Identification of the Proapoptotic Mechanism of Astragalosides in Rheumatoid Arthritis Therapy Based on HPLC, Bioinformatics and Network Pharmacology.

Authors

Tingting Li, Yihang Zhu, Mengru Li, Xiaoya Cui, Hui Jiang

Published in

Current pharmaceutical design. Oct 01, 2026. Epub Oct 01, 2026.

Abstract

Astragalosides (ASTs), principal active saponins derived from Astragalus, exert prominent therapeutic efficacy against Rheumatoid Arthritis (RA). However, few studies have investigated the molecular mechanism of ASTs in RA therapy.
AST components were qualitatively and quantitatively analyzed by HPLC. RA-related Differentially Expressed Genes (DEGs) were acquired from the GSE77298 dataset, and AST target genes were predicted via multiple databases. Core hub genes and signaling pathways were screened through bioinformatics analyses, including GO/KEGG enrichment, PPI network and MCODE modularity analysis. Molecular docking was performed to evaluate the binding affinity between ASTs and core apoptotic genes. Cell phenotypic assays, qRT-PCR, Western blot and CASP8 siRNA interference experiments were conducted to validate the regulatory effect of ASTs on the CASP8-ATM-XIAP-CASP3 axis in MH7A cells.
In total, 5781 DEGs were obtained from the GSE77298 dataset, 496 ASTs-related genes were predicted, among which 156 intersected. They were enriched in 3345 significant GO terms and 121 significant KEGG pathways. Bioinformatic and experimental analyses validated that ATM, CASP8, and XIAP mediate AST-induced MH7A cell apoptosis via the CASP8-ATM-XIAP-CASP3 axis.
ASTs decrease cellular proliferation and induce apoptosis in MH7A cells. Moreover, ASTs reduced the expression of XIAP and increased the expression of ATM and CASP8 at both the mRNA and protein levels. In addition, ASTs reversed the effects of siRNA-mediated CASP8 silencing on the mRNA expression of CASP3, ATM, and XIAP.
ASTs can promote apoptosis in MH7A cells, and the underlying mechanism may involve regulation of the CASP8-ATM-XIAP-CASP3 signaling axis.

PMID:
42861752
Bibliographic data and abstract were imported from PubMed on 12 Oct 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.