharmaceutica 68:201206.
Silva, I. and D. M. G. SantAna. 1995. Noções
sobre o organismo humano e a utilização de
plantas medicinis. Assoeste-Editora Educativa,
Cascavel, Paraná, Brazil.
Solecki, R. S. 1975. Shanidar IV, a Neanderthal
ower burial in northern Iraq. Science
Stevenson, M. C. 1915. Ethnobotany of the Zuni
Indians. Smithsonian Institution Bureau of
American Ethnology Annual Report, No. 30.
Smithsonian Institution, Washington, D.C.
Stojanović, G., N. Radu lović, T. Hashimoto, and
R. Palić. 2005. In vitro antimicrobial activity
of extracts of four Achillea species: The
composition of Achillea clavennae L. (Aster-
aceae) extract. Journal of Ethnopharmacology
Sulyok, K. and L. Siklos. 1998. Lajor Atya
Tanascai. Hungalibri Kiado, Budapest.
Todorova, M., A. Trendalova, B. Mikhova, A.
Vitkova, and H. Duddeck. 2007. Chemotypes
in Achillea collina based on sesquiterpene
lactone prole. Phytochemistry 68:17221730.
Tozyo, T., Y. Yoshimura, K. Sakurai, N. Uchida,
Y. Takeda, H. Nakai, and H. Ishii. 1994.
Novel antitumor sesquiterpenoids in Achillea
millefolium. Chemical and Pharmaceutical
Bulletin (Tokyo) 42:10961100.
Trendalova, A., M. Todorova, B. Mikhova, A.
Vitkova, and H. Duddeck. 2006. Sesquiter-
pene lactones from Achillea collina J. Becker ex
Reichenb. Phytochemistry 67:764770.
Unlü, M., D. Daferera, E. Dönmez, M. Polissiou,
B. Tepe, and A. Sökmen. 2002. Compositions
and the in vitro antimicrobial activities of the
essential oils of Achillea setacea and Achillea
teretifolia (Compositae). Journal of Ethnophar-
macology 83:117121.
van Meeuwen, J. A., N. Korthagen, P. C. de
Jong, A. H. Piersma, and M. van den Berg.
2007. (Anti)estrogenic effects of phytochem-
icals on human primary mammary broblasts,
MCF-7 cells and their co-culture. Toxicology
and Applied Pharmacology 221:372383.
Verzár-Petri, G., B. N. Cuong, J. Tamas, L.
Radics, and K. Ujszaszi. 1979. The main
azulenogenous sesquiterpene lactones of Achil-
lea millefol ium L. ssp. collina as compounds in
the plant kingdom. Planta Medica 36:273
Vestal, P. 1940. Notes on a collection of plants
from the Hopi Indian region of Arizona made
by J. G. Owens in 1891. Botanical Museum
Leaets (Harvard University) 8(8):153168.
Werner, I., S. Glasl, A. Presser, E. Haslinger, and
J. Jurenitsch. 2003. Sesquiterpenes from
Achillea pannonica Scheele. Zeitschrift für
Naturforschung 58:303307.
———, ———, and G. Reznicek. 2006. Infra-
red spectroscopy as a tool for chemotaxonomic
investigations within the Achillea millefolium
group. Chemistry and Biodiversity 3:2733.
Whiting, A. F. 1939. Ethnobotany of the Hopi.
Museum of Northern Arizona Bulletin #15.
Wichtl, M. 2004. Herbal drugs and phytopharma-
ceuticals: A handbook for practice on a scientic
basis. Third [English] edition. Medpharm Sci-
entic Publishers, Stuttgart, Germany.
Yaeesh, S., Q. Jamal, A. U. Khan, and A. H. Gilani.
2006. Studies on hepatoprotective, antispas-
modic and calcium antagonist activities of the
aqueous-methanol extract of Achillea millefo-
lium. Phytotherapy Research 20:546551.
Zand, R. S., D. J. Jenkins, and E. P. Diamandis.
2000. Steroid hormone activity of avonoids
and related compounds. Breast Cancer
Research and Treatment 62:3549.
Zitterl-Eglseer, K., J. Jurenitsch, S. Korhammer,
E. Haslinger, S. Sosa, R. Della Loggia, W.
Kubelka, and C. Franz. 1991. Entzündung-
shemmede sesq uiterpenla ctone vo n Achillea
setacea. Planta Medica 57:444446.
... Yarrow (Achillea millefolium) is widely grown due to great importance in the cosmetics, health, and pharmaceutical industries. This species is used in the treatment of intestinal, gastric, liver, and bile disorders (Applequist and Moerman 2011;Strzępek-Gomółka et al. 2021). In addition, it is used as an appetite-enhancing drug due to its bitter taste, wound healing and also against skin inflammations (Chou et al. 2013). ...
