443
Introduction
Cardiovascular diseases remain a prominent killer today, including myocardial infarctions, strokes, and thromboses that can arise from pathologies associated with coagulation (Chistokhodova et al., 2002; Rang et al., 2007; Buch et al., 2010; Eisenreich & Rauch, 2011). Over activity of the coagulation cascade (hypercoagulation) increases the risk of thromboses formation (Mekhfi et al., 2004). This can easily lead to thromboembolisms which block blood flow and lead to ischemia with sub-sequent damage to the afflicted organs (Bruno et al., 2001). Hereditary defects and habits, such as smoking, increase blood coagulability (Rang et al., 2007). On the other hand, anticoagulants (such as heparin and war-farin), antiplatelet drugs (aspirin) as well as fibrinolyt-ics (streptokinase) decrease blood coagulation and the risk of thrombus formation (Vane & Botting, 2003; Rang et al., 2007).
The use of plants as remedies for various ailments has formed the basis of our modern medicinal sciences
(Hutchings et al., 1996). According the World Health Organization (2008) approximately 80% of Asia and Africa’s population use traditional medicine as a form of healthcare for treatment of diseases including blood disorders. Plant extracts can be an alternative to cur-rently used antiplatelet agents, as they constitute a rich source of bioactive chemicals. Compounds such as alkaloids, xanthones, coumarins, anthraquinones, fla-vonoids, stilbenes, and naphthalenes have been reported to have an effect on platelet aggregation (Aburjai, 2000; Elliott Middleton et al., 2000; Chen et al., 2001; Chung et al., 2002). Furthermore, polyphenol-rich diets have been shown to be beneficial in vascular functioning including platelet aggregation in humans (Murphy et al., 2003). In this article, the effects of herbal remedies on blood parameters are reviewed. Literature was obtained through use of Scopus and PubMed databases, as well as Google Scholar using the following search parameters, or combinations thereof: “anticoagulant,” “antiplatelet,”
ReseaRch aRtIcle
Herbal remedies affecting coagulation: A review
Werner Cordier and Vanessa Steenkamp
Department of Pharmacology, School of Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa
abstractContext: Herbal remedies are used to treat a large variety of diseases, including blood-related disorders. However, a number of herbal preparations have been reported to cause variations in clotting time, this is mainly by disruption of the coagulation cascade.Objective: The compiling of plants investigated for effects on the coagulation cascade.Methods: Information was withdrawn from Google Scholar and the journal databases Scopus and PubMed.Results: Sixty-five herbal remedies were identified with antiplatelet, anticoagulant, or coagulating ability. Bioactive compounds included polyphenols, taxanes, coumarins, saponins, fucoidans, and polysaccharides.Conclusion: Although research has been conducted on the effect of herbal remedies on coagulation, most information relies on in vitro assays. Contradictory evidence is present on bleeding risks with herbal uses, though herb–drug interactions pose a threat. As the safety of many herbals has not been proven, nor their effect on blood parameters determined, the use of herbal preparations before undergoing any surgical procedure should discontinued.Keywords: Antiplatelet, antithrombotic, anticoagulant, extract, perioperative bleeding
Address for Correspondence: Vanessa Steenkamp, Department of Pharmacology, School of Medicine, Faculty of Health Sciences, University of Pretoria, P.O. Box X323, Arcadia, 0007, Pretoria, South Africa. Tel +27-12-3192547. Fax: +27-12-3192411. E-mail: [email protected]
(Received 12 May 2010; revised 11 July 2011; accepted 03 August 2011)
Pharmaceutical Biology, 2012; 50(4): 443–452© 2012 Informa Healthcare USA, Inc.ISSN 1388-0209 print/ISSN 1744-5116 onlineDOI: 10.3109/13880209.2011.611145
Pharmaceutical Biology
2012
50
4
443
452
12 May 2010
11 July 2011
03 August 2011
1388-0209
1744-5116
© 2012 Informa Healthcare USA, Inc.
10.3109/13880209.2011.611145
NPHB
611145
Phar
mac
eutic
al B
iolo
gy D
ownl
oade
d fr
om in
form
ahea
lthca
re.c
om b
y Q
ueen
's U
nive
rsity
on
04/3
0/13
For
pers
onal
use
onl
y.
444 W. Cordier and V. Steenkamp
Pharmaceutical Biology
“coagulation,” “plant,” “extract,” “herbal,” and “remedy” and articles published prior to and including 2011.
Herbals and their effect on blood parametersVarious plants are used ethnomedicinally for use in blood-related treatments as blood tonics, to prevent excessive bleeding, to treat hemorrhoids, and as wound dressing to staunch blood flow. The efficacy and safety of herbal preparations are not always clearly defined though, and the use of these may cause increased perioperative bleeding risk due to disrupted coagulation (Beckert et al., 2007). Whether these preparations have direct effects on the coagulation system or cause disruption due to drug interactions is not always known (Beckert et al., 2007). Plants studied for effects on coagulation in vitro and/or in vivo, as well as possible bioactive constituents, are listed in Table 1.
Various models exist to screen for activity, though popular experiments include effects on prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin time (TT) both in vitro and ex vivo, while bleeding time and protection against thromboembolism-induced death are monitored in vivo. Since in vitro activ-ity does not always translate to in vivo activity, continued research in this area is of essence.
Although the majority of plants decrease platelet activation and aggregation, it should be kept in mind that many factors are at play. Microtubule stabilization from taxanes (Kim & Yun-Choi, 2010) and increased membrane fluidity from garlic-saponins (Su et al., 1996; Liao & Li, 1997) maintains a disaggregated platelet form. Harmane- and harmine-induced reduction of tyrosine phosphorylation limits calcium mobilization and arachidonic acid liberation, which decreases platelet aggregation (Im et al., 2009). The coagulation cascade is attenuated by various phytochemicals such as polyphe-nols, sulfated polysaccharides, lapachol, allicin, and thio-sulfates through inhibition or decreased activity of tissue factor (Lee et al., 2003, 2004), thrombin (Medeiros et al., 2008; Zhang et al., 2008), vitamin K-epoxide reductase (Preusch & Smalley, 1990), plasminogen activator, phos-pholipase, thromboxane A
2, lipoxygenase (Srivastava,
1986; Beckert et al., 2007), thiol enzymes (coenzyme A and 3-hydroxy-3-methylglutaryl coenzyme A reductase) (Liao & Li, 1997), and other clotting factors, as well as potentiation of heparin co-factor II (Medeiros et al., 2008; Mao et al., 2009), and increased fibrinolysis. Coumarin compounds have the ability to affect coagulation through scavenging of reactive oxygen species, inhibiting cyclic nucleotide phosphodiesterases, inhibiting the activity of vitamin K-dependent γ-carboxylase (activation of coagulation factors) and prostaglandin synthesis (Hoult & Paya, 1996; Coppinger et al., 2004). Increased coagu-lation could be explained through synthesis of protein networks and increased erythrocyte aggregation, such as with Ankaferd Blood Stopper® (Goker et al., 2008), or activation of several clotting factors or platelets due to glycoconjugates (Pawlaczyk et al., 2010).
Adverse effects after herbal usageFour plants have mainly been implicated in spontaneous or perioperative bleeding, which has been attributed to a drug–herb interaction (Table 2). Such interactions are especially of importance when used together with war-farin which has a narrow therapeutic window (Lee et al., 2004; Beckert et al., 2007; Jurgens & Whelan, 2009). St. John’s wort has been found to increase the metabolism of warfarin in humans and animals thereby decreasing its efficacy (Roby et al., 2000). Catechins (found to have antiplatelet activity) as well as vitamin K present in green tea would appear to antagonize the anticoagulant effects of warfarin (Taylor & Wilt, 1999). Intraoperative bleeding has been reported after the consumption of Aloe tablets− due to a possible herb–drug interaction with sevoflurane (Steenkamp & Stewart, 2007).
