Yu Xiaojin, Wang Zhenyu, Shu Zunpeng, Li Zhengqing, Ning Yuan, Yun Keli, Bai Haina, Liu Ruihai, Liu Wenli
School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150090, China; College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150040, China.
School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150090, China.
Biomed Pharmacother. 2017 Apr;88:1-10. doi: 10.1016/j.biopha.2016.12.130. Epub 2017 Jan 13.
The cardiotoxicity of arsenic trioxide (ATO) limits its clinical application in cancer treatment. Evidences suggest that sorbus has antioxidant activity and its consumption has been linked with improved cardioprotection. In this study, we investigated the cardio-protective effect and mechanisms of Sorbus pohuashanensis (Hante) Hedl. flavonoids (SPF) against ATO in BALB/c mice and H9c2 cells. Eleven major flavonoids were confirmed by ultra-performance liquid chromatography electrospray ionization quadrupole time of flight mass spectrometry (UPLC-ESI-Q-TOF-MS). SPF recovered the ATO-induced disordered electrocardiogram (ECG) and abnormal cardiac structure in the heart of mice. At the same time, SPF significantly reduced levels of creatine kinase (CK), creatine kinase-MB (CK-MB) lactate dehydrogenase (LDH), and glutamic oxaloacetic transaminase (GOT) against ATO-induced injury and inhibited ATO-induced apoptosis both in vivo and in vitro. In addition, SPF regulated ATO-induced oxidative stress damage by increasing the levels of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in vivo and in vitro, and reducing reactive oxygen species (ROS). Analysis of the oxidative stress pathways showed that SPF prevented the ATO-induced downregulation of phosphorylated protein kinase B (p-Akt) in vivo and in vitro. Pre-treatment of H9c2 cells with SPF inhibited attenuation of nuclear factor (Nrf2) and heme oxygenase (HO-1). Hence, SPF could be used as a preventive and therapeutic plant ingredient against ATO-induced cardiotoxicity.
三氧化二砷（ATO）的心脏毒性限制了其在癌症治疗中的临床应用。有证据表明，花楸具有抗氧化活性，食用花楸与改善心脏保护作用有关。在本研究中，我们调查了花楸（Sorbus pohuashanensis (Hante) Hedl.）黄酮类化合物（SPF）对BALB/c小鼠和H9c2细胞中ATO诱导的心脏毒性的保护作用及其机制。通过超高效液相色谱电喷雾电离四极杆飞行时间质谱（UPLC-ESI-Q-TOF-MS）鉴定了11种主要黄酮类化合物。SPF恢复了ATO诱导的小鼠心脏心电图（ECG）紊乱和心脏结构异常。同时，SPF显著降低了肌酸激酶（CK）、肌酸激酶同工酶-MB（CK-MB）、乳酸脱氢酶（LDH）和谷草转氨酶（GOT）的水平，减轻了ATO诱导的损伤，并在体内和体外抑制了ATO诱导的细胞凋亡。此外，SPF通过在体内和体外提高超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GSH-Px）的水平，并减少活性氧（ROS），来调节ATO诱导的氧化应激损伤。氧化应激途径分析表明，SPF在体内和体外均能防止ATO诱导的磷酸化蛋白激酶B（p-Akt）下调。用SPF预处理H9c2细胞可抑制核因子（Nrf2）和血红素加氧酶（HO-1）的衰减。因此，SPF可作为一种预防和治疗ATO诱导的心脏毒性的植物成分。
