Chrysophanol Mitigates Chronic Heart Failure in Rats by Modulating ROS-Mediated Parthanatos and Pyroptosis

Abstract

Chronic heart failure (CHF) triggers a cascade of events involving parthanatos and pyroptosis, culminating in cellular malfunction, inflammation, and tissue degeneration. This study aims to inquire into the inherent mechanism of chrysophanol (CHR) in the treatment of CHF.

In vitro, we cultured the rat embryonic cardiomyocyte cell line H9c2. Parthanatos was initiated through N-methyl-N′-nitro-N′-nitrosoguanidine (MNNG) induction, followed by treatment with varying concentrations of CHR. The evaluation of parthanatos and pyroptosis in cardiomyocytes was assessed by western blotting. In vivo, the transverse aortic constriction (TAC) model was used to simulate CHF. The hemodynamic indices were performed to evaluate cardiac function in rats. The degree of inflammatory cell infiltration and fibrosis within cardiac tissue was assessed using hematoxylin and eosin staining and Masson's trichrome staining, respectively. Cardiac tissues were obtained and subjected to immunohistochemical analysis to assess PARP-1 expression. Subsequently, dual immunofluorescence staining (caspase-1 and NLRP3) was conducted, aiming to comprehensively evaluate the status of parthanatos and pyroptosis in the cardiac tissues of rats.

In contrast to the MNNG or TAC group, the groups administered with CHR exhibited an inhibitory effect on Reactive oxygen species (ROS) expression, as well as parthanatos and pyroptosis proved by cell and animal experiments (P < 0.05). The reduced expression of PAR, PARP-1, AIF, NLRP3, IL-1β, caspase-1, and cleaved-GSDMD compared with the MNNG or TAC group proved it (P < 0.05). Moreover, compared with the TAC group, CHR significantly improved the cardiac histology of TAC rats. These findings collectively suggested the potential of CHR in ameliorating CHF.

CHR may mitigate CHF in rats by modulating ROS-mediated parthanatos and pyroptosis.