1. Discovery and biological evaluation of the novel naturally occurring diterpene pepluanone as antiinflammatory agent.
- Author
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Corea G, Fattorusso E, Lanzotti V, Di Meglio P, Maffia P, Grassia G, Ialenti A, and Ianaro A
- Subjects
- Acute Disease, Animals, Anti-Inflammatory Agents isolation & purification, Anti-Inflammatory Agents pharmacology, Carrageenan, Cell Line, Cyclooxygenase 2 biosynthesis, Dinoprostone antagonists & inhibitors, Dinoprostone biosynthesis, Diterpenes isolation & purification, Diterpenes pharmacology, Edema chemically induced, Edema drug therapy, Macrophages drug effects, Macrophages metabolism, Magnetic Resonance Spectroscopy, Male, Mice, NF-kappa B antagonists & inhibitors, NF-kappa B metabolism, Nitric Oxide antagonists & inhibitors, Nitric Oxide biosynthesis, Nitric Oxide Synthase Type II antagonists & inhibitors, Nitric Oxide Synthase Type II biosynthesis, RNA, Messenger biosynthesis, Rats, Rats, Wistar, Structure-Activity Relationship, Tumor Necrosis Factor-alpha antagonists & inhibitors, Tumor Necrosis Factor-alpha biosynthesis, Anti-Inflammatory Agents chemistry, Diterpenes chemistry, Euphorbia chemistry
- Abstract
From the whole plant of Euphorbia peplus L., a new diterpene based on a rare pepluane skeleton, named pepluanone (1), was isolated together with a known pepluane diterpene (2). The stereostructure of pepluanone was determined on the basis of an extensive NMR study, MS data, and chemical reaction. The ability of these compounds to act as antiinflammatory agents has been evaluated for the first time by in vivo tests on carrageenin-induced rat paw edema, an experimental model of acute inflammation. Comparison of the bioactivity of pepluanone and compound 2 in terms of chemical structure, evidenced the high efficiency of pepluanone and the absence of appreciable activity for compound 2, thus giving a first insight into the structure-activity relationship. Further in vitro experiments performed on pepluanone let us hypothesize that its activity could be explained in reducing the production of nitric oxide, prostaglandin E(2), and TNF-alpha by inhibiting the expression of inducible nitric oxide synthase, cyclooxygenase-2, and TNF-alpha mRNA through the down-regulation of NF-kappaB binding activity.
- Published
- 2005
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