Bitter but beneficial: salicylic acid and willow bark

After the last half-marathon I ran two weeks ago my longer runs have been hampered a bit by a nagging inflammation in my right lower hip muscle (piriformis strain: it’s a pain in the butt).  I was reflecting on this mild misfortune this weekend as I was reaching the home stretch of a very pretty 12-miler near the water, which went right past a clump of willows in early flower.  (Salix lasiolepsis…I think.  Salix laevigata is also native here, but the loose open buds looked more like lasiolepsis).  This provided an ample reminder of the general awesomeness of willow bark’s key pharmaceutical component, salicylic acid, and its more famous derivative, acetylsalicylic acid.

Willows by the water: a stand of flowering Salix.

Willow flowers just past the fuzzy pussy-willow stage. These look right for S. lasiolepsis; S. laevigata flowers stay more compact and fuzzy.

Good for a whole range of what ails you:

One of the more well-publicized botanical myths is that aspirin comes from willow bark.  This is only a short hop from the truth.  The actual anti-inflammatory produced metabolically by willow is salicylic acid–depending on the species and time of year, willow bark contains between 0.08 – 12.6% salicin, the metabolic precursor of salicylic acid.  Salicylic acid (historically purified in large quantities by boiling the bark of white willow, Salix alba) is readily acetylated into acetylsalicylic acid, trademarked as Aspirin.  You might have made acetylsalicylic acid back in chemistry class, or you leave aspirin tablets somewhere damp, you might notice a vinegary smell as they hydrolyze back to salicylic acid and acetic acid. Curiously, while Bayer still holds the trademark on “Aspirin”, “aspirin” is generic.  A/aspirin (hmm…not sure what the trademark rule is on capitalization at the start of a sentence) is part of the NSAID group of anti-inflammatory drugs–useful at reducing fever and throbbing pain.   Aspirin also exerts a potent anticoagulant effect by inhibiting the platelet aggregant thromboxane, so many people take it to reduce the risk of stroke or blood clots following surgery.

Salicin and salicylic acid, found in willow bark, and acetylsalicylic acid, better known as aspirin.

Salicyclic acid is also anti-inflammatory but is probably more recognized for its antibiotic effects; it’s one of the most common topical treatments for the bacteria that cause acne.  This handy dermatological property is of course just a human co-option of the plant’s own defense system: salicylic acid is produced by plants in response to stress, and reduce their vulnerability to bacterial infection.

It’s not all good news though…

The reason we don’t take salicylic acid orally as a pain killer is partly because the pharmacokinetics are a little different from aspirin, but mostly because salicylic acid is very rough on the stomach.  Acetylsalicylic acid is less irritating (for reasons I have been hard-pressed to discern–it’s a weaker acid, but at stomach acid pH that shouldn’t make a difference), but it can still cause ulcers and stomach bleeding if taken in too high an amount or with other NSAIDs.  What’s more, the conjugate base of salicylic acid, salicylate, is damaging to the hair cells of the inner ear in some people (salicylate sensitivity).  Chronic aspirin consumption can cause tinnitus when the acetylsalicylic acid hydrolyzes back to salicylic acid in the bloodstream.

Extra nitty gritty: this bitter pill to swallow has a pleasant aftertaste

So. Pretty versatile, right?  A quick hunt through the scientific literature for salicylic acid entries yields a complex mixture of rheumatology, dermatology, cardiology, botany, auditory and gustatory references.

Wait, gustatory…?  Yes.  Because as you know if you’ve ever had the misfortune of having to down an aspirin without a glass of water, salicylic acid and acetylsalicylic acid taste just awful–they’re the very definition of bitter.  This was, in fact, a significant hitch in marketing acetylsalicylic acid early in its commercial development, and pharmacologists tried out a range of less effective and even toxic variants to try to make it more palatable before resigning themselves to just mixing it into a sugary syrup or coating the pills.

Curiously, the bitterness of salicylic acid and its derivatives has become an independent asset to science, because they’re the perfect compounds to study the physiology and chemistry underlying bitter taste detection.  Salicin (basically salicylic acid with a glucose ether instead of a carboxylic acid) was recently used to study the crystal structure of the “bitterness” taste receptor hTAS2R16.

Why aspirin tastes so bad: two proposed models for the interaction of salicin (blue) with key amino acids (green) in the bitterness taste receptor hTAS2R16. From Sakurai et al., J. Biol Chem 2010.

So if you find yourself near fresh water in the next couple weeks, enjoy the budding willows, but don’t take a bite out of the bark.

 

Advertisements

5 thoughts on “Bitter but beneficial: salicylic acid and willow bark

  1. Pingback: Steel magnolias: using magnolol to combat arthritis | A bouquet from Mendel

  2. I have an alllergy to acdytsalicylicy acid.. should I try a compound called alleviate which contains salicin for knee pain?

    • Hi Mary! I’m a PhD and not an MD, so double check with a doctor, but I would suggest avoiding salicin too. There’s enough similarity between the two structures that the part of acetylsalicylic acid that aggravates your immune system could well be shared with salicin. There are lots of other NSAID-type pain relievers without any salicylates (like ibuprofen/Advil, acetaminophen/Tylenol, naproxen/Alleve), so why risk it?

  3. “Acetylsalicylic acid is less irritating (for reasons I have been hard-pressed to discern–it’s a weaker acid, but at stomach acid pH that shouldn’t make a difference)”
    Maybe I can help — the reason aspirin irritates the stomach is not because of its acidity inside the stomach itself, but because some of it crosses through the mucus barrier and into the cells lining the stomach. That’s where it does its damage. So I would expect salicylic acid to do more damage. I’d also imagine that without the acetyl group, salicylic acid would cross the barrier more easily, so more would get in to do damage. (I don’t know if this is what happens; it’s an educated guess.)

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s