Psoralidin significantly improved cardiac function and survival in adriamycin-injured mice by ameliorating mitochondrial dysfunction, oxidative stress, and apoptosis via the SIRT1/PPARγ signaling pathway.
Does psoralidin improve adriamycin-induced cardiotoxicity in BALB/c mice and HL-1 cardiomyocytes?
Psoralidin demonstrates cardioprotective effects against adriamycin-induced cardiotoxicity in preclinical models via activation of the SIRT1/PPARγ signaling pathway.
p-value: p=<0.05
INTRODUCTION: Adriamycin (ADR) is an efficient and common broad-spectrum anticancer drug. However, the cumulative and dose-dependent toxicity induced by ADR severely limits its application in the clinic. Previous studies found that psoralidin (PSO) exhibits remarkable therapeutic effects against multiple cancers. OBJECTIVES: The aim of this study was to determine if PSO has beneficial effects on ADR-induced cardiotoxicity and to investigate the underlying mechanisms. METHODS: ADR-induced cardiotoxicity models were established in BALB/c mice and HL-1 cardiomyocytes. A series of experimental methods were used to evaluate the effects of PSO on cardiac function indicators, blood biochemical parameters, histopathology, oxidative stress, apoptosis, mitochondrial function, fibrosis, and SIRT1/PPARγ signaling. RESULTS: PSO significantly improved cardiac function indicators, blood biochemical parameters, and mitochondrial function and reduced the degree of myocardial fibrosis, oxidative stress, and apoptosis in ADR-injured mice. PSO significantly increased cell viability, inhibited the release of LDH, reduced oxidative stress and apoptosis, and improved mitochondrial function in ADR-injured HL-1 cells. Moreover, we also demonstrated there was cross-talk between SIRT1 and PPARγ, as shown by SIRT1 siRNA significantly decreasing the expression of PPARγ and GW9662 (a PPARγ antagonist), which remarkably reduced the expression of SIRT1. CONCLUSION: In summary, this study proved for the first time the beneficial effect of PSO on ADR-induced cardiotoxicity through activation of the SIRT1/PPARγ signaling pathway. Therefore, these findings may favor PSO as a potential cardioprotective drug candidate to alleviate ADR-induced cardiotoxicity in the clinic and improve the application of ADR in oncotherapy.
Liang et al. (Tue,) conducted a other in Adriamycin-induced cardiotoxicity. Psoralidin vs. Adriamycin alone or vehicle control was evaluated on Cardiac function, survival rate, and cell viability (p=<0.05). Psoralidin significantly improved cardiac function and survival in adriamycin-injured mice by ameliorating mitochondrial dysfunction, oxidative stress, and apoptosis via the SIRT1/PPARγ signaling pathway.
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