Ginkgo biloba L. (Ginkgoaceae) has been found to increase bleeding risks, especially during concomitant use of anticoagulants or antiplatelet drugs (Kim et al., 2010). However, an open-label, randomized, crossover study reported that there was no difference in bleed-ing times or platelet aggregation between ticlopidine (250 mg) and ticlopidine/Ginkgo biloba (250/80 mg) treatment groups (Kim et al., 2010).
A clinical study in which Gingko biloba, garlic, Asian ginseng [Panax ginseng C.A. Meyer (Araliaceae)], St. John’s wort, and saw palmetto were given to adult volun-teers (5 cycles of 4 weeks, 2 week treatment and 2 week wash-out) indicated that these plants were unable to induce any changes to in vivo platelet function (Beckert et al., 2007).
Increased blood coagulation time has been noted when using warfarin with Peumus boldus Molina (Monimiaceae), Dong quai, and garlic. Whether this is due to additive anticoagulant activity or increased plasma concentration of warfarin has as yet not been established (Lambert & Cormier, 2001; Basila & Yuan, 2005).
Discussion
As with all research, it is imperative to use a variety of methods to elucidate the mechanism of action of a com-pound or extract. Single assays are more likely to lead to false positives or inaccurate data, and the advantages or disadvantages must be weighed to magnify the value of a test. Furthermore, in vivo assays are of great importance, as in vitro studies do not always predict the effect of an herbal or compound once pharmacodynamic and phar-macokinetic profiles come into play.
A review of the literature indicated that many herb-als reduce clotting via inhibition of coagulation factors or platelet activity. Furthermore, the majority of experi-ments to determine activity were carried out in vitro, with limited in vivo analyses. It is of great importance to vali-date in vitro results in animal studies, as there is always the chance that absorption, metabolism, or excretion may lead to significant changes in the herbals effect on coagulation. Many phytochemicals, such as coumarins,
Phar
mac
eutic
al B
iolo
gy D
ownl
oade
d fr
om in
form
ahea
lthca
re.c
om b
y Q
ueen
's U
nive
rsity
on
04/3
0/13
For
pers
onal
use
onl
y.
Herbal remedies affecting coagulation 445
© 2012 Informa Healthcare USA, Inc.
Tab
le 1
. Her
bal
rem
edie
s aff
ecti
ng
coag
ula
tion
.Fa
mily
Pla
nt
Ver
nac
ula
r n
ame
(use
s if
sta
ted
)E
ffec
t (p
hyt
och
emic
al if
sta
ted
)R
efer
ence
sA
nti
thro
mbi
n a
ctiv
ity
Ap
iace
aeA
nge
lica
sin
ensi
s (O
liv.
) D
iels
Don
g q
uai
(m
enst
rual
sym
pto
ms)
An
tith
rom
bin
act
ivit
ya (cou
mar
ins
sugg
este
d)
Page
& L
awre
nce
, 199
9; C
amp
os-
Toim
il et
al.,
200
2; B
asila
& Y
uan
, 20
05A
ralia
ceae
Hed
era
heli
x L
.C
omm
on iv
yA
nti
thro
mb
in a
ctiv
itya
de
Med
eiro
s et
al.,
200
0
Tetr
apan
ax p
apyr
ifer
us
C. K
och
Ric
e p
aper
pla
nt
An
tith
rom
bin
act
ivit
yaC
his
tokh
odov
a et
al.,
200
2A
ster
acea
eB
iden
s tr
ipar
tita
L.
Thre
e-lo
be
beg
gart
icks
An
tith
rom
bin
act
ivit
yaG
oun
et a
l., 2
002
Mon
ostr
omat
acea
eM
onos
trom
a la
tiss
imu
m (
Keu
tzin
g)
Wit
troc
kK
elp
Incr
ease
d a
PT
T a
nd
TTa (
sulf
ated
p
olys
acch
arid
es)
Mao
et a
l., 2
009
Eu
ph
orb
iace
aeC
roto
n z
ambe
sicu
s M
üel
l Arg
.To
nd
ibon
ham
ey (
men
stru
al p
ain
)D
ecre
ased
thro
mb
in a
ctiv
itya
(dit
erp
enes
su
gges
ted
)R
ober
t et a
l., 2
010
Ja
trop
ha c
urc
as L
inn
.P
hys
ic n
ut (
abor
tifa
cien
t,
hae
mos
tati
c)P
roco
agu
lan
t wh
en c
once
ntr
ated
, an
tico
agu
lan
t wh
en d
ilute
da
Oso
niy
i & O
naj
obi,
2003
Fab
acea
eC
assi
a pe
ters
ian
a B
elle
.D
war
f cas
sia
Incr
ease
d P
TaC
ord
ier
et a
l., 2
011
Faga
ceae
Qu
erce
s ro
bur
L.
En
glis
h o
akA
nti
thro
mb
in a
ctiv
itya
Gou
n e
t al.,
200
2G
ram
inea
eFe
stu
ca ju
bata
Low
eFe
scu
eA
nti
thro
mb
in a
ctiv
itya
de
Med
eiro
s et
al.,
200
0H
alor
agac
eae
Gu
nn
era
tin
ctor
ia (
Mol
ina)
Mir
bC
hile
an r
hu
bar
bA
nti
thro
mb
in a
ctiv
itya
de
Med
eiro
s et
al.,
200
0La
min
aria
ceae
Lam
inar
ia ja
pon
ica
Are
sch
oug
Kom
bu
Incr
ease
d c
oagu
lati
on ti
mes
a (lo
w
mol
ecu
lar
wei
ght f
uco
idan
s)W
ang
et a
l., 2
010
Lau
race
aeLa
uru
s az
oric
a (S
enb.
) Fr
anco
Azo
res
lau
rel
An
tith
rom
bin
act
ivit
yad
e M
edei
ros
et a
l., 2
000
Lyth
race
aeLa
gers
troe
mia
indi
ca L
inn
.C
rap
e m
yrtl
eA
nti
thro
mb
in a
ctiv
itya
Ch
isto
khod
ova
et a
l., 2
002
Ly
thru
m s
alic
aria
L.
Pu
rple
loos
estr
ife
(ast
rin
gen
t,
styp
tic)
Incr
ease
d c
oagu
lati
on ti
mes
a,b ,
thou
gh th
rom
bu
s fo
rmat
ion
b
(gly
coco
nju
gate
s)
Paw
lacz
yk e
t al.,
201
0
Myr
icac
eae
Myr
ica
ceri
fera
Big
elow
Bay
ber
ry (
anal
gesi
c)A
nti
thro
mb
in a
ctiv
itya
Ch
isto
khod
ova
et a
l., 2
002
Myr
sin
acea
eA
rdis
ia c
ren
ata
Rox
b.C
oral
ber
ryA
nti
thro
mb
in a
ctiv
itya
Ch
isto
khod
ova
et a
l., 2
002
Myr
tace
aeC
alli
stem
on la
nce
olat
us
(Sm
.) S
wee
tB
ottl
ebru
shA
nti
thro
mb
in a
ctiv
itya
Ch
isto
khod
ova
et a
l., 2
002
M
agn
olia
vir
gin
ian
a Li
nn
.Sw
eetb
ay m
agn
olia
(in
tern
al p
ain
s,
feve
r)A
nti
thro
mb
in a
ctiv
itya
Ch
isto
khod
ova
et a
l., 2
002
Ph
aeop
hyc
eae
Les
son
ia v
ados
a Se
arle
sB
row
n s
eaw
eed
Incr
ease
d c
oagu
lati
on ti
mes
a (f
uco
idan
s)C
han
día
& M
atsu
hir
o, 2
008
Pin
acea
eLa
rix
sibi
rica
Led
eb.
Sib
eria
n la
rch
Incr
ease
d a
PT
Ta (ar
abin
ogal
acta
n)
Dro
zd e
t al.,
200
8P
olyg
onec
eae
An
tigo
non
lept
opu
s H
ook.
& A
rn.
Mex
ican
cre
eper
An
tith
rom
bin
act
ivit
yaC
his
tokh
odov
a et
al.,
200
2R
osac
eae
San
guis
orba
offi
cin
alis
L.
