Anti-Inflammatory Activity of Berenjenol and Related Compounds

Abstract

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 μmol/ear) as well as in the test of subchronic inflammation induced by repeated application of TPA (57 % inhibition, 7 × 1 μmol/ear). Moreover, while it reduced the expression of both COX-2 (65 % inhibition at 50 μM) and iNOS (80 % inhibition at 50 μM), it was not active against TNF-α and IL-1β 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 μmol/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.

Abbreviations

COX:cyclooxygenase

DMSO:dimethyl sulfoxide

FBS:fetal bovine serum

IL-1β:interleukin-1β

LPS:lipopolysaccharide

MTT:3-(4,5-dimethylthiazolyl)-2,5-diphenyl-tetrazolium bromide

NOS:nitric oxide synthase

PBS:phosphate-buffered saline

PKC:protein kinase C

TNF-α:tumor necrosis factor-α

TPA:12-O-tetradecanoylphorbol 13-acetate

Key words

Oxandra cf. xylopioides - Annonaceae - berenjenol - anti-inflammatory activity - cyclooxygenase - nitric oxide synthase

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