Finerenone

Finerenone, a novel high-selective aldosterone receptor antagonist, exhibits powerful anti-inflammatory and antifibrotic effects in previous researches. The aim of our study was to investigate of it on peritoneal fibrosis. In our current research, we found that high glucose could induce epithelial mesothelial transformation (EMT) of peritoneal mesothelial cells (HPMCs). Under high glucose stimulation, the addition of finerenone could alleviate high glucose induced EMT and disordered cytoskeleton rearrangement in HPMCs. Moreover, finerenone decreased the expression of enhancer of zeste homolog 2 (EZH2). Results of rescue experiment showed that after overexpression of EZH2 in the presence of finerenone, the protective effect of finerenone on EMT, migration capacity and cytoskeleton rearrangement was counteracted by EZH2 overexpression. The above results have also been demonstrated in in vivo experiments. These findings imply that finerenone could alleviate EMT and peritoneal fibrosis via regulating EZH2. More studies are needed to validate it and explore further mechanism.

Cardiovascular complications, particularly diabetic cardiomyopathy and heart failure, are leading causes of morbidity and mortality in patients with diabetes mellitus. This study aimed to investigate the therapeutic potential of finerenone and exenatide, individually and in combination, in mitigating diabetes-induced cardiac injury. Finerenone, a non-steroidal mineralocorticoid receptor antagonist, exhibits strong anti-fibrotic and anti-inflammatory properties in cardiovascular and renal diseases. Exenatide, a glucagon-like peptide-1 receptor agonist, is recognized for its glucose-lowering effects and additional cardioprotective actions, including antioxidant and anti-inflammatory activities. The combination of these agents was hypothesized to exert synergistic effects by targeting complementary pathological pathways involved in diabetic cardiomyopathy progression. Type 1 diabetes was induced in rats by a single high-dose streptozotocin injection. Animals were divided into five groups: control, STZ, STZ with finerenone, STZ with exenatide, and STZ with both finerenone and exenatide. Cardiac tissues and serum samples were analyzed for oxidative stress markers (TOS, TAS), inflammatory cytokines (IL-6, IL-1β, TNF-α), and myocardial injury biomarkers (cTnT, cTnI) through RT-qPCR and Western blotting. NRF2 pathway activation was also evaluated to assess antioxidant responses. STZ-induced diabetic rats showed significant increases in hyperglycemia, inflammation, oxidative stress, and myocardial injury. Treatment with either finerenone or exenatide alone improved several parameters; however, the combination therapy provided the most substantial cardioprotective effects, with marked reductions in oxidative stress and inflammation and enhanced NRF2 expression. These findings suggest that the combined administration of finerenone and exenatide offers superior protection against diabetes-induced cardiac injury compared to monotherapies, supporting a dual-targeted therapeutic approach for diabetic cardiomyopathy.