Tetramethylpyrazine inhibits angiotensin II-increased NAD(P)H oxidase activity and subsequent proliferation in rat aortic smooth muscle cells.

Tetramethylpyrazine (TMP) is the major component extracted from the Chinese herb, Chuanxiong, which is widely used in China for the treatment of cardiovascular problems. The aims of this study were to examine whether TMP may alter angiotenisn II (Ang II)-induced proliferation and to identify the putative underlying signaling pathways in rat aortic smooth muscle cells. Cultured rat aortic smooth muscle cells were preincubated with TMP and then stimulated with Ang II, [3H]-thymidine incorporation and the ET-1 expression was examined. Ang II increased DNA synthesis which was inhibited by TMP (1-100 microM). TMP inhibited the Ang II-induced ET-1 mRNA levels and ET-1 secretion. TMP also inhibited Ang II-increased NAD(P)H oxidase activity, intracellular reactive oxygen species (ROS) levels, and the ERK phosphorylation. Furthermore, TMP and antioxidants such as Trolox and diphenylene iodonium decreased Ang II-induced ERK phosphorylation, and activator protein-1 reporter activity. In summary, we demonstrate for the first time that TMP inhibits Ang II-induced proliferation and ET-1, partially by interfering with the ERK pathway via attenuation of Ang II-increased NAD(P)H oxidase and ROS generation. Thus, this study delivers important new insight in the molecular pathways that may contribute to the proposed beneficial effects of TMP in cardiovascular disease.

Inhibition of cyclic strain-induced endothelin-1 secretion by baicalein in human umbilical vein endothelial cells.

Baicalein is a flavonoid extracted from the root of Scutellaria baicalensis Georgi, a medicinal plant traditionally used in Oriental medicine. Among its biological activities, baicalein has been reported to exhibit antioxidant effects. Endothelin-1 (ET-1) is a potent vasopressor synthesized by endothelial cells both in culture and in vivo. The aims of this study were to test the hypothesis that baicalein may alter strain-induced ET-1 secretion and to identify the putative underlying signaling pathways in endothelial cells. We show that baicalein inhibited strain-induced ET-1 secretion. Baicalein also inhibited strain-increased reactive oxygen species (ROS) formation and the extracellular signal-regulated kinases (ERK) phosphorylation. Using a reporter gene assay, baicalein and the antioxidant Trolox also attenuated the strain-stimulated activator protein-1 (AP-1) reporter activity. We conclude that baicalein inhibits strain-induced ET-1 gene expression, partially by interfering with the ERK pathway via attenuation of ROS formation. These results highlight the molecular pathways that may contribute to the beneficial effects of baicalein in the vascular system such as stroke prevention.