Gre
at b
urn
etA
nti
thro
mb
in a
ctiv
itya
Gou
n e
t al.,
200
2T
rop
aeol
acea
eTr
opae
olu
m m
aju
s L
.In
dia
n c
ress
An
tith
rom
bin
act
ivit
yad
e M
edei
ros
et a
l., 2
000
Vac
cin
iace
aeV
acci
niu
m v
itis
-ida
ea L
.Li
ngo
nb
erry
An
tith
rom
bin
act
ivit
yaG
oun
et a
l., 2
002
Vio
lace
aeV
iola
tric
olor
L.
Hea
rtse
ase
An
tith
rom
bin
act
ivit
yaG
oun
et a
l., 2
002
V
iola
yed
oen
sis
Mak
ino
Her
ba
Vio
lae
(an
tife
bri
le,
det
oxif
ant)
Incr
ease
d c
oagu
lati
on ti
mes
a (d
icou
mar
ins:
dim
eres
cule
tin
, eu
ph
orb
etin
, esc
ule
tin
)
Zh
ou e
t al.,
200
9
Zin
gib
erac
eae
Hed
ychi
um
gar
dner
ian
um
Ros
c.K
ahili
gin
ger
An
tith
rom
bin
act
ivit
yad
e M
edei
ros
et a
l., 2
000
(Con
tin
ued
)
Phar
mac
eutic
al B
iolo
gy D
ownl
oade
d fr
om in
form
ahea
lthca
re.c
om b
y Q
ueen
's U
nive
rsity
on
04/3
0/13
For
pers
onal
use
onl
y.
446 W. Cordier and V. Steenkamp
Pharmaceutical Biology
Fam
ilyP
lan
tV
ern
acu
lar
nam
e (u
ses
if s
tate
d)
Eff
ect (
ph
ytoc
hem
ical
if s
tate
d)
Ref
eren
ces
An
tipl
atel
et a
ctiv
ity
Aga
vace
aeYu
cca
schi
dige
ra R
oezl
.M
ohav
e yu
cca
Dec
reas
ed p
late
let a
ggre
gati
on a
nd
lip
id p
erox
idat
ion
a (p
olyp
hen
ols
and
res
vera
trol
)
Ola
s et
al.,
200
2
An
acar
dia
ceae
Rhu
s ve
rnic
iflu
a St
okes
Lacq
uer
tree
(p
rom
otin
g b
lood
flow
, re
mov
ing
blo
od s
tasi
s)D
ecre
ased
pla
tele
t agg
rega
tion
, ca
lciu
m m
obili
zati
on, P
AC
-1 a
nd
P-
sele
ctin
mem
bra
ne-
rece
pto
r ex
pre
ssio
na a
nd
thro
mb
otic
-in
du
ced
dea
th/p
aral
ysis
b (
isom
alto
l an
d p
enta
gallo
yl g
luco
se)
Jeon
et a
l., 2
006
Ap
iace
aeP
etro
seli
nu
m c
risp
um
L.
Pars
ley
(art
eria
l hyp
erte
nsi
on,
card
iac
dis
ease
s)D
ecre
ased
pla
tele
t agg
rega
tion
a,b ,
incr
ease
d ta
il b
leed
ing
tim
eb
(pol
yph
enol
s su
gges
ted
)
Mek
hfi
et a
l., 2
004;
Gad
i et a
l., 2
009
Are
cace
aeC
alam
us
quiq
euse
tin
ervi
us
Bu
rret
.R
atta
n p
alm
(h
yper
ten
sion
)D
ecre
ased
col
lage
n-i
nd
uce
d
pla
tele
t agg
rega
tion
a (qu
iqu
elig
nan
B
, C, D
, F a
nd
H)
Ch
ang
et a
l., 2
010
Ast
erac
eae
Ach
ille
a fa
lcat
a L
.Ya
rrow
(h
aem
orrh
agia
)A
nti
pla
tele
t act
ivit
ya (1,
8-ci
neo
le,
p-cy
men
e or
β-t
hu
jon
e su
gges
ted
)A
bu
rjai
& H
ud
aib,
200
6
A
rtem
isia
dra
cun
culu
s L
.Ta
rrag
on (
anti
coag
ula
nt)
Dec
reas
ed p
late
let a
dh
esio
n,
pro
tein
sec
reti
ona (
pol
yph
enol
s su
gges
ted
)
Shah
riya
ry &
Yaz
dan
par
ast,
200
7
So
lida
go c
hile
nsi
s M
eyen
Gol
den
rod
(an
ti-i
nfl
amm
ator
y)D
ecre
ased
pla
tele
t agg
rega
tion
aR
afae
l et a
l., 2
009
Cis
tace
aeC
istu
s la
dan
ifer
us
L.
Gu
m r
ockr
ose
(an
tiox
idan
t)D
ecre
ased
pla
tele
t agg
rega
tion
a (p
olyp
hen
ols
sugg
este
d)
Mek
hfi
et a
l., 2
004
Cla
vici
pit
acea
eB
eau
veri
a ba
ssia
na
(Bal
s.-C
riv)
V
uill
.W
hit
e m
usc
ard
ine
Dec
reas
ed p
late
let a
ggre
gati
ona
(bas
siat
in)
Kag
amiz
ono
et a
l., 1
995
Eq
uis
etac
eae
Equ
iset
um
arv
ense
L.
Fiel
d h
orse
tail
(hae
mos
tati
c)D
ecre
ased
pla
tele
t agg
rega
tion
a (p
olyp
hen
ols
sugg
este
d)
Mek
hfi
et a
l., 2
004
Eri
cace
aeA
rbu
tus
un
edo
L.
Stra
wb
erry
tree
(as
trin
gen
t)D
ecre
ased
pla
tele
t agg
rega
tion
a (p
olyp
hen
ols
sugg
este
d)
Mek
hfi
et a
l., 2
004
Form
ula
tion
con
sist
ing
of R
osac
eae,
Z
ingi
ber
acea
e, S
anta
lace
ae a
nd
Z
ingi
ber
acea
e, r
esp
ecti
vely
Hon
eyle
ss h
erba
l for
mu
la (P
runu
s m
ume
Sieb
old
& Z
ucc
., A
mom
um
sem
en R
oxb.
, San
tali
albu
m L
. an
d
Am
omum
tsao
-ko
Rox
b., r
espe
ctiv
ely)
Je-H
o-Ta
ng
(Jap
anes
e ap
rico
t, s
ain
, sa
nd
lew
ood
an
d b
lack
car
dam
om,
resp
ecti
vely
)
Dec
reas
ed p
late
let a
ggre
gati
on,
calc
ium
mob
iliza
tion
a
Jeon
et a
l., 2
008
Hym
enoc
hae
tace
aeIn
onot
us
obli
quu
s L
.C
hag
a m
ush
room
Dec
reas
ed p
late
let a
ggre
gati
ona
(nov
el tr
ipep
tid
e)H
yun
et a
l., 2
006
Lab
iata
eA
nis
omel
es in
dica
(L
.) K
un
tze
Ind
ian
cat
min
t (h
yper
ten
sion
)D
ecre
ased
pla
tele
t agg
rega
tion
a (c
emb
ran
e-ty
pe
dit
erp
enoi
ds:
2
nov
el, o
vato
dio
lide
and
4,
5-ep
oxov
atod
iolid
e)
Ch
en e
t al.,
200
8
Lyth
race
aeP
un
ica
gran
atu
m L
.P
omeg
ran
ate
(hea
lth
ton
ic)
Dec
reas
ed p
late
let a
ggre
gati
on,
calc
ium
mob
iliza
tion
, th
rom
box
ane
A2
syn
thes
is, h
ydro
gen
per
oxid
e sy
nth
esis
a (p
olyp
hen
ols
sugg
este
d)
Mat
tiel
lo e
t al.,
200
9
Mor
acea
eFi
cus
cari
ca L
.C
omm
on fi
gD
ecre
ased
pla
tele
t agg
rega
tion
aG
ilan
i et a
l., 2
008
(Con
tin
ued
)
Tab
le 1
. (C
onti
nu
ed)
Phar
mac
eutic
al B
iolo
gy D
ownl
oade
d fr
om in
form
ahea
lthca
re.c
om b
y Q
ueen
's U
nive
rsity
on
04/3
0/13
For
pers
onal
use
onl
y.
