Distribution of ingenol derivatives in Euphorbia plants and UV-dependent promotion of ingenol production in greenhouse-grown Euphorbia plants

• Contents of total ingenol derivatives of 50 Euphorbia plants. • Existence of ingenol derivatives in Jatropha , Acalypha , Codiaeum , and Excoecaria. • Euphorbia tithymaloides 'Nanus' might be a better source for ingenol production. • Better greenhouse covering material for the production of ingenol derivatives. Resource discovery for producing biologically active phytochemicals plays an important role in industrial crops area. Ingenol-3-angelate, one of the most concerned macrocyclic diterpenoids, has been approved for clinical treatment of actinic keratosis and industrially produced by a semi-synthesis approach using hydrolysis products of ingenol derivatives. Ingenol derivatives are considered exclusive among Euphorbia genus at a quite low level. In search for high-ingenol plant species from the Euphorbiaceae family, ultra-high performance liquid chromatography coupled with mass spectrometry (UHPLC-MS) was performed for the quantitative analysis of the free ingenol content in the hydrolyzed methanol extract of 61 selected plant species, including 50 Euphorbia plants, 9 plants from other Euphorbiaceae genera, and 2 Phyllanthaceae plants. The ingenol derivatives in E. milii and E. cotinifolia which contained high level of ingenol esters were further identified by UHPLC-MS. Amounts of ingenol diterpenes varied among the samples. The highest free ingenol content (527.82 ± 38.19 μmol/kg of dry herb weight) was found in a variation, E. tithymaloides 'Nanus', followed by E. tithymaloides (402.81 ± 28.89 μmol/kg), E. milii (391.30 ± 43.51 μmol/kg), E. ammak (379.75 ± 34.68 μmol/kg), and E. trigona (357.07 ± 34.29 μmol/kg). The results revealed the trace amount of ingenol derivatives in some Jatropha, Acalypha, Codiaeum , and Excoecaria plants for the first time and confirmed the higher level of ingenol esters in some Euphorbia plants cultivated under polycarbonate panel with higher UV transmission than those grown under double layer glass. The secondary metabolites varied distinctively among different Euphorbia sections. This work suggested more applicable sources for ingenol production and better greenhouse covering material for Euphorbia plants cultivation in consideration of ingenol derivatives.