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Exploring the effective components of honey-processed licorice (Glycyrrhiza uralensis Fisch.) in attenuating Doxorubicin-induced myocardial cytotoxicity by combining network pharmacology and in vitro experiments

异甘草素 甘草 甘草苷元 药理学 化学 甘草苷 化学 心肌保护 传统医学 生物化学 生物 医学 药物发现 色谱法 替代医学 病理 高效液相色谱法 缺血 心脏病学
作者
Peijun Sun,Huixian Chen,Xiaoyu Fan,Ao Wang,Lujie Lu,Guangchao Yang,Jining Liu,Weifeng Yao,Feng Ding,Jie Ding,Jianmei Liu,Tulin Lu,Lihong Chen
出处
期刊:Journal of Ethnopharmacology [Elsevier]
卷期号:329: 118178-118178 被引量:1
标识
DOI:10.1016/j.jep.2024.118178
摘要

Licorice is widely used clinically as one of the most famous traditional Chinese herbs. Its herb roasted with honey is called honey-processed licorice (HPL). Modern studies have shown that HPL has a stronger cardioprotective ability compared to raw licorice (RL), however the material basis and mechanism of action of the potential cardioprotection have not been fully elucidated. To screen and validate the material basis of cardioprotection exerted by HPL and to preliminarily predict the potential mechanism of action. UPLC-QTOF-MS/MS was used to analyze HPL samples with different processing levels, and differential compounds were screened out through principal component analysis. Network pharmacology and molecular docking were applied to explore the association between differential compounds and doxorubicin cardiomyopathy and their mechanisms of action were predicted. An in vitro model was established to verify the cardioprotective effects of differential compounds. Six differential compounds were screened as key components of HPL for potential cardioprotection. Based on network pharmacology, 113 potential important targets for the treatment of Dox-induced cardiotoxicity were screened. KEGG enrichment analysis predicted that the PI3K-Akt pathway was closely related to the mechanism of action of active ingredients. Molecular docking results showed that the six differential compounds all had good binding activity with Nrf2 protein. In addition, in vitro experiments had shown that five of the active ingredients (liquiritin, isoliquiritin, liquiritigenin, isoliquiritigenin, and licochalcone A) can significantly increase Dox-induced H9c2 cell viability, SOD activity, and mitochondrial membrane potential, significantly reduces MDA levels and inhibits ROS generation. Liquiritin, isoliquiritin, liquiritigenin, isoliquiritigenin and licochalcone A are key components of HPL with potential cardioprotective capabilities. Five active ingredients can alleviate Dox-induced cardiotoxicity by inhibiting oxidative stress and mitochondrial damage.
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