Protective effect of dioscin against doxorubicin-induced cardiotoxicity via adjusting microRNA-140-5p-mediated myocardial oxidative stress

Abstract

Clinical application of doxorubicin (DOX) is limited because of its cardiotoxicity. Thus, exploration of effective lead compounds against DOX-induced cardiotoxicity is necessary. The aim of the present study was to investigate the effects and possible mechanisms of dioscin against DOX-induced cardiotoxicity. The in vitro model of DOX- treated H9C2 cells and the in vivo models of DOX-treated rats and mice were used in this study. The results showed that discoin markedly increased H9C2 cell viability, decreased the levels of CK, LDH, and improved histopathological and electrocardio- gram changes in rats and mice to protect DOX-induced cardiotoxicity. Furthermore, dioscin significantly inhibited myocardial oxidative insult through adjusting the levels of intracellular ROS, MDA, SOD, GSH and GSH-Px in vitro and in vivo. Our data also indicated that dioscin activated Nrf2 and Sirt2 signaling pathways, and thereby affected the expression levels of HO-1, NQO1, Gst, GCLM, Keap1 and FOXO3a through decreasing miR-140-5p expression level. In addition, the level of intracellular ROS was significantly increased in H9C2 cells treated by DOX after miR-140-5p mimic transfection, as well as the down-regulated expression levels of Nrf2 and Sirt2, which were markedly reversed by dioscin. In conclusion, our data suggested that dioscin alleviated DOX-induced cardiotoxicity through modulating miR-140-5p-mediated myocardial oxidative stress. This natural product should be developed as a new candidate to alleviate cardiotoxicity caused by DOX in the future.

Doxorubicin cardiomyopathy is ameliorated by acacetin via Sirt1‐mediated activation of AMPK/Nrf2 signal molecules

“…Several natural active compounds, for example dioscin, sulforaphane, resveratrol and quercetin, have been reported also to confer protection against doxorubicin cardiotoxicity by reducing ROS production and regulating apoptosis-related proteins via activating Sirt1, 32 Nrf2, 41 Bmi-1 expression 42 or adjusting microR-NA-140-5p. 43 Although these natural compounds show promising therapeutic potential, their low solubility and low bioavailability are barriers for drug development. Acacetin is a novel Sirt1 activator that mediates activation of AMPK/Nrf2 signals.…”

Dioscin protects against coronary heart disease by reducing oxidative stress and inflammation via Sirt1/Nrf2 and p38 MAPK pathways

“…In the current study, dioscin significantly increased SOD, CAT and GSH levels and decreased MDA levels in CHD model pigs. In addition, Zhao et al (29) suggested that dioscin alleviated doxorubicin-induced cardiotoxicity through modulating miR-140-5p-mediated myocardial oxidative stress.…”

Natural Product Interventions for Chemotherapy and Radiotherapy-Induced Side Effects

“…Curcumin also protects the myocardium against doxorubicin-induced cardiotoxicity in mouse hearts and primary cardiomyocytes, probably via upregulating 14-3-3γ expression (He et al, 2018 ). Natural steroid saponin dioscin found abundantly in legumes and yams, alleviates doxorubicin-induced cardiotoxicity by regulating miR-140-5p-mediated myocardial oxidative stress (Zhao et al, 2018 ).…”