Scientific Name(s): Salix alba L., Salix fragilis L., Salix purpurea L.
Common Name(s): Crack willow, Purple osier willow/basket willow, Weidenrinde, White willow, Willow
The genus Salix has nearly 450 species. Most willows are found in temperate and arctic zones, but some species can be located in subtropical and tropical zones. They are geographically distributed in all continents except Antarctica and Australia. Willows include small trees, shrubs, and groundcovers, and many species are dioecious with male and female catkins (flowers) on separate plants. The catkins are cylindrical in shape, measuring 6 to 7 cm in length. The male flowers are yellow, and the female flowers are green. Insect pollinated, different species of willow hybridize freely. Willow trees may grow 6 to 18 m in height. Medicinal willow bark is collected in the early spring from young branches (2 to 3 years of age). Other species of Salix have similar chemistry and pharmacology. The plant species has been used in various ecosystem restoration projects, particularly for erosion control, because of its fibrous root system.1, 2
The medicinal use of willow dates back 6,000 years. Ancient civilizations used willow tree extracts to treat pain, inflammation, and musculoskeletal conditions. Assyrian clay tablets excavated by archaeologists document these uses of willow and also in treating fever. Egyptians used willow to treat joint pain and inflammatory conditions associated with wounds. Chinese civilizations used willow to treat fever, pain, colds, hemorrhages, goiter, and rheumatic fever and applied willow as an antiseptic for wounds and abscesses. Physicians of ancient Greece, including Dioscorides who wrote the precursor to all modern pharmacopeias, prescribed willow for its analgesic and anti-inflammatory properties.3, 4, 5
North American willows have also been used in folk medicine. Most of the European medicinal willows were introduced to the Americas and escaped cultivation. In the late 19th century, salicylic acid was widely used in place of willow bark, and its derivative, aspirin, was discovered to be less irritating to the mouth and stomach.6, 7
Salicylate derivatives are the primary medicinal constituents of willow bark. While small amounts of salicylic acid can be detected in most species, the principle salicylates of S. alba are the phenolic ester glycoside salicortin8, 9 and glycoside salicin, its acid hydrolysis product. Although salicin is considered the major active constituent, there is research interest in the anticancer activity of polyphenols and flavonoids in willow bark.10
Salicin is hydrolyzed in the intestine to saligenin (o-hydroxybenzyl alcohol), which is absorbed and then oxidized to salicylic acid.11 Salicortin and other related salicylates are chemically unstable (ie, to boiling water for teas)12 and to avoid the loss of these compounds, careful drying of the bark is required.12, 13, 14 Extraction protocols, used to avoid decomposition of the native glycosides, have been developed. Most standards for medicinal willow bark require salicylates to be present in more than 1% of dry weight, but are difficult to achieve with many species. This has stimulated surveys of the salicylate content of many other species of Salix15, 16 as well as aspen (Populus), which also contains salicylates.17 While the leaves generally contain lower concentrations of salicylates than the bark, several species contain medicinally useful quantities of salicylates in their leaves.18
A number of analytical approaches have been used to quantify salicylates in willows, including spectrophotometry,19 thin-layer chromatography (TLC),20 high-performance liquid chromatography (HPLC) after enzymatic deglycosylation,21 capillary electrophoresis,22 and an electrochemical method known as square wave voltammetry.23 A method using gas chromatography of silyl derivatives of salicylates gave results comparable to those of HPLC.24 An HPLC method was used to compare the salicylate content of different cultivated clones of Salix myrsinifolia grown in a single location.25 An HPLC method led to the identification of 13 compounds in 2 pharmaceutical preparations used in clinical trials containing willow bark extract.26 Nuclear magnetic resonance spectra of the principle salicylates of willows have been reported and assigned.27
The ecological role of salicylates has also been investigated.28 Naringenin glycosides,29 oligomeric procyanidins,30 and condensed tannins, presumably derived from the simpler flavonols, have been obtained from commercial willow barks. The chemical variation among northern willow species has also been studied.31
Uses and Pharmacology
The ester glycosides salicortin, tremulacin, and fragilin can be considered to be prodrugs of salicylic acid, which deliver this compound into the systemic circulation without irritating the GI tract.32 Salicylic acid inhibits cyclooxygenase enzymes, which are involved in prostaglandin synthesis. The anti-inflammatory efficacy of tremulacin, a derivative of salicin, has been studied.33, 34
Willow bark and leaf extracts have documented anticancer activity. Mechanism of action may be associated with tumor inhibition leading to apoptosis, DNA damage, an affect on cell membranes, and/or denaturation of proteins.35, 36
In vitro data
The leaves of S. safsaf inhibited growth of acute myeloid leukemia cells.37 Another report found that willow extract killed 75% to 80% of abnormal cells harvested from 7 patients with acute lymphoblastic leukemia and 13 patients with acute myeloid leukemia.35 Willow bark extract inhibited tumor cell growth and induced apoptosis in human colon and lung cancer cell lines. The inhibitory effects were dose dependent.36
Anti-inflammatory and antioxidant activity
