Danshen (Salvia miltiorhiza) inhibits Leu27 IGF-II-induced hypertrophy in H9c2 cells.

Abstract

In this study, we used ICI 182 780 (ICI), an estrogen receptor (ER) antagonist, to investigate the estrogenic activity of Danshen, and to further explored whether Danshen extract can block Leu27IGF-II-induced hypertrophy in H9c2 cardiomyoblast cells. We first used an IGF-II analog Leu27IGF-II, which specifically activates IGF2R signaling cascades and induces H9c2 cardiomyoblast cell hypertrophy. However, Danshen extract completely inhibited Leu27IGF-II-induced cell size increase, ANP and BNP hypertrophic marker expression, and IGF2R induction. We also observed that Danshen extract inhibited calcineurin protein expression and NFAT3 nuclear translocation, leading to suppression of Leu27IGF-II-induced cardiac hypertrophy. Moreover, the anti-Leu27IGF-II-IGF2R signaling effect of Danshen was totally reversed by ICI, which suggest the cardio protective effect of Danshen is mediated through estrogen receptors. Our study suggests that, Danshen exerts estrogenic activity, and thus, it could be used as a selective ER modulator in IGFIIR induced hypertrophy model.

• Authors: Tsung-Jung Ho, Hsi Chin Wu, V Bharath Kumar, Wei-Wen Kuo, Yueh-Shan Weng, Yu-Lan Yeh, B Mahalakshmi, Cecilia Hsuan Day, Chi-Cheng Li, Chih-Yang Huang
• Journal: Environmental toxicology (Environ Toxicol) Vol. 35 Issue 10 Pg. 1043-1049 (Oct 2020) ISSN: 1522-7278 [Electronic] United States
• PMID: 32415908 (Publication Type: Journal Article)
• Copyright: © 2020 Wiley Periodicals, Inc.

Chemical References

• Drugs, Chinese Herbal
• Estrogen Receptor Antagonists
• Receptor, IGF Type 2
• Receptors, Estrogen
• insulin-like growth factor II, Leu(27)-
• dan-shen root extract
• Fulvestrant
• Insulin-Like Growth Factor II
• Calcineurin

Topics

• Animals
• Calcineurin (metabolism)
• Cardiomegaly (prevention & control)
• Cell Enlargement (drug effects)
• Cell Line
• Cell Survival (drug effects)
• Drugs, Chinese Herbal (isolation & purification, pharmacology)
• Estrogen Receptor Antagonists (pharmacology)
• Fulvestrant (pharmacology)
• Insulin-Like Growth Factor II (analogs & derivatives, pharmacology)
• Myoblasts, Cardiac (drug effects, metabolism, pathology)
• Protein Transport
• Rats
• Receptor, IGF Type 2 (metabolism)
• Receptors, Estrogen (metabolism)
• Salvia miltiorrhiza (chemistry)
• Signal Transduction