Herbal remedies affecting coagulation 447
© 2012 Informa Healthcare USA, Inc.
Fam
ilyP
lan
tV
ern
acu
lar
nam
e (u
ses
if s
tate
d)
Eff
ect (
ph
ytoc
hem
ical
if s
tate
d)
Ref
eren
ces
Ru
tace
aeM
urr
aya
omph
aloc
arpa
Hay
ata
Ora
nge
jasm
ine
Dec
reas
ed p
late
let a
ggre
gati
ona
(cou
mar
ins:
om
ph
aloc
arp
inol
, 5,
7-d
imet
hox
y-8-
(3’-
met
hyl
-2’-
oxob
uty
l)-c
oum
arin
, mu
rrag
lein
in,
min
um
icro
line,
ace
ton
ide,
ep
imu
rpan
icu
lol s
enei
oate
)
Ch
en e
t al.,
200
3; C
hia
et a
l., 2
008
Taxa
ceae
Taxu
s cu
spid
ata
Sieb
old
& Z
ucc
.Ja
pen
ese
yew
An
tip
late
let a
ctiv
itya (
taxi
nin
e,
taxa
nin
e A
, B, 2
-dea
ceto
xyta
xin
ine,
ta
xaci
n, t
axch
inin
B, t
axol
)
Kim
& Y
un
-Ch
oi, 2
010
Urt
icac
eae
Urt
ica
dioï
ca L
.St
ingi
ng
net
tle
(pro
stat
ic
hyp
erp
lasi
a)D
ecre
ased
pla
tele
t agg
rega
tion
aM
ekh
fi e
t al.,
200
4
Zin
gib
erac
eae
Alp
inia
mu
tica
Rox
b.Sm
all s
hel
l gin
ger
Dec
reas
ed a
rach
idon
ic a
cid
-in
du
ced
pla
tele
t agg
rega
tion
a (c
ard
amon
in, p
inoc
emb
rin
e, 5
,6-
deh
ydro
kaw
ain
)
Jan
tan
et a
l., 2
008
C
urc
um
a ar
omat
ica
Val
eton
Cu
rcu
ma
Dec
reas
ed A
DP-
, col
lage
n-
and
ar
ach
idon
ic a
cid
-in
du
ced
pla
tele
t ag
greg
atio
na (c
urc
um
in)
Jan
tan
et a
l., 2
008
C
urc
um
a lo
nga
L.
Turm
eric
(m
enst
rual
dis
ord
ers)
Dec
reas
ed p
late
let a
ggre
gati
ona
(ar-
turm
eron
e, c
urc
um
in,
ture
mor
one)
Lee
, 200
6
C
urc
um
a xa
nth
orrh
iza
Rox
b.Ja
va tu
rmer
icD
ecre
ased
AD
P-, c
olla
gen
- an
d
arac
hid
onic
aci
d-i
nd
uce
d p
late
let
aggr
egat
ion
a (xa
nth
orrh
izol
)
Jan
tan
et a
l., 2
008
K
aem
pfer
ia r
otu
nda
Lin
n.
Pea
cock
gin
ger
Dec
reas
ed a
rach
idon
ic a
cid
-in
du
ced
pla
tele
t agg
rega
tion
a (3
-dea
cety
lcro
tep
oxid
e)
Jan
tan
et a
l., 2
008
Z
ingi
ber
offici
nal
e R
osco
eG
inge
r (a
nti
-em
etic
)A
nti
pla
tele
t act
ivit
ya (8-
par
adol
)N
urt
jah
ja-T
jen
dra
pu
tra
et a
l., 2
003;
K
ruth
et a
l., 2
004;
Bas
ila &
Yu
an,
2005
Z
ingi
ber
zeru
mbe
t Sm
ith
Sham
poo
gin
ger
Dec
reas
ed A
DP-
, col
lage
n-
and
ar
ach
idon
ic a
cid
-in
du
ced
pla
tele
t ag
greg
atio
na (
zeru
mb
one)
Jan
tan
et a
l., 2
008
Zygo
ph
ylla
ceae
Per
gan
um
har
mal
a L
.H
arm
al (
anti
-em
etic
)D
ecre
ased
col
lage
n-i
nd
uce
d
pla
tele
t agg
rega
tion
, cal
ciu
m
mob
iliza
tion
, ara
chid
onic
aci
d
liber
atio
n, P
LCγ2
an
d p
rote
in
tyro
sin
e p
hos
ph
oryl
atio
na (h
arm
ane
and
har
min
e)
Im e
t al.,
200
9
An
tith
rom
boti
c an
d an
tipl
atel
et
acti
vity
Alli
acea
eA
lliu
m s
ativ
um
L.
Gar
lic (c
ard
iova
scu
lar
con
dit
ion
s)A
nti
coag
ula
nt a
ctiv
ity,
dec
reas
ed
pla
tele
t agg
rega
tion
a (al
licin
, th
iosu
lfin
ates
, ad
enos
ine,
par
affin
ic
pol
ysu
lfid
es a
nd
ajo
ene)
Sriv
asta
va, 1
986;
Ros
e et
al.,
199
0;
Bas
ila &
Yu
an, 2
005;
Bec
kert
et a
l.,
2007
(Con
tin
ued
)
Tab
le 1
. (C
onti
nu
ed)
Phar
mac
eutic
al B
iolo
gy D
ownl
oade
d fr
om in
form
ahea
lthca
re.c
om b
y Q
ueen
's U
nive
rsity
on
04/3
0/13
For
pers
onal
use
onl
y.
448 W. Cordier and V. Steenkamp
Pharmaceutical Biology
Fam
ilyP
lan
tV
ern
acu
lar
nam
e (u
ses
if s
tate
d)
Eff
ect (
ph
ytoc
hem
ical
if s
tate
d)
Ref
eren
ces
Ara
liace
aeP
anax
gin
sen
g C
.A. M
eyer
Kor
ean
gin
sen
gD
ecre
ased
pla
tele
t agg
rega
tion
, in
crea
sed
TTa (
sap
onin
s an
d
gin
sen
osid
es s
ugg
este
d)
Bas
ila &
Yu
an, 2
005;
Bec
kert
et a
l.,
2007
; Lau
et a
l., 2
009
P
anax
not
ogin
sen
g (B
urk
) F.
