Cryptotanshinone attenuates isoprenaline-induced cardiac fibrosis in mice associated with upregulation and activation of matrix metalloproteinase-2

Abstract

Cryptotanshinone is an active ingredient of Salvia miltiorrhiza that has been used in traditional Chinese medicine for treating cardiovascular disorders. Thus, we investigated the effects of cryptotanshinone on cardiac fibrosis induced by isoprenaline and examined whether cardiac matrix metalloproteinase (MMP)-2 is involved in this process. Male C57BL/6 mice received a daily injection of 0.9% saline, 3 mg/kg isoprenaline or isoprenaline plus 20 mg/kg cryptotanshinone by gastric gavage for 2 weeks. In this study we demonstrated that cryptotanshinone was able to significantly ameliorate isoprenaline-induced cardiac fibrosis, which was associated with a marked upregulation and activation of MMP-2 in the ventricular myocardium. Additionally, we demonstrated that cryptotanshinone dose-dependently upregulated and activated MMP-2 in cultured cardiac fibroblasts. Moreover, incubation with cryptotanshinone also prevented the isoprenaline-induced downregulation and inactivation of MMP-2 in cultured cardiac fibroblasts. Taken together, our data suggest that cryptotanshinone is a novel and potent antifibrotic agent. The present findings further our understanding of the role of MMP-2 in cardiac fibrosis and the antifibrotic mechanisms of cryptotanshinone.