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

作　　者：王百才 赵耀 耿若愚 马冲 刘天华 胡君萍[1] 杨建华[1,2] WANG Bai-cai;ZHAO Yao;GENG Ruo-yu;MA Chong;LIU Tian-hua;HU Jun-ping;YANG Jian-hua(College of Pharmacy,Xinjiang Medical University,Urumqi 830017,China;The First Affiliated Hospital,Xinjiang Medical University,Urumqi 830011,China)

机构地区：[1]新疆医科大学药学院,乌鲁木齐830017 [2]新疆医科大学第一附属医院,乌鲁木齐830011

出　　处：《天然产物研究与开发》2024年第3期400-414,共15页Natural Product Research and Development

基　　金：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)。

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。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 fraction,n-butanol fraction and water fraction of the F.vulgare cortex.According to the mass spectrometry fragmentation rule,reference 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 compounds 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-hepatic fibrosis activity and mechanism of monomeric compounds were verified in vitro.The results showed that dihydrocapsaicin,harmine and isoscopoletin had a good inhibitory effect on activated HSC-T6(P<0.01,0.001),and could inhibit the expression ofα-SMA(P<0.01,0.001).Dihydrocapsaicin and harmine had strong pro-apoptotic effects and could down-regulate the relative expression of Bax/Bcl-2 and Caspase3(P<0.05,0.01).It is indicated that the pharmacodynamic substances of F.vulgare cortex against liver fibrosis may be dihydrocapsaicin,harmine,isoscopoletin,scopoletin,7-hydroxycoumarin,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 

分 类 号：R932[医药卫生—生药学]