Exploring the Mechanism of Guiyuan Decoction in Treating Sj?gren's Syndrome Based on Network Pharmacology and Experimental Validation
10.13359/j.cnki.gzxbtcm.2025.10.024
- VernacularTitle:基于网络药理学与实验验证探讨归元饮治疗干燥综合征的作用机制
- Author:
Jinming MA
1
;
Yueyue CHEN
Author Information
1. 南京中医药大学,江苏南京 210023
- Keywords:
Guiyuan Decoction;
Sj?gren's syndrome;
stigmasterol;
NLRP3;
CASP3;
inflammatory factors;
network pharmacology;
molecular docking;
experimental validation;
mice;
submandibular gland cells
- From:
Journal of Guangzhou University of Traditional Chinese Medicine
2025;42(10):2521-2531
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the therapeutic mechanism of Guiyuan Decoction(GYD,with Rehmanniae Radix as the principal herb)in Sj?gren's syndrome(SS).Methods Active components of GYD were retrieved from network pharmacology databases,and potential targets for SS were predicted.Common targets were identified via Venn analysis,followed by construction of a"herb-compound-target"network.Protein-protein interaction(PPI)networks were generated,and Gene Ontology(GO)functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were performed using the DAVID platform.Molecular docking was employed to evaluate binding affinities between core components and key target proteins.In vivo and in vitro experiments were conducted to validate predictions based on literature and docking results.Results A total of 318 bioactive components in GYD and 148 disease-related overlapping targets were identified.GO and KEGG analyses yielded 921 functional terms and 159 signaling pathways,respectively.Molecular docking revealed stigmasterol exhibited the strongest binding affinity with caspase-3(CASP3),while quercetin,kaempferol,andβ-sitosterol also showed robust interactions with core targets.Experimental validation demonstrated that both GYD and its active constituent stigmasterol significantly downregulated protein expression levels of CASP3,NLR family pyrin domain containing 3(NLRP3),apoptosis-associated speck-like protein containing a CARD(ASC),interleukin-1β(IL-1 β),and Caspase-1 in submandibular gland tissues of Sj?gren's syndrome mice and in lipopolysaccharide(LPS)-stimulated submandibular gland cells.Furthermore,they effectively reduced the concentrations of interleukin-6(IL-6),interleukin-1β(IL-1 β),and tumor necrosis factor-α(TNF-α)in peripheral blood and cell culture supernatants of Sj?gren's syndrome mice.Conclusion Integrated network pharmacology and molecular docking suggest that GYD exerts anti-SS effects primarily via stigmasterol-mediated modulation of CASP3.Experimental evidence confirms that GYD and stigmasterol attenuate inflammatory responses and may ameliorate SS by targeting CASP3 to suppress NLRP3 inflammasome activation.
