Protective Effects and Mechanisms of Psoralidin Against Adriamycin-induced Cardiotoxicity

Overview

Journal J Adv Res

Specialties General Medicine
Science

Date 2022 Sep 13

PMID 36100330

Authors

Zhenxing Liang

Ying Chen

Zheng Wang

Xue Wu

Chao Deng

Changyu Wang

Wenwen Yang

Ye Tian

Shaofei Zhang

Chenxi Lu

Yang Yang

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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Psoralidin inhibits osteosarcoma growth and metastasis by downregulating ITGB1 expression via the FAK and PI3K/Akt signaling pathways.

Cheng S, Liu S, Chen B, Du C, Xiao P, Luo X Chin Med. 2023; 18(1):34.

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