Scutellarin alleviates interstitial fibrosis and cardiac dysfunction of infarct rats by inhibiting TGFβ1 expression and activation of p38-MAPK and ERK1/2.

Abstract

BACKGROUND AND PURPOSE:

Interstitial fibrosis plays a causal role in the development of heart failure after chronic myocardial infarction (MI), and anti-fibrotic therapy represents a promising strategy to mitigate this pathological process. The purpose of this study was to investigate the effect of long-term administration of scutellarin (Scu) on cardiac interstitial fibrosis of myocardial infarct rats and the underlying mechanisms.

EXPERIMENTAL APPROACH:

Scu was administered to rats that were subjected to coronary artery ligation. Eight weeks later, its effects on cardiac fibrosis were assessed by examining cardiac function and histology. The number and collagen content of cultured cardiac fibroblasts exposed to angiotensin II (Ang II) were determined after the administration of Scu in vitro. Protein expression was detected by Western blot technique, and mRNA levels by quantitative reverse transcription-PCR.

KEY RESULTS:

The echocardiographic and haemodynamic measurements showed that Scu improved the impaired cardiac function of infarct rats and decreased interstitial fibrosis. Scu inhibited the expression of FN1 and TGFβ1, but produced no effects on inflammatory cytokines (TNFα, IL-1β and IL-6) in the 8 week infarct hearts. Scu inhibited the proliferation and collagen production of cardiac fibroblasts (CFs) and the up-regulation of FN1 and TGFβ1 induced by Ang II. The enhanced phosphorylation of p38-MAPK and ERK1/2 in both infarct cardiac tissue and cultured CFs challenged by Ang II were suppressed by Scu.

CONCLUSIONS AND IMPLICATIONS:

Long-term administration of Scu improved the cardiac function of MI rats by inhibiting interstitial fibrosis, and the mechanisms may involve the suppression of pro-fibrotic cytokine TGFβ1 expression and inhibition of p38 MAPK and ERK1/2 phosphorylation.

• Authors: Zhenwei Pan, Weiming Zhao, Xiangying Zhang, Bing Wang, Jinghao Wang, Xuelin Sun, Xuantong Liu, Shuya Feng, Baofeng Yang, Yanjie Lu
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 162 Issue 3 Pg. 688-700 (Feb 2011) ISSN: 1476-5381 [Electronic] England
• PMID: 20942814 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Chemical References

• Cytokines
• Drugs, Chinese Herbal
• Glucuronates
• Tgfb1 protein, rat
• Transforming Growth Factor beta1
• scutellarin
• Apigenin
• Collagen
• MAPK1 protein, human
• Mitogen-Activated Protein Kinase 1
• p38 Mitogen-Activated Protein Kinases

Topics

• Animals
• Apigenin (therapeutic use)
• Collagen (metabolism)
• Cytokines (metabolism)
• Drugs, Chinese Herbal (therapeutic use)
• Echocardiography
• Erigeron
• Fibrosis
• Glucuronates (therapeutic use)
• Heart Failure (complications, drug therapy, physiopathology)
• Hemodynamics (drug effects, physiology)
• Male
• Mitogen-Activated Protein Kinase 1 (metabolism)
• Myocardial Infarction (complications, drug therapy, pathology, physiopathology)
• Phytotherapy
• Rats
• Rats, Wistar
• Transforming Growth Factor beta1 (metabolism)
• Ventricular Dysfunction, Left (etiology, physiopathology)
• Ventricular Remodeling (drug effects)
• p38 Mitogen-Activated Protein Kinases (metabolism)