Salix alba
Synonyms
No documentation
Vernacular Name
White Willow, White Willow Bark, Wild Countryside White Willow [1],[2]
Description
Salix alba is a member of the Salicaceae family and is easily recognizable by the white underside of its narrow leaves.[1] S. alba bark has been advocated for the treatment of pyrexia since the time of Hippocrates, it was a letter published by the Reverend Edward Stone in 1763 that infused the scientific community with regained interest in the remedy.[3] An active constituent of S. alba, salicin, was crystallized by Pierre-Joseph Leroux in 1829 and acetylsalicylic acid, also known as aspirin, subsequently synthesized by Charles Frederic Gerhardt in 1853.[3] However, acetylsalicylic acid produces irreversible inhibition of platelet aggregation. As a result, therapy with S. alba has remained popular as salicin appears to be less likely to induce irreversible platelet aggregation while still alleviating inflammatory conditions, providing analgesia and acting as an effective anti-migraine agent.[4]
S. alba is a perennial tree that grows up to 20m. It has a wide, spreading crown with narrowly oval, toothed leaves that have a whitish tone on the underside giving it the name ‘White willow.[2] The flowers are long catkins and are either male or female on a single tree making propagation possible only if a male plant and female plant are grown for the purpose of obtaining seed.
Origin / Habitat
S. alba is native to Europe and parts of Asia. While not a native species to North America, its rapid growth and easy cultivation has allowed it to flourish by river beds, streams and any area that can supply the root system with the amount of moisture needed. The plant cannot tolerate shade.
Chemical Constituents
Plant Part Used
Bark[2]
Medicinal Use
General
Analgesic
Inflammatory conditions
Antipyretic
Most Frequently Reported Uses
Analgesic
Inflammatory conditions[11],[12],[13]
Dosage
Dosage range
Salicin equivalent of 120-240mg for the treatment of lower back pain.
Salicin equivalent of 240mg for osteoarthritis pain.[5],[6]
Most Common Dosage
No documentation
Standardized to
Standardized to 15% salicin.
Pharmacology
Pre-clinical
Salicin, the primary active constituent found in Salix alba, is hydrolyzed to saligenin in the lower intestine by intestinal bacteria, slowly absorbed and subsequently oxidized to salicylic acid.[9],[14] The pharmacokinetic and in vivo pharmacological studies in rats indicate that salicin is able to act as an antipyretic agent without producing simultaneous gastric injury because salicin acts as a pro-drug for saligenin and salicylic acid formation.[9] The in vivo studies utilizing rats showed that oral administration of salicin abolished yeast-induced pyrexia and prevented onset of pyrexia when administered concomitantly with yeast.[9] The serum collected from human volunteers following administration of a standardized willow bark extract corresponding to 240mg of salicin showed salicylic acid to be the primary metabolite with peak levels reached after 2 hours.[15] When compared to the synthetic salicylate dose required to produce analgesia, administration of the therapeutic dose of willow bark extract produced lower serum salicylate levels; thus, the plethora of desired effects, including analgesia, produced by consumption of willow bark extract cannot be attributed solely to salicylic acid formation.[13],[15],[16] Murine animal models were employed to study the anti-inflammatory, analgesic and antipyretic effects of willow bark extract as compared to the effects of acetylsalicylic acid; the results indicated that only the highest acetylsalicylic acid dose employed (600 mg/kg) produced similar potency to the three doses of willow bark extract (60, 100, 120 mg/kg) for analgesia and anti-inflammation.[16]
The laboratory studies that attempted to elucidate additional mechanisms that might explain the production of analgesic, anti-inflammatory, and additional properties showed that cyclooxygenase-2 and lipoxygenase, important enzymes in the mediation of pain and inflammatory disorders, were inhibited; these findings may indicate that synergy amongst the constituents comprising willow bark produces increased effectiveness when compared to the effects produced by isolated constituents.[17],[18] Further support for this finding is garnered from experiments assessing the effects of an ethanolic Salix extract on human monocyte prostaglandin-E2 release, an important mediator of inflammation; the results indicated that Salix extract inhibited cyclooxygenase-2 mediated prostaglandin-E2 release independent of salicin and salicylate metabolites while also inhibiting lipopolysaccharide-induced release of inflammatory mediators tumor necrosis factor-alpha and interleukin-1beta.[19] The data appear to indicate that the anti-inflammatory activities associated with Salix extract are attributable to multiple-constituent synergy leading to the inhibition of cyclooxygenase.[19],[20] In vitro studies employing ovine neutrophils have also shown that the hydroethanolic extract of S. alba possesses potent anti-inflammatory activity.[20] This mechanism appears to be attributable to its dose-dependent inhibitory actions on both neutrophil adhesion and superoxide production.[20] Taken together, these findings indicate that multiple mechanisms of action underlie the anti-inflammatory action associated with S. alba extract.
