菊苣提取物抗阿霉素心脏毒性作用挖掘及验证

doi:10.19803/j.1672-8629.20230118

摘要/Abstract

摘要： 目的挖掘并验证菊苣提取物抗阿霉素心脏毒性的潜在作用。方法进行文献研究,整合菊苣抗心肌损伤的研究进展;基于网络药理学探讨菊苣抗心肌损伤机制,分析其与阿霉素心脏毒性机制的重合性;采用15 mg·kg^-1阿霉素单次腹腔注射建立心脏毒性小鼠模型,给予低、中、高剂量菊苣水提物（3.8 、19 、38 g·kg^-1）干预8 d,验证菊苣抗阿霉素心脏毒性的潜在作用。结果在菊苣抗心肌损伤领域共有13篇文章,均为基础研究,包括菊苣醇提物、菊苣酸以及菊苣多糖等药物,包括纳米铅、脓毒症致心肌损伤等动物模型;菊苣心脏保护作用机制主要为抗炎抗氧化应激,涉及ErbB、MAPK、PI3K-Akt等信号通路及TP53、Src、STAT3、AKT1等核心靶点,与阿霉素心脏毒性发病机制有较大重合性;菊苣水提物可显著升高模型小鼠心脏系数及终末体重,降低模型小鼠心脏组织匀浆及血清NT-ProBNP、CK-MB、LDH、AST水平,改善模型小鼠心脏组织纤维排列紊乱,核固缩等情况。结论菊苣具有抗阿霉素心脏毒性的潜在作用,值得进一步挖掘与研究,以指导阿霉素及菊苣的临床合理应用。

关键词: 菊苣, 阿霉素, 心脏毒性, 网络药理学, 药效挖掘, 药效验证, 小鼠

Abstract: Objective To explore and validate the potential role of chicory extract against adriamycin cardiotoxicity. Methods Related literature was reviewed to sum up advances in research on protective effects of chicory against myocardial injury. Based on network pharmacology, the mechanism of chicory against myocardial injury was explored, and its coincidence with the cardiotoxicity mechanism of adriamycin was analyzed. A mouse model of cardiotoxicity was established using a single intraperitoneal injection of 15 mg·kg^-1 adriamycin, and low, medium and high doses of chicory water extract (3.8, 19, 38 g·kg^-1) were administered for 8 d to verify the potential effects of chicory against adriamycin cardiotoxicity. Results There were 13 articles on the effect of chicory against myocardial injury, all of which were concerned with basic research, involving chicory alcohol extract, chicory acid, chicory polysaccharide, andanimal models of myocardial injury caused by nano-lead and sepsis. The protective mechanism of chicory heart was mainly anti-inflammation and anti-oxidation stress, involving such signal pathways as ErbB, MAPK and PI3K-Akt as well as TP53, Src, STAT3, AKT1 and other core targets, which overlapped with the pathogenesis of adriamycin cardiotoxicity to a great extent. Chicory water extract could significantly increase the cardiac coefficient and terminal body weight of model mice, reduce the mouse levels of NT-ProBNP, CK-MB, LDH, and AST in the cardiac tissue homogenate and serum, and improve their disorder of cardiac tissue fiber arrangement and nuclear pyknosis. Conclusion Chicory has the potential effect of anti-adriamycin cardiotoxicity, which is worthy of more exploration and research to guide the rational clinical use of adriamycin and chicory.

Key words: chicory, adriamycin, cardiac toxicity, network pharmacology, drug effect excavation, pharmacodynamic validation, mice

中图分类号:

R972
R994.11

殷玉玲, 胡楚涓, 张晓朦, 王雨, 张冰, 林志健. 菊苣提取物抗阿霉素心脏毒性作用挖掘及验证[J]. 中国药物警戒, 2023, 20(8): 858-865.

YIN Yuling, HU Chujuan, ZHANG Xiaomeng, WANG Yu, ZHANG Bing, LIN Zhijian. Mining and validation of anti-adriamycin cardiotoxic effect of chicory extract[J]. Chinese Journal of Pharmacovigilance, 2023, 20(8): 858-865.

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