Chrysophanol Protects Against Acute Heart Failure by Inhibiting JNK1/2 Pathway in Rats.

BACKGROUND Acute heart failure (AHF) usually requires urgent therapy. Myocardial damage, oxidative stress, and inflammation are major components in the pathology of AHF. This study was designed to investigate the effects of chrysophanol on AHF. MATERIAL AND METHODS Sprague-Dawley rats were injected with isoprenaline hydrochloride to construct AHF rat models. AHF rats were treated with normal saline (negative control), chrysophanol, the combination of chrysophanol and SP600125, or benazepril (positive control) using sham rats as blank controls. Echocardiography, histological staining, and enzyme activity analysis were performed to assess the heart functions and myocardial damage. Effects on apoptosis, oxidative stress (OS), and inflammation were evaluated by biochemical analysis, TUNEL staining, and ELISA. RESULTS Chrysophanol improved the parameters of cardiac functions and alleviated the myocardial damage accompanied by the reduction of creatine kinase and lactate dehydrogenase activity. Meanwhile, chrysophanol inhibited the myocardial apoptosis along with the upregulation of Bcl-2 and downregulation of Bax and cleaved caspase-3. AHF-induced abnormal changes of OS parameters (MDA, GPx, CAT, SOD) and inflammatory markers (IL-6, IL-1ß, TNF-alpha, IFN-γ) were alleviated by chrysophanol. Benazepril treatment showed similar results with chrysophanol, while the addition of SP600125 enhanced the chrysophanol-mediated protection effects in AHF rats. Western blot analysis demonstrated that chrysophanol inhibited the phosphorylation of JNK1/2 and its upstream/downstream factors. CONCLUSIONS Chrysophanol improved cardiac functions and protected against myocardial damage, apoptosis, OS, and inflammation by inhibiting activation of the JNK1/2 pathway in AHF rat models. These finding indicate that chrysophanol may be a promising approach for treatment of AHF.