Full-text available
Nanoparticles (NPs) are an emerging tool for mitigating environmental stresses. Although beneficial roles of NPs have been reported in some plants, there is little data on magnesium (Mg)-NPs in alleviating drought stress. Therefore, the field experiment was conducted to study changes in biochemical attributes and essential oil (EO) compositions of yarrow (Achillea millefolium L.) plants under drought stress and Mg-NPs in 2016 and 2017. Irrigation regimes were used in two levels as well-watered (irrigation intervals of 7 days) and drought stress (irrigation intervals of 14 days) conditions, and Mg-NPs were sprayed on leaves in four levels (0, 0.1, 0.3, and 0.5 g L⁻¹). The results showed drought stress led to increased electrolyte leakage (EL), proline, carotenoid, anthocyanin, and total flavonoid content (TFC). However, flowers yield and EO yield were lower in plants exposed to drought stress as compared to well-watered conditions. The 0.3 and 0.5 g L⁻¹ Mg-NPs were more effective in alleviating drought stress by enhancing these traits. Heat map results showed that EL and TSS represented the high variability upon different treatments. The GC and GC/MS results represented that α-pinene (8.60–12.20%), 1,8-cineol (9.03–14.02%), camphor (6.84–9.80%), α-bisabolol (8.54–18.81%), chamazulene (14.23–22.50%), and caryophyllene oxide (7.20–9.80%) were the min EO constitutes of yarrow plants. Totally, drought decreased monopertens but increased sesquiterpenes of EO. To sum up, foliar applied Mg-NPs in a range of 0.3–0.5 g L⁻¹ can be recommended as effective tool to improve plant yield through changes in biochemical attributes of yarrow plants.
... The aerial parts of the flowering plant contain 0.2-1.2% of essential oil, flavonoids, vitamin K, chromium, bitter material ahilein, resin, sterols, tannins, etc. exhibiting anticoagulant and anti-inflammatory effects. The essential oil, with the most abundant components: pinene, 1,8-cineole, thujone, camphor, limonene, and borneol shows antimicrobial, anti-inflammatory, antioxidant, and antispasmodic effects [1,5,6]. ...
... Achillea millefolium L. (yarrow), the best-known plant in this genus, is traditionally used in folk medicine for the treatment of lung (asthma and bronchitis), dyspepsia, and hepatobiliary disorders; skin inflammation; and headaches [2,3]. Previous research studies showed that A. millefolium L. has a disinfectant, anti-inflammatory, antispasmodic, anthelminthic, and antibacterial properties [1,4,5]. In addition, yarrow extracts are valued for their antioxidant activity, and have been shown to lower blood pressure, act as a diuretic, treat urinary tract infections, and relieve uterine and menstrual symptoms [1,[6][7][8]. ...
Full-text available
In this study, the extraction efficiency of natural deep eutectic solvents (NADES) based on choline chloride as a hydrogen bond acceptor (HBA) and five different hydrogen bond donors (HBD; lactic acid, 1,4-butanediol, 1,2-propanediol, fructose and urea) was evaluated for the first time for the isolation of valuable bioactive compounds from Achillea millefolium L. The phytochemical profiles of NADES extracts obtained after ultrasound-assisted extraction were evaluated both spectrophotometrically (total phenolic content (TPC) and antioxidant assays) and chromatographically (UHPLC-MS and HPLC-UV). The results were compared with those obtained with 80% ethanol, 80% methanol, and water. The highest TPC value was found in the lactic acid-based NADES (ChCl-LA), which correlated with the highest antioxidant activity determined by the FRAP analysis. On the other hand, the highest antiradical potential against ABTS+• was determined for urea-based NADES. Phenolic acids (chlorogenic acid and dicaffeoylquinic acid isomers), flavones (luteolin and apigenin), and their corresponding glucosides were determined as the dominant individual phenolic compounds in all extracts. The antibacterial and antifungal properties of the extracts obtained against four bacterial cultures and two yeasts were evaluated using two methods: the agar dilution method to obtain the minimum inhibitory concentration (MIC) and the minimum bactericidal or fungicidal concentration (MBC or MFC), and the disc diffusion method. ChCl-LA had the lowest MIC and MBC/MFC with respect to all microorganisms, with an MIC ranging from 0.05 mg mL−1 to 0.8 mg mL−1, while the water extract had the weakest inhibitory activity with MIC and MBC/MFC higher than 3.2 mg mL−1.