Clinical
The clinical studies assessing the efficacy of extract of S. alba in the treatment of chronic lower back pain and osteoarthritis have been completed. In a randomized, double-blind, placebo-controlled study, patients suffering from acute exacerbations of chronic low-back pain were given extract of S. alba standardized to 120mg salicin, extract of S. alba standardized to 240mg salicin or placebo for four weeks.[5],[12] S. alba extract dose-dependently attenuated the perception of pain when compared to placebo.[5] The percentage of pain-free patients in the last week of treatment was 39% for the 240mg salicin group, 21% for the 120mg salicin group and 6% for the placebo group with significantly more patients in the placebo group employing the rescue pain medication, tramadol, during the course of the study.[5] When the effectiveness of a S. alba extract standardized to 240mg salicin was compared to that of 12.5mg rofecoxib, the open, randomized, post-marketing study revealed improvements in the Arhus Low Back Pain Index, pain and physical impairment indices with no significant differences being found between the effectiveness of the two treatments at the doses employed.[12],[21] Reviews of herbal medicine for the treatment of low back pain concluded that these studies provide moderate evidence that a daily dose of extract of S. alba standardized to contain either 240mg or 120mg salicin reduces pain (in a dose-dependent manner) when compared to placebo and moderate evidence that there are no differences in effectiveness when an extract of S. alba standardized to 240mg salicin is compared to 12.5mg rofecoxib.[11],[12] A double-blind, randomized, placebo-controlled clinical trial investigated the efficacy of S. alba extract, in a dose corresponding to 240mg per day, in the treatment of knee/hip osteoarthritis.[6],[17] The willow bark extract demonstrated a moderate analgesic effect with a significant reduction observed in the measurement of pain by both patient and physician when compared to placebo; furthermore, the Salix extract was well tolerated in patients and the study concluded that low-dose willow bark extract may be a suitable treatment for patients unable to take traditional non-steroidal anti-inflammatory agents due to their production of gastrointestinal adverse effects.[6],[17]
Despite significant scientific advances, the etiology of the migraine is incompletely understood. Research has shown that agonists of serotonin-1B/1D receptors provide effective pain relief for many patients if taken early in the progression of a migraine.[22] Further evidence supporting a role for serotonin in the pathophysiology of migraine is garnered from the use of agents targeting serotonin-2A/2C receptors to produce effective migraine prophylactic therapy in a substantial number of patients.[23] A ligand binding study showed that S. alba interacted with the serotonin-1D receptor subtype while also antagonizing the serotonin-2A/2C receptor subtypes.[10] A completed prospective, open-label study examined the effectiveness of a daily dose of 600 mg Salix alba, in combination with 600 mg Tanacetum parthenium, in migraine prophylaxis. The results indicated that attack frequency (57.2 and 61.7 percent reduction at six and twelve weeks, respectively), attack intensity (38.7 and 62.6 percent reduction at six and twelve weeks, respectively) and attack duration (67.2 and 76.2 percent reduction at six and twelve weeks, respectively) were reduced following the combination therapy for a twelve-week period with no adverse effects reported.[10] The results of the ligand binding study indicate that S. alba interacts with serotonin receptors in a triptan-like manner.[10] Hence, willow bark may reduce neuronal firing and the release of sensory neuropeptides and thereby inhibit the subsequent cranial vasodilatation and neurogenic inflammation characteristic of a migraine attack.[10]
Interaction and Depletions
Interaction with other Herbs
No documentation
Interaction with Drugs
- Agents with potential or established nephrotoxicity and/or hepatotoxicity
- Non-steroidal anti-inflammatory agents
- Antiplatelet agents
- Anticoagulant agents
- Additional agents that may increase bleeding
- Antihypertensive agents
- Antihyperlipidemic agents
- Anti-seizure agents
- Anti-migraine agents
- Agents used in the treatment of gout
- Agents with antioxidant activity
- Agents that interact with acetylsalicylate therapy
- Carbonic anhydrase inhibitors
- Sedative-hypnotic agents
Precautions and Contraindications
Side effects
Caution is advised in patients with bleeding disorders and those taking supplements that may increase bleeding.
