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The effect of Tokishakuyakusan, a Chinese herbal medicine, was examined, in vivo, in women with luteal insufficiency and in women with normal menstrual cycles. Luteal insufficiency was determined by daily measurement of basal body temperature and plasma progesterone levels. Tokishakuyakusan improved luteal insufficiency. Furthermore, the effects of Tokishakuyakusan on prolactin, gonadotropins, steroids, angiotensin II, ANP and renin levels in the blood of women with normal menstrual cycles were studied, as were the medicine's effects on estrogens, pregnenediol and LH in the urine of the same women. Tokishakuyakusan had no adverse effect on hormonal levels in either blood or urine. Furthermore, no clinical side effects were detected. These results suggest that Tokishakuyakusan improves luteal insufficiency in women but does not affect the hormonal levels of women with normal menstrual cycles.

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 μM). 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.

Tanshinone IIA extracted from Danshen, a popular medicinal herb used in traditional Chinese medicine, exhibits cardio-protective effects. However, the mechanism of its cardioprotective effect is not well established. The aims of this study were to examine whether tanshinone IIA may alter angiotensin II (Ang II)-induced cell proliferation and to identify the putative underlying signaling pathways in rat cardiac fibroblasts. Cultured rat cardiac fibroblasts were pre-treated with tanshinone IIA and stimulated with Ang II, cell proliferation and endothelin-1 (ET-1) expression were examined. The effect of tanshinone IIA on Ang II-induced reactive oxygen species (ROS) formation, and extracellular signal-regulated kinase (ERK) phosphorylation were also examined. In addition, the effect of tanshinone IIA on nitric oxide (NO) production, and endothelial nitric oxide synthase (eNOS) phosphorylation were tested to elucidate the intracellular mechanism. The increased cell proliferation and ET-1 expression by Ang II (100 nM) were partially inhibited by tanshinone IIA. Tanshinone IIA also inhibited Ang II-increased ROS formation, and ERK phosphorylation. In addition, tanshinone IIA was found to increase the NO generation, and eNOS phosphorylation. N^G-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NOS, and the short interfering RNA transfection for eNOS markedly attenuated the inhibitory effect of tanshinone IIA on Ang II-induced cell proliferation. The results suggest that tanshinone IIA prevents cardiac fibroblast proliferation by interfering with the generation of ROS and involves the activation of the eNOS-NO pathway.

Angiotensin II and its antagonists were used as permeant probes to investigate the mechanism of transdermal iontophoretic delivery of peptide/protein drugs and compare the effect of hydrophobic difference between the peptides drugs on the skin permeability. Transport of angiotensin II and its antagonists through excised rabbit pinna skin were enhanced with iontophoresis by monophase periodically pulsed current, amplituide=1mA, frequency=1000Hz and on/off ratio equals 50%. The delivery rate was proportional both to the current intensity and pulse duration of the stimulation. Results showed that the permeation rate of [Sar, Ile] Angiotensin II > [Sar,Ala]Angiotensin II > Angiotensin II. Iontophoretic mobility and hydrophobicity were the key factors dominating the transdermal iontophoretic delivery rate of angiotensin II and its antagonists.