Content uploaded by Başar Altınterim
All content in this area was uploaded by Başar Altınterim on Nov 20, 2014
Content may be subject to copyright.
Karaelmas Fen ve Mühendislik Dergisi / Karaelmas Science and Engineering Journal 3 (1), 37-39, 2013
Karaelmas Science and Engineering Journal
Journal home page: http://fbd.beun.edu.tr Review
*Corresponding author: firstname.lastname@example.org
Effects of Willow Bark (Salix alba) and Its Salicylates on Blood Coagulant
ALTINTERİM Bitkisel Ürünler, İzzet Paşa M., İzzet Paşa C. No:7/C–1 /Elazığ, Turkey
The herb white willow (Salix alba), also known as willow bark, is used to treat pain and fever. It is also used for myalgias,
osteoarthritis, dysmenorrheal, gouty arthritis, rheumatoid arthritis, gout, common cold, inﬂuenza, and weight loss. White
willow contains a substance (salicine) that is converted by the body into a salicylate similar to the blood-thinner aspirin. Over
the last twenty years, another use for aspirin has emerged connected with the discovery of its anti-thrombotic action.
Keywords: Willow bark, Blood oagulant, Salicine
The concentration of salicin is actually much lower in
willow bark than in other salix species. Willow bark has
several different components, including ﬂavonoids, tan-
nins, and salicin. Salicin is considered the main active
ingredient as it is metabolized to salicylic acid. The other
components of willow bark are thought to have lipox-
ygenase-inhibiting and antioxidant effects as well as
prevent prostaglandin and cytokine release. The active
substance of the common white willow, a glycoside of
salicylic acid known as salicin, was isolated in 1829 by
Leroux, who also demonstrated its antipyretic properties
(Chrubasik and Shvartzman 1999). The effects of willow
bark attributed to the salicin compounds include anal-
gesic, anti-inﬂammatory, antipyretic, and antiplatelet
activity (Fiebich and Apel 2003).
Salicylic acid is one of numerous phenolic compounds,
deﬁ ned as compounds containing an aromatic ring with
a hydroxyl group or its derivative, found in plants. There
has been considerable speculation that phenolics in gen-
eral function as plant growth regulators (Aberg 1981).
Willow species contain only a low quantity of the pro-
drug salicine which is metabolized during absorption
into various salicylate derivatives. Herbs with salicylate
constituents help to reduce platelet aggregation and
prevent blood clotting. Salicylate inhibits the platelets’
production of a compound called thromboxane A2 that
controls the ability of the platelet to adhere to other
platelets. Salicylate is the basis of aspirin. Herbs contain-
ing salicylate include meadowsweet, poplar and willow
or willowbark (Vlachojannis et al. 2011).
2. The Mechanisms of Action
A variety of stimuli, including thrombin, adenosine
diphosphate (ADP), and collagen, are known to cause
platelet activation, spreading, and aggregation. Adenos-
ine diphosphate is stored within the dense granules of
platelets and is released upon cell activation, but it causes
only modest reversible aggregation. Nonetheless, ADP
plays an important role in initiating signals that lead to
platelet shape changes and to the synthesis of thrombox-
ane A2, which is a potent activator of platelets. When a
platelet is activated and its dense granules release their
contents, ADP binds to its receptors on the same and
neighboring platelets, as does thromboxane A2 to its
receptor. Adenosine diphosphate ampliﬁ es the platelet’s
response to other agonists.
This adhesion cascade leads to the formation of large
platelet aggregates that are both procoagulant and pro-
inﬂ ammatory. The resulting thrombus can easily occlude
the lumen of an already narrowed atherosclerotic
coronary artery, thereby causing a myocardial infarction
(Quick 1966, Ruggeri 2002).
Aspirin impairs both ADP release and secondary ADP-
dependent platelet aggregation. Weiss reported that
aspirin’s effect on platelets was rapid and irreversible,
inhibiting platelet aggregation for the duration of a
platelet’s life. Together with the ﬁ ndings from several
other groups, Dr. Weiss’s discovery was a key step in
understanding the mechanism by which low doses of
aspirin could prevent coronary and cerebral thrombosis
(Weiss and Aledort 1967).
