Yellow Wine Polyphenolic Compounds prevents Doxorubicin‐induced cardiotoxicity through activation of the Nrf2 signalling pathway

Abstract

Doxorubicin (DOX) is considered as the major culprit in chemotherapy‐induced cardiotoxicity. Yellow wine polyphenolic compounds (YWPC), which are full of polyphenols, have beneficial effects on cardiovascular disease. However, their role in DOX‐induced cardiotoxicity is poorly understood. Due to their antioxidant property, we have been suggested that YWPC could prevent DOX‐induced cardiotoxicity. In this study, we found that YWPC treatment (30 mg/kg/day) significantly improved DOX‐induced cardiac hypertrophy and cardiac dysfunction. YWPC alleviated DOX‐induced increase in oxidative stress levels, reduction in endogenous antioxidant enzyme activities and inflammatory response. Besides, administration of YWPC could prevent DOX‐induced mitochondria‐mediated cardiac apoptosis. Mechanistically, we found that YWPC attenuated DOX‐induced reactive oxygen species (ROS) and down‐regulation of transforming growth factor beta 1 (TGF‐β1)/smad3 pathway by promoting nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2) nucleus translocation in cultured H9C2 cardiomyocytes. Additionally, YWPC against DOX‐induced TGF‐β1 up‐regulation were abolished by Nrf2 knockdown. Further studies revealed that YWPC could inhibit DOX‐induced cardiac fibrosis through inhibiting TGF‐β/smad3‐mediated ECM synthesis. Collectively, our results revealed that YWPC might be effective in mitigating DOX‐induced cardiotoxicity by Nrf2‐dependent down‐regulation of the TGF‐β/smad3 pathway.

Vanillin Prevents Doxorubicin-Induced Apoptosis and Oxidative Stress in Rat H9c2 Cardiomyocytes

“…Several plant-derived polyphenols have drawn attention in pharmaceutical field thanks to their ability to reduce oxidation species synthesis and accumulation in human body [ 5 , 20 , 21 , 52 , 53 ]. Recently, it was reported that curcumin is able to ameliorate the doxo cardiotoxic effect in vitro and in vivo [ 22 , 24 ].…”

“…However, a concomitant reduction in anti-cancer efficacy and side effects intensification have radically hampered the following clinical trials investigation [ 18 , 19 ]. Recently, due to their well-known antioxidant properties, many attentions have been paid to the plant-derived polyphenols as a possible strategy in the prevention of doxo-induced cardiotoxicity [ 5 , 20 , 21 ]. Speaking of which, it has been reported that curcumin, a natural phenol abundant in turmeric, is able to ameliorate the doxo-induced cardiotoxic effect both in vitro and in vivo studies [ 22 , 23 , 24 ].…”

Orosomucoid 1 Attenuates Doxorubicin‐Induced Oxidative Stress and Apoptosis in Cardiomyocytes via Nrf2 Signaling

“…Nuclear factor-like 2 (Nrf2) is an important member of the cap collar family of basic leucine zipper transcription factors; it plays a role in the antioxidant defense system by regulating the expression of antioxidant enzymes [ 17 , 18 ]. During conditions of oxidative stress, Nrf2 is activated, translocated to the nuclear region, and combined with the antioxidant response element located in the promoter region of phase II antioxidant enzyme genes, such as heme oxygenase 1 ( HO-1 ).…”

Therapeutic Effects of Specialized Pro-Resolving Lipids Mediators on Cardiac Fibrosis via NRF2 Activation

“…This result suggested that NRF2 is involved in the LXA4-induced reduction in the level of inflammatory factors. [173] and Hiebert et al [52]).…”

“…LXA4 can activate NRF2 by inducing the phosphorylation of Ser40 of NRF2 to induce nuclear translocation. Phosphorylated NRF2 can form a heterodimer with sMAF and bind to ARE, leading to the transcription of antioxidant genes, such as HO-1, NQO-1, SOD, and TXN (modified from Lin et al [ 173 ] and Hiebert et al [ 52 ]).…”