Institute of Traditional Chinese Medicine Research, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
J Cardiovasc Pharmacol. 2011 Mar;57(3):340-7. doi: 10.1097/FJC.0b013e31820a0da1.
Salvia miltiorrhiza (Danshen) has been widely used in China and other Asian countries for treating various cardiovascular diseases resulting from its ability to improve coronary microcirculation and increase coronary blood flow. Tanshinone IIA (Tan IIA), the major active lipophilic ingredient responsible for the beneficial actions of Salvia miltiorrhiza, has been shown to induce vasodilation in coronary arteries. Because our recent study identified Tan IIA as a new member of the phytoestrogens, we hypothesized that its action might be mediated by estrogen receptor (ER) in vascular endothelial cells. The aim of the present study was to assess whether cardiovascular protection exerted by Tan IIA is mediated by the ER signal pathway and whether the genomic or nongenomic action of ER is involved within arteries and vascular endothelial cells. The effect of Tan IIA on blood vessels was investigated by vascular ring assay using endothelium-intact and endothelium-denuded rat aortas. Similar to estrogen, Tan IIA caused an nitric oxide- and endothelium-dependent relaxation, which was blocked by ER antagonist ICI 182,780. Primary cardiac microvascular endothelial cells were used as a model to study the cellular and molecular mechanisms of Tan IIA-induced vasorelaxation. We demonstrate that Tan IIA is capable of activating the estrogen receptor signal pathway, leading to increased endothelial nitric oxide synthase gene expression, nitric oxide production, ERK1/2 phosphorylation, and Ca mobilization. Collectively, these effects contribute to Tan IIA's vasodilative activity effects of y ER antagonist Cnt of cardiovascular diseases. Our findings support a continued effort in discovering and developing novel phytoestrogens as an alternative hormone replacement therapy for safer and more effective treatment of cardiovascular diseases.
丹参在中国和其他亚洲国家被广泛用于治疗各种心血管疾病，因为它能够改善冠状动脉微循环并增加冠状动脉血流量。丹参酮 IIA（Tan IIA）是丹参中主要的亲脂性活性成分，负责丹参的有益作用，已被证明可引起冠状动脉扩张。因为我们最近的研究将 Tan IIA 鉴定为植物雌激素的新成员，所以我们假设它的作用可能是通过血管内皮细胞中的雌激素受体（ER）介导的。本研究的目的是评估 Tan IIA 发挥心血管保护作用是否通过 ER 信号通路介导，以及 ER 的基因组或非基因组作用是否涉及动脉和血管内皮细胞。使用完整内皮和去内皮的大鼠主动脉血管环测定法研究 Tan IIA 对血管的作用。与雌激素类似，Tan IIA 引起一氧化氮和内皮依赖性松弛，该松弛被 ER 拮抗剂 ICI 182,780 阻断。原代心脏微血管内皮细胞被用作研究 Tan IIA 诱导血管松弛的细胞和分子机制的模型。我们证明 Tan IIA 能够激活雌激素受体信号通路，导致内皮型一氧化氮合酶基因表达、一氧化氮产生、ERK1/2 磷酸化和 Ca 动员增加。总之，这些作用有助于 Tan IIA 的血管扩张活性，可能对心血管疾病的治疗具有重要意义。我们的发现支持继续努力发现和开发新型植物雌激素，作为更安全、更有效的替代激素替代疗法，用于治疗心血管疾病。
