Paeoniflorin inhibits doxorubicin-induced cardiomyocyte apoptosis by downregulating microRNA-1 expression

Abstract

Doxorubicin (DOX) is an effective anthracycline anti-tumor antibiotic. Because of its cardiotoxicity, the clinical application of DOX is limited. Paeoniflorin (PEF), a monoterpene glucoside extracted from the dry root of Paeonia, is reported to exert multiple beneficial effects on the cardiovascular system. The present study was designed to explore the protective effect of PEF against DOX-induced cardiomyocyte apoptosis and the underlying mechanism. In cultured H9c2 cells, PEF (100 µmol/l) was added for 2 h prior to exposure to DOX (5 µmol/l) for 24 h. Cell viability, creatine kinase activity, cardiomyocyte apoptosis, intracellular reactive oxygen species (ROS) levels, and the expression of microRNA-1 (miR-1) and B-cell lymphoma 2 (Bcl-2) were measured following treatment with PEF and/or DOX. The results showed that treatment with DOX notably induced cardiomyocyte apoptosis, concomitantly with enhanced ROS generation, upregulated miR-1 expression and downregulated Bcl-2 expression. These effects of DOX were significantly inhibited by pretreatment of the cells with PEF. These results suggest that the inhibitory effect of PEF on DOX-induced cardiomyocyte apoptosis may be associated with downregulation of miR-1 expression via a reduction in ROS generation.

Rutin Protects against Pirarubicin‐Induced Cardiotoxicity through TGF‐β1‐p38 MAPK Signaling Pathway

“…In this study, pretreatment with RUT greatly prevented cell apoptosis of H9c2 cells exposed to THP. Similar antiapoptotic effects have been observed using other plant-derived compounds such as paeoniflorin, which prevented DOX-induced ROS generation and suppressed apoptosis of H9c2 cells [ 26 ]. Similarly, another antioxidant, edaravone, was shown to attenuate ROS production, reduce oxidative stress, and inhibit cell apoptosis in H9c2 cells treated with high glucose levels [ 27 ].…”

Current state of phenolic and terpenoidal dietary factors and natural products as non-coding RNA/microRNA modulators for improved cancer therapy and prevention

“…Paeoniflorin also inhibited glioma cell growth (U87) and induced apoptosis in glioma cells via upregulation of miR-16 and suppressed MMP9 expression [357] . In addition, paeoniflorin showed protective effects on doxorubicin-treated cardiomyocetes via suppressed miR-1 expression and inhibition of doxorubicin-induced apoptosis in cardiomyocetes [358] . A list of microRNAs regulated by di-, sesqui- and monoterpenes is presented in Table 11 .…”

Paeoniflorin inhibits cell viability and invasion of liver cancer cells via inhibition of Skp2

“…Paeoniflorin (PF) is a bioactive component isolated from the paeony root, which exerts multiple immunoregulatory, anti-hyperglycemic and anti-hypotensive effects (9,10). PF has been suggested to possess anti-tumor functions in a variety of human cancer types, including liver cancer (11)(12)(13)(14)(15). However, PF did not affect normal hepatocyte growth, and was demonstrated to induce apoptosis via endoplasmic reticulum (ER) stress and activation of the mitochondria-dependent pathway (16).…”