Cryptotanshinone Attenuates Cardiac Fibrosis via Downregulation of COX-2, NOX-2, and NOX-4

Abstract

Cryptotanshinone (CTS), a bioactive constituent extracted from a Chinese traditional herb Danshen (Salvia miltiorrhiza), demonstrates multiple protective effects against cardiovascular diseases. The present study was designed to explore the effects of CTS in vitro by cultured adult rat cardiac fibroblasts stimulated with angiotensin II (Ang II) and in vivo by rats with acute myocardial infarction. Our data showed that in cardiac fibroblasts, CTS attenuated Ang II-induced upregulation of fibronectin, connective tissue growth factor, cyclooxygenase-2, and normalized Ang II-induced upregulation of extracellular signal-regulated kinases 1/2 (ERK1/2). Meanwhile, CTS depressed the Ang II-stimulated upregulation of NAD(P)H oxidase 2 and 4 (NOX-2 and NOX-4) and reactive oxygen species production. Similar results were observed in acute myocardial infarction rats with oral administration of CTS, which relieved the pathological changes accompanying myocardial infarction. In conclusion, CTS may exert antifibrotic effects in vitro by inhibiting Ang II-induced extracellular signal-regulated kinases 1/2 phosphorylation and the expression of cyclooxygenase-2, NOX-2, and NOX-4, and also improved the pathological changes and relieved cardiac fibrosis in vivo.

Searching for new mechanisms of myocardial fibrosis with diagnostic and/or therapeutic potential

“…Interestingly, scavenging NOX2‐dependent superoxide anion in cardiac fibroblasts inhibits collagen production . Furthermore, inhibiting angiotensin II‐induced up‐regulation of NOX2 or NOX4 using cryptotanshinone [a bioactive constituent extracted from a Chinese traditional herb Danshen ( Salvia miltiorrhiza )] in rat fibroblasts reduces ROS production and prevents myofibroblast transdifferentiation . In agreement with this, inhibition of NOX2 and NOX4 with this compound reduces fibrosis upon myocardial infarction .…”

Cryptotanshinone, a Stat3 inhibitor, suppresses colorectal cancer proliferation and growth in vitro

“…Cryptotanshinone (CPT) is a quinoid diterpene purified from the root of medicinal plant Danshen (Salvia miltiorrhiza) that has been widely used in the clinic for various diseases, including cardiac fibrosis [8], acute lung injury [9], and arthritis [10]. CPT has been previously shown to inhibit growth and induce apoptosis in a number of human cancer cell lines [11].…”

Taurocholate Induces Cyclooxygenase-2 Expression via the Sphingosine 1-phosphate Receptor 2 in a Human Cholangiocarcinoma Cell Line

“…Effect of TCA-induced ERK1/2 and Akt Activation on COX-2 Expression-It has been well documented that COX-2 expression is regulated by ERK1/2 and Akt in various cell types (8,(35)(36)(37)(38). To further delineate the role of S1PR2-mediated ERK1/2 and Akt activation in TCA-induced COX-2 expression in HuCCT1 cells, selective chemical inhibitors of MEK1/2 and Akt were used.…”