Protective effect of RA on myocardial infarction induced-cardiac fibrosis via AT1R/p38 MAPK pathway signaling and modulation of the ACE2/ACE ratio.
J Agric Food Chem. 2016 Aug 19. Epub 2016 Aug 19. PMID: 27538767
Rosmarinic acid (α-o-caffeoyl-3,4-dihydroxyphenyl lactic acid, RA), a major active constituent of Rosmarinus officinalis Linn. (rosemary), having significant anti-inflammatory, anti-apoptotic and anti-oxidant effects. However, the cardioprotection of RA is still not understood. Present study was designed, for the first time, to investigate the cardioprotection of RA on myocardial infarction (MI) induced-cardiac fibrosis and clarify the possible mechanisms. MI was induced in adult rats by left anterior descending coronary artery ligation, and animals were then administered RA (50, 100, 200 mg/kg) by gavage. Compared with the model group, RA treatment ameliorated the changes in left ventricular systolic pressure (LVSP), +dp/dtmax, and -dp/dtmax after 4 weeks. This was associated with attenuation of infarct size, collagen volume fraction (CVF), expression of collagen I, collagen III, alpha smooth muscle actin (α-SMA), and hydroxyproline (Hyp) concentrations. RA treatment was also associated with decreased angiotensin-converting enzyme (ACE) expression and increased ACE2 expression, as well as decreased expression of angiotensin type 1 receptor (AT1R) and phospho-p38 mitogen-activated protein kinase(p38 MAPK). Thus, RA can protect against cardiac dysfunction and fibrosis following MI, likely due to decreasing ACE expression and increasing ACE2 expression via AT1R/ p38 MAPK pathway.