瑞香狼毒（L.）DC 花的乙醇提取物通过减轻 H9c2 细胞中的细胞凋亡和调节线粒体动力学来减轻阿霉素诱导的心脏毒性。
Ethanol extracts of Rhaponticum uniflorum (L.) DC flowers attenuate doxorubicin-induced cardiotoxicity via alleviating apoptosis and regulating mitochondrial dynamics in H9c2 cells.
机构信息
Institute of Pharmaceutical Chemistry and Pharmacology, Inner Mongolia Minzu University, Tongliao, 028000, Inner Mongolia Autonomous Region, PR China; Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao, 028000, Inner Mongolia Autonomous Region, PR China.
Key Laboratory of Mongolian Medicine Research and Development Engineering, Ministry of Education, Tongliao, 028000, Inner Mongolia Autonomous Region, PR China.
出版信息
J Ethnopharmacol. 2022 Apr 24;288:114936. doi: 10.1016/j.jep.2021.114936. Epub 2022 Jan 7.
ETHNOPHARMACOLOGICAL RELEVANCE
Loulu flowers (LLF) is the inflorescence of Rhaponticum uniflorum (L.) DC. (R. uniflorum), a member of the Compositae family. This plant possesses heat-clearing properties, detoxification effects, and is therefore frequently used for the treatment of cardiovascular diseases.
AIM OF THIS STUDY
This study aimed to investigate the cardioprotective effects of ethanol extracts of LLF against doxorubicin (DOX)-induced cardiotoxicity and explore the associated mechanisms.
MATERIAL AND METHODS
Ethanol extracts of LLF were prepared and analyzed by LC-ESI-MS/MS. DOX-treated H9c2 cells and DOX-treated zebrafish models were used to explore the cardioprotective effect of ethanol extracts on myocardial function. The effects of LLF on DOX-induced cytotoxicity in H9c2 cells were investigated by MTT assay. Reactive Oxygen Species (ROS) levels, mitochondrial membrane potential (MMP), and nuclear translocation of NF-κB p65 were examined using fluorescent probes. The expression level of Bax, Bcl-2, PARP, caspase-3, cleaved-caspase3, caspase9, IκBα, p-IκBα, IKK, p-IKK, p65, p-p65, OPA1, Mfn1, MFF and Fis 1 and GAPDH was determined by western blotting.
RESULTS
Twenty-five compounds were detected in ethanol extracts of LLF, include Nicotinamide, Coumarin, Parthenolide, and Ligustilide. Pre-treatment with LLF attenuated the DOX-induced decrease in viability and ROS production in H9c2 cells. Moreover, LLF treatment maintained the mitochondrial membrane integrity and suppressed apoptosis by upregulating expression level of Bcl-2 and downregulating the expression level of Bax, cleaved-caspase-3, cleaved-caspase-9 and cleaved-PARP. In addition, LLF significantly inhibited the DOX-induced activation of NF-κB signaling. Cells treated with DOX showed aberrant expression of mitochondrial dynamics related proteins, and these effects were alleviated by LLF pre-treatment. In conclusion, these results show that LLF can alleviate DOX-induced cardiotoxicity by blocking NF-κB signaling and re-balancing mitochondrial dynamics.
CONCLUSION
Ethanol extracts of LLF is a potential treatment option to against DOX-induced cardiotoxicity.
民族药理学相关性
绿萝花（LLF）是旋覆花属（Raponticum uniflorum）（R. uniflorum）的花序，属于菊科。该植物具有清热、解毒的功效，因此常用于治疗心血管疾病。
研究目的
本研究旨在探讨绿萝花乙醇提取物对阿霉素（DOX）诱导的心脏毒性的保护作用，并探讨其相关机制。
材料和方法
采用 LC-ESI-MS/MS 法制备和分析绿萝花乙醇提取物。采用 DOX 处理的 H9c2 细胞和 DOX 处理的斑马鱼模型，探讨乙醇提取物对心肌功能的保护作用。采用 MTT 法检测绿萝花对 H9c2 细胞中 DOX 诱导的细胞毒性的影响。采用荧光探针检测活性氧（ROS）水平、线粒体膜电位（MMP）和 NF-κB p65 的核转位。采用 Western blot 法检测 Bax、Bcl-2、PARP、caspase-3、cleaved-caspase3、caspase9、IκBα、p-IκBα、IKK、p-IKK、p65、p-p65、OPA1、Mfn1、MFF 和 Fis1 和 GAPDH 的表达水平。
结果
在绿萝花乙醇提取物中检测到 25 种化合物，包括烟酰胺、香豆素、白头翁内酯和蛇床子素。绿萝花预处理可减轻 DOX 诱导的 H9c2 细胞活力下降和 ROS 产生。此外，绿萝花通过上调 Bcl-2 的表达水平和下调 Bax、cleaved-caspase-3、cleaved-caspase-9 和 cleaved-PARP 的表达水平，维持线粒体膜的完整性，抑制细胞凋亡。此外，绿萝花显著抑制 DOX 诱导的 NF-κB 信号转导的激活。用 DOX 处理的细胞表现出线粒体动力学相关蛋白的异常表达，这种作用可以通过绿萝花预处理来缓解。总之，这些结果表明，绿萝花通过阻断 NF-κB 信号转导和重新平衡线粒体动力学，可减轻 DOX 诱导的心脏毒性。
结论
绿萝花乙醇提取物可能是一种对抗 DOX 诱导的心脏毒性的治疗选择。
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