Mechanism of Cuscutae Semen-Salviae Miltiorrhizae Radix et Rhizoma in Regulating IL-6/STAT3 Signaling Pathway to Treat Recurrent Spontaneous Abortion Based on Network Pharmacology and Cell Experiment Validation
10.13422/j.cnki.syfjx.20251001
- VernacularTitle:基于网络药理学研究和细胞实验验证探讨菟丝子-丹参调控IL-6/STAT3信号通路治疗复发性流产的作用机制
- Author:
Haoxian WANG
1
;
Jiuxian LI
1
;
Yan LIU
1
;
Shuo SUN
1
;
Xiangyu LI
1
;
Ke ZHANG
1
;
Yuyu WANG
1
Author Information
1. The First Affiliated Hospital of Henan University of Chinese Medicine，Zhengzhou 450000，China
- Publication Type:Journal Article
- Keywords:
network pharmacology;
molecular docking;
Cuscutae Semen-Salviae miltiorrhizae Radix et Rhizoma;
recurrent spontaneous abortion;
interleukin （IL）-6/signal transducer and activator of transcription 3（STAT3） signaling pathway
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2025;31(20):22-30
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the mechanism of action of Cuscutae Semen-Salviae Miltiorrhizae Radix et Rhizoma in the treatment of recurrent spontaneous abortion （RSA） through network pharmacology， molecular docking， and cell experiment verification. MethodsThe Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and UniPort databases were used to screen and organize the active ingredients and corresponding targets of Cuscutae Semen-Salviae Miltiorrhizae Radix et Rhizoma. The potential therapeutic targets of RSA were screened in Online Mendelian Inheritance in Man （OMIM）， GeneCards database， DrugBank database， DisGeNET database， and Therapeutic Target Database （TTD）. The potential core targets of Cuscutae Semen-Salviae miltiorrhizae Radix et Rhizoma for treating RSA were further screened by constructing a protein-protein interaction （PPI） network and topological analysis. Meanwhile， the Database for Annotation， Visualization and Integrated Discovery （DAVID） was chosen to perform enrichment analysis on intersection targets. On this basis， AutoDock software was used for molecular docking， and the data were imported into PyMOL software for visualization and composition. Finally， the cell counting kit-8 （CCK-8） experiment， Transwell cell invasion assay， and Western blot were used to detect the effects of serum containing Cuscutae Semen-Salviae miltiorrhizae Radix et Rhizoma on HTR-8/SVneo cells and observe the effects on the interleukin （IL）-6/signal transducer and activator of transcription 3（STAT3） signaling pathway and related proteins. ResultsThrough network pharmacology analysis， a total of 69 active ingredients， 73 potential therapeutic targets， and 17 core targets， including IL-6， IL-10， and STAT3， were collected. The 73 common targets were enriched in 614 Gene Ontology （GO） entries and 57 Kyoto Encyclopedia of Genes and Genomes （KEGG） signaling pathways. The molecular docking results indicated that IL-6 and STAT3 had good binding ability with the main active ingredients， including matrine， cryptotanshinone， and tanshinone ⅡA. The cell experiment results showed that， compared with those of the control group， after 24 hours of treatment with the drug-containing serum， the survival and invasion rates of HTR-8/SVneo cells were significantly increased （P<0.05）， and the expression of IL-6/STAT3 signaling pathway and related proteins IL-10 and c-Myc was significantly elevated （P<0.05）. Moreover， the trend of action in the drug-containing serum group was consistent with that of pathway agonists. ConclusionCuscutae Semen-Salviae miltiorrhizae Radix et Rhizoma may enhance the survival rate and invasive activity of HTR-8/SVneo cells to further prevent and treat RSA by activating the IL-6/STAT3 signaling pathway and upregulating the expression of downstream factors IL-10 and c-Myc in the pathway.
