Pseudoamaolides A-O, anti-inflammatory triterpene spiroketal lactones from seeds of Pseudolarix amabilis

Abstract

Fifteen new triterpenoids (1–15), along with twenty known ones (16–35), were isolated from Pseudolarix amabilis. The triterpenoid structures include multiple skeleton types, such as 2,3-seco-cycloartane, 3,4-seco-cycloartane, 3,4:9,10-diseco-cycloartane, and 3,4:8,9:9,10-triseco-cycloartane, as elucidated by extensive spectroscopy (1D NMR, 2D NMR, HRESIMS, and IR) and single-crystal X-ray diffraction. The anti-inflammatory activities of compounds 1–35 were evaluated. Compounds 3, 11, 16, 24, 25, and 26 suppressed the transcription of the NF-κB-dependent reporter gene in LPS-induced 293T/NF-κB-Luc cells with IC50 values of 0.12, 0.10, 0.30, 0.09, 0.49, and 0.35 μM, respectively. In addition, compound 16 showed anti-inflammatory activity against xylene-induced ear swelling in vivo with an inhibition rate of 44.7 % (30 mg/kg). Compound 16 significantly improved the disease activity index (DAI) of ulcerative colitis at a dose of 400 mg/kg in a dextran sodium sulfate (DSS)-induced mouse model of experimental ulcerative colitis (P < 0.01).