Murad Research Institute for Modernized Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, PR China.
Vascul Pharmacol. 2010 Sep-Oct;53(3-4):169-76. doi: 10.1016/j.vph.2010.07.001. Epub 2010 Jul 17.
The goal of this study was to investigate the mechanism underlaying the vasodilatory effect of paeonol, a major active element from the root bark of Chinese herbs Paeonia suffruticosa Andr. and Cynanchum paniculatum (Bunge) Kitagawa. Paeonol relaxed isolated rat aorta rings by 95.6% while the 10(-6) M forskolin-induced vasodilatation used as 100%. The EC(50) of vasodilatation by paeonol is 2.9x10(-4) M. Although paeonol exerted endothelium-independent relaxation, L-NAME treatment inhibited paeonol-induced vasodilation of endothelium intact rings, while indomethacin did not. Both L-NAME and ODQ did not affect paeonol relaxation in the rings without endothelium. In addition, paeonol markedly elevated NO generation in cultured endothelial cells. Pre-treatment of propranolol, glibenclamide, TEA and BaCl(2) did not affect paeonol relaxation of endothelium removed rings. On the other hand, pre-treated of rings (without endothelium) with paeonol markedly blocked vasoconstriction induced by AngII, PGF(2alpha), 5-HT, dopamine, vasopressin, endothelin-1 and PE. The paeonol incubation also significantly attenuated KCl-induced contraction which mainly depended on Ca(2+) influx. In Ca(2+)-free medium (containing 10(-4) M of EGTA and 60 mM of KCl), paeonol suppressed the contraction curve of CaCl(2). In addition, paeonol also inhibited contraction by PE in Ca(2+) free solution (containing 10(-4) M of EGTA) which mainly relied on intracellular Ca(2+) release. Whole-cell patch-clamp experiment showed that paeonol shifted the I-V curve and the peak value of calcium currents was significantly inhibited. In conclusion, our study suggested that voltage-dependent and receptor-operated Ca(2+) channel, as well as intracellular Ca(2+) release were all inhibited by paeonol. An intracellular Ca(2+) regulatory mechanism may be responsible to potent vasodilatory effect of paeonol.
本研究的目的是探讨丹皮酚（牡丹皮和徐长卿的主要活性成分）舒张血管的作用机制。丹皮酚使分离的大鼠主动脉环舒张 95.6%，而 10(-6)M 的 forskolin 诱导的血管舒张作用为 100%。丹皮酚的血管舒张 EC(50)为 2.9x10(-4)M。尽管丹皮酚发挥了非内皮依赖性的舒张作用，但 L-NAME 处理抑制了内皮完整环中丹皮酚诱导的血管舒张，而吲哚美辛则没有。L-NAME 和 ODQ 均不影响无内皮的环中丹皮酚的舒张作用。此外，丹皮酚显著增加培养的内皮细胞中一氧化氮的产生。普萘洛尔、格列本脲、TEA 和 BaCl(2) 的预处理不影响内皮去除环中丹皮酚的舒张作用。另一方面，丹皮酚预处理（无内皮）的环明显阻断了 AngII、PGF(2alpha)、5-HT、多巴胺、血管加压素、内皮素-1 和 PE 诱导的血管收缩。丹皮酚孵育还显著减轻了 KCl 诱导的收缩，该收缩主要依赖于 Ca(2+)内流。在不含 Ca(2+)的培养基（含有 10(-4)M 的 EGTA 和 60mM 的 KCl）中，丹皮酚抑制了 CaCl(2)引起的收缩曲线。此外，丹皮酚还抑制了在不含 Ca(2+)溶液（含有 10(-4)M 的 EGTA）中由 PE 引起的收缩，该收缩主要依赖于细胞内 Ca(2+)释放。全细胞膜片钳实验表明，丹皮酚使 I-V 曲线移位，钙电流峰值明显受到抑制。综上所述，本研究表明，电压依赖性和受体操纵性 Ca(2+)通道以及细胞内 Ca(2+)释放均被丹皮酚抑制。细胞内 Ca(2+)调节机制可能是丹皮酚强效舒张血管作用的原因。
