Emodin alleviates CRS4-induced mitochondrial damage via activation of the PGC1α signaling.

Cardiorenal syndrome type 4 (CRS4), a progressive deterioration of cardiac function secondary to chronic kidney disease (CKD), is a leading cause of death in patients with CKD. In this study, we aimed to investigate the cardioprotective effect of emodin on CRS4. C57BL/6 mice with 5/6 nephrectomy and HL-1 cells stimulated with 5% CKD mouse serum were used for in vivo and in vitro experiments. To assess the cardioprotective potential of emodin, we employed a comprehensive array of methodologies, including echocardiography, tissue staining, immunofluorescence staining, biochemical detection, flow cytometry, real-time quantitative PCR, and western blot analysis. Our results showed that emodin exerted protective effects on the function and structure of the residual kidney. Emodin also reduced pathologic changes in the cardiac morphology and function of these mice. These effects may have been related to emodin-mediated suppression of reactive oxygen species production, reduction of mitochondrial oxidative damage, and increase of oxidative metabolism via restoration of PGC1α expression and that of its target genes. In contrast, inhibition of PGC1α expression significantly reversed emodin-mediated cardioprotection in vivo. In conclusion, emodin protects the heart from 5/6 nephrectomy-induced mitochondrial damage via activation of the PGC1α signaling. The findings obtained in our study can be used to develop effective therapeutic strategies for patients with CRS4.

Astragaloside IV attenuates myocardial dysfunction in diabetic cardiomyopathy rats through downregulation of CD36-mediated ferroptosis.

Diabetic cardiomyopathy (DCM), one of the major complications of type 2 diabetes, is a leading cause of heart failure and death in advanced diabetes. Although there is an association between DCM and ferroptosis in cardiomyocytes, the internal mechanism of ferroptosis leading to DCM development remains unknown. CD36 is a key molecule in lipid metabolism that mediates ferroptosis. Astragaloside IV (AS-IV) confers various pharmacological effects such as antioxidant, anti-inflammatory, and immunomodulatory. In this study, we demonstrated that AS-IV was able to recover the dysfunction of DCM. In vivo experiments showed that AS-IV ameliorated myocardial injury and improved contractile function, attenuated lipid deposition, and decreased the expression level of CD36 and ferroptosis-related factors in DCM rats. In vitro experiments showed that AS-IV decreased CD36 expression and inhibited lipid accumulation and ferroptosis in PA-induced cardiomyocytes. The results demonstrated that AS-IV decreased cardiomyocyte injury and myocardial dysfunction by inhibiting ferroptosis mediated by CD36 in DCM rats. Therefore, AS-IV regulated the lipid metabolism of cardiomyocytes and inhibited cellular ferroptosis, which may have potential clinical value in DCM treatment.