Targeted isolation of guaiane-type sesquiterpenoids from Daphne retusa Hemsl. with anti-psoriasis activities using a combination of MassIVE and NPExtractor strategy.

The psoriasis is a prevalent chronic inflammatory skin disorder, in which the inflammatory reaction plays an essential role. The genus Daphne contains numerous secondary metabolites with anti-inflammatory activity, which makes it possible to isolate the compounds with anti-inflammatory activity targeted from Daphne Retusa Hemsl. Herein, daphusanes A-P (1-16), sixteen unprecedented guaiane-type sesquiterpenes, along with eighteen known analogues (17-34) were targeting isolated from D. Retusa via molecular networking. The structures of 1-16 were established through NMR spectroscopy analysis, NMR and ECD calculations and single-crystal X-ray diffraction. All the isolated compounds were tested for their anti-inflammatory activity of the compounds against RAW264.7. The preliminary structure-activity relationships of the sesquiterpenoids for the anti-inflammatory activity were summarized. Importantly, 5 showed significant anti-psoriasis activity in imiquimod-induced psoriasis murine model. The metabolomics and Western blot results showed that 5 achieved anti-psoriasis effects by affecting steroid hormone biosynthesis which then affect the RORγT signaling pathway.