Protective effects and mechanisms of psoralidin against adriamycin-induced cardiotoxicity.
Protective effects and mechanisms of psoralidin against adriamycin-induced cardiotoxicity.
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DOI：
10.1016/j.jare.2021.12.007
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发表时间：
2022-09
影响因子：
10.7
通讯作者：
Yang, Yang
中科院分区：
文献类型：
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作者：
Liang, Zhenxing;Chen, Ying;Wang, Zheng;Wu, Xue;Deng, Chao;Wang, Changyu;Yang, Wenwen;Tian, Ye;Zhang, Shaofei;Lu, Chenxi;Yang, Yang
提出的方案描述了 PSO 通过激活 SIRT1/PPARγ 信号通路来防止 ADR 诱导的心脏毒性的机制。 PSO对阿霉素（ADR）引起的心脏毒性的有益作用，表现为改善线粒体功能障碍、心肌纤维化、氧化应激和细胞凋亡。PSO通过调节SIRT1/PPARγ信号通路来保护ADR引起的心脏毒性。PSO被证明是一种潜在的心脏保护药物候选物，可减轻ADR引起的心脏毒性，并扩大ADR在肿瘤治疗中的应用。阿霉素（ADR）是一种高效、常用的广谱抗癌药物。然而，ADR引起的累积性和剂量依赖性毒性严重限制了其在临床的应用。先前的研究发现补骨脂素（PSO）对多种癌症具有显着的治疗效果。本研究的目的是确定 PSO 是否对 ADR 引起的心脏毒性具有有益作用并调查其潜在机制。在 BALB/c 小鼠和 HL-1 心肌细胞中建立了 ADR 诱导的心脏毒性模型。采用一系列实验方法评价PSO对心功能指标、血液生化参数、组织病理学、氧化应激、细胞凋亡、线粒体功能、纤维化和SIRT1/PPARγ信号传导的影响。 PSO显着改善ADR损伤小鼠的心功能指标、血液生化参数和线粒体功能，降低心肌纤维化、氧化应激和细胞凋亡程度。 PSO 显着增加细胞活力，抑制 LDH 的释放，减少氧化应激和细胞凋亡，并改善 ADR 损伤的 HL-1 细胞中的线粒体功能。此外，我们还证明SIRT1和PPARγ之间存在串扰，如SIRT1 siRNA显着降低PPARγ和GW9662（PPARγ拮抗剂）的表达，GW9662显着降低SIRT1的表达。总之，本研究首次证明了 PSO 通过激活 SIRT1/PPARγ 信号通路对 ADR 诱导的心脏毒性产生有益作用。因此，这些发现可能有利于PSO作为潜在的心脏保护药物候选药物，以减轻ADR引起的临床心脏毒性，并改善ADR在肿瘤治疗中的应用。
Proposed scheme depicting the mechanisms by which PSO protects against ADR-induced cardiotoxicity by activating the SIRT1/PPARγ signaling pathway. The beneficial effect of PSO on Adriamycin (ADR)-induced cardiotoxicity, which is manifested in amelioration of mitochondrial dysfunction, myocardial fibrosis, oxidative stress, and apoptosis PSO protects ADR-induced cardiotoxicity via regulating SIRT1/PPARγ signaling pathway PSO is proved to be a potential cardioprotective drug candidate to alleviate ADR-induced cardiotoxicity in clinical and amplify the application of ADR in oncotherapy. 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. The aim of this study was to determine if PSO has beneficial effects on ADR-induced cardiotoxicity and to investigate the underlying mechanisms. 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. 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. 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.
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影响因子：
9.3
作者：
Quagliariello V;De Laurentiis M;Rea D;Barbieri A;Monti MG;Carbone A;Paccone A;Altucci L;Conte M;Canale ML;Botti G;Maurea N
通讯作者：
Maurea N
影响因子：
2.9
作者：
Jin, Zhiliang;Yan, Wei;Xu, Yanhua
通讯作者：
Xu, Yanhua
影响因子：
44.1
作者：
Dong, JW;Zhu, HF;Zhou, ZN
通讯作者：
Zhou, ZN
影响因子：
37.8
作者：
Chen, Si;Zhang, Yishuai;Yan, Chen
通讯作者：
Yan, Chen
影响因子：
82.9
作者：
通讯作者：
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