Patintingan Cyntia Gracesella, Louisa Melva, Juniantito Vetnizah, Arozal Wawaimuli, Hanifah Silmi, Wanandi Septelia Inawati, Thandavarayan Rajarajan
Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
J Exp Pharmacol. 2023 Jul 26;15:307-319. doi: 10.2147/JEP.S413256. eCollection 2023.
Doxorubicin, an anthracycline class of anticancer, is an effective chemotherapeutic agent with serious adverse effects, mainly cardiotoxicity. Several possible causes of doxorubicin cardiotoxicity are increased oxidative stress, nucleic acid and protein synthesis inhibition, cardiomyocyte apoptosis, and mitochondrial biogenesis disruptions. (MO), a naturally derived medicine, is known for its antioxidative properties and activity in alleviating mitochondrial dysfunction. To determine the potency and possible cardioprotective mechanism of MO leaves aqueous extract via the mitochondrial biogenesis pathway in doxorubicin-induced rats.
Twenty-four Sprague-Dawley rats were divided into four groups of six. The first group was normal rats; the second group was treated with doxorubicin 4 mg/kg BW intraperitoneally once weekly for four weeks; the third and fourth groups were treated with doxorubicin 4 mg/kg BW intraperitoneally once weekly, and MO leaves extract at 200 mg/kg BW or 400 mg/kg BW orally daily, for four weeks. At the end of the fourth week, blood and cardiac tissues were obtained and analyzed for cardiac biomarkers, mitochondrial DNA copy number, mRNA expressions of peroxisome-activated receptor-gamma coactivator-1 alpha (PGC-1α), the nuclear factor erythroid 2-related factor 2 (Nrf2), superoxide dismutase 2 (SOD2), caspase 3, the activity of glutathione peroxidase (GPx), levels of 8-hydroxy-2-deoxyguanosine (8-OH-dG), and malondialdehyde.
MO leaves extract was shown to decrease biomarkers of cardiac damage (LDH and CK-MB), malondialdehyde levels, and GPx activity. These changes align with the reduction of mRNA expressions of caspase-3, the increase of mRNA expressions of PGC-1α and Nrf2, and the elevation of mitochondrial DNA copy number. MO leaves extracts did not influence the mRNA expressions of superoxide dismutase 2 (SOD2) or the levels of 8-OH-dG.
leaves extract ameliorates doxorubicin-induced cardiotoxicity by reducing apoptosis and restoring gene expression of PGC-1α and Nrf2, a key regulator in mitochondrial biogenesis.
阿霉素是一种蒽环类抗癌药，是一种有效的化疗药物，但有严重的副作用，主要是心脏毒性。阿霉素心脏毒性的几种可能原因是氧化应激增加、核酸和蛋白质合成抑制、心肌细胞凋亡以及线粒体生物发生破坏。毛喉鞘蕊花（MO）是一种天然药物，以其抗氧化特性和减轻线粒体功能障碍的活性而闻名。为了确定MO叶水提取物通过线粒体生物发生途径在阿霉素诱导的大鼠中的效力和可能的心脏保护机制。
将24只Sprague-Dawley大鼠分为四组，每组6只。第一组为正常大鼠；第二组每周一次腹腔注射4mg/kg体重的阿霉素，共四周；第三组和第四组每周一次腹腔注射4mg/kg体重的阿霉素，同时每天口服200mg/kg体重或400mg/kg体重的MO叶提取物，共四周。在第四周结束时，采集血液和心脏组织，分析心脏生物标志物、线粒体DNA拷贝数、过氧化物酶体激活受体γ共激活因子-1α（PGC-1α）、核因子红细胞2相关因子2（Nrf2）、超氧化物歧化酶2（SOD2）、半胱天冬酶3的mRNA表达、谷胱甘肽过氧化物酶（GPx）活性、8-羟基-2-脱氧鸟苷（8-OH-dG）水平和丙二醛水平。
MO叶提取物显示可降低心脏损伤生物标志物（乳酸脱氢酶和肌酸激酶同工酶）、丙二醛水平和GPx活性。这些变化与半胱天冬酶-3 mRNA表达的降低、PGC-1α和Nrf2 mRNA表达的增加以及线粒体DNA拷贝数的升高一致。MO叶提取物不影响超氧化物歧化酶2（SOD2）的mRNA表达或8-OH-dG水平。
叶提取物通过减少细胞凋亡和恢复线粒体生物发生的关键调节因子PGC-1α和Nrf2的基因表达来改善阿霉素诱导的心脏毒性。