The peculiar effectiveness of aspirin in thrombosis is
based on its irreversible inhibition of the COX enzyme in
platelets which make thromboxane A2 (TXA2), the potent
Altınterim / Effects of Willow Bark (Salix alba) and Its Salicylates on Blood Coagulant
pro-aggregatory and vasoconstrictive prostaglandin. Of
all the aspirin-like drugs, only aspirin permanently inac-
tivates the enzyme (by attaching an acetyl group close
to the active site), and thus makes the Arachidonic acid
metabolism, controlled by cyclooxygenases. Arachidonic
acid is liberated from the cells by phospholipase A2, and
converted by cyclooxygenases via unstable endoperox-
ides to prostaglandins.
In endothelial cells prostacyclin is preferentially pro-
duced, while blood platelets generate thromboxane A2.
platelet incapable of synthesizing TXA2 for the rest of its
life (about 10 days). Regular low doses of aspirin have
a cumulative effect and inactivate platelet COX without
affecting much the synthesis in blood vessels of prosta-
cyclin–which exert potent vas-dilatory and anti-platelet
effects (Szczeklik et al. 1979).
It is important to realize that salicin from willow can be
split off by the body to create salicylic acid, providing
anti-inﬂ ammatory and pain-relieving actions with the
same COX–2 inhibition properties as aspirin; although
salicin will not function as an anticoagulant (blood thin-
ner) like aspirin (Bradley 1992, Newall et al. 1996).
This effect on the urine may lead to decreased blood
levels and therapeutic effects of several drugs, including
aspirin and other salicylates (choline salicylate, mag-
nesium salicylate, salsalate, sodium salicylate, sodium
thiosalicylate). It may be advisable to avoid these citrate
compounds during therapy with aspirin or salicylates
except under medical supervision.
White willow contains a substance that is converted by
the body into a salicylate similar to aspirin. It is therefore
possible that taking NSAIDs and white willow could
lead to increased risk of side effects, just as would occur
if you combined NSAIDs with aspirin.
To some extent salicylate-containing herbs work by treat-
ing the cause of the pain and by interfering with pain
transmission. These herbs are generally not as effective
for psychogenic pain or pain not related to inﬂ ammation
or tissue destruction. Salicylates may also have activity
in the central nervous system to reduce pain sensation.
Willow bark contain high concentrations of salicylates
have been reported to exhibit antiplatelet activity. Prepa-
rations from Salix species, the natural NSAID, contain a
total of more than 1% salicylates. Salicylate concentra-
tions in the range causing analgesia are achieved with
daily consumption of extract standardized at least on 240
mg Salicilin (ESCOP Monograph). Salicylate side-effects
may occur during treatment. However, blood coagula-
tion is less affected than with acetylsalicylate (Chrubasik
and Shvartzman 1999).
Toxicity is far less with willow bark than with aspirin
due to the low levels of salicylates in the plant products.
There is a potential for interaction with salicylate-con-
taining medications and other non-steroidal antiinﬂ am-
matory medications (NSAIDs). There is not expected
to be a negative interaction with anticoagulant medica-
tions. Tannins may interfere with absorption of other
medications. Nowadays, synthetic acetylsalicylic acid
is used not only as an analgesic and antipyretic, but to
prevent myocardial infarctions, strokes and colorectal
cancer. Some herbalists recommend willow bark extract
as a natural substitute for aspirin to achieve these same
beneﬁ ts. In Germany, willow bark is often taken along
with aspirin to enhance the therapeutic effects while
minimizing side effects (Peirce 1999).
Willow bark is an important bitter tonic with marked
astringent properties, making it useful in chronic
hypersecretory states, such as mucus discharges, pas-
sive hemorrhage, leucorrhea, humid asthma, diarrhea
and dysentery. In the treatment of inﬂ ammatory joint
disease Willow is unlikely to provide the same relief as
aspirin, and if applied as a simple for its salicin content,
will typically require such large doses that the tannins
become potentially toxic (Bergner 2001). Usual dosage of
salicin recommended for back pain is 120–240 mg, with
the higher dose found to be more effective. Up to a week
of therapy may be needed before beneﬁt is seen. Willow
bark has been used for up to 3 months without adverse
effects (Food and Drug Administration 2003). Aspirin is
composed of synthetic acetylsalicylic acid. Natural sali-
cylic acid is reported to produce fewer side effects than
synthetic acetylsalicylic acid (Hathcock 1997).