H.C
hen
San
gi (
hae
mos
tati
c, c
ard
iova
scu
lar
dis
ease
s)D
ecre
ased
pla
tele
t agg
rega
tion
a,b ,
incr
ease
d c
oagu
lati
on ti
mes
a , b
leed
ingb
(sa
pon
ins
and
gi
nse
nos
ides
su
gges
ted
)
Su e
t al.,
199
6; L
iao
& L
i, 19
97; Y
ao
et a
l., 2
008;
Lau
et a
l., 2
009
P
anax
qu
inqu
efol
ium
Lin
nA
mer
ican
gin
sen
gD
ecre
ased
pla
tele
t agg
rega
tion
, ad
hes
ion
, in
crea
sed
TT,
pla
tele
t fl
uid
itya
Bas
ila &
Yu
an, 2
005;
Lau
et a
l., 2
009
Fab
acea
eG
lycy
rrhi
za g
labr
a L
.Li
cori
ceD
irec
t an
tith
rom
bin
act
ivit
y on
ex
osit
e 1a , i
ncr
ease
d b
leed
ing
effec
t, d
ecre
ased
thro
mb
us
size
, p
late
let a
ggre
gati
onb (
glyc
yrrh
izin
su
gges
ted
)
Fran
cish
etti
et a
l., 1
997;
Gou
n e
t al.,
20
02; M
end
es-S
ilva
et a
l., 2
003
M
aack
ia a
myr
ensi
s L
.A
mu
r m
aack
iaD
ecre
ased
coa
gula
tion
, th
rom
bu
s si
ze, p
oten
tiat
ion
of e
nd
oth
eliu
m-
dep
end
ent v
asod
ilata
tion
b
(iso
flav
onol
s su
gges
ted
)
Plo
tnik
ova
et a
l., 2
009
Form
ula
tion
con
sist
ing
of
Paeo
nia
ceae
, Ap
iace
ae, A
ster
acea
e,
Cyp
erac
eae,
Ast
erac
eae
and
La
mia
ceae
, res
pec
tive
ly
Peo
ny
gen
us,
Cn
idiu
m g
enu
s,
Car
tham
us
tin
ctor
ius
L.,
Cyp
eru
s ge
nu
s, s
auss
ure
a ge
nu
s an
d S
alvi
a m
ilti
orrh
iza
Bu
nge
Peo
ny,
cn
idiu
m, s
afflow
er,
cyp
eru
s, s
auss
ure
a an
d D
ansh
en
(hae
mos
tasi
s)
Dec
reas
ed p
late
let a
ggre
gati
ona ,
incr
ease
d ta
il b
leed
ing
tim
eb
(ros
mar
inic
aci
d s
ugg
este
d)
Mak
ino
et a
l., 2
002
Gin
kgoa
ceae
Gin
kgo
bilo
ba L
.G
inkg
o b
ilob
a (c
ogn
itiv
e fu
nct
ion
)D
ecre
ased
pla
tele
t agg
rega
tion
a , d
ecre
ased
thro
mb
osis
form
atio
n
and
dea
th/p
aral
ysis
, no
effec
t on
ble
edin
g or
coa
gula
tion
ti
mes
b , in
crea
sed
ble
edin
g ri
sk
wit
h w
arfa
rin
an
d c
ilost
azol
(g
inko
glid
es)
Ros
enb
latt
& M
ind
el, 1
997;
M
atth
ews,
199
8; B
asila
& Y
uan
, 20
05; R
yu e
t al.,
200
9
Lau
race
aeLi
nde
ra o
btu
silo
ba L
.Ja
pen
ese
spic
ebu
sh (
bru
ises
, in
flam
mat
ion
)D
ecre
ased
pla
tele
t agg
rega
tion
a , d
ecre
ased
dea
th/p
aral
ysis
b
Lee
et a
l., 2
010
Um
bili
cari
acea
eU
mbi
lica
ria
escu
len
ta (
Miy
osh
i)
Min
ksSe
ogi (
ble
edin
g tr
eatm
ent)
Dec
reas
ed p
late
let a
ggre
gati
on,
no
effec
t on
coa
gula
tion
tim
es a
nd
fi
bri
nol
ytic
act
ivit
ya , dec
reas
ed
dea
th/p
aral
ysis
, in
crea
se ta
il b
leed
ing
tim
eb (
ph
enol
ics
sugg
este
d)
Kim
& L
ee, 2
006
Stau
nch
ing
acti
vity
Form
ula
tion
con
tain
ing
Ara
liace
aeP
anax
not
ogin
sen
g (B
urk
) F.
H.C
hen
Yun
nan
Bai
yao
(wou
nd
hea
ling)
-Pa
n e
t al.,
200
6Fo
rmu
lati
on c
onsi
stin
g of
La
mia
ceae
, Fab
acea
e, V
itac
eae,
Z
ingi
ber
acea
e an
d U
rtic
acea
e
Thym
us
vulg
aris
L.,
Gly
cyrr
hiza
gl
abra
, Vit
is v
inif
era
L.,
Alp
inia
offi
cin
aru
m H
ance
, Urt
ica
dioï
ca
An
kafe
rd B
lood
Sto
pp
er®
(w
oun
d
hea
ling)
Red
uce
d b
leed
ing
tim
e an
d v
olu
meb
Gok
er e
t al.,
200
8
aPT
T, a
ctiv
ated
par
tial
thro
mb
opla
stin
tim
e; P
T, p
roth
rom
bin
tim
e; T
T, th
rom
bin
tim
e.a In
vit
ro a
ssay
.bIn
/ex
vivo
ass
ay.
Tab
le 1
. (C
onti
nu
ed)
Phar
mac
eutic
al B
iolo
gy D
ownl
oade
d fr
om in
form
ahea
lthca
re.c
om b
y Q
ueen
's U
nive
rsity
on
04/3
0/13
For
pers
onal
use
onl
y.
Herbal remedies affecting coagulation 449
© 2012 Informa Healthcare USA, Inc.
Tab
le 2
. Her
bal
rem
edie
s w
hic
h h
ave
bee
n r
epor
ted
to a
dve
rsel
y aff
ect c
lott
ing.
Pla
nt
vern
acu
lar
Pati
ent
Her
bal
usa
geP
roce
du
re/m
edic
atio
nIn
cid
ence
Com
men
tsD
osag
eD
ura
tion
Gin
kgo
bilo
ba65
(M
)N
SN
SH
ip a
rth
rop
last
yP
osto
per
ativ
e w
oun
d h
emor
rhag
e—
61 (
M)
40 m
g (3
–4×
dai
ly)
6 m
onth
sSp
onta
neo
us
Sub
arac
hn
oid
hem
orrh
age
No
oth
er c
ause
s fo
un
d72
(F
)50
mg
(3×
dai
ly)
NS
Spon
tan
eou
sSu
bd
ura
l hem
atom
aN
o ot
her
cau
ses
fou
nd
33 (
F)
120
mg
(dai
ly)
2 ye
ars
Spon
tan
eou
sB
ilate
ral h
emat
omas
Pro
lon
ged
ble
edin
g ti
me,
nor
mal
ized
aft
er
cess
atio
n o
f her
bal
56 (
M)
40 m
g (3
× d
aily
)18
mon
ths
Spon
tan
eou
sIn
trac
ereb
ral h
emor
rhag
eN
o ot
her
cau
ses
fou
nd
34 (
M)
2 ta
ble
ts (d
aily
)N
SLa
par
osco
pic
ch
olec
yste
ctom
yP
ersi
sten
t hem
orrh
age
from
gal
l bla
dd
erT
ran
sfu
sion
req
uir
ed70
(M
)40
mg
(2×
dai
ly)
NS
Spon
tan
eou
s, 3
25 m
g as
pir
in d
aily
Hyp
hem
aA
pp
eare
d w
ith
in 1
wee
k of
sta
rtin
g h
erb
al
78 (
F)
NS
NS
Stab
le w
arfa
rin
usa
geIn
trac
ereb
ral h
emor
rhag
eA
pp
eare
d w
ith
in 2
mon
ths
of c
onco
mit
ant
her
bal
usa
ge77
(F
)12
0 m
g (d
aily
)N
SH
ip a
rth
rop
last
y, a
spir
in u
sage
(cea
sed
10
th d
ay p
osto
per
atio
n)
Per
sist
ent b
lood
y d
rain
age
from
wou
nd
(o
ver
3 w
eeks
)O
nly
rep
orte
d a
spir
in u
sage
init
ially
, b
leed
ing
ceas
ed a
fter
ces
sati
on o
f her
bal
73 (
M)
NS
6 m
onth
sM
inor
trau
ma
and
ble
edin
g te
nd
enci
esH
emor
rhoi
dal
ble
edin
g, e
cch
ymos
isB
leed
ing
grad
ual
ly s
top
ped
aft
er c
essa
tion
of
her
bal
Gar
lic87
(M
)2
g (d
aily
)N
SSp
onta
neo
us
Epid
ura
l hem
atom
aE
leva
ted
ble
edin
g ti
me,
nor
mal
ized
3 d
ays
afte
r h
erb
al c
essa
tion
72 (
M)
NS
NS
Tra
nsf
usi
on a
fter
tran
sure
thra
l pro
stat
e re
acti
onB
leed
ing
Imp
aire
d p
late
let f
un
ctio
n 3
mon
ths
afte
r st
arti
ng
her
bal
aga
in32
(F
)H
eavy
usa
geN
SB
reas
t au
gmen
tati
onH
emat
oma
Pro
lon
ged
ble
edin
g ti
me,
nor
mal
ized
1
wee
k af
ter
her
bal
ces
sati
onG
inse
ng
72 (
F)
200
mg
(dai
ly)
1 m
onth
Spon
tan
eou
sV
agin
al b
leed
ing
—44
(F
)Fa
ce c
ream
NS
Spon
tan
eou
sV
agin
al b
leed
ing
—39
(F
)O
ral a
nd
top
ical
NS
Spon
tan
eou
sM
enom
etro
rrh
agia
Stop
ped
10
day
s af
ter
her
bal
ces
sati
onD
ansh
en62
(M
)N
S2
wee
ksM
itra
l val
ve r
epla
cem
ent,
sta
ble
war
fari
n
usa
ge (
5 m
g)C
hes
t pai
n, d
ysp
nea
, fat
igu
e, p
eric
ard
ial,
and
rig
ht p
leu
ral fl
uid
col
lect
ion
sIN
R >
8.4
, aP
TT
> 1
20 s
NS,
not
sta
ted
; M, m
ale;
F, f
emal
e. T
able
com
pri
sed
Izza
t et a
l. (1
998)
, Ben
t et a
l. (2
005)
, an
d B
ecke
rt e
t al.
