Improved heart failure by Rhein lysinate is associated with p38MAPK pathway.

The present study aimed to explore the role of Rhein lysinate (RHL) in neonatal rat ventricular myocytes (NRVMs) and congestive heart failure induced by co-arctation of the abdominal aorta. Male Sprague-Dawley rats were divided into 3 groups randomly: co-arctation of abdominal aorta group (A group, n=10), sham operation group (SH group, n=10) and RHL treatment rats (A+RHL group, n=10). To establish an oxidative stressed cardiomyocyte model, NRVMs were treated with 10 µM HO for 24 h. MTT assay indicated that HO treatment reduced primary cardiomyocyte viability in a time- and dose- dependent manner, whereas RHL abolished the detrimental effects of HO, indicating a protective role of RHL. Further study demonstrated that HO-induced reactive oxygen species (ROS) production was reversed by RHL. Then, TUNEL staining was carried out and the results revealed that HO markedly enhanced primary cardiomyocyte apoptosis. Conversely, RHL incubation decreased HO-induced cell apoptosis, indicating the protective role of RHL in primary cardiomyocytes. Furthermore, abnormal p38 activation was identified in the failed heart. Notably, treatment with RHL reduced p38 activation. In addition, RHL significantly enhanced the expression of anti-apoptotic protein, B cell lymphoma (Bcl)-2, however markedly reduced the protein level of Bcl-2 associated X, apoptosis regulator in primary cardiomyocytes, indicating its anti-apoptotic role in the cardiac setting. Overall, RHL protects heart failure primarily by reducing ROS production and cardiomyocyte apoptosis via suppressing p38 mitogen activated protein kinase activation.