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广金钱草提取物抗胆汁淤积性肝损伤的活性成分筛选及其作用机制研究
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| 篇名： | 广金钱草提取物抗胆汁淤积性肝损伤的活性成分筛选及其作用机制研究 |
| TITLE： | Study on screening of active components from Desmodium styracifolium（ Osb.） Merr. extract against cholestatic liver injury and its mechanism of action |
| 摘要： | 目的 阐明广金钱草提取物（DME）抗胆汁淤积性肝损伤（CLI）的活性成分，并验证其作用靶点与分子机制，为广金钱草的临床应用及保肝新药研发提供科学依据。方法采用高效液相色谱法建立19批DME的指纹图谱，并进行相似度评价和共有峰指认；采用石胆酸（LCA）诱导HepG2细胞损伤建立体外CLI模型，评价DME体外抗CLI的作用；采用Spearman相关性分析、灰色关联度分析和偏最小二乘回归分析评价DME抗CLI的谱效关系，初步筛选核心活性成分；通过分子对接、表面等离子共振技术预测并验证核心活性成分与法尼醇X受体（FXR）的结合能力；采用qRT-PCR、Westernblot、免疫荧光染色实验验证核心活性成分对CLI模型细胞中FXR/胆汁酸盐输出泵（BSEP）通路相关分子表达的影响。结果19批DME指纹图谱中共标定12个共有峰，相似度均大于0.990；共指认出4个共有峰，分别为6号峰（夏佛塔苷）、7号峰（异荭草苷）、11号峰（异夏佛塔苷）、12号峰（异牡荆苷）。80μg/mLDME对CLI模型细胞的保护作用最好，作用24h后细胞存活率为（75.66±4.60）%。谱效关系研究结果显示，夏佛塔苷与DME抗CLI的关联性最强，为核心活性成分。靶点预测与验证结果显示，夏佛塔苷与FXR的结合能为－8.1kcal/mol，平衡解离常数为27.3μmol/L。机制研究结果显示，100μmol/L夏佛塔苷可显著升高CLI模型细胞中FXR、BSEP蛋白及其编码基因Nr1h4、Abcb11的mRNA表达水平（P＜0.05）。结论夏佛塔苷可能是DME抗CLI的核心活性成分，其作用机制可能与激活FXR/BSEP通路有关。 |
| ABSTRACT： | OBJECTIVE To identify the active components of Desmodium styracifolium （Osb.） Merr. extract （DME） against cholestatic liver injury （CLI）， and to verify its target and molecular mechanism， so as to provide scientific evidence for the clinical application of D.styracifolium （Osb.） Merr. and the development of new hepatoprotective agents.METHODS High-performance liquid chromatography was applied to establish fingerprints of 19 batches of DME， followed by similarity evaluation and identification of common peaks. An in vitro CLI model was constructed by lithocholic acid （LCA）-induced injury in HepG2 cells to evaluate the in vitro protective effect of DME against CLI. Spearman correlation analysis， grey relational analysis and partial least-squares regression analysis were adopted to investigate the spectrum-effect relationship of DME against CLI and preliminarily screen the core active components. Molecular docking and surface plasmon resonance technology were used to predict and verify the binding capacity between core active components and farnesoid X receptor （FXR）. qRT-PCR， Western blot and immunofluorescence staining tests were performed to validate the influences of core active components on the expression of molecules related to FXR/bile salt export pump （BSEP） pathway in CLI model cells.RESULTS A total of 12 common peaks were calibrated in the fingerprints of 19 batches of DME， and the similarity values were all above 0.990. Four common peaks were identified， namely peak 6 （schaftoside）， peak 7 （isoorientin）， peak 11 （isoschaftoside） and peak 12 （isovitexin）. DME at 80 μg/mL exerted the optimal protective effect on CLI-model cells， and the cell viability reached （75.66±4.60）% after 24 h of treatment. Spectrum-effect analysis revealed that schaftoside possessed the strongest correlation with the anti-CLI activity of DME and served as the core active component. Target prediction and validation results showed that the binding energy between schaftoside and FXR was －8.1 kcal/mol， and the equilibrium dissociation constant was 27.3 μmol/L. Mechanistic experiments demonstrated that 100 μmol/L schaftoside significantly elevated the expression levels of FXR and BSEP， and mRNA of their encoded genes Nr1h4 ， Abcb11 in CLI-model cells （ P ＜0.05）.CONCLUSIONS Schaftoside may be the core active component of DME against CLI， and its mechanism may be related to the activation of FXR/BSEP pathway. |
| 期刊： | 2026年第37卷第17期 |
| 作者： | 黄涛；陈超；韦文华；韦柳婷；李波；高雅；曹后康 |
| AUTHORS： | HUANG Tao，CHEN Chao，WEI Wenhua，WEI Liuting，LI Bo，GAO Ya，CAO Houkang |
| 关键字： | 广金钱草提取物；胆汁淤积性肝损伤；谱效关系；夏佛塔苷；FXR/BSEP通路；活性成分 |
| KEYWORDS： | cholestatic liver injury;spectrum-effect relationship;schaftoside;FXR/BSEP pathway;active components |
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