The solubility increases markedly in alkaline pH and is
more than 100-fold higher for the sodium salts as com-
pared to the free acids. Salicylates, in contrast to aspi-
rin, have unique physicochemical properties. These are
caused by the close steric neighborhood of the acetate
hydroxyl group to the carboxyl group. This allows the
formation of a chelate ring structure and facilitates the
release of protons. The major functional consequence
is the action of salicylate as protonophore, for example,
in mitochondrial membranes, to uncouple oxidative
phosphorylation because of the abolition of the mem-
brane impermeability to protons. Neither aspirin nor
other salicylates exhibit comparable physicochemical
properties (Blumenthal et al. 1998, Schrör 2009). Unlike
ASA (synthetic acetylsalicylic acid, naturally occurring
salicine (salicylic acid) does not irreversibly inhibit plate-
let aggregation, reducing the potential for a bleeding
Altınterim / Effects of Willow Bark (Salix alba) and Its Salicylates on Blood Coagulant 39
Willow is certainly a giving herb. Numerous species have
a long history of use as a safe and effective pain-relieving
medicine. As is the case when using all of nature’s heal-
ers, it is recommended that you consult with a trained
herbalist or other complementary medicine practitioner
Aberg, B. 1981. Plant growth regulators. XLI. Monosubstituted
benzoic acids. Swedish J. Agric. Res. 11: 93–105.
Bergner, P. 2001. Salix: Willow bark and NSAID. Medical
Herbalism. Mat. Med. and Phar. 3: 2–7.
Blumenthal, M., Busse WR., Goldberg A., Gruenwald, J.,
Hall, T., Riggins, CW., Rister, RS., eds. Klein S., Rister, RS.
1998. The Complete German Commission E Monographs
Therapeutic Guide to Herbal Medicines. Austin, TX: Am.
Bot. Coun.. Boston: Integrative Medicine Communication.
Bradley, PR. 1992. British Herbal Compendium, vol 1.
Bournemouth, Dorset, UK. British Herbal Med. Ass. 224–6.
Chrubasik, S., Shvartzman, P. 1999. Rheumatic Pain Treatment
With Willow Bark (Salicis Cortex). Coherence, 1. 1/99.
Fiebich, BL, Appel K. 2003. Anti-inﬂammatory effects of
willow bark extract. Clin. Phar. Ther. 74: 96.
Food and Drug Administration, 2003. HHS: Labeling for
oral and rectal over-the-counter drug products containing
aspirin and nonaspirin salicylates; Reye’s syndrome
warning. Final rule. Fed. Regist. 68: 18861-9.
Hathcock, J. 1997. Vitamin and Mineral Safety. Council for
Responsible Nutrition:Washington DC. 30-32, 39, 41-46, 49-50.
MacLagan, TJ. 1876. The treatment of acute rheumatism by
salicin. Lancet. 342-383.
Newall, CA., Anderson, LA., Philpson, JD. 1996. Herbal
Medicine. A Guide for Healthcare Professionals. London, UK.
The Pharmaceutical Press. 296.
Quick, AJ. 1966. Salicylates and bleeding: the aspirin tolerance
test. Am. J. Med. Sci. 252:265–9.
Peirce, A. 1999. The American Pharmaceutical Association practical
guide to natural medicines. New York. William Morrow and
Ruggeri, ZM. 2002. Platelets in atherothrombosis. Nat. Med. 8:
Schrör, K. 2009. Acetylsalicylic Acid. Weinheim. ISBN: 978–3–
527–32109–4 Copyright. WILEY-VCH Verlag GmbH & Co.
KGaA. 29 p.
Szczeklik, A., Nizankowski, R., Skawinski, S., Szczeklik,
J., Gluszko, P., Gryglewski, RJ. 1979. Successful therapy
of advanced arteriosclerosis obliterans with prostacyclin.
Vlachojannis, J., Magora, F., Chrubasik, S. 2011. Willow
Species and Aspirin: Different Mechanism of Actions.
Phytotherapy Res., 25: 1102–1104.
Weiss, HJ, Aledort, LM. 1967. Impaired platelet-connective-
tissue reaction in man after aspirin ingestion. Lancet, 2: