Salicylic Acid and Willow Tree Bark

A sample of Salicylic Acid can be found in the Historical Medicinal Collection in the Department of Pharmacology in Trinity College Dublin, based in St. James’s University Hospital. The sample was acquired from ‘Hopkin & Williams LTD’, Chadwell Heath, Essex, England. A sample of Willow Tree Bark can also be found in the collection, of unknown origin.

Latin name: Salix (2-(Hydroxymethyl)phenyl β-D-glucopyranoside)

Found in Willow tree bark 

Active Ingredient - Salicin which is a precursor for Salycylic acid 

Historical Use: The philosopher, Hippocrates (460–370 bc) recommended chewing willow bark to patients suffering from high temperature and pain (Gross & Greenberg 1948; Riddle 1999). He also prescribed a brew of willow leaves to ease the excruciating pains of childbirth. 

Where its found :

Willow trees are native to Europe, Asia, and North America. They grow in moist environments, near rivers, lakes, and wetlands.

Uses/indications :

• Pain Relief: Headaches, muscle pain, back pain, osteoarthritis, and rheumatoid arthritis.

• Anti-inflammatory: Reduces joint inflammation in arthritis.

• Antipyretic (Fever-Reducing): Used to manage fever in colds and flu.

• Cardiovascular Benefits: Mild blood-thinning effect similar to aspirin.

• Skin Conditions: Used topically for warts, acne, and psoriasis.

Drug-Drug Interactions:

• Anticoagulants & Antiplatelets (Warfarin, Aspirin, and Heparin) → These drugs increase the risks of bleeding due to salicin’s antiplatelet effect.

• NSAIDs (Ibuprofen, Naproxen) - May cause increased risks of Ulcers and GI irritation

• Methotrexate → Potential toxicity due to reduced clearance of the drug. Salicylic acid (from salicin metabolism) competes with methotrexate for renal excretion, leading to reduced clearance of methotrexate. Methotrexate accumulation cause issues such as liver toxicity and renal damage.

Contradiction: Bleeding disorder and GERD/PED

• Salicylic acid reduces platelet aggregation, slowing clot formation.

• In people with bleeding disorders, this can lead to excessive, uncontrolled bleeding.

• Salicylic acid reduces prostaglandin production, which lowers stomach mucus secretion.

• This weakens the protective stomach lining, making it more susceptible to acid damage.

Mechanism of action of Salicylic Acid:

Primarily affects inflammatory pathways, platelets, and pain receptors.

Mechanism of Action: Salicin is converted to Salicylic acid in the liver. Salicylic acid inhibits Cyclooxygenase Enzymes (COX-1 & COX-2). This reduces prostaglandin synthesis, leading to decreased pain, inflammation, and fever. It also has mild Antiplatelet activity, similar to aspirin, reducing clot formation.
Pharmacokinetics: Salicin is absorbed in the intestine, hydrolyzed by intestinal bacteria into saligenin (salicyl alcohol), and then oxidized in the liver to salicylic acid by alcohol and aldehyde dehydrogenases. Salicylic acid undergoes glucuronidation, sulfation, and glycine conjugation before being excreted primarily through the kidneys.

Side effects: Common:

• Stomach irritation

• Nausea

• Heartburn

• Mild dizziness

Serious (but rare):

• Gastrointestinal bleeding

• Tinnitus (ringing in ears, similar to aspirin overdose)

• Allergic reactions (rash, swelling, difficulty breathing)

• Liver or kidney dysfunction in high doses

Reyes syndrome in children - chicken pox

How is it isolated: Salicin can be isolated from willow bark by hot water or ethanol extraction, followed by filtration, concentration, and crystallisation to obtain the purified compound.

Salicin is a natural precursor to salicylic acid, which is the active metabolite of aspirin (acetylsalicylic acid). Aspirin, a synthetic derivative, is more potent because it irreversibly inhibits COX enzymes, whereas salicylic acid (from salicin) reversibly inhibits COX enzymes, making aspirin more effective as an anti-inflammatory and blood thinner.

Samples #35.1/43, #35.2/43, #36/43 from left to right