Icariin protects cardiomyocytes against ischaemia/reperfusion injury by attenuating sirtuin 1-dependent mitochondrial oxidative damage.

BACKGROUND AND PURPOSE: Icariin, a major active ingredient in traditional Chinese medicines, is attracting increasing attention because of its unique pharmacological effects against ischaemic heart disease. The histone deacetylase, sirtuin-1, plays a protective role in ischaemia/reperfusion (I/R) injury, and this study was designed to investigate the protective role of icariin in models of cardiac I/R injury and to elucidate the potential involvement of sirtuin-1. EXPERIMENTAL APPROACH: I/R injury was simulated in vivo (mouse hearts), ex vivo (isolated rat hearts) and in vitro (neonatal rat cardiomyocytes and H9c2 cells). Prior to I/R injury, animals or cells were exposed to icariin, with or without inhibitors of sirtuin-1 (sirtinol and SIRT1 siRNA). KEY RESULTS: In vivo and in vitro, icariin given before I/R significantly improved post-I/R heart contraction and limited the infarct size and leakage of creatine kinase-MB and LDH from the damaged myocardium. Icariin also attenuated I/R-induced mitochondrial oxidative damage, decreasing malondialdehyde content and increasing superoxide dismutase activity and expression of Mn-superoxide dismutase. Icariin significantly improved mitochondrial membrane homeostasis by increasing mitochondrial membrane potential and cytochrome C stabilization, which further inhibited cell apoptosis. Sirtuin-1 was significantly up-regulated in hearts treated with icariin, whereas Ac-FOXO1 was simultaneously down-regulated. Importantly, sirtinol and SIRT1 siRNA either blocked icariin-induced cardioprotection or disrupted icariin-mediated mitochondrial homeostasis. CONCLUSIONS AND IMPLICATIONS: Pretreatment with icariin protected cardiomyocytes from I/R-induced oxidative stress through activation of sirtuin-1 /FOXO1 signalling.

Chloroform fraction of Scutellaria barbata D. Don inhibits the growth of colorectal cancer cells by activating miR­34a.

Scutellaria barbata D. Don (SB) is a well known formula in traditional Chinese medicine, which exhibits potent anticancer effects on various cancers. Many miRNAs play crucial roles in the regulation of cancer, for instance, miR­34a functions as a tumor suppressor, and is often downregulated during cancer. In this study, we investigated the role of ECSB in suppressing the growth of human colon cancer HCT­8 cells, and whether this is mediated by regulation of miR­34a and its downstream target genes, using real-time PCR and western blot analysis. ECSB treatment significantly inhibited the proliferation of HCT­8 cells and promoted apoptosis in a dose-dependent manner. In addition, ECSB treatment significantly increased the level of miR­34a expression and decreased the levels of Bcl-2, Notch1/2 and Jagged1 expression. Furthermore, knockdown of miR­34a expression through transfection of anti-miR­34a oligonucleotide was significantly reversed by ECSB treatment. Likewise, knockdown of miR­34a resulted in significant upregulation of Bcl-2, Notch1/2 and Jagged1 expression, which was reversed following ECSB treatment. Therefore, this study reveals that ECSB inhibited cancer cell growth via promoting apoptosis and inhibiting proliferation, through regulation of miR­34a. These findings further support the use of ECSB as an effective therapeutic agent against colon cancer.