Division of Life Science and Center for Chinese Medicine, The Hong Kong University of Science and Technology, Hong Kong, China.
PLoS One. 2012;7(12):e51670. doi: 10.1371/journal.pone.0051670. Epub 2012 Dec 21.
Fo Shou San (FSS) is an ancient herbal decoction comprised of Chuanxiong Rhizoma (CR; Chuanxiong) and Angelicae Sinensis Radix (ASR; Danggui) in a ratio of 2:3. Previous studies indicate that FSS promotes blood circulation and dissipates blood stasis, thus which is being used widely to treat vascular diseases. Here, we aim to determine the cellular mechanism for the vascular benefit of FSS. The treatment of FSS reversed homocysteine-induced impairment of acetylcholine (ACh)-evoked endothelium-dependent relaxation in aortic rings, isolated from rats. Like radical oxygen species (ROS) scavenger tempol, FSS attenuated homocysteine-stimulated ROS generation in cultured human umbilical vein endothelial cells (HUVECs), and it also stimulated the production of nitric oxide (NO) as measured by fluorescence dye and biochemical assay. In addition, the phosphorylation levels of both Akt kinase and endothelial NO synthases (eNOS) were markedly increased by FSS treatment, which was abolished by an Akt inhibitor triciribine. Likewise, triciribine reversed FSS-induced NO production in HUVECs. Finally, FSS elevated intracellular Ca(2+) levels in HUVECs, and the Ca(2+) chelator BAPTA-AM inhibited the FSS-stimulated eNOS phosphorylation. The present results show that this ancient herbal decoction benefits endothelial function through increased activity of Akt kinase and eNOS; this effect is causally via a rise of intracellular Ca(2+) and a reduction of ROS.
佛手散(FSS)是一种古老的草药方剂,由川芎(CR;川芎)和当归(ASR;当归)按 2:3 的比例组成。先前的研究表明,FSS 能促进血液循环,消散血瘀,因此被广泛用于治疗血管疾病。在这里,我们旨在确定 FSS 对血管有益的细胞机制。FSS 的治疗逆转了同型半胱氨酸诱导的大鼠主动脉环中乙酰胆碱(ACh)诱发的内皮依赖性松弛受损。像自由基清除剂特布他林(tempol)一样,FSS 减弱了培养的人脐静脉内皮细胞(HUVEC)中同型半胱氨酸刺激的 ROS 生成,并且还如荧光染料和生化测定所测量的那样刺激了一氧化氮(NO)的产生。此外,FSS 处理明显增加了 Akt 激酶和内皮型一氧化氮合酶(eNOS)的磷酸化水平,该作用被 Akt 抑制剂曲昔派特(triciribine)所消除。同样,曲昔派特也逆转了 FSS 诱导的 HUVEC 中 NO 的产生。最后,FSS 增加了 HUVEC 中的细胞内 Ca(2+)水平,而 Ca(2+)螯合剂 BAPTA-AM 抑制了 FSS 刺激的 eNOS 磷酸化。这些结果表明,这种古老的草药方剂通过增加 Akt 激酶和 eNOS 的活性来有益于内皮功能;这种作用是通过细胞内 Ca(2+)的升高和 ROS 的减少来引起的。