Inhibitory effect of quecetin on the MMP-9 proteolytic activity.

SARAGUSTI A; ORTEGA G; CABRERA JL; CHIABRANDO GA

Montevideo, Uruguay.

Congreso; I Reunión Latinoamericana de Química Medicinal; 2007

LatQuiMed

Quercetin is one of the most commonly flound flavonoid in human diet with remarkable array of biochemical and pharmacological actions including anti-inflammatory, anti-oxidant, and anti-tumoral effects (1). Several invitro and invivo studies have been performed in order to elucidate the mechanisms underlying its biological activities. This natural compound has been demonstrated that affect the activity of many mammalian enzyme systems (2). Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that play an important role in the inflammatory process y remodelation of the extracellular matrix (ECM) (3). MMP-9 belongs to the gelatinase subgroup of the MMPs, and has been associated with the pathology of several inflammatory diseases, such as astheroclerosis, vascular diseases, ocular diseases, and increased risk of tumor invasion and metastasis (4). Therefore, inhibition of MMPs is one important area of research for the development of anti-inflammatory and anti-tumoral drugs (5). The objective of the present study was to investigate the inhibitory effect of quercetin on MMP-9 proteolytic activity. We evaluated the inhibitory effect of quercetin on pro-MMP-9 and active MMP-9 proteolytic activity by zymography assay. Conditioned cultured medium of J774 (J774-CCM) acrophage cell line was used as a source of pro-MMP-9 and active MMP-9 was obtained by incubation of J774-CCM with p-Aminophenylmercuric acetate (APMA) solution. We tested several concentration of quercetin (25, 50, 75, 100 y 200 uM) and two different conditions of incubation (in gel and in solution). Our results demonstrated that quercetin inhibits pro-MMP-9 and active MMP-9 activity in a dose dependent manner and could be a potential anti-inflammaty and anti-tumoral drug. 1.- Erlund I. Nutrition Res. 2004. 24: 851-874. 2.- Middleton E Jr. et al. Pharmacology Reviews 2000. 52: 673-751. 3.- Nagase H, Woessner JF.  J. Biol. Chem. 1999. 274: 21491-21494. 4.- Sternlich MD, Werb  Z. Annual Rev. Cell Dep. Biol. 2001. 17:463-516. 5.- Overall CM, Lopez-Otín C. Nature 2002. 2: 657-672.