(200
7).
Phar
mac
eutic
al B
iolo
gy D
ownl
oade
d fr
om in
form
ahea
lthca
re.c
om b
y Q
ueen
's U
nive
rsity
on
04/3
0/13
For
pers
onal
use
onl
y.
450 W. Cordier and V. Steenkamp
Pharmaceutical Biology
polyphenolis, saponins, and salicylates, were elucidated as potent inhibitors, but the concentrations of these may be of such insignificant levels that they pose no threat. Also, depending on manufacturing and processing pro-cedure concentrations and activity of extracts might dif-fer (Chukwumah et al., 2007). Herbals have been found to alter the metabolism of anticoagulants as well as other medication through induction or suppression of certain genes. Induction of CYP2C9 (which is responsible for warfarin metabolism) remains a possible mechanism by which herbals cause a decrease in anticoagulant plasma concentration (Henderson et al., 2002).
Saw et al. (2006) reported that 21% of medical ward patients co-ingested herbs with antiplatelet or antico-agulant therapy. Of the latter, 10.5% were at risk of poten-tial herb–drug interaction. Uncontrolled anticoagulation therapy may result in altered international normalized ratio (INR), spontaneous bleeding and can prove fatal. Whether purported herbals have the ability to cause an increased risk of perioperative bleeding is not yet certain, as conflicting reports are available (Beckert et al., 2007).
conclusion
Cardiovascular thrombotic disease results in widespread mortality and hospitalization, which can be successfully reduced through the use of anticoagulant medicines. The growing use of herbal remedies represents a serious risk of bleeding and thrombosis for patients taking antico-agulants. A relatively small number of studies have been carried out to determine the effect of herbal remedies on coagulation. There is, however, reports describing the effect of herbals on coagulation and platelet function indicating that herbal preparations show significant dis-ruption of the coagulation cascade. As the safety of many herbals has not been proven, nor their effect on blood parameters determined, the use of herbal preparations before undergoing any surgical procedure should rather be ceased. Patients on anticoagulant therapy should be warned against the concurrent use of herbals, and have their INR checked within a week of starting herbal rem-edy use.
Declaration of interest
The authors report no declarations of interest.
ReferencesAburjai T, Hudaib M. (2006). Antiplatelet, antibacterial and antifungal
activities of Achillea falcata extracts and evaluation of volatile oil composition. Pharmacognosy Magnazine, 2, 191–198.
Aburjai TA. (2000). Anti-platelet stilbenes from aerial parts of Rheum palaestinum. Phytochemistry, 55, 407–410.
Basila D, Yuan CS. (2005). Effects of dietary supplements on coagulation and platelet function. Thromb Res, 117, 49–53; discussion 65.
Beckert BW, Concannon MJ, Henry SL, Smith DS, Puckett CL. (2007). The effect of herbal medicines on platelet function: An in vivo experiment and review of the literature. Plast Reconstr Surg, 120, 2044–2050.
Bent S, Goldberg H, Padula A, Avins AL. (2005). Spontaneous bleeding associated with Ginkgo biloba: A case report and systematic review of the literature: A case report and systematic review of the literature. J Gen Intern Med, 20, 657–661.
Bruno O, Schenone S, Ranise A, Bondavalli F, Barocelli E, Ballabeni V, Chiavarini M, Bertoni S, Tognolini M, Impicciatore M. (2001). New polycyclic pyrimidine derivatives with antiplatelet in vitro activity: Synthesis and pharmacological screening. Bioorg Med Chem, 9, 629–636.
Buch MH, Prendergast BD, Storey RF. (2010). Antiplatelet therapy and vascular disease: An update. Ther Adv Cardiovasc Dis, 4, 249–275.
Campos-Toimil M, Orallo F, Santana L, Uriarte E. (2002). Synthesis and vasorelaxant activity of new coumarin and furocoumarin derivatives. Bioorg Med Chem Lett, 12, 783–786.
Chandía NP, Matsuhiro B. (2008). Characterization of a fucoidan from Lessonia vadosa (Phaeophyta) and its anticoagulant and elicitor properties. Int J Biol Macromol, 42, 235–240.
Chang CL, Zhang LJ, Chen RY, Wu CC, Huang HC, Roy MC, Huang JP, Wu YC, Kuo YH. (2010). Quiquelignan A-H, eight new lignoids from the rattan palm Calamus quiquesetinervius and their antiradical, anti-inflammatory and antiplatelet aggregation activities. Bioorg Med Chem, 18, 518–525.
Chen JJ, Chang YL, Teng CM, Lin WY, Chen YC, Chen IS. (2001). A new tetrahydroprotoberberine N-oxide alkaloid and anti-platelet aggregation constituents of Corydalis tashiroi. Planta Med, 67, 423–427.
Chen KS, Wu CC, Chang FR, Chia YC, Chiang MY, Wang WY, Wu YC. (2003). Bioactive coumarins from the leaves of Murraya omphalocarpa. Planta Med, 69, 654–657.
Chen YL, Lan YH, Hsieh PW, Wu CC, Chen SL, Yen CT, Chang FR, Hung WC, Wu YC. (2008). Bioactive cembrane diterpenoids of Anisomeles indica. J Nat Prod, 71, 1207–1212.
Chia YC, Chang FR, Wang JC, Wu CC, Chiang MY, Lan YH, Chen KS, Wu YC. (2008). Antiplatelet aggregation coumarins from the leaves of Murraya omphalocarpa. Molecules, 13, 122–128.
Chistokhodova N, Nguyen C, Calvino T, Kachirskaia I, Cunningham G, Howard Miles D. (2002). Antithrombin activity of medicinal plants from central Florida. J Ethnopharmacol, 81, 277–280.
Chukwumah Y, Walker L, Vogler B, Verghese M. (2007). Changes in the phytochemical composition and profile of raw, boiled, and roasted peanuts. J Agric Food Chem, 55, 9266–9273.
Chung MI, Weng JR, Wang JP, Teng CM, Lin CN. (2002). Antiplatelet and anti-inflammatory constituents and new oxygenated xanthones from Hypericum geminiflorum. Planta Med, 68, 25–29.
Coppinger JA, Cagney G, Toomey S, Kislinger T, Belton O, McRedmond JP, Cahill DJ, Emili A, Fitzgerald DJ, Maguire PB. (2004). Characterization of the proteins released from activated platelets leads to localization of novel platelet proteins in human atherosclerotic lesions. Blood, 103, 2096–2104.
