Mechanism of total flavonoids of Carthamus tinctorius L.against he-patic fibrosis based on LC-MS/MS combined with network pharma-cology and pharmacology experiments
10.12092/j.issn.1009-2501.2025.05.002
- VernacularTitle:基于LC-MS/MS结合网络药理学、分子对接及体内外实验探究红花总黄酮抗肝纤维化的作用机制
- Author:
Mingqi LI
1
;
Yinghe WANG
;
Xiaolu ZHAO
;
Xiaomei BAO
;
Xin YUE
;
Guiqiang REN
;
Yue-hong MA
Author Information
1. 内蒙古医科大学基础医学院,呼和浩特 010110,内蒙古自治区;内蒙古医科大学基础医学院,内蒙古自治区分子病理学重点实验室,呼和浩特 010110,内蒙古自治区
- Publication Type:Journal Article
- Keywords:
LC-MS/MS;
network pharmacology;
molecular docking;
hepatic fibrosis;
pharmacologi-cal experiments
- From:
Chinese Journal of Clinical Pharmacology and Therapeutics
2025;30(5):586-598
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To elucidate the pharmacody-namic and network pharmacological mechanisms of total flavonoids of Carthamus tinctorius L.,to ex-plore their key targets and related pathways,and to clarify their mechanism of action against hepatic fibrosis.METHODS:The total flavonoids of Cartha-mus tinctorius L.were determined by LC-MS/MS and analysed for their compositions;the active in-gredients were screened by TCMSP database,SWISS ADME database and literature search;the targets related to total flavonoids of Carthamus tinctorius L.were screened by Swiss Target Predic-tion database;and the targets related to hepatic fi-brosis were screened by GeneCards database;the anti-hepatic fibrosis targets of total flavonoids of Carthamus tinctorius L.were obtained by taking the intersection of Venny.2.1.0;the protein interac-tions were analysed by STRING database;the visu-alization analysis was carried out by Cytoscape soft-ware;the GO function and KEGG pathway analysis was carried out by Metascape platform;and molec-ular docking was verified by using AutoDock soft-ware for the core targets and active ingredients.The mechanism of anti-hepatic fibrosis of total fla-vonoids of Carthamus tinctorius L.was verified by animal model and in vitro cell experiments.RE-SULTS:A total of 41 flavonoid components were identified in Carthamus tinctorius L.Through the network pharmacological analysis,149 anti-hepatic fibrosis targets of total flavonoids of Carthamus tinctorius L.were obtained,including 23 core tar-gets.The GO enrichment analyses involved a total of three aspects,namely,biological process(BP),cellular component(CC),and molecular function(MF).KEGG enrichment results showed that PI3K/Akt and MAPK are pathways involved in the devel-opment of hepatic fibrosis.Molecular docking veri-fied that the active ingredients Quercetin,Acacetin and Glabridin were tightly bound to Akt1 and HI-FIA,respectively.In animal model experiments,it was observed by HE and Masson staining that fibro-plasia was reduced,collagen deposition was re-duced,inflammatory cell infiltration was reduced,and fibrotic liver tissues were improved in total fla-vonoids of Carthamus tinctorius L.administration group.In isolated cell experiments:Western blot-ting results suggested that total flavonoids of Car-thamus tinctorius L.could decrease the hepatic fi-brosis marker factor α-SMA,Collagen1(P＜0.01)and PI3K,Akt protein expression(P＜0.01).CONCLU-SION:Total flavonoids of Carthamus tinctorius L.ex-erted anti-hepatic fibrosis effects through multi-components,multi-targets and multi-pathways,and their mechanism of action may be achieved by regulating the PI3K/Akt signalling pathway.
