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 micromol/ear) as well as in the test of subchronic inflammation induced by repeated application of TPA (57% inhibition, 7x1 micromol/ear). Moreover, while it reduced the expression of both COX-2 (65% inhibition at 50 microM) and iNOS (80% inhibition at 50 microM), 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 micromol/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.
Aquila
Silvia
S
Departament de Farmacología, Facultat de Farmàcia, Universitat de València, Spain.
Rojano
Benjamin
B
Recio
María C
MC
Giner
Rosa M
RM
Schinella
Guillermo R
GR
Debenedetti
Silvia L
SL
Saez
Jairo
J
Ríos
José Luis
JL
D000818:Animals; D029061:Annonaceae / Q000737:chemistry; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha; C521026:berenjenol; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D013755:Tetradecanoylphorbol Acetate