Ursolic acid modulates MMPs, collagen-I, α-SMA, and TGF-β expression in isoproterenol-induced myocardial infarction in rats

Abstract

<jats:p> In the present study, the modulatory effect of ursolic acid (UA) on cardiac fibrosis and mitochondrial and lysosomal enzymes activity in isoproterenol-induced myocardial infarction (MI) in rats were examined. Isoproterenol hydrochloride (ISO; 85 mg/kg body weight) was administered subcutaneously for first two consecutive days. ISO-induced MI in rats significantly decreased the activities of mitochondrial tricarboxylic acid cycle enzymes and respiratory chain enzymes while increased the activities of lysosomal glycohydrolases and cathepsins. The expression of matrix metalloproteinase 2 (MMP-2), MMP-9, collagen type I, α-smooth muscle actin (α-SMA), and transforming growth factor-β (TGF-β) were upregulated in ISO-induced MI in rats. UA administration to rats showed increased activities of mitochondrial tricarboxylic acid cycle enzymes and respiratory chain enzymes and decreased activities of lysosomal glycohydrolases and cathepsins in ISO-induced rats. Furthermore, expression of MMP-2, MMP-9, collagen type I, α-SMA, and TGF-β downregulated in UA-administered rats. Thus, our results demonstrate that UA has an anti-fibrotic effect and attenuates the mitochondrial and lysosomal dysfunction in ISO-induced MI in rats. </jats:p>

Anti-inflammatory and anti-apoptotic effect of zingiberene on isoproterenol-induced myocardial infarction in experimental animals

“…Radhiga et al reported that ursolic acid attenuated MMPs expression in isoproterenol-induced MI in experimental rats. 72 AKT signal transduction pathway plays an important role in apoptotic cell death through modulating several anti-apoptotic proteins expression. Li et al reported that ulinastatin against ISO-induced chronic heart failure through the PI3 K Akt, p38 MAPK, and NF-kB pathways.…”

Research Progress of Therapeutic Enzymes and Their Derivatives: Based on Herbal Medicinal Products in Rheumatoid Arthritis

“…Besides, Celastrol, Ikarisoside, and AKBA (mastic acid active ingredient) suppress the activity of MMP9, one of the transcription factor NF-κB-mediated genes (Choi et al, 2010;Xiao et al, 2018). Ursolic acid inhibits the expression of MMP-9, while the catechins extracted from green tea shows a good inhibitory effect on the expression and activity of MMP1 and MMP13 (Fechtner et al, 2017;Radhiga et al, 2019). PG201, the aforementioned new herbal drug, was reported to amplify the expression of TIMP-2, thus elevating the ration of TIMP2/MMP2 in synovial tissue and fluid in CIA rabbits and mice.…”

Improvement of cardiac function by mesenchymal stem cells derived extracellular vesicles through targeting miR-497/Smad7 axis

“…In addition, it was reported that VEGF could promote the proliferation of vascular endothelial cells and induce angiogenesis, and VEGF has a protective effect on MI rats [ 25 ]. Collagen type 1 and α- SMA are important markers of myocardial fibrosis, and the high expression of them could promote cellular fibrosis [ 26 ]. It is reported that collagen type 1, α- SMA, and TGF- β were remarkably increased in the MI model.…”