Effects of Morellofavone from Garcinia dulcis on the Relaxation Response, Malondialdehyde Levels and Histology of Cisplatin-Treated Rat Aorta

Abstract

This study aimed to investigate an acute and protective effect of morelloflavone isolated from Garcinia dulcis on the relaxation and structural damage of thoracic aorta, and the oxidative status of cisplatintreated rat. Male Wistar rats were used and either cisplatin (7.5mg/kg) or vehicle (0.9% NaCl) was given intraperitoneally. An acute vasorelaxing effect of morelloflavone (10^-12 -10^-5 M) and its mechanism of action were tested in isolated thoracic aortic rings of control (intact endothelium and denuded) and of cisplatintreated rats on day 7 after the injection. To study the protective role of morelloflavone in cisplatin-treated rat, the animals were further divided into three groups, vehicle control, cisplatin- and cisplatin+morelloflavonetreated group. Morelloflavone (0.1, 1, 10 mg/kg, i.p.) were given twice, 1 day and 10 minutes before cisplatin injection. Seven days after the treatment, the contractile response of isolated thoracic aorta to 10^-10 -10-5 M phenylephrine (PE) and the vasorelaxing responses to 10^-12-10^-5 M acetylcholine (ACh) and sodium nitroprusside (SNP) were investigated along with plasma malondialdehyde (MDA) level determination and histological study. It was found that the vasorelaxing effect of morelloflavone cannot be observed in denuded control aortic rings and found less in cisplatin-treated groups than in the endothelium-intact control group. The contraction response to PE was significantly higher in cisplatin-treated group, whereas the relaxation response to ACh was found significantly lower when compared to control. Morelloflavone (1 mg/kg) treatment was able to improve the contractile responses to PE, and the vasorelaxing responses to ACh. Histological examination revealed that the tunica media proliferation in cisplatin group was restored by morelloflavone treatment. Plasma MDA level which increased significantly in cisplatin group was also suppressed by morelloflavone treatment. It is concluded that morelloflavone possesses free radical scavenging property in vivo and can act as a vasodilator in which its mechanism of action is likely to involve endothelium-dependent nitric oxide signaling pathway.