Orallo Francisco, Camiña Mercedes, Alvarez Ezequiel, Basaran Hélène, Lugnier Claire
Departamento de Farmacología, Facultad de Farmacia, Universidad de Santiago de Compostela, Santiago de Compostela (La Coruña), Spain.
Planta Med. 2005 Feb;71(2):99-107. doi: 10.1055/s-2005-837774.
The potential vasorelaxant, antioxidant and cyclic nucleotide phosphodiesterase (PDE) inhibitory effects of the citrus-fruit flavonoids naringin and (+/-)-naringenin were comparatively studied for the first time in this work. (+/-)-Naringenin (1 microM - 0.3 mM) did not affect the contractile response induced by okadaic acid (OA, 1 microM). However, (+/-)-naringenin relaxed, in a concentration-dependent manner, the contractions elicited by phenylephrine (PHE, 1 microM) or by a high extracellular KCl concentration (60 mM) in intact rat aortic rings. Mechanical removal of endothelium and/or pretreatment of aorta rings with glibenclamide (GB, 10 microM) or tetraethylammonium (TEA, 2 mM) did not significantly modify the vasorelaxant effects of this flavanone. (+/-)-Naringenin (10 microM - 0.1 mM) did not alter the basal uptake of 4) Ca2+ but decreased the influx of 45Ca2+ induced by PHE and KCl in endothelium-containing and endothelium-denuded rat aorta. (+/-)-Naringenin (10 microM - 0.1 mM) was ineffective to scavenge superoxide radicals (O*2-) generated by the hypoxanthine (HX)-xanthine oxidase (XO) system and/or to inhibit XO activity. (+/-)-Naringenin (0.1 mM) significantly increased the production of cGMP and cAMP decreased by PHE (1 microM) and high KCl (60 mM) in cultured rat aortic myocytes. (+/-)-Naringenin preferentially inhibited calmodulin (CaM)-activated PDE1, PDE4 and PDE5 isolated from bovine aorta with IC50 values of about 45 microM, 60 microM and 68 microM, respectively. In contrast, the 7-rhamnoglucoside of (+/-)-naringenin, naringin (1 microM - 0.3 mM), was totally inactive in all experiments. These results indicate that the vasorelaxant effects of (+/-)-naringenin seem to be basically related to the inhibition of PDE1, PDE4 and PDE5 activities.
在本研究中，首次对柑橘类水果黄酮柚皮苷和（±）-柚皮素的潜在血管舒张、抗氧化及环核苷酸磷酸二酯酶（PDE）抑制作用进行了比较研究。（±）-柚皮素（1微摩尔至0.3毫摩尔）不影响冈田酸（OA，1微摩尔）诱导的收缩反应。然而，（±）-柚皮素以浓度依赖性方式舒张完整大鼠主动脉环中去氧肾上腺素（PHE，1微摩尔）或高细胞外氯化钾浓度（60毫摩尔）引发的收缩。机械去除内皮和/或用格列本脲（GB，10微摩尔）或四乙铵（TEA，2毫摩尔）预处理主动脉环，并未显著改变该黄烷酮的血管舒张作用。（±）-柚皮素（10微摩尔至0.1毫摩尔）不改变基础45Ca2+摄取，但减少了PHE和氯化钾在含内皮和去内皮大鼠主动脉中诱导的45Ca2+内流。（±）-柚皮素（10微摩尔至0.1毫摩尔）对清除次黄嘌呤（HX）-黄嘌呤氧化酶（XO）系统产生的超氧阴离子自由基（O*2-）和/或抑制XO活性无效。（±）-柚皮素（0.1毫摩尔）显著增加培养的大鼠主动脉肌细胞中由PHE（1微摩尔）和高钾（60毫摩尔）降低的cGMP和cAMP生成。（±）-柚皮素优先抑制从牛主动脉分离的钙调蛋白（CaM）激活的PDE1、PDE4和PDE5，IC50值分别约为45微摩尔、60微摩尔和68微摩尔。相比之下，（±）-柚皮素的7-鼠李糖苷柚皮苷（1微摩尔至0.3毫摩尔）在所有实验中完全无活性。这些结果表明，（±）-柚皮素的血管舒张作用似乎主要与抑制PDE1、PDE4和PDE5活性有关。