An animal model in rats demonstrated that a standardized willow bark extract, on a milligram per kilogram basis, was as effective as acetylsalicylic acid (ASA) in reducing various inflammatory mediators.38
In vitro data
Eighty-two patients with chronic arthritic pain were randomly assigned to receive a willow bark preparation or placebo for 2 months. Mild efficacy for improvement in pain symptoms with few adverse reactions were reported.40 Analysis of blood samples from a small study of 3 patients receiving a single dose of willow bark extract equivalent to salicin 240 mg found only moderate inhibition of cyclooxygenase.41
Two 6-week, randomized, double-blind, clinical trials examined the efficacy of willow bark in treating 127 outpatients with hip or knee osteoarthritis and 26 outpatients with active rheumatoid arthritis. Patients with osteoarthritis received either salicin 240 mg/day, diclofenac 100 mg/day, or placebo. Patients with rheumatoid arthritis received salicin 240 mg/day or placebo. No efficacy was demonstrated in either disease state with willow bark.42 An open-label, 6-week study evaluated a product with salicin 120 to 240 mg/day compared with conventional treatment in patients (n = 128) with coxarthrosis and gonarthrosis. No significant difference between treatments was seen for therapeutic effects, and there were fewer adverse events in the group receiving the willow bark product.54
Lower back pain
A 4-week, double-blind, clinical trial tested 2 oral doses of willow bark extract containing salicin 120 mg or 240 mg against placebo in 191 patients. Primary outcome measure was the number of patients requiring relief medication (tramadol) 5 out of 7 days during the final week of the study. Pain index measures showed reduction in relief medication with both doses of salicin. Patients receiving the 240 mg dose had more improvement in pain index measures. Moderate efficacy was demonstrated with both doses of salicin for short-term treatment of acute episodes of chronic nonspecific lower back pain.43 Postmarketing surveillance of a proprietary willow bark extract product reported no serious adverse reactions.44
Another 4-week, randomized, controlled study tested oral willow bark extract (salicin) 240 mg against rofecoxib 12.5 mg/day in 183 patients. Rofecoxib is no longer available, however both the salicin and rofecoxib group improved by 44% on pain index measures. There was no difference in efficacy between the 2 treatment groups.45
A multicenter, observational study (N = 436) evaluated the long-term safety, efficacy, and tolerability as well as co-medication patterns of any concomitant analgesics during administration of a willow bark extract product (23% to 26% total salicin) in adults with rheumatic pain mostly due to osteoarthritis and back pain. The study employed no strict drug regimen by protocol. Over 60% of patients used the willow bark extract as monotherapy, almost 30% used concomitant nonsteroidal anti-inflammatory drugs (NSAIDS) (ie, diclofenac, ibuprofen), 5.7% used other analgesics like gabapentin, and only 3.9% co-medicated with an NSAID plus an opioid. Significant reductions in mean pain intensity were observed after 3 weeks via both patients’ and physicians’ ratings, which were clinically relevant at 6-months with a 45.6% reduction from baseline. The herbal product was well tolerated; no adverse effects were related to use of the willow bark extract.55
A 4-week trial involving 51 patients treated with Salicis cortex extract salicin 240 mg/day found that the plant had little effect on platelet aggregation when compared with a daily cardioprotective dose of acetylsalicylate 100 mg.46 The total serum salicylate concentration of salicin was bioequivalent to acetylsalicylate 50 mg.
The American College of Rheumatology guidelines on the management of gout (2012) voted that the use of various oral complementary agents, including willow bark, was inappropriate for the treatment of an acute attack of gout.53
Willow is available in several dosage forms including tablets, capsules, powder, and liquid. Willow bark has been used for analgesia at daily doses of 1 to 3 g of bark, corresponding to salicin 60 to 120 mg. A clinical study of lower back pain used willow bark at a daily dose of salicin 120 to 240 mg.43 A proprietary extract of willow bark, Assalix, was standardized to contain 15% salicin. The pharmacokinetics of salicylic acid delivered from willow bark have been studied, and the plasma half-life is approximately 2.5 hours.47 Another pharmacokinetic study of salicylic acid from salicin found peak levels within 2 hours after oral administration.48
Pregnancy / Lactation
Information regarding safety and efficacy during pregnancy and lactation is lacking.
In general, drug interactions associated with salicylates may apply to willow-containing products; however the actual salicylate content is likely to be low.49 Therefore, avoid use with alcohol, barbiturates, sedatives, and other salicylate-containing products because of additive irritant effects and adverse reactions on the GI tract and platelet function. Willow may also interact with oral anticoagulants (eg, warfarin)50 seizure medications (eg, phenytoin, valproate acid), and other medications (eg, methotrexate).
Reports from clinical trials primarily document GI discomfort such as nausea, stomachache, dizziness, and rash. One review article reported an anaphylactic reaction to willow bark in a 25-year-old patient.51 A dog developed life-threatening intestinal bleeding after eating food containing willow.52
Toxicity information on the use of willow bark is limited. However, because the same toxicity associated with salicylates also applies to willow, people using the product should monitor for blood in stools, tinnitus, nausea or vomiting, and any stomach or kidney toxicity.
This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.
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