Effects of pomegranate extracts on MMP-1, TIMP-1, MMP-1/TIMP-1 ratio, and type I collagen to inhibit right ventricular fibrosis in animal models

Pulmonary arterial hypertension (PAH) may cause myocardial fibrosis. The process involves collagenase, the metalloproteinase matrix (MMPs), and tissue inhibitors of metalloproteinase (TIMPs). The accumulation of type I collagen in the right ventricular heart muscle may result in right ventricular fibrosis. Pomegranate extracts contain active ellagic acid ingredients with anti-inflammatory, antiproliferative, antioxidant, and ACE inhibitory effects on tissue fibrosis with no side effects. The aim of this study to evaluate the effectiveness of pomegranate extracts on the fibrosis process due to PAH especially on right ventricular myocardium by observing the number of cells expressing MMP-1, TIMP-1, MMP-1/TIMP-1 ratio and type 1 collagen on the right ventricular heart muscle of pulmonary arterial hypertension (PAH) animal models. This study is an experimental laboratory research conducted on Sprague-Dawley white mice (Rattus norvegicus). Subjects were grouped as control and treatment groups that received CMC for two and four weeks, respectively. Monocrotaline was injected to mice to induce pulmonary arterial hypertension. MMP-1 expression of the right ventricular heart muscle in the control group was lower (p < 0.001 and p < 0.001). The number of cells expressed in TIMP-1 was higher in the control group than the observed pomegranate extracts for two weeks and four weeks (p < 0.001). The ratio of cell numbers expressing MMP-1/TIMP-1 was higher in the pomegranate extract group than in the control group (p < 0.001). The number of cells expressing type I collagen in the pomegranate extract group was lower than that of the control group (p < 0.001). According to the result, pomegranate extracts may inhibit the initial process of fibrogenesis.