ABSTRACT Purpose: Oxidative stress and apoptosis contribute to the pathological basis of doxorubicin (DOX)-induced cardiotoxicity. Columbianadin (CBN) is one of the main bioactive constituents isolated from the root of Angelica pubescens. Herein, we intended to explore the potential role and molecular basis of CBN in DOX-induced cardiotoxicity. Methods: C57BL/6 mice were subjected to DOX (15 mg/kg/day, i.p.) to generate DOX-induced cardiotoxicity. CBN (10 mg/kg/day, i.p.) was administered for four week following DOX injection. Results: DOX administered markedly dampened cardiac function, increased cardiac injury, excessive reactive oxygen species (ROS) production, and cardiomyocyte loss. These alterations induced by DOX significantly alleviated by CBN treatment. Mechanistically, our results demonstrated that the CBN exerts cardioprotection role against DOX by up-regulating silent information regulator 1 (Sirt1) and decreasing acetylation of forkhead box O1 (FOXO1). Moreover, Sirt1 inhibition with Ex-527 significantly blunt the beneficial effect of CBN on DOX-induced cardiotoxicity, including cardiac dysfunction, ROS, and apoptosis. Conclusion: Collectively, CBN attenuated oxidative stress and cardiomyocyte apoptosis in DOX-induced cardiotoxicity through maintaining Sirt1/FOXO1 signaling pathway. Our results demonstrated that CBN might be used to treat DOX-related cardiotoxicity.

Abstract Glutathione S-transferases (GSTs) are proteins synthesized in plants and responsible for their tolerance to environmental stresses. However, little information is available on the GST gene family of sweet potato, a globally important crop. The genetic evolution of GSTs in sweet potato remains unclear. The present study investigated the GST gene family in sweet potato by transcriptomic and comparative genomic analyses. A total of 51 GSTs were identified. Gene expression analysis showed differential expression patterns of the GSTs between two investigated varieties. Some GST expression levels were either up- or downregulated under oxidative, salinity and drought stresses. The results of the investigation provided new insights on the GST gene family in sweet potato, which may further the understanding of the roles of these genes in regulating abiotic stresses.