Background Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by synovial hyperplasia, persistent inflammation, and progressive joint destruction. Ginkgetin (GK), a biflavonoid derived from Ginkgo biloba, exhibits strong anti-inflammatory and antioxidant properties. However, its therapeutic potential and underlying molecular mechanisms in RA remain insufficiently understood. Methods An integrative strategy combining network pharmacology, transcriptomic profiling, molecular docking, and in vitro experiments was applied to elucidate the mechanisms of GK against RA. Differentially expressed genes (DEGs) were identified from four GEO datasets of RA synovial tissues, and overlapping targets between GK and RA were screened. Gene Ontology (GO), KEGG pathway enrichment, and protein–protein interaction (PPI) analyses were conducted to identify key pathways and hub genes. Molecular docking and single-cell transcriptomic analyses were performed to predict binding interactions and cellular localization. Finally, MH7A synovial fibroblasts were used to validate GK’s effects on inflammation, proliferation, migration, and apoptosis. Results Thirty-two potential therapeutic targets of GK in RA were identified, among which six hub genes (CXCR4, HIF1A, STAT1, VEGFA, CDK1, and CCNB1) were highlighted. Enrichment analyses indicated that these targets were primarily involved in the HIF-1, VEGF, and cell cycle signaling pathways. Molecular docking demonstrated strong binding affinities between GK and key proteins. In vitro, GK inhibited LPS-induced proliferation and migration of MH7A cells, reduced IL-6 and IL-1β expression, and promoted apoptosis. qRT-PCR analysis confirmed that GK downregulated all six hub genes, indicating its multi-target regulatory activity on hypoxia, angiogenesis, and inflammatory signaling. Conclusion GK exerts anti-inflammatory, anti-proliferative, and pro-apoptotic effects in RA synovial fibroblasts by modulating multiple signaling pathways, particularly the HIF-1α/VEGFA, STAT1, and CXCR4 axes. These findings provide mechanistic insight into GK’s pharmacological actions and support its potential as a novel multi-target therapeutic candidate for RA.<Table Float="No" ID="Taba"> <tgroup cols="2"> <colspec align="left" colname="c1" colnum="1" /> <colspec align="left" colname="c2" colnum="2" /> <tbody> <row> <entry align="left" nameend="c2" namest="c1"> Key Points •Network pharmacology identified six hub genes (CXCR4, HIF1A, STAT1, VEGFA, CDK1, CCNB1) linking Ginkgetin (GK) to rheumatoid arthritis pathology. •Molecular docking confirmed strong binding affinities of GK with key targets, supporting its multitarget pharmacological potential. •GK inhibits proliferation and migration, suppresses inflammatory cytokines, and promotes apoptosis in LPS-stimulated MH7A synovial fibroblasts. •These findings provide mechanistic evidence supporting GK as a promising multi-target candidate for rheumatoid arthritis therapy. </entry> </row> </tbody> </tgroup> </Table>

Therapeutic effects of ginkgetin on rheumatoid arthritis: evidence from network pharmacology and experimental validation

期刊论文
发表日期：

2026年4月11日

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Chengcheng Zhao,
Hui Yu,
Jiachen Wang,
Ke Xu,
Mingyi Yang,
Peng Xu

摘要

Background

Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by synovial hyperplasia, persistent inflammation, and progressive joint destruction. Ginkgetin (GK), a biflavonoid derived from Ginkgo biloba, exhibits strong anti-inflammatory and antioxidant properties. However, its therapeutic potential and underlying molecular mechanisms in RA remain insufficiently understood.

Methods

An integrative strategy combining network pharmacology, transcriptomic profiling, molecular docking, and in vitro experiments was applied to elucidate the mechanisms of GK against RA. Differentially expressed genes (DEGs) were identified from four GEO datasets of RA synovial tissues, and overlapping targets between GK and RA were screened. Gene Ontology (GO), KEGG pathway enrichment, and protein–protein interaction (PPI) analyses were conducted to identify key pathways and hub genes. Molecular docking and single-cell transcriptomic analyses were performed to predict binding interactions and cellular localization. Finally, MH7A synovial fibroblasts were used to validate GK’s effects on inflammation, proliferation, migration, and apoptosis.

Results

Thirty-two potential therapeutic targets of GK in RA were identified, among which six hub genes (CXCR4, HIF1A, STAT1, VEGFA, CDK1, and CCNB1) were highlighted. Enrichment analyses indicated that these targets were primarily involved in the HIF-1, VEGF, and cell cycle signaling pathways. Molecular docking demonstrated strong binding affinities between GK and key proteins. In vitro, GK inhibited LPS-induced proliferation and migration of MH7A cells, reduced IL-6 and IL-1β expression, and promoted apoptosis. qRT-PCR analysis confirmed that GK downregulated all six hub genes, indicating its multi-target regulatory activity on hypoxia, angiogenesis, and inflammatory signaling.

Conclusion

GK exerts anti-inflammatory, anti-proliferative, and pro-apoptotic effects in RA synovial fibroblasts by modulating multiple signaling pathways, particularly the HIF-1α/VEGFA, STAT1, and CXCR4 axes. These findings provide mechanistic insight into GK’s pharmacological actions and support its potential as a novel multi-target therapeutic candidate for RA.

Key Points

•Network pharmacology identified six hub genes (CXCR4, HIF1A, STAT1, VEGFA, CDK1, CCNB1) linking Ginkgetin (GK) to rheumatoid arthritis pathology.

•Molecular docking confirmed strong binding affinities of GK with key targets, supporting its multitarget pharmacological potential.

•GK inhibits proliferation and migration, suppresses inflammatory cytokines, and promotes apoptosis in LPS-stimulated MH7A synovial fibroblasts.

•These findings provide mechanistic evidence supporting GK as a promising multi-target candidate for rheumatoid arthritis therapy.