Tanshinone IIA inhibits angiotensin II-induced cell proliferation in rat cardiac fibroblasts

Paul Chan, Ju Chi Liu, Li Jen Lin, Po Yuan Chen, Tzu-Hurng Cheng, Jaung Geng Lin, Hong Jye Hong

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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. NG-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.

Original languageEnglish
Pages (from-to)381-394
Number of pages14
JournalAmerican Journal of Chinese Medicine
Volume39
Issue number2
DOIs
Publication statusPublished - 2011

    Fingerprint

Keywords

  • Angiotensin II
  • Cardiac Fibroblast Proliferation
  • Nitric Oxide
  • Tanshinone IIA
  • Traditional Chinese Medicine

ASJC Scopus subject areas

  • Complementary and alternative medicine

Cite this