Tetramethylpyrazine inhibits agiontensin II-induced nuclear factor-kappaB activation and bone morphogenetic protein-2 downregulation in rat vascular smooth muscle cells / 生理学报

Tetramethylpyrazine (TMP), an effective component of traditional Chinese medicine Chuanxiong, is commonly used to resolve embolism. Its possible therapeutic effect against atherosclerosis has received considerable attention recently. Angiotensin II (Ang II) is highly implicated in the proliferation of vascular smooth muscle cells (VSMCs), resulting in atherosclerosis. The mechanisms of TMP in the proliferation of VSMCs induced by Ang II remain to be defined. The present study was aimed to study the effect of TMP on Ang II-induced VSMC proliferation through detection of nuclear factor-kappaB (NF-kappaB) activity and bone morphogenetic protein-2 (BMP-2) expression. Primary cultured rat aortic smooth muscle cells were divided into the control group, Ang II group, Ang II + TMP group and TMP group. Cells in each group were harvested at different time points (15, 30 and 60 min for detection of NF-kappaB activity; 6, 12 and 24 h for measurement of BMP-2 expression). NF-kappaB activation was identified as nuclear staining by immunohistochemistry. BMP-2 expression was observed through Western blot, immunohistochemistry and in situ hybridization. The results showed that: (1) Ang II stimulated the activation of NF-kappaB. Translocation of NF-kappaB p65 subunit from cytoplasm to nucleus appeared as early as 15 min, peaked at 30 min (P<0.01) and declined after 1 h. (2) TMP inhibited Ang II-induced NF-kappaB activation (P<0.01). (3) Ang II increased BMP-2 expression at 6 h but declined it significantly at 12 and 24 h (P<0.01). (4) BMP-2 expression was also kept at high level at 6 h in Ang II + TMP group but maintained at the normal level at 12 and 24 h. (5) There was no significant difference in NF-kappaB activation and BMP-2 expression between the control group and TMP group. These results indicate that TMP inhibits Ang II-induced VSMC proliferation through repression of NF-kappaB activation and BMP-2 reduction, and BMP-2 expression is independent of the NF-kappaB pathway. In conclusion, TMP has therapeutic potential for the treatment of atherosclerosis.

Anticarcinogenic Effect of Red Ginseng on the Development of Liver Cancer Induced by Diethylnitrosamine in Rats

Anticarcinogenic effect of red ginseng (Panax ginseng C.A. Meyer cultivated in JiLin, China) on the development of liver cancer induced by diethylnitrosamine (DEN) in rats was studied, especially in preventive and curative groups. In the preventive group, the rats were given with DEN concomitantly with red ginseng fluid, and in the curative group, the rats were administered with red ginseng fluid after they developed liver cancer nodules induced by DEN. The result of the preventive group revealed that the developmental rate of liver cancer in the experimental group was 14.3%, while 100% in the control group, with the difference being statistically significant. DNA, RNA, glycogen, gamma-GT, SDH, and 5'-NT were maintained at relatively normal level in experimental group, and decreased or increased in the control group. The result of curative group showed that hepatoma nodules of the DEN-red ginseng group I were smaller than those of control group I, the structure of hepatic tissue was well preserved, the area with gamma-GT positive was smaller, and the ultrastructure of hepatocytes was normal. The average life span the DEN-red ginseng group II and the DEN control group II were 72.8 and 42.3 days, respectively. To sum up, all findings on preventive and curative groups had clearly proved that the red ginseng had the anticarcinogenic effect on the development of liver cancer induced by DEN in rats.