Ivy’s on My Mind

The three-leaf triads of poison ivy are common in North America except in cities and deserts.  Most people I know have had the rash.  Native remedies treated it topically with a plant that grew nearby:  jewelweed.  Modern workers have guessed that jewelweed’s secret was lawsone, a red dye that binds to proteins and is also found in the herbs for making henna.  But it turns out, lawsone is ineffective against ivy rash, in fact, jewelweed works only as well as soap. 

And that implicates the herb’s saponins, which are suds-forming steroid-like molecules with sugar groups attached.  They’re detergents.  And what saponins wash off are urushiols, which are allergenic sap oils found in each of poison ivy, poison oak and poison sumac.  This is like modern first aid for exposure to ivy:  washing that skin within 10-15 minutes. 

Why wash?  Because even air alone rapidly converts urushiols into reactive quinones, which affix themselves to certain skin proteins.  The newly modified proteins then trigger a delayed response by the skin’s network of immune cells.  The protein CD1a has now been identified as a key factor for this pathway in mice.  Another ivy study in mice found that the protein interleukin-33 (IL-33) facilitates calcium flow into neurons.  When investigators blocked either IL-33 or the neuron site, there was less inflammation and scratching.  So, drug chemists now have multiple biochemical targets for treatment of ivy rash.

Basically, an allergy-like response causes swelling, and swelling causes the itch.  The prior commercial therapies included antihistamines to quench immune responses and cortisone or analgesics to reduce the itch.  Some older products contain multivalent metal salts or oxides:  these are astringent substances that relieve itch presumably by shrinking skin tissue to normal size.  Examples are calamine lotion (zinc oxide and ferric oxide) and Burow’s solution (aluminum sulfate and calcium acetate).  Tannin-containing (and thus astringent) extracts such as witch hazel are also used on rash.  Beyond that, talc is used as a dry lubricant to reduce chafing. 

It would be better if we could prevent the symptoms.  Some reports indicate that oral dosing with urushiols may reduce our sensitivity to poison ivy.  Eating ivy oils sounds odd but deer do it.  And in fact, people eat urushiols in the form of mango fruit, actually mostly in its skin.  And cashews and ginkgo have related compounds.  [In an odd twist, it matters whether the eater’s first exposure is to ivy or to mangoes.]  

Our gastrointestinal tract doesn’t normally absorb substances as oily as these unless they can be saponified (broken down into soaps) by bile or get emulsified (with a soap-like additive).  Urushiols can be saponified because their relative acidity is in the same range as for lipids.  

An alternative strategy provides molecular cognates that block the immune response.  Thus, urushiol analog 5-methyl-3-n-pentadecylcatechol (5-Me-PDC) is a “tolerogen”:  it reduces sensitivity to ivy oil, yet is only a slight sensitizer to itself.  5-Me-PDC works both topically and by intravenous injection.  And it has relationships between sensitization and cross-reactivity. 

Herbal anti-ivy meds don’t yet leverage most of these insights; hopefully they will soon.  One option I’d like to see is masking the affected skin proteins with biofilms like bacteria do – except that we don’t how the microbes pull that off.

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Food for Thought:

V. Abrams Motz et al., “The effectiveness of jewelweed, Impatiens capensis, the related cultivar I. balsamina and the compound, lawsone in preventing post poison ivy exposure contact dermatitis,” Journal of Ethnopharmacology, 143(1):314-318 (2012).  ABSTRACT:  https://www.ncbi.nlm.nih.gov/pubmed/22766473

J.H. Kim et al., “CD1a on Langerhans cells controls inflammatory skin disease,” Nature Immunology (2016).  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5791155/pdf/nihms-800443.pdf

Monash University, “Immune breakthrough:  Unscratching poison ivy’s rash,” ScienceDaily (August 23, 2016).  http://www.sciencedaily.com/releases/2016/08/160823103242.htm

B. Liu et al., “IL-33/ST2 signaling excites sensory neurons and mediates itch response in a mouse model of poison ivy contact allergy,” Proceedings of the National Academy of Science of the U.S.A., 113(47):E7572-E7579 (Nov. 22, 2016). https://www.pnas.org/content/early/2016/11/04/1606608113/tab-article-info

K. Hershko, I. Weinberg and A. Ingber, “Exploring the mango-poison ivy connection: the riddle of discriminative plant dermatitis,” Contact Dermatitis, 52(1):3-5 (2005).  ABSTRACT:  https://www.ncbi.nlm.nih.gov/pubmed/15701120

I.S. Dunn et al., “Influence of chemical reactivity of urushiol-type haptens on sensitization and the induction of tolerance,” Cellular Immunology, 97(1):189-196 (1986).  ABSTRACT:  https://www.ncbi.nlm.nih.gov/pubmed/3742608

E.S. Watson et al., “Immunological studies of poisonous anacardiaceae: production of tolerance in guinea pigs using 3-n-pentadecylcatechol-“modified” autologous blood cells,” Journal of Pharmaceutical Sciences, 70(7):785-789 (1981). ABSTRACT:  https://www.ncbi.nlm.nih.gov/pubmed/6455512

J.-L. Stampf et al., “Induction of tolerance to poison ivy urushiol in the guinea pig by epicutaneous application of the structural analog 5-methyl-3-n-pentadecylcatechol,” Journal of Investigative Dermatology, 86(5):535-538 (1986).  ABSTRACT:  https://www.ncbi.nlm.nih.gov/pubmed/2943824