荠菜水提取物通过上调抗氧化酶减轻阿霉素引起的心脏毒性。
Water Extract of Capsella bursa-pastoris Mitigates Doxorubicin-Induced Cardiotoxicity by Upregulating Antioxidant Enzymes.
发表日期:2023 Nov 02
作者:
Yuhui Jeong, Sun-Ho Lee, Jangho Lee, Min-Sun Kim, Yu-Geon Lee, Jin-Taek Hwang, Sang-Yoon Choi, Ho-Geun Yoon, Tae-Gyu Lim, Seung-Hyun Lee, Hyo-Kyoung Choi
来源:
Stem Cell Research & Therapy
摘要:
阿霉素(DOX)是一种有效的化疗药物,会以累积和剂量依赖性方式引起心脏毒性。本研究的目的是研究荠菜热水提取物 (CBW) 对 DOX 诱导的心脏毒性 (DICT) 的影响。我们利用 H9c2 大鼠心肌细胞和 MDA-MB-231 人乳腺癌细胞来评估 CBW 对 DOX 诱导的细胞死亡的影响。测量 H9c2 细胞中的超氧化物歧化酶 (SOD) 水平、活性氧 (ROS) 产生和耗氧率。 C57BL/6 小鼠接受 DOX 和 CBW 治疗,以评估它们对各种心脏参数的影响。人诱导的多能干细胞来源的心肌细胞也被用来研究 DOX 诱导的电生理变化和 CBW 的潜在改善作用。 UPLC-TQ/MS 分析鉴定出 CBW 中的七种黄酮类化合物,其中木犀草素-7-O-葡萄糖苷和异荠草苷为主要化合物。 CBW 抑制 DOX 诱导的 H9c2 大鼠心肌细胞死亡,但不影响 DOX 诱导的 MDA-MB-231 人乳腺癌细胞死亡。 CBW 以剂量依赖性方式增加 SOD 水平,减少 ROS 产生并增加 H9c2 细胞的耗氧率。与单独使用 DOX 治疗的小鼠相比,使用 DOX 和 CBW 联合治疗的 C57BL/6 小鼠的心率、RR 间期、QT 和 ST 延长显着恢复。 CBW 与 DOX 联合给药可有效减轻小鼠心脏组织中的胶原蛋白积累和细胞死亡,并降低血清中肌酸激酶 (CK) 和乳酸脱氢酶 (LDH) 的水平。此外,CBW 改善了人诱导多能干细胞来源的心肌细胞中 DOX 诱导的病理电生理特征。 CBW 可以通过稳定 SOD 和清除 ROS 来预防 DICT。 CBW 中黄酮类化合物的存在,特别是木犀草素-7-O-葡萄糖苷和异荠草素,可能有助于其保护作用。这些结果表明 CBW 作为减轻 DOX 引起的心脏毒性的传统治疗选择的潜力。
Doxorubicin (DOX), an effective chemotherapeutic drug, causes cardiotoxicity in a cumulative and dose-dependent manner. The aim of this study is to investigate the effects of hot-water extract of Capsella bursa-pastoris (CBW) on DOX-induced cardiotoxicity (DICT). We utilized H9c2 rat cardiomyocytes and MDA-MB-231 human breast cancer cells to evaluate the effects of CBW on DOX-induced cell death. Superoxide dismutase (SOD) levels, reactive oxygen species (ROS) production, and oxygen consumption rate were measured in H9c2 cells. C57BL/6 mice were treated with DOX and CBW to assess their impact on various cardiac parameters. Human-induced pluripotent stem-cell-derived cardiomyocytes were also used to investigate DOX-induced electrophysiological changes and the potential ameliorative effects of CBW. UPLC-TQ/MS analysis identified seven flavonoids in CBW, with luteolin-7-O-glucoside and isoorientin as the major compounds. CBW inhibited DOX-induced death of H9c2 rat cardiomyocytes but did not affect DOX-induced death of MDA-MB-231 human breast cancer cells. CBW increased SOD levels in a dose-dependent manner, reducing ROS production and increasing the oxygen consumption rate in H9c2 cells. The heart rate, RR interval, QT, and ST prolongation remarkably recovered in C57BL/6 mice treated with the combination of DOX and CBW compared to those in mice treated with DOX alone. Administration of CBW with DOX effectively alleviated collagen accumulation, cell death in mouse heart tissues, and reduced the levels of creatinine kinase (CK) and lactate dehydrogenase (LDH) in serum. Furthermore, DOX-induced pathological electrophysiological features in human-induced pluripotent stem-cell-derived cardiomyocytes were ameliorated by CBW. CBW may prevent DICT by stabilizing SOD and scavenging ROS. The presence of flavonoids, particularly luteolin-7-O-glucoside and isoorientin, in CBW may contribute to its protective effects. These results suggest the potential of CBW as a traditional therapeutic option to mitigate DOX-induced cardiotoxicity.