Tanshinone IIA inhibits myocardial remodeling induced by pressure overload via suppressing oxidative stress and inflammation: Possible role of silent information regulator 1.

Abstract

Tanshinone IIA (Tan) exerts potential protective effects against cardiovascular diseases. Oxidative stress and inflammation are involved in cardiac hypertrophy. Activation of silent information regulator 1 (SIRT1) signaling has been suggested to attenuate cardiac hypertrophy. This study aims to evaluate the antioxidative and anti-inflammatory effects of Tan treatment in pressure overload-induced myocardial remodeling and elucidated its potential mechanisms. Sprague-Dawley rats were treated with Tan in the absence or presence of the SIRT1 inhibitor sirtinol (Snl) and then subjected to transverse aortic constriction (TAC). Tan conferred cardioprotective effects by improving cardiac function, reducing apoptosis and myocardial remodeling, upregulating SIRT1, Bcl-2 expressions, and downregulating Bax and caspase-3 expressions. Snl attenuated these effects by inhibiting SIRT1 signaling. Tan treatment also reduced myocardium malondialdehyde (MDA) content, and cardiac inflammatory cytokines (TNF-α and IL-6) and increased myocardium superoxide dismutase (SOD) level. However, these effects were also abolished by Snl. In conclusion, these results indicate that Tan significantly attenuates TAC-induced myocardial remodeling possibly due to its strong anti-oxidative and anti-inflammatory activity. Importantly, SIRT1 signaling activation is involved in this process.

• Authors: Jun Feng, Shusheng Li, Huawen Chen
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 791 Pg. 632-639 (Nov 15 2016) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 27693799 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Elsevier B.V. All rights reserved.

Chemical References

• Abietanes
• Cytokines
• Proto-Oncogene Proteins c-bcl-2
• tanshinone
• Caspase 3
• Sirt1 protein, rat
• Sirtuin 1

Topics

• Abietanes (pharmacology, therapeutic use)
• Animals
• Aorta (drug effects, physiopathology)
• Apoptosis (drug effects)
• Atrial Remodeling (drug effects)
• Caspase 3 (metabolism)
• Cytokines (metabolism)
• Gene Expression Regulation, Enzymologic (drug effects)
• Male
• Oxidative Stress (drug effects)
• Pressure (adverse effects)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Rats
• Rats, Sprague-Dawley
• Signal Transduction (drug effects)
• Sirtuin 1 (metabolism)
• Vasoconstriction (drug effects)
• Ventricular Remodeling (drug effects)