Cytoprotective Mechanism of Cyanidin and Delphinidin against Oxidative Stress-Induced Tenofibroblast Death.

Age-related rotator cuff tendon degeneration is related to tenofibroblast apoptosis. Anthocyanins reduce oxidative stress-induced apoptotic cell death in tenofibroblasts. The current study investigated the presence of cell protective effects in cyanidin and delphinidin, the most common aglycon forms of anthocyanins. We determined whether these anthocyanidins have antiapoptotic and antinecrotic effects in tenofibroblasts exposed to H2O2, and evaluated their biomolecular mechanisms. Both cyanidin and delphinidin inhibited H2O2-induced apoptosis in a dose-dependent manner. However, at concentrations of 100 µg/ml or greater, delphinidin showed cytotoxicity against tenofibroblasts and a decreased antinecrotic effect. Cyanidin and delphinidin both showed inhibitory effects on the H2O2-induced increase in intracellular ROS formation and the activation of ERK1/2 and JNK. In conclusion, both cyanidin and delphinidin have cytoprotective effects on cultured tenofibroblasts exposed to H2O2. These results suggest that cyanidin and delphinidin are both beneficial for the treatment of oxidative stress-mediated tenofibroblast cell death, but their working concentrations are different.

Antiapoptotic effects of anthocyanins on rotator cuff tenofibroblasts.

Degeneration of the rotator cuff tendon, which involves apoptosis of the tenofibroblasts, is one of the most common shoulder problems that can lead eventually to a full-thickness rotator cuff tendon tear. The current authors evaluated both the ability of anthocyanins, which are powerful antioxidants, to reduce apoptosis in oxidation-stressed rotator cuff tenofibroblasts, and the molecular mechanism for this antiapoptotic action. Anthocyanins demonstrated a dose-dependent ability to inhibit H(2)O(2)-induced apoptosis in cultured tenofibroblasts, as assessed by MTT assay and FACS analysis. H(2)O(2) increased the phosphorylation of extracellular regulated kinase1/2 (ERK1/2) and of c-Jun N-terminal kinase (JNK) and the production of reactive oxygen species (ROS). In contrast, treatment with anthocyanins decreased this activation of ERK1/2 and JNK, as confirmed by Western blot analysis, and reduced the production of ROS, as verified by fluorescent microscopic and FACS analyses. These findings suggest that anthocyanins, by suppressing JNK, ERK1/2, and intracellular ROS production, have a concentration-dependent antiapoptotic effect on rotator cuff tenofibroblasts exposed to an oxidative stressor, and may have therapeutic potential.