Cordier W, Cromarty AD, Botha E, Steenkamp V. (2011). Effects of selected South African plant extracts on haemolysis and coagulation. Hum Exp Toxicol. DOI: 10.1177/0960327111398675.
de Medeiros JM, Macedo M, Contancia JP, Nguyen C, Cunningham G, Miles DH. (2000). Antithrombin activity of medicinal plants of the Azores. J Ethnopharmacol, 72, 157–165.
Drozd NN, Kuznetsova SA, Lapikova ES, Davydova AI, Makarov VA, Kuznetsov BN, Butylkina AI, Vasil’eva NIu, Skvortsova GP. (2008). [Anticoagulant activity of arabinogalactane sulfate and cedar bark extract studied in vitro]. Eksp Klin Farmakol, 71, 30–34.
Eisenreich A, Rauch U. (2011). PI3K inhibitors in cardiovascular disease. Cardiovasc Ther, 29, 29–36.
Elliott Middleton JR, Chithan K, Theoharis CT. (2000). The effects of plant flavonoids on mammalian cells: Implications for inflammation, heart disease, and cancer. Pharmacol Rev, 52, 673–751.
Francischetti IM, Monteiro RQ, Guimarães JA, Francischetti B. (1997). Identification of glycyrrhizin as a thrombin inhibitor. Biochem Biophys Res Commun, 235, 259–263.
Gadi D, Bnouham M, Aziz M, Ziyyat A, Legssyer A, Legrand C, Lafeve FF, Mekhfi H. (2009). Parsley extract inhibits in vitro and
Phar
mac
eutic
al B
iolo
gy D
ownl
oade
d fr
om in
form
ahea
lthca
re.c
om b
y Q
ueen
's U
nive
rsity
on
04/3
0/13
For
pers
onal
use
onl
y.
Herbal remedies affecting coagulation 451
© 2012 Informa Healthcare USA, Inc.
ex vivo platelet aggregation and prolongs bleeding time in rats. J Ethnopharmacol, 125, 170–174.
Gilani AH, Mehmood MH, Janbaz KH, Khan AU, Saeed SA. (2008). Ethnopharmacological studies on antispasmodic and antiplatelet activities of Ficus carica. J Ethnopharmacol, 119, 1–5.
Goker H, Haznedaroglu IC, Ercetin S, Kirazli S, Akman U, Ozturk Y, Firat HC. (2008). Haemostatic actions of the folkloric medicinal plant extract Ankaferd Blood Stopper. J Int Med Res, 36, 163–170.
Goun EA, Petrichenko VM, Solodnikov SU, Suhinina TV, Kline MA, Cunningham G, Nguyen C, Miles H. (2002). Anticancer and antithrombin activity of Russian plants. J Ethnopharmacol, 81, 337–342.
Henderson L, Yue QY, Bergquist C, Gerden B, Arlett P. (2002). St John’s wort (Hypericum perforatum): Drug interactions and clinical outcomes. Br J Clin Pharmacol, 54, 349–356.
Hoult JR, Payá M. (1996). Pharmacological and biochemical actions of simple coumarins: Natural products with therapeutic potential. Gen Pharmacol, 27, 713–722.
Hutchings A, Scott AG, Lewis G, Cunningham A. (1996). Zulu Medicinal Plants − An Inventory. University of Natal Press, Pietermaritzburg.
Hyun KW, Jeong SC, Lee DH, Park JS, Lee JS. (2006). Isolation and characterization of a novel platelet aggregation inhibitory peptide from the medicinal mushroom Inonotus obliquus. Peptides, 27, 1173–1178.
Im JH, Jin YR, Lee JJ, Yu JY, Han XH, Im SH, Hong JT, Yoo HS, Pyo MY, Yun YP. (2009). Antiplatelet activity of beta-carboline alkaloids from Perganum harmala: A possible mechanism through inhibiting PLCgamma2 phosphorylation. Vascul Pharmacol, 50, 147–152.
Izzat MB, Yim AP, El-Zufari MH. (1998). A taste of Chinese medicine! Ann Thorac Surg, 66, 941–942.
Jantan I, Raweh SM, Sirat HM, Jamil S, Yasin YHM, Jalil J, Jamal JA (2008). Inhibitory effect of compounds from Zingiberaceae species on human platelet aggregation. Phytomedicine 15, 306–309.
Jeon WK, Lee JH, Kim HK, Lee AY, Lee SO, Kim YS, Ryu SY, Kim SY, Lee YJ, Ko BS. (2006). Anti-platelet effects of bioactive compounds isolated from the bark of Rhus verniciflua Stokes. J Ethnopharmacol, 106, 62–69.
Jeon WK, Kim YE, Park SO, Kwon DY, Ahn SW, Lee JH, Ji MS, Ko BS. (2008). The modified Je-Ho-Tang, Korean herbal medicine, inhibits whole-blood aggregation and platelet adhesion to collagen under flow. Thromb Res, 122, 804–809.
Jurgens T, Whelan AM. (2009). Advising patients on the use of natural health products to treat premenstrual syndrome. Can Pharmacists J, 142, 228–233.
Kagamizono T, Nishino E, Matsumoto K, Kawashima A, Kishimoto M, Sakai N, He BM, Chen ZX, Adachi T, Morimoto S. (1995). Bassiatin, a new platelet aggregation inhibitor produced by Beauveria bassiana K-717. J Antibiot, 48, 1407–1412.
Kim MS, Lee KA. (2006). Antithrombotic activity of methanolic extract of Umbilicaria esculenta. J Ethnopharmacol, 105, 342–345.
Kim SY, Yun-Choi HS. (2010). A comparative optical aggregometry study of antiplatelet activity of taxanes from Taxus cuspidata. Thromb Res, 125, e281–e284.
Kim BH, Kim KP, Lim KS, Kim JR, Yoon SH, Cho JY, Lee YO, Lee KH, Jang IJ, Shin SG, Yu KS. (2010). Influence of Ginkgo biloba extract on the pharmacodynamic effects and pharmacokinetic properties of ticlopidine: An open-label, randomized, two-period, two-treatment, two-sequence, single-dose crossover study in healthy Korean male volunteers. Clin Ther, 32, 380–390.
Krüth P, Brosi E, Fux R, Mörike K, Gleiter CH. (2004). Ginger-associated overanticoagulation by phenprocoumon. Ann Pharmacother, 38, 257–260.
Lambert FP, Cormier A. (2001). Potential interaction between warfarin and boldo-fenugreek. Pharmacother, 21, 509–512.
Lau AJ, Toh DF, Chua TK, Pang YK, Woo SO, Koh HL. (2009). Antiplatelet and anticoagulant effects of Panax notoginseng: Comparison of raw and steamed Panax notoginseng with Panax ginseng and Panax quinquefolium. J Ethnopharmacol, 125, 380–386.
Lee HS. (2006). Antiplatelet property of Curcuma longa L. rhizome-derived ar-turmerone. Bioresour Technol, 97, 1372–1376.
Lee J-O, Kim C, Lee S-W, Oak M-H. (2010). Antiplatelet and antithrombotic activities of Lindera obtusiloba extract in vitro and in vivo. Biomol Ther, 18, 205–210.
Lee MH, Son YK, Han YN. (2002). Tissue factor inhibitory flavonoids from the fruits of Chaenomeles sinensis. Arch Pharm Res, 25, 842–850.
Lee MH, Son YK, Han YN. (2004). Tissue factor inhibitory sesquiterpene glycoside from Eriobotrya japonica. Arch Pharm Res, 27, 619–623.
Liao FL, Li B. (1997). Inhibition of shear-induced platelet aggregation by Chinese herbal medicines. Clin Hemorheol Microcirc, 17, 315–318.
Makino T, Wakushima H, Okamoto T, Okukubo Y, Saito K, Kano Y. (2002). Effects of Kangen-karyu on coagulation system and platelet aggregation in mice. Biol Pharm Bull, 25, 523–525.
Mao W, Li H, Li Y, Zhang H, Qi X, Sun H, Chen Y, Guo S. (2009). Chemical characteristic and anticoagulant activity of the sulfated polysaccharide isolated from Monostroma latissimum (Chlorophyta). Int J Biol Macromol, 44, 70–74.
