Inhibition of Acute and Chronic Inflammatory Responses by the Hydroxybenzoquinonic Derivative Rapanone

Abstract

Rapanone (2,5-dihydroxy-3-tridecyl-1,4-benzoquinone), a natural compound isolated from Myrsine guianensis growing in the Andean highlands of Colombia, was studied in different in vitro and in vivo models as a potential antioxidant and anti-inflammatory drug. Rapanone showed a mild anti-lipoperoxidative profile in rat liver microsomes and inhibited potently degranulation (IC₅₀ of 9.8 μM) and superoxide chemiluminescence (IC₅₀ of 3.0 μM) in human neutrophils. In addition, rapanone is a selective and potent human synovial PLA₂ inhibitor (IC₅₀ of 2.6 μM). In vivo experiments using the carrageenan paw oedema and the zymosan air pouch model in mice as well as the adjuvant arthritis model in rats have proved that rapanone is very efficient in controlling the inflammatory process by different administration routes.

Abbreviations

AA:arachidonic acid

COX-1:cyclo-oxygenase-1

COX-2:cyclo-oxygenase-2

cPLA₂:cytosolic phospholipase A₂

IL-1β:interleukin-1beta

5-LO:5-lipoxygenase

LTB₄:leukotriene B₄

MTT:3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

PGE₂:prostaglandin E₂

PLA₂:phospholipase A₂

sPLA₂:secretory phospholipase A₂

TPA:12-O-tetradecanoylphorbol-13-acetate

Key words

Myrsine guianensis - Myrsinaceae - rapanone - anti-inflammatory activity - phospholipase A₂ inhibition - elastase degranulation - interleukin-1β production - mouse air pouch - adjuvant arthritis

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