Cryptotanshinone Inhibits STAT3 Signaling to Alleviate Cardiac Fibrosis in Type 1-like Diabetic Rats.

Cryptotanshinone is an active principal ingredient isolated from Salvia miltiorrhiza (Danshen), a medicinal plant used in China to treat cardiac disorders. The objective of this study was to investigate the effect of cryptotanshinone on myocardial fibrosis in diabetic rats. In streptozotocin-induced type 1 diabetic model hyperglycemic rats (STZ-treated rats), fasting blood glucose levels and heart weight/body weight ratio were markedly increased but both were not modified by cryptotanshinone. Additionally, cardiac performance in catheterized STZ-treated rats was improved. The histological results from Masson staining showed that cryptotanshinone attenuated cardiac fibrosis in STZ-treated rats. Moreover, both the mRNA and protein levels of the signal transducer and activator of transcription 3 (STAT3), matrix metalloproteinase-9, and connective tissue growth factor were reduced by cryptotanshinone in high glucose-cultured cardiomyocytes, similar to the reductions observed in the hearts of STZ-treated rats. In conclusion, while STAT3 regulates matrix metalloproteinase-9 and connective tissue growth factor expression in diabetic rats with cardiac fibrosis, cryptotanshinone inhibited fibrosis to improve cardiac function by suppressing the STAT3 pathway. Cryptotanshinone is suitable as an alternative remedy for therapy of cardiac fibrosis.