Strophiofimbrins A and B: Two Rearranged Norditerpenoids with Novel Tricyclic Carbon Skeletons from Strophioblachia fimbricalyx.

Two rearranged norditerpenoids with novel tricyclic carbon skeletons, strophiofimbrin A (1) and strophiofimbrin B (2), were isolated from Strophioblachia fimbricalyx. Their structures were established by 1D/2D NMR spectroscopy, HRESIMS, quantum chemistry calculations, and X-ray diffraction analyses. 1 and 2 represented the first examples of diterpenoids with unprecedented 5/6/7-fused ring systems. In the proposed biosynthetic pathway, they were suspected to derive from cleistanthane norditerpenoids via ring opening, expansion, cyclization, and rearrangement based on the existence of phenanthrenone and cleistanthane diterpenoids from Strophioblachia and Trigonostemon, two closely related genera of the Euphorbiaceae family. Furthermore, compounds 1 and 2 exhibited significant proliferation inhibition and obvious neuroprotective effects.

Increased epoxyeicosatrienoic acids may be part of a protective mechanism in human ulcerative colitis, with increased CYP2J2 and reduced soluble epoxide hydrolase expression.

BACKGROUND: Previous preclinical evidence has suggested that the elevation of epoxyeicosatrienoic acids (EETs) derived from the cytochrome P450 (CYP) epoxygenases-dependent metabolism of arachidonic acid has important anti-inflammatory effects. However, the levels of EETs and their synthetic and metabolic enzymes in human ulcerative colitis has not been evaluated. METHOD: To evaluate EETs and the expression of relevant CYP isoforms and the metabolizing enzyme, soluble epoxide hydrolase (sEH), tissue biopsies were collected from 16 pairs of ulcerative colitis patients' tissues and matched with adjacent non-inflamed tissues. EETs were extracted from tissue homogenates and analyzed by liquid chromatography coupled with tandem mass spectrometry. RESULTS: The concentration of EETs was higher in ulcerative colitis tissues compared with matched adjacent non-inflamed tissues (1.91 ±â€¯0.98 ng/mg vs. 0.96 ±â€¯0.77 ng/mg, mean ±â€¯SD, P < 0.01). As shown by immunohistochemistry, sEH was present in the cytoplasm and intestinal mucosa and showed a decline in ulcerative colitis tissues compared with matched adjacent non-inflamed tissues. Western blot analyses showed reduced sEH expression in ulcerative colitis tissues compared with matched adjacent non-inflamed tissues, whereas CYP2J2 increased in ulcerative colitis tissues (P < 0.05). However, there was no statistically significant difference observed in CYP2C8 and CYP2C9 protein expression between them (P > 0.05). CONCLUSION: Our data suggest that the increase in EET levels may be part of a protective mechanism in ulcerative colitis. Furthermore, the concentration of EETs could be a key factor for drug therapy for ulcerative colitis.