Gancao Nourishing-Yin decoction ameliorates endothelial inflammaging induced by serum from rheumatoid arthritis patients.

BACKGROUND AND AIM: Inhibiting inflammaging is key to preventing cardiovascular complications in rheumatoid arthritis (RA) patients. Gancao Nourishing-Yin decoction (GCNY), a Chinese herbal remedy, has shown anti-inflammatory and antioxidative effects. This study explores the efficacy and mechanism of GCNY in reducing endothelial inflammaging in RA.

EXPERIMENTAL PROCEDURE: Human umbilical vein endothelial cells (HUVECs) were cultured with RA serum to construct an endothelial inflammaging cell model. Cell viability, reactive oxygen species (ROS), and senescence-associated β-galactosidase (SA-β-gal) staining assays were performed to evaluate the effects of GCNY. GCNY components were identified using liquid chromatography-mass spectrometry (LC-MS/MS). The potential mechanisms of GCