Anti-Inflammatory Activity of Berenjenol and Related Compounds

Berenjenol (1), isolated from Oxandra cf. xylopioides (Annonaceae), was tested on two different experimental models of inflammation. The compound showed anti-inflammatory activity in the test of acute mouse ear edema induced by TPA (54% inhibition, 1 mu mol/ear) as well as in the test Of subchronic inflammation induced by repeated application of TPA (57% inhibition, 7 x 1 mu mol/ear). Moreover, while it reduced the expression of both COX-2 (65% inhibition at 50 mu M) and iNOS (80% inhibition at 50 mu M), it was not active against TNF-alpha and IL-1 beta in murine macrophages (RAW 264.7) stimulated with LPS. Structural modification of 1 gave two derivatives, berenjenol acetate (2) and 3-oxo-berenjenol (3). Of these, the latter had a high degree of activity in the acute test (66% inhibition, 1.1 mu mol/ear), whereas the former showed no enhanced pharmacological properties. interestingly, the original compound exhibited higher activity than either of its derivatives in the subchronic model. We thus concluded that whereas 3-oxidation of 1 (compound 3), but not 3-acetylation (2). increases the activity in the acute model of inflammation, structural modification of 1 does not enhance the compound's effects in the subchronic model.