Matthews MK Jr. (1998). Association of Ginkgo biloba with intracerebral hemorrhage. Neurology, 50, 1933–1934.
Mattiello T, Trifirò E, Jotti GS, Pulcinelli FM. (2009). Effects of pomegranate juice and extract polyphenols on platelet function. J Med Food, 12, 334–339.
Medeiros VP, Queiroz KC, Cardoso ML, Monteiro GR, Oliveira FW, Chavante SF, Guimaraes LA, Rocha HA, Leite EL. (2008). Sulfated galactofucan from Lobophora variegata: Anticoagulant and anti-inflammatory properties. Biochemistry Mosc, 73, 1018–1024.
Mekhfi H, El Haouari M, Legssyer A, Bnouham M, Aziz M, Atmani F, Remmal A, Ziyyat A. (2004). Platelet anti-aggregant property of some Moroccan medicinal plants. J Ethnopharmacol, 94, 317–322.
Mendes-Silva W, Assafim M, Ruta B, Monteiro RQ, Guimarães JA, Zingali RB. (2003). Antithrombotic effect of glycyrrhizin, a plant-derived thrombin inhibitor. Thromb Res, 112, 93–98.
Murphy KJ, Chronopoulos AK, Singh I, Francis MA, Moriarty H, Pike MJ, Turner AH, Mann NJ, Sinclair AJ. (2003). Dietary flavanols and procyanidin oligomers from cocoa (Theobroma cacao) inhibit platelet function. Am J Clin Nutr, 77, 1466–1473.
Nurtjahja-Tjendraputra E, Ammit AJ, Roufogalis BD, Tran VH, Duke CC. (2003). Effective anti-platelet and COX-1 enzyme inhibitors from pungent constituents of ginger. Thromb Res, 111, 259–265.
Olas B, Wachowicz B, Stochmal A, Oleszek W. (2002). Anti-platelet effects of different phenolic compounds from Yucca schidigera Roezl. bark. Platelets, 13, 167–173.
Osoniyi O, Onajobi F. (2003). Coagulant and anticoagulant activities in Jatropha curcas latex. J Ethnopharmacol, 89, 101–105.
Page RL, Lawrence JD (1999). Potentiation of warfarin by Dong Quai. Pharmacother, 19, 870–876
Pan SF, Sun Y, Li F, Li GH, Jin DD, Zhang ZM, Luo ZJ, Ye ZX, Hu JH, Qiu GX. (2006). [Effects of Yunnan Baiyao on peri-operative bleeding of patients undergoing cervical open-door laminoplasty: A multi-center randomized double-blind placebo-control trial]. Zhonghua Yi Xue Za Zhi, 86, 1888–1890.
Pawlaczyk I, Czerchawski L, Kanska J, Bijak J, Capek P, Pliszczak-Król A, Gancarz R. (2010). An acidic glycoconjugate from Lythrum salicaria L. with controversial effects on haemostasis. J Ethnopharmacol, 131, 63–69.
Plotnikova AM, Shulgau ZT, Plotnikova TM, Aliev OI, Kulesh NI, Mischenko NP, Fedoreyev SA. (2009). Antithrombogenic and antiplatelet activities of extract from Maackia amyrensis wood. Bull Exp Biol Med, 147, 204–207.
Preusch PC, Smalley DM. (1990). Vitamin K1 2,3-epoxide and quinone reduction: Mechanism and inhibition. Free Radic Res Commun, 8, 401–415.
Rafael L, Teresinha N, Moritz JC, Maria IG, Eduardo MD, Tânia SF. (2009). Evaluation of antimicrobial and antiplatelet aggregation effects of Solidago chilensis Meyen. Int J Green Pharmacy, 3, 35–39.
Rang HP, Dale MM, Ritter JM, Flower RJ. (2007). Haemostasis and thrombosis. In: Rang and Dale’s Pharmacology 6th edition. Churchill Livingstone (Elsevier), pp 332–345.
Phar
mac
eutic
al B
iolo
gy D
ownl
oade
d fr
om in
form
ahea
lthca
re.c
om b
y Q
ueen
's U
nive
rsity
on
04/3
0/13
For
pers
onal
use
onl
y.
452 W. Cordier and V. Steenkamp
Pharmaceutical Biology
Robert S, Baccelli C, Devel P, Dogné JM, Quetin-Leclercq J. (2010). Effects of leaf extracts from Croton zambesicus Müell. Arg. on hemostasis. J Ethnopharmacol, 128, 641–648.
Roby CA, Anderson GD, Kantor E, Dryer DA, Burstein AH. (2000). St John’s Wort: Effect on CYP3A4 activity. Clin Pharmacol Ther, 67, 451–457.
Rose KD, Croissant PD, Parliament CF, Levin MB. (1990). Spontaneous spinal epidural hematoma with associated platelet dysfunction from excessive garlic ingestion: A case report. Neurosurgery, 26, 880–882.
Rosenblatt M, Mindel J. (1997). Spontaneous hyphema associated with ingestion of Ginkgo biloba extract. N Engl J Med, 336, 1108.
Ryu KH, Han HY, Lee SY, Jeon SD, Im GJ, Lee BY, Kim K, Lim KM, Chung JH. (2009). Ginkgo biloba extract enhances antiplatelet and antithrombotic effects of cilostazol without prolongation of bleeding time. Thromb Res, 124, 328–334.
Saw JT, Bahari MB, Ang HH, Lim YH. (2006). Potential drug-herb interaction with antiplatelet/anticoagulant drugs. Complement Ther Clin Pract, 12, 236–241.
Shahriyary L, Yazdanparast R. (2007). Inhibition of blood platelet adhesion, aggregation and secretion by Artemisia dracunculus leaves extracts. J Ethnopharmacol, 114, 194–198.
Srivastava KC. (1986). Evidence for the mechanism by which garlic inhibits platelet aggregation. Prostaglandins Leukot Med, 22, 313–321.
Steenkamp V, Stewart MJ. (2007). Medicinal applications and toxicological activities of Aloe products. Pharm Biol, 45, 411–420.
Su Y, Zhao Y, Zhang Z, Yue N. (1996). Effects of panaxatriol saponins isolated from sanchi (Panax pseudo-ginseng var. notoginseng) on animal platelet function and thrombosis. Chinese Traditional and Herbal Drugs, 27, 666–669.
Taylor JR, Wilt VM. (1999). Probable antagonism of warfarin by green tea. Ann Pharmacother, 33, 426–428.
Vane JR, Botting RM. (2003). The mechanism of action of aspirin. Thromb Res, 110, 255–258.
Wang J, Zhang Q, Zhang Z, Song H, Li P. (2010). Potential antioxidant and anticoagulant capacity of low molecular weight fucoidan fractions extracted from Laminaria japonica. Int J Biol Macromol, 46, 6–12.
World Health Organization. (2008). Fact Sheet no 134: Traditional medicine. Available at http://www.who.int/mediacentre/factsheets/fs134/en/. Accessed on 11 March 2011.
Yao Y, Wu WY, Liu AH, Deng SS, Bi KS, Liu X, Guo DA. (2008). Interaction of salvianolic acids and notoginsengnosides in inhibition of ADP-induced platelet aggregation. Am J Chin Med, 36, 313–328.
Zhang S, Yin T, Ling X, Liang H, Zhao Y. (2008). Interactions between thrombin and natural products of Millettia speciosa Champ. using capillary zone electrophoresis. Electrophoresis, 29, 3391–3397.
Zhou HY, Hong JL, Shu P, Ni YJ, Qin MJ. (2009). A new dicoumarin and anticoagulant activity from Viola yedoensis Makino. Fitoterapia, 80, 283–285.
Phar
mac
eutic
al B
iolo
gy D
ownl
oade
d fr
om in
form
ahea
lthca
re.c
om b
y Q
ueen
's U
nive
rsity
on
04/3
0/13
For
pers
onal
use
onl
y.