Diterpenoids with Potent Anti-Psoriasis Activity from Euphorbia helioscopia L.

Psoriasis, an immune-mediated inflammatory skin disorder, seriously affects the quality of life of nearly four percent of the world population. <i>Euphorbia helioscopia</i> L. is the monarch constituent of Chinese ZeQi powder preparation for psoriasis, so it is necessary to illustrate its active ingredients. Thus, twenty-three diterpenoids, including seven new ones, were isolated from the whole herb of <i>E. helioscopia</i> L. Compounds <b>1</b> and <b>2</b>, each featuring a 2,3-dicarboxylic functionality, are the first examples in the <i>ent</i>-2,3-<i>sceo</i>-atisane or the <i>ent</i>-2,3-<i>sceo</i>-abietane family. Extensive spectroscopic analysis (1D, 2D NMR, and HRMS data) and computational methods were used to confirm their structures and absolute configurations. According to the previous study and NMR data from the jatropha diterpenes obtained in this study, some efficient ¹H NMR spectroscopic rules for assigning the relative configurations of 3<i>α</i>-benzyloxy-jatroph-11<i>E</i>-ene and 7,8-<i>seco</i>-3<i>α</i>-benzyloxy-jatropha-11<i>E</i>-ene were summarized. Moreover, the hyperproliferation of T cells and keratinocytes is considered a key pathophysiology of psoriasis. Anti-proliferative activities against induced T/B lymphocytes and HaCaT cells were tested, and IC₅₀ values of some compounds ranged from 6.7 to 31.5 μM. Compounds <b>7</b> and <b>11</b> reduced the secretions of IFN-<i>γ</i> and IL-2 significantly. Further immunofluorescence experiments and a docking study with NF-<i>κ</i>B P65 showed that compound <b>13</b> interfered with the proliferation of HaCaT cells by inhibiting the NF-<i>κ</i>B P65 phosphorylation at the protein level.