Rhein ameliorates transverse aortic constriction-induced cardiac hypertrophy via regulating STAT3 and p38 MAPK signaling pathways

Abstract

The progression from compensatory hypertrophy to heart failure is difficult to reverse, in part due to extracellular matrix fibrosis and continuous activation of abnormal signaling pathways. Although the anthraquinone rhein has been examined for its many biological properties, it is not clear whether it has therapeutic value in the treatment of cardiac hypertrophy and heart failure. In this study, we report for the first time that rhein can ameliorate transverse aortic constriction (TAC)-induced cardiac hypertrophy and other cardiac damage in vivo and in vitro. In addition, rhein can reduce cardiac hypertrophy by attenuating atrial natriuretic peptide, brain natriuretic peptide, and β-MHC expression; cardiac fibrosis; and ERK phosphorylation and transport into the nucleus. Furthermore, the inhibitory effect of rhein on myocardial hypertrophy was similar to that of specific inhibitors of STAT3 and ERK signaling. In addition, rhein at therapeutic doses had no significant adverse effects or toxicity on liver and kidney function. We conclude that rhein reduces TAC-induced cardiac hypertrophy via targeted inhibition of the molecular function of ERK and downregulates STAT3 and p38 MAPK signaling. Therefore, rhein might be a novel and effective agent for treating cardiac hypertrophy and other cardiovascular diseases.

Retinal Microenvironment‐Protected Rhein‐GFFYE Nanofibers Attenuate Retinal Ischemia‐Reperfusion Injury via Inhibiting Oxidative Stress and Regulating Microglial/Macrophage M1/M2 Polarization

“…[ 51 ] Our previous study reported that STAT3 may be associated with the polarization of microglia in RIR injury and that rhein can inhibit the activation of the STAT3 signaling pathway; however, the ability of rhein to regulate the STAT3 signaling pathway in RIR injury has not been reported. [ 9 , 24 , 52 ] Our in vitro and in vivo results show that Rh‐GFFYE can inhibit the phosphorylation of STAT3 protein, which is similar to our previous report on the mechanism of action of ginsenoside Rg3 liposomes in RIR injury. [ 9a ] These results provide a rationale for the regulation of microglia polarization by the natural product rhein.…”