Objective: To explore the influence of Tanshinone II A on the type I and II collagen synthesis of CFB induced by angiotensin II (Ang II) as well as the possible mechanism of down-regulating CTGF level. Methods:The CFB fibrosis model was induced by angiotensin II stimulation and treated by different concentra- tions of Tanshinone II A. The following items were investigated such as type I, ? collagen mRNA levels. Mean- while, Western blot and RT-PCR were employed to detect CTGF and CTGF-mRNA separately. Results:The type I and the ? collagen mRNA levels of CFB stimulated by Ang II were higher than those of the DMSO group, while the tanshinone II A treatment can decrease the I and the II collagen mRNA levelin a concentration-depen- dent manner. The collagen mRNA level return to normal at 50μmol/L tanshinone II A. The CTGF and the CT- GF-mRNA levels of CFB stimulated by Ang II were higher than those of the DMSO group. The tanshinone II A can reduce the level of CTGF and CTGF-mRNA. After the administration of exogenous CTGF, the anti-collagen synthesis effects of tanshinone II A were attenuated with the maximum effect at 10μmol/L, while exogenous CTGF treatment did not change CTGF-mRNA levels. Conclusion:Tanshinone II A can lower the type I and ? collagen synthesis of cardica fibroblasts induced by Ang II with possible mechanism by reducing CTGF levels.
-- FENG Jun, LI Shu-sheng, TU En-yuan. Influence Type I and m Collagen Synthesis of Cardiac Fiboblasts Induced by Angiotensin H with Possible Mechanism of Down-regulating CTGF. Zhong Guo Zhong Yi Ji Zheng. 2012; 21 (4): 560-561, 573.
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.
--Chan, P., J.C. Liu, L.J. Lin, P.Y. Chen, T.H. Cheng, J.G. Lin, H.J. Hong. Tanshinone IIA inhibits angiotensin II-induced cell proliferation in rat cardiac fibroblasts. Am J Chin Med, 2011. 39 (2):381-394.
Research on the inhibitory effect of Tanshinone IIA on breast cancer cell proliferation
Zhao P-w, Niu J-z, Wang J-f, Hao Q-x, Yu J, et al. Research on the inhibitory effect of Tanshinone IIA on breast cancer cell proliferation. Zhong Guo Yao Li Xue Tong Bao. 2010; 26(7): 903-906
The proliferation rate of T47D and MDA-MB-231 cells influenced by 1×10-6 mol·L-1 and 1×10-7 mol·L-1 Tanshinone IIA was analyzed by MTT assay. Estrogen receptor antagonist ICI182, 780 was employed as a tool. Level of ER? and ER? mRNA in T47D cells was quantified by Real-time RT-PCR assay. Expression of ER? and ER? protein was measured by flow cytometry. The proliferation rates of T47D cells treated with Tanshinone IIA decreased significantly. Such effects could be partly blocked by ICI182, 780. Meanwhile, the proliferation rates of MDA-MB-231 cells treated with Tanshinone IIA decreased much more dramatically. Real-time RT-PCR and flow cytometry results showed that Tanshinone IIA could induce elevation of ER? and ER?, especially ER? mRNA and protein expression level in T47D cells. Tanshinone IIA shows inhibitory effects on proliferation of breast cancer cell lines.