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

Angiotensin II
Fibroblasts
Cell Proliferation
Nitric Oxide Synthase Type III
Phosphorylation
Reactive Oxygen Species
Nitric Oxide
NG-Nitroarginine Methyl Ester
Extracellular Signal-Regulated MAP Kinases
Endothelin-1
tanshinone
Salvia miltiorrhiza
Chinese Traditional Medicine
Medicinal Plants
Small Interfering RNA
Transfection

Keywords

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

ASJC Scopus subject areas

  • Complementary and alternative medicine

Cite this

Tanshinone IIA inhibits angiotensin II-induced cell proliferation in rat cardiac fibroblasts. / Chan, Paul; Liu, Ju Chi; Lin, Li Jen; Chen, Po Yuan; Cheng, Tzu-Hurng; Lin, Jaung Geng; Hong, Hong Jye.

In: American Journal of Chinese Medicine, Vol. 39, No. 2, 2011, p. 381-394.

Research output: Contribution to journalArticle

Chan, Paul ; Liu, Ju Chi ; Lin, Li Jen ; Chen, Po Yuan ; Cheng, Tzu-Hurng ; Lin, Jaung Geng ; Hong, Hong Jye. / Tanshinone IIA inhibits angiotensin II-induced cell proliferation in rat cardiac fibroblasts. In: American Journal of Chinese Medicine. 2011 ; Vol. 39, No. 2. pp. 381-394.
@article{49fe49585d044fb1adb2d7ced1f47bdd,
title = "Tanshinone IIA inhibits angiotensin II-induced cell proliferation in rat cardiac fibroblasts",
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.",
keywords = "Angiotensin II, Cardiac Fibroblast Proliferation, Nitric Oxide, Tanshinone IIA, Traditional Chinese Medicine",
author = "Paul Chan and Liu, {Ju Chi} and Lin, {Li Jen} and Chen, {Po Yuan} and Tzu-Hurng Cheng and Lin, {Jaung Geng} and Hong, {Hong Jye}",
year = "2011",
doi = "10.1142/S0192415X11008890",
language = "English",
volume = "39",
pages = "381--394",
journal = "American Journal of Chinese Medicine",
issn = "0192-415X",
publisher = "World Scientific Publishing Co. Pte Ltd",
number = "2",

}

TY - JOUR

T1 - Tanshinone IIA inhibits angiotensin II-induced cell proliferation in rat cardiac fibroblasts

AU - Chan, Paul

AU - Liu, Ju Chi

AU - Lin, Li Jen

AU - Chen, Po Yuan

AU - Cheng, Tzu-Hurng

AU - Lin, Jaung Geng

AU - Hong, Hong Jye

PY - 2011

Y1 - 2011

N2 - 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.

AB - 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.

KW - Angiotensin II

KW - Cardiac Fibroblast Proliferation

KW - Nitric Oxide

KW - Tanshinone IIA

KW - Traditional Chinese Medicine

UR - http://www.scopus.com/inward/record.url?scp=79953661402&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79953661402&partnerID=8YFLogxK

U2 - 10.1142/S0192415X11008890

DO - 10.1142/S0192415X11008890

M3 - Article

VL - 39

SP - 381

EP - 394

JO - American Journal of Chinese Medicine

JF - American Journal of Chinese Medicine

SN - 0192-415X

IS - 2

ER -