Assessment of Ursolic Acid on in vitro Model of Cardiac Fibrosis

Cardiac fibroblasts (CFs) which consist ۷۰% of the cells in adult myocardium, play a vital role in the progress of cardiac fibrosis. As a plant-based therapeutic metabolite, ursolic acid (UA) has multiple intracellular and extracellular targets. Current results also show that UA significantly reduces the increase in serum index enzymes (creatine kinase, lactate dehydrogenase) caused by myocardial infarction, which indicates the therapeutic effect of UA in reducing the complications after myocardial infarction. This study aimed to evaluate the effect of UA on Angiotensin ۲ (Ang II) - treated neonatal rat cardiac fibroblasts. The cardiac fibroblasts were isolated from two-day-old Wistar rats. In vitro model of cardiac fibrosis was induced using ۵۰۰ nm Ang II + ۱۰۰ M ascorbic acid (AA) for ۴۸ h. Subsequently, the cells were treated with ۵ and ۱۰ μM UA for ۲۴ and ۴۸ h for amelioration of fibrosis. Masson's trichrome staining and Real-Time PCR were performed to evaluate the effects of UA. Ang II could induce partial fibrosis in CFs as demonstrated by checking some fibrotic markers at RNA and protein levels. The best results of UA treatment in amelioration of cardiac fibrosis were obtained from ۱۰ μM/L UA after ۲۴ h. The results of this study demonstrated that UA acted partially as an anti-fibrotic agent and could reduce the severity of fibrosis in Ang II-treated CFs. These findings could provide a therapeutic option in controlling and improvement of cardiac fibrosis symptoms.

Keywords:

Angiotensin ۲ (Ang II) , Cardiac fibroblasts (CFs) , Ursolic Acid