Effects of maslinic acid on isoproterenol-induced myocardial fibrosis in mice

Abstract

Objective: To investigate the effect of maslinic acid (MA) on isoproterenol (ISO)-induced myocardial fibrosis in mice. Methods: ISO was used to induce myocardial fibrosis in adult male C57BL/6 mice, and MA was administered for two weeks to detect the effects of MA on cardiac function and fibrosis. Molecular changes of fibrosis markers and signaling pathways were detected by RT-PCR and western blotting. Phosphate buffer saline (PBS), PBS+SB203580 (p38 MAPK inhibitor), PBS+MA, ISO, ISO+SB203580, ISO+MA were added to the primary cultured rat fibroblasts. Cells were collected after 48 h for subsequent detection. Results: In this study, the mouse model of myocardial fibrosis was successfully established. The left ventricular faction shortening (FS) and maximum rate of rise and maximum rate of fall of pressure in left ventricular chamber (±dp/dt) of the ISO+MA group were significantly higher than those of the ISO group ((35.1±1.8)% vs (28.5±2.6)%, (7 256±153) mmHg/s vs (6 402±240) mmHg/s, (7 156±163) mmHg/s vs (6 319±219) mmHg/s, all P<0.05). The levels of interstitial and perivascular collagen deposition in the ISO+MA group were higher than those in the ISO group (P<0.05), the relative mRNA levels of COL-1, COL-3 and TGF-β in the ISO+MA group were significantly lower than those in the ISO group, with the relative expression levels of 1.70±0.24 vs 3.69±0.34, 1.72±0.56 vs 4.84±0.82, 1.52±0.19 vs 2.64±0.29, respectively (all P<0.05). The phosphorylation levels of p38 MAPK, Smad3 and protein expression level of TGF-β1 in ISO+MA group were lower than those in ISO group (relative expression levels were 1.67±0.35 vs 2.61±0.58, 1.68±0.23 vs 2.52±0.19,1.56±0.15 vs 2.48±0.26, respectively, all P<0.05). The results of in vitro cell experiments showed that the mRNA levels of COL-1, COL-3 and TGF-β in the SB203580 and MA groups were significantly lower than those in the ISO group (relative expression levels were 2.25±0.51, 2.16±0.48 vs 5.29±1.21; 1.58±0.34, 1.69±0.29 vs 4.97±1.32; 1.41±0.31, 1.55±0.38 vs 3.53±0.56, respectively, all P<0.05). The phosphorylation levels of p38 MAPK and Smad3 in the SB203580 MA groups was significantly lower than those in the ISO group, and the protein expression level of TGF-β1 was lower than that in the ISO group (1.81±0.18, 1.77±0.16 vs 2.56±0.32; 1.85±0.21, 1.81±0.17 vs 2.48±0.37; 1.84±0.24, 1.72±0.17 vs 2.52±0.29, all P<0.05). Conclusion: Maslinic acid can inhibit the phosphorylation of p38 MAPK, thereby preventing the canonical TGF-β1/Smads fibrosis signaling pathway to achieve an anti-fibrosis role.