Croton tiglium oil is responsible for the intense inflammation and deep neocollagenesis in Hetter’s phenol-croton oil chemical peel
Description
Classically, Croton tiglium oil (CO) is mixed with phenol, water, and an emulsifying agent in Baker-Gordon’s or Hetter’s formulas of deep peels. There is controversy of specific roles of CO and phenol. Phenol was thought to be the main agent of the formula while CO acts as a penetration enhancer, until Hetter introduced the CO strength grading. CO activity could be related to its pro-inflammatory compounds. To better clarify the role of CO (Delasco, Council Bluffs, IA) in these formulas and identify the presence of pro-inflammatory compounds, we performed a chemical study using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and an in vivo domestic pig model experiment (2 males and 2 females, 4-5 months old, 30-35 kg). Phorbol esters are tetracyclic diterpenoids and are mainly produced by different species of Euphorbiaceae, like C. tiglium; these compounds are responsible for a pro-inflammatory activity. The intensity of inflammation depends on the position that the acyl groups linked to the tiglian nucleus. Phorbol esters present unusual structural features that undergo neutral loss of mono or diesters from different mechanisms of fragmentation, producing the ion m/z 311 related to the phorbol basic skeleton, and the transition m/z 311 → 293 that is normally related to the loss of a water molecule due the presence of hydroxyl groups in the phorbol structure. The LC-MS/MS analysis suggested the presence of phorbol structures in oil composition. The MRM monitoring data propose that structures of phorbol esters lost their acyl chains (529.27 → 311, 501.27 → 311, 473.23 → 311, respectively), and a molecule of water (311 → 293) (Fig1S). The identification of these compounds in this CO from Delasco confirmed that this vegetal matrix can be responsible for the pronounced inflammatory effect observed on skin after application of phenol-deep chemical peel formula containing croton oil.