Elsevier

Phytomedicine

Volume 13, Issue 6, 12 June 2006, Pages 442-445
Phytomedicine

Vascular effects of 7-epiclusianone, a prenylated benzophenone from Rheedia gardneriana, on the rat aorta

https://doi.org/10.1016/j.phymed.2005.01.014Get rights and content

Abstract

The vascular effects of 7-epiclusianone on the rat aorta were investigated. In the rat aortic rings with functional endothelia, 7-epiclusianone up to 10 μM induced a concentration-dependent vasodilatation of the sustained contractions induced by phenylephrine (0.3 μM). At concentrations higher than 10 μM, 7-epiclusianone induced a concentration-dependent contraction in the aortic rings. The vasodilator effect of 7-epiclusianone was drastically decreased with L-NAME (100 μM) as well as in endothelium-denuded aortic rings. Moreover, indomethacin (10 μM) induced a significant shift to the left in the vasodilator but did not modify the vasoconstrictor effect of 7-epiclusianone. In arteries without pre-contraction, 7-epiclusianone (3–100 μM) induced concentration-dependent contraction only in endothelium-intact and in the presence of L-NAME (100 μM). This effect was inhibited by indomethacin (10 μM) and ZM230487 (1 μM), selective inhibitors of cyclooxygenase and of 5-lipoxygenase, respectively. We can conclude that at low concentrations 7-epiclusianone induces an endothelium-dependent vasodilator effect in rat aortic rings. At higher concentrations and in conditions where NO synthase was inhibited, 7-epiclusianone induces a vasocontractile effect. Nitric oxide seems to participate in the vasodilatation, while endothelial cyclooxygenase- and 5-lipoxygenase-derived products play a role in the vasoconstrictor effect.

Introduction

Polyprenylated benzophenones have been described as antioxidant, free radical scavengers; as antiulcer agents; as inhibitors of iNOS and COX-2 expression in colon carcinoma; and as apoptosis inducers (Pan et al., 2001; Tanaka et al., 2000; Yamaguchi et al., 2000a, Yamaguchi et al., 2000b), demonstrating a broad spectrum of biological activities for this class of compounds. The association of antioxidant and anti-inflammatory effect with vasodilatation would be relevant for the treatment of cardiovascular illnesses such as atherosclerosis and ischemia.

7-epiclusianone (Fig. 1) is a prenylated benzophenone isolated as the main constituent from Rheedia gardneriana Miers ex Planch & Triana (Santos et al., 1998). The biological activities of this substance remain poorly investigated. There is only one previous report demonstrating in vitro activity of 7-epiclusianone against trypomastigotes of Trypanosoma cruzi (Alves et al., 1999). In the present work, we began the investigation of the effects of 7-epiclusianone on the vascular system.

Section snippets

Experimental procedure

Animal experiments were performed according to the recommendations of the Brazilian Council for Animal Care and to the directives of the Ethics Committee of the Universidade Federal de Minas Gerais. Male Wistar rats (200–250 g each) were killed by cervical dislocation and exsanguinated. The aortic rings were mounted and maintained in Krebs-Henseleit solution of the following composition (mM): NaCl 110.8, KCl 5.9, NaHCO3 25.0, MgSO4 1.07, CaCl2 2.49, NaH2PO4 2.33 and glucose 11.51, as described

Results and discussion

In endothelium-intact aortic rings, 7-epiclusianone induced concentration-dependent relaxation with a maximal effect (Emax) of 61.7±3.3% and an IC50 value of 8.1±1.5 μM (Fig. 2) in rat aortic rings pre-contracted with phenylephrine (0.3 μM). This vasodilator effect was dramatically reduced (Emax=25.7±7.9%) in endothelium-denuded arteries (Fig. 2A). Acetylcholine, a well-known endothelium-dependent vasodilator, also induced a concentration-dependent vasodilator effect with an Emax of 70.6±6.2% and

Acknowledgements

To the National Research Council (CNPq; Brazil) for research fellowships (A.J.C., V.S.L., M.H.S., T.J.N., S.F.C.) and Research foundation from Minas Gerais (FAPEMIG; Brazil) for financial support.

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