Vasorelaxant effect on rat isolated pulmonary artery and mechanism of action of rosewood extract (Dalbergia cochinchinensis Pierre)

Abstract

Rosewood (Dalbergia cochinchinensis Pierre) is a tree species endemic to Southeast Asia. Several phenolic compounds and flavonoids found in the leaves of rosewood may manifest many biological effects that are of interest in natural medicines. The preliminary study of rosewood leaf extract (RE) found that RE inhibited phosphodiesterase-5 (PDE5), which is highly expressed in the lung, providing vasorelaxation. This study sought to evaluate the vasorelaxant effect of RE on the pulmonary artery (PA) isolated from male Wistar rats using the organ bath technique. Then the mechanisms of action of RE were studied on PA. Lastly, this study aims to evaluate the acute toxicity of RE and prunasin, which is one of the chemical constituents in RE, on isolated vascular smooth muscle cells (VSMCs). The assessment of cell viability was conducted using a MTT assay. RE (0.001-1000µg/mL) relaxed the endothelium-intact PA (EC50=4.61µg/mL, Emax=93.39%), an effect that was reduced by endothelium removal of PA (Emax=44.40%, p<0.001). In the endothelium-intact PA, pre-incubation with NG-nitro-L-arginine methyl ester or apamin/charybdotoxin decreased RE-induced relaxation, but indomethacin had no effect in this situation. However, the endothelium-denuded PA, preincubation with 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one, iberiotoxin, 4-aminopyridine, glibenclamide or BaCl2 had no effect. As well, pretreatment of endothelium-denuded PA with RE (5 and 100µg/mL) did not modify SNP-induced relaxation and had no effect on extracellular Ca2+influx and intracellular Ca2+release. Isolated VSMCs incubated in RE for 1 h showed no cytotoxicity. In summary, PA relaxation induced by RE was endothelium-dependent and mainly involved the activation of endothelial nitric oxide release and endothelium-derived hyperpolarizing factor production without being toxic to smooth muscle cells.

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