03 December 2019

Salicin

Salicin is an

active secondary metabolite produced by the genus Salix, primarily produced within the bark.

Introduction

Bark from the White Willow Tree (Salix alba) has a long history of use, dating back to the time of Hippocrates in 400BC, where chewing on the bark was recommended to reduce fever and inflammation. It has been used extensively throughout history, in both European and Chinese medicine, ever since [2, 3]. The bark contains flavonoids, tannins and salicylates, with the active constituent thought to be Salicin [4].

Structure

2D Structure of Salicin (Compound)[1] -  White Willow Tree (Salix alba)[2] - closeup of bark[3]

History

The first early clinical trial were held in the 18th Century, that investigated willow bark as a cure for ‘agues’, and hailed a success [5]. The study was published in 1763 by the Royal Society of London, but the compound went in and out of popularity, until 1828 where the active component Salicin was isolated and synthesised into salicylic acid. The acid became a cure-all, used to tackle Scarlet fever, diphtheria, measles, cholera, rabies and anthrax. This extensive use led to serious side effects, including damage to the gastrointestinal system. The improved synthesis in 1897, into acetylsalcyclic acid (ASA) by the Bayer Company reduced these side effects, though it didn’t gain popularity for some time as heroin had just been manufactured as a non-addictive substitute for the pain-reliever morphine and anti-cough codeine [6]. In 1899, ASA was marketed under the trade name Aspirin, now no longer trademarked but a general name for medicinal acetylsalcyclic acid. It became known for its antithrombotic action and the beneficial effects of low-dose aspirin as a secondary prevention of coronary disease and ischemic stroke, during the 20th Century [6].

Current trials and use

New findings are still being uncovered, with large scale trails investigating the ability to reduce myocardial infarction as a primary preventative, or as a preventative against cancer. Studies have also drawn attention to the prevention of recurrence of venous thrombosis by aspirin, which, while less effective than anticoagulant treatment, may have a better risk-benefit balance for long-term treatment due to its lower bleeding risk than anticoagulants [6]. The raw willow bark is still used as an anti-inflammatory agent in the human body, for lower back pain, osteoarthritis, headache and inflammatory conditions, such as bursitis and tendonitis [3]. It is even marketed as a weight-loss or sports performance food supplement. It’s easy to get hold of, online or at herbalist store, where recommended dosages vary widely, and there is usually no restriction on length of use [4]. Salix bark, listed by the EU as a basic substance, is also used as a fungicide that works through emphasising a crops self-defence mechanism [4].


Figure 3. Willow Bark Supplement form, powder or chips.

Risk Assessment

Even with the long history, medicinal research and variety of uses, an EFSA risk assessment of Salix alba bark found there was very limited data related to toxicity. The assessment used both recent online sources from journal articles but found that older compendium style books the most helpful for metabolite composition. It was decided the composition was all that was needed as the bark is unlikely to contain any adulterants, due to the simple manufacturing process, and the most likely pathway was through oral consumption [4]. The risk highlighted was anaphylactic reactions to the salicylates. Other adverse effects found were considered to be of low relevance due to the bark having relatively low concentrations of salicin (even in large doses - 6 grams per day!), and also the presence of compounds with gastroprotective action. However, it noted that there was potential for large heavy metal contamination of the willow bark [4]. Salix species have in recent history been used for phytoremediation, due to their ability to clean soil contaminated with hazardous compounds, such as heavy metals. These hazardous substances may accumulate in the tree, which could pose a risk to consumers if bark is taken from a tree on contaminated soil [7]. Overall the White Willow Bark was not considered a high risk substance but suggested that more research was needed into its toxicity and heavy metal contamination within the bark [7].

 

Salicin is a compound with a very long history, with mysteries still surrounding it. Using it as a supplement seems to have no ill-effect to your health but it may be wise to check the tree source!

In-text References and Figures:

[1] PubChem. 2019. 2D Structure of Salicin (Compound). PubChem: [Cited 28/11 2019]. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/salicin#section=2D-Structure

[2] Room NH. White Willow Bark (Salix alba). [Cited 28/11/19 2019]. Available from: https://naturalhealingroom.com/shop/herbs-spices/herbs-a-to-z/herbs-v-z-herbs-a-to-z/white-willow-bark-salix-alba/

[3] Roots MF. 2017. White Willow Bark Tincture. [Cited 26/11 2019]. Available from: https://madefromroots.com/product/white-willow-bark-tincture-1oz/

[4] Matyjaszczyk E, Schumann R. 2018. Risk assessment of white willow (Salix alba) in food. EFSA Journal 16. DOI: 10.2903/j.efsa.2018.e16081.

[5] Wood JN. 2015. From plant extract to molecular panacea: a commentary on Stone (1763) ‘An account of the success of the bark of the willow in the cure of the agues’. Philosophical Transactions of the Royal Society B: Biological Sciences 370:20140317. DOI: 10.1098/rstb.2014.0317.

[6] Rosendaal FR, Reitsma PH. 2014. 5000 years old and still going strong. Journal of Thrombosis and Haemostasis 12:1763-1763. DOI: 10.1111/jth.12752.

[7] Matyjaszczyk E, Schumann R. 2019. Cadmium contamination in food supplements containing white willow (Salix alba) bark. Journal of Consumer Protection and Food Safety 14:179-182. DOI: 10.1007/s00003-018-1199-0.