Ethnopharmacological relevance Achillea erba-rotta subsp. moschata (Wulfen) I.Richardson (syn. A. moschata Wulfen) (Asteraceae) is an alpine endemic plant whose aerial parts are harvested by the locals mainly for the digestive properties. Despite its widespread use, few studies have been conducted to date to verify its properties. Aim of the study The purpose of the work was to meet the tradition confirming with experimental data the popular belief that the consumption of this species offers beneficial effects to the gastrointestinal system. Materials and methods Using Soxhlet apparatus, the dried aerial parts of A. erba-rotta subsp. moschata were successively extracted with petroleum ether (PET), dichloromethane (DCM) and methanol (MeOH). The essential oil (EO) was obtained by hydrodistillation using a Clevenger apparatus while infusion (AE) was prepared following the traditional local recipe. Their chemical characterization was performed by various techniques including SPME-GC/MS, GC/MS and HPLC/MS-MS. An in vitro biological screening was carried out. The influence of AE on lipid digestion was monitored by titration of free fatty acids (FFA) during pancreatic lipase activity with the pH-stat method. For all extracts and EO, the anti-Helicobacter pylori activity was assessed by the broth microdilution method, the influence on cell viability was evaluated against NCI–N87, OE21 and Caco-2 cell lines and a preliminary toxicity evaluation was done using Brine Shrimp lethality (BSL) assay. The anti-inflammatory potential was evidenced by interleukin IL-1- induced IL8 expression on Caco-2 cells. Results AE increased by 15% the FFA releasing compared to the pancreatic lipase alone. PET, DCM and MeOH extracts as well as AE and EO were considered active against the growth of both antimicrobial susceptible and resistant strains of H. pylori with MIC values starting from 16 μg/mL. PET and DCM (IC50 = 89 μg/mL and 96 μg/mL, respectively, against Caco-2 cell line) extracts showed the high effect on cell viability while the EO reduced in 50% of cell viability at 1.48 μL/mL (NCI–N87 cells), 1.42 μL/mL (OE21 cells), and 3.44 μL/mL (Caco-2 cells) corroborating the BSL results. In different degrees, all extracts and EO inhibited the IL-1β-stimulated IL-8 production in Caco-2 cells. Conclusions The obtained data are encouraging and provide a scientific basis for the traditional use of A. erba-rotta subsp. moschata as a digestive agent although they need to be further corroborated by studies involving the investigation of both the in vivo activities and the role of the compounds detected in the extracts.
The present study aimed to determine the chemical composition and antioxidant activity of immortelle (Helichrysum italicum (Roth) G. Don) and yarrow (Achillea millefolium L.) essential oils isolated from the aerial plant parts on a semi-industrial scale by steam and water-steam distillation, respectively. The qualitative composition of the essential oils obtained was determined by GC/MS and their quantitative composition by GC/FID method. Their antioxidant activity was estimated by using DPPH, ABTS and FRAP assays. The most abundant components in the immortelle essential oil were a-pinene (22.4%), g-curcumene (13.2%), neryl acetate (9.8%) and b-selinene (8.7%), while yarrow essential oil contained 1,8-cin-eole (25.5%), CIS-thujone (10.8%), camphor (7.3%) and artemisia ketone (6.9%) in the highest percentage. According to the EC 50 values yarrow essential oil showed better radical (DPPH and ABTS) scavenging activity than immortelle essential oil (7.71 mg/cm 3 vs. 8.94 mg/cm 3 after 20 minutes of incubation with DPPH radical ; and 26.03 mg/cm 3 vs. 88.52 mg/cm 3 after 24 minutes incubation with ABTS radical, respectively). On the other hand, immortelle essential oil showed better ferric ion reducing power (7.16 mgEFe2+/g vs. 5.72 mgEFe2+/g essential oil) in comparison to yarrow essential oil. However, the results obtained indicated a low antioxidant activity of both essential oils studied.
