Department of Pharmaceutical Engineering, School of Life and Health Sciences, Huzhou College, Huzhou 313000, China.
Qinghai Provincial Key Laboratory of Tibetan Medicine Research and CAS Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau Biology, Xining 810008, China.
Int J Mol Sci. 2023 Feb 6;24(4):3174. doi: 10.3390/ijms24043174.
Doxorubicin (Dox) is one of the most frequently prescribed anti-cancer drugs. However, treatment with Dox is limited due to cumulative cardiotoxicity. 3--β-d-Sophorosylkaempferol-7--{3--[2(E)-2,6-dimethyl-6-hydroxyocta-2,7-dienoyl]}-α-L-rhamnoside (F-A), kaempferol 3-sophoroside 7-rhamnoside (F-B), and hippophanone (F-C) were successfully obtained by purification and separation of seabuckthorn seed residue in our previous research. This study was undertaken to investigate the protective effect of three flavonoids against Dox-induced H9c2 cell apoptosis. Cell proliferation was detected by MTT assay. 2',7'-Dichlorofluorescein diacetate (DCFH-DA) was used to determine the production of intracellular reactive oxygen species (ROS). ATP content was measured using an assay kit. Transmission electron microscopy (TEM) was used to observe changes in mitochondrial ultrastructure. The expression levels of proteins (p-JNK, JNK, p-Akt, Akt, p-P38, P38, p-ERK, ERK, p-Src, Src, Sab, IRE1α, Mfn1, Mfn2, and cleaved caspase-3) were evaluated by Western blot. Molecular docking was performed using AutoDock Vina. The three flavonoids could significantly relieve Dox-induced cardiac injury and inhibit cardiomyocyte apoptosis. The mechanisms were mainly related to the stability of mitochondrial structure and function maintained by suppressing the production of intracellular ROS, p-JNK and cleaved caspase-3, and increasing ATP contents and protein expression of mitochondrial mitofusin (Mfn1, Mfn2), Sab and p-Src. Pretreatment with flavonoids from Linn. can reduce Dox-induced H9c2 cell apoptosis based on the 'JNK-Sab-Ros' signal pathway.
阿霉素（Dox）是最常开的抗癌药物之一。然而，由于累积性心脏毒性，Dox 的治疗受到限制。在我们之前的研究中，通过纯化和分离沙棘种子残渣，成功获得了 3-β-D-槐糖苷-7-[3-[2(E)-2,6-二甲基-6-羟基辛-2,7-二烯酰基]-α-L-鼠李糖苷（F-A）、槐糖苷 3-槐糖苷 7-鼠李糖苷（F-B）和山楂酮（F-C）。本研究旨在探讨三种类黄酮对 Dox 诱导的 H9c2 细胞凋亡的保护作用。通过 MTT 检测法检测细胞增殖。使用 2',7'-二氯荧光素二乙酸酯（DCFH-DA）测定细胞内活性氧（ROS）的产生。使用试剂盒测定 ATP 含量。通过透射电子显微镜（TEM）观察线粒体超微结构的变化。通过 Western blot 评估蛋白质（p-JNK、JNK、p-Akt、Akt、p-P38、P38、p-ERK、ERK、p-Src、Src、Sab、IRE1α、Mfn1、Mfn2 和裂解 caspase-3）的表达水平。使用 AutoDock Vina 进行分子对接。三种类黄酮可显著缓解 Dox 诱导的心脏损伤并抑制心肌细胞凋亡。其机制主要与通过抑制细胞内 ROS、p-JNK 和裂解 caspase-3 的产生，以及增加 ATP 含量和线粒体融合蛋白（Mfn1、Mfn2）、Sab 和 p-Src 的蛋白表达来维持线粒体结构和功能的稳定性有关。类黄酮预处理可以减少 Dox 诱导的 H9c2 细胞凋亡，其作用机制可能与 JNK-Sab-Ros 信号通路有关。
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