S. alba is contraindicated in patients with a known allergy or hypersensitivity to members of the Salix species, to salicylates and to acetylsalicylic acid.[28] S. alba supplements should be used with extreme caution in atopic patients; anaphylaxis requiring administration of epinephrine has been reported following ingestion of an herbal pollen compound predominately comprised of S. alba, Taraxacum officinalis and Artemisia vulgaris in an atopic patient.[29] Patients are advised to consult their medical practitioner/seek medical attention if allergic symptoms occur.
Patients suffering from kidney, liver, immunosuppressive or chronic diseases (e.g. diabetes) should not begin any medicinal therapy without a consultation with their medical practitioner. Patients should always inform their medical practitioner about any herbal supplements and/or vitamins that the patient is taking and consult with their medical practitioner before beginning any novel treatment.
S. alba should be used with caution in those with medical conditions where the use of acetylsalicylic acid is contraindicated. Toxicities that should be considered before consumption of Salix species supplements as the salicylate constituents have a similar mechanism of action to that of acetylsalicylic acid and caution is advised accordingly.[24]
Pregnancy
Patients planning to become pregnant, who are pregnant or breastfeeding should not use S. alba supplements without first consulting their medical practitioner.[25] Maternal salicylate use during lactation may produce adverse events (e.g. rash, platelet abnormalities) in infants’ breastfed by mothers compliant with salicylate therapy.[26]
Age limitation
Salicylate-containing medications and herbal supplements are contraindicated in children due to the risk for Reye syndrome, a potentially life-threatening disorder characterized by acute non-inflammatory encephalopathy and hepatic failure.[24],[27]
Adverse reaction
Salix extract supplements appear to be generally well tolerated but adverse effects have been reported and may include gastrointestinal disturbances, blood pressure instability, hypertriglyceridemia, hyperuricemia, edema and headache.[6],[13]
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References
- United States Department of Agriculture. Natural Resources Conservation Service. The PLANTS Database. Available from: http://plants.usda.gov. [Accessed on 15th June 2009].
- Gruenwald J, Brendler T, Jaenicke C. PDR for Herbal Medicines. 2nd ed. Montvale, New Jersey; Medical Economics Company; 2000:807-809.
- Greenwood D. Antimicrobial Drugs: Chronicle of a twentieth century medical triumph. Oxford, United Kingdom: Oxford University Press; 2008. 47-48.
- Escop (ed). ESCOP Monographs: The scientific foundation for herbal medicinal products. 2nd ed. Stuttgart, Germany: Georg Thieme Verlag; 2003. 446.
- Chrubasik S. Treatment of low back pain exacerbations with willow bark extract: a randomized double-blind study. Am J Med. 2000;109(1). 9-14.
- Schmid B. Efficacy and tolerability of a standardized willow bark extract in patients with osteoarthritis: randomized placebo-controlled, double blind clinical trial. Phytother Res. 2001;15(4):344-350.