Full-text available
The aggressive triple-negative breast cancer (TNBC) is a challenging disease due to the absence of tailored therapy. The search for new therapies results in an intensive research focusing on natural sources. Achillea fragrantissima (A. fragrantissima) is a traditional medicine from the Middle East region. Various solvent extracts from different A. fragrantissima plant’s parts, including flowers, leaves, and roots, were tested on TNBC MDA-MB-231 cells. Using liquid chromatography, the fingerprinting revealed rich and diverse compositions for A. fragrantissima plant parts using polar to non-polar solvent extracts indicating possible differences in bioactivities. Using CellTiter-Glo™ viability assay, the half-maximal inhibitory concentration (IC50) values were determined for each extract and ranged from 32.4 to 161.7 µg/mL. The A. fragrantissima flower dichloromethane extract had the lowest mean IC50 value and was chosen for further investigation. Upon treatment with increasing A. fragrantissima flower dichloromethane extract concentrations, the MDA-MB-231 cells displayed, in a dose-dependent manner, enhanced morphological and biochemical hallmarks of apoptosis, including cell shrinkage, phosphatidylserine exposure, caspase activity, and mitochondrial outer membrane permeabilization, assessed using phase-contrast microscopy, fluorescence-activated single cell sorting analysis, Image-iT™ live caspase and mitochondrial transition pore opening activity, respectively. Anticancer target prediction and molecular docking studies revealed the inhibitory activity of few A. fragrantissima flower dichloromethane extract-derived metabolites against carbonic anhydrase 9, enzyme reported for its anti-apoptotic properties. In conclusion, these findings suggest promising therapeutic values of the A. fragrantissima flower dichloromethane extract against TNBC development.
Several exotic plants (non‐native) are used in Brazilian traditional medicine and are known worldwide for their possible diuretic actions. Among the wide variety of plants, standing out Achillea millefolium L., Camellia sinensis L. Kuntze, Crocus sativus L., Hibiscus sabdariffa Linn., Petroselinum crispum (Mill.) A.W. Hill, Taraxacum officinale (L.) Weber, and Urtica dioica L., whose effects have already been the subject of some scientific study. In addition, we also discussed other exotic species in Brazil used popularly, but that still lack scientific studies, like the species Arctium lappa L., Carica papaya L., Catharanthus roseus (L.) G. Don, Centella asiatica (L.) Urb, Citrus aurantium L., and Persea americana Mill. However, generally, clinical studies on these plants are scarce. In this context, different plant species can be designated for further comprehensive studies, therefore, promoting support for developing an effective medicine to induce diuresis.
In the current study, gelatin (Ge)‐sodium alginate (SA) based edible films containing 0, 1, 2, and 3% (w/w) yarrow essential oil (YEO) were prepared using casting method. The physical, morphological, chemical and antimicrobial properties of these films were investigated. Results indicated that elongation at break (EB), water vapor permeability (WVP), and swelling ratio (SR) increased , while tensile strength (TS), moisture content (MC), and solubility (Sol) decreased with increasing YEO content. Also, the contact angle (CA) increased from 60.11 to 89.07 by increasing YEO indicating an increase in surface hydrophobicity and also an increase in heterogeneity and unevenness in the surface of the film. The non‐significant difference was observed between the color index involving lightness, and yellowness in the SA‐G film containing 0, 1, 2, and 3% YEO (P>0.05); however, the addition of YEO significantly caused to change the overall color difference (ΔE) (P<0.05). Fourier transform infrared spectroscopy (FTIR) analysis revealed an interaction between Ge‐SA and YEO. Results obtained indicated that the antimicrobial and antioxidant properties improved, and total phenolic content (TPC) increased with increasing YEO content. Maximum diameter of the inhibition zone of the G‐SA films belonged to the Pseudomonas aeruginosa, which reached 26.7 mm in the film containing 3% YEO. Result indicates the possibility of using Ge‐SA film containing YEO as an active food packaging film.
Full-text available
Yarrow (Achillea millefolium Aggregat) is traditionally used against bleeding. Aqueous hot extracts were turbid and shortened the recalcification time, a global test of the blood coagulation. The residue obtained by membrane filtration of these extracts was the active fraction. This residue is probably located mostly in the stem. By pressure obtained juice elongated the blood coagulation. Compared with non-flowering and wilthed material, the blooming herb showed best effects. The storage conditions had no effect on the activity of the herb.
This book, which contains 99 chapters, focuses on the growing body of knowledge on the role of various dietary plants in reducing disease. Most of the expert reviews define and support the actions of bioflavonoids, antioxidants and similar materials that are part of dietary vegetables, dietary supplements and nutraceuticals. The book's chapters have various general groupings. Some herbal remedies are being developed based upon historic and cultural uses of certain plants and their constituents in disease prevention and health promotion. Discussions of Japanese, African, Korean and South American plants and their extracts help understanding of their potential roles in health as well as historical evidence for their usefulness. Since the goal of this book is to get experts to explore the ways nutraceutical supplements or foods and herbal medicines prevent disease and cancer or promote health, a major section focuses on many plants and health promotion. These include health concerns such as glucose lowering, bone mineral changes, cramps, cognitive function, osteoarthritis, sleep, skin health, weight reduction, eye protection and many others. The conclusions and recommendations from the various chapters will provide a basis for change as well as application of new extracts and botanicals in preventing cancers and health promotion.