天然产物研究与开发2024,Vol.36Issue(3) :400-414.DOI:10.16333/j.1001-6880.2024.3.004

基于谱效关系的茴香根皮抗肝纤维化有效成分筛选及其机制探讨

Screening on the effective components of Foeniculum vulgare Mill.cortex against liver fibrosis and its mechanism based on spectrum-effect relationship

王百才 赵耀 耿若愚 马冲 刘天华 胡君萍 杨建华
天然产物研究与开发2024,Vol.36Issue(3) :400-414.DOI:10.16333/j.1001-6880.2024.3.004

基于谱效关系的茴香根皮抗肝纤维化有效成分筛选及其机制探讨

Screening on the effective components of Foeniculum vulgare Mill.cortex against liver fibrosis and its mechanism based on spectrum-effect relationship

王百才 1赵耀 1耿若愚 1马冲 1刘天华 1胡君萍 1杨建华2
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作者信息

  • 1. 新疆医科大学药学院,乌鲁木齐 830017
  • 2. 新疆医科大学药学院,乌鲁木齐 830017;新疆医科大学第一附属医院,乌鲁木齐 830011
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摘要

为探讨茴香根皮治疗肝纤维化的化学成分,揭示其药效物质基础和作用机制.本研究应用UPLC-Orbitrap-MS/MS技术定性鉴别茴香根皮95%乙醇提取物、石油醚部位、乙酸乙酯部位、正丁醇部位和水部位的化学成分,根据质谱裂解规律和对照品验证及文献检索推测鉴定了各组分的58个共有化合物;采用MTT法检测各组分对HSC-T6细胞增殖的影响,谱效关系筛选抗肝纤维化潜在活性化合物,结果显示茴香根皮抗肝纤维化贡献较大的成分是二氢辣椒碱、去氢骆驼蓬碱、异莨菪亭;体外实验验证单体化合物抗肝纤维化活性及机制,结果表明二氢辣椒碱、去氢骆驼蓬碱和异莨菪亭对活化的HSC-T6具有较好的抑制作用(P<0.01、P<0.001),均可以抑制α-SMA的表达(P<0.01、P<0.001);二氢辣椒碱和去氢骆驼蓬碱具有较强的促凋亡作用,可以下调Bax/Bcl-2和Caspase3的相对表达量(P<0.05、P<0.01).表明茴香根皮抗肝纤维化的药效物质可能为二氢辣椒碱、去氢骆驼蓬碱和异莨菪亭、东莨菪内酯、7-羟基香豆素等,其机制可能是通过抑制肝星状细胞活化、调节Bax/Bcl-2的表达发挥作用,体现了茴香根皮多成分多靶点抗肝纤维化的作用特点.

Abstract

In order to explore the chemical constituents of Foeniculum vulgare Mill.cortex in the treatment of liver fibrosis,and to reveal its pharmacodynamic material basis and mechanism of action.In this study,UPLC-Orbitrap-MS/MS technology was used to qualitatively identify the chemical constituents of the ethanol extract,petroleum ether fraction,ethyl acetate frac-tion,n-butanol fraction and water fraction of the F.vulgare cortex.According to the mass spectrometry fragmentation rule,ref-erence substance verification and literature search,58 common compounds of each component were speculated and identified.MTT assay was used to detect the effect of each component on the proliferation of HSC-T6 cells,and the potential active com-pounds against liver fibrosis were screened by spectrum-effect relationship.The results of spectrum-effect relationship showed that dihydrocapsaicin,harmine and isoscopoletin contributed more to the anti-hepatic fibrosis of F.vulgare cortex.The anti-he-patic fibrosis activity and mechanism of monomeric compounds were verified in vitro.The results showed that dihydrocapsai-cin,harmine and isoscopoletin had a good inhibitory effect on activated HSC-T6(P<0.01,0.001),and could inhibit the ex-pression of α-SMA(P<0.01,0.001).Dihydrocapsaicin and harmine had strong pro-apoptotic effects and could down-regu-late the relative expression of Bax/Bcl-2 and Caspase3(P<0.05,0.01).It is indicated that the pharmacodynamic sub-stances of F.vulgare cortex against liver fibrosis may be dihydrocapsaicin,harmine,isoscopoletin,scopoletin,7-hydroxycouma-rin,etc.The mechanism may be to inhibit the activation of hepatic stellate cells and regulate the expression of Bax/Bcl-2,which reflects the multi-component and multi-target anti-liver fibrosis characteristics of F.vulgare cortex.

关键词

茴香根皮/肝纤维化/肝星状细胞/灰色关联度/谱效关系

Key words

Foeniculum vulgare Mill.cortex/liver fibrosis/hepatic stellate cells/grey correlation degree/spectrum-effect rela-tionship

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基金项目

国家自然科学基金(81560688)

新疆天然药物有效成分与药物释放技术重点实验室项目(XJDX1713)

出版年

2024
天然产物研究与开发
中国科学院成都文献情报中心

天然产物研究与开发

CSTPCD北大核心
影响因子:0.783
ISSN:1001-6880
参考文献量28
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