- Qizhen D, Jerz G, Winterhalter P. Preparation of three flavonoids from the bark of Salix alba by high-speed chromatographic separation. J Liq Chromatogr Relat Technol. 2004;27(20):3257-3264.
- Poblocka-Olech L, Krauze-Baranowska M. SPE-HPTLC of procyanidins from the barks of different species and clones of Salix. J Pharm Biomed Anal. 2008;48(3):965-968.
- Akao T. Evaluation of salicin as an antipyretic prodrug that does not cause gastric injury. Planta Med. 2002;68(8):714-718.
- Shrivastava R. Tanacetum parthenium and Salix alba (MIG-RL®) combination in migraine prophylaxis: A prospective, open-label study. Clin Drug Investig. 2006;26(5): 287-296.
- Vlachojannis JE. A systematic review on the effectiveness of willow bark for musculoskeletal pain. Phytother Res. 2009;23(7):897-900.
- Gagnier JJ, van Tulder M, Berman B, Bombardier C. Herbal medicine for low back pain. Cochrane Database Syst Rev. 2006;2:CD004504.
- Chrubasik S. Willow bark extract, a useful alternative for the treatment of osteoarthritis: comment on the editorial by Marcus and Suarez-Almazor. Arthritis Rheum. 2003;48(1):278-280.
- Meier B, Sticher O, Julkunen-Tiitto R. Pharmaceutical aspects of the use of willows in herbal remedies. Planta Med. 1988;54(6):559-560.
- Schmid B. Pharmacokinetics of salicin after oral administration of a standardized willow bark extract. Eur J Clin Pharmacol. 2001;57(5):387-391.
- Loniewski I, Glinko A, Samochowiec L. Standardized willow bark extract: a potent anti-inflammatory drug. Focus Altern Complement Ther. 2002;7:100.
- Williamson EM. Synergy and other interactions in phytomedicines. Phytomedicine. 2001;8(5):401-409.
- Wagner I. Influence of willow bark extract on cyclooxygenase activity and on tumor necrosis factor alpha or interleukin 1 beta release in vitro and ex vivo. Clin Pharmacol Ther. 2003;73(3):272-274.
- Fiebich BL, Chrubasik S. Effects of an ethanolic salix extract on the release of selected inflammatory mediators in vitro. Phytomedicine. 2004;11(2-3):135-138.
- Farinacci M. Immunomodulatory activity of plant residues on ovine neutrophils. Vet Immunol Immunopathol. 2008;126(1-2):54-63.
- Chrubasik S. Treatment of low back pain with a herbal or synthetic anti-rheumatic: a randomized controlled study. Willow bark extract for low back pain. Rheumatology (Oxford). 2001;40(12):1388-1393.
- Tfelt-Hansen P, De Vries P, Saxena PR. Triptans in migraine: a comparative review of pharmacology, pharmacokinetics and efficacy. Drugs. 2000;60(6):1259-1287.
- Massiou H, Bousser MG. Prophylactic drug treatment of migraine. Rev Neurol (Paris). 2005;161(6-7):681-684.
- American Diabetes Association. Aspirin therapy in diabetes. Diabetes Care. 2004; 27(1): S72-S73.
- Ernst E. Herbal medicinal products during pregnancy? Phytomedicine. 2002;9:352-354.
- Pray WS. Nonprescription products for the pregnant and breast-feeding patient. US Pharm. 2007;32(9):10-14.
- Schror K. Aspirin and Reye syndrome: a review of the evidence. Paediatr Drugs. 2007;9(3):195-204.
- Boullata JI. Anaphylactic reaction to a dietary supplement containing willow bark. Ann Pharmacother. 2003;37(6):832-835.
- Chivato T, Juan F, Montoro A, Laguna R. Anaphylaxis induced by ingestion of a pollen compound. J Investig Allergol Clin Immunol. 1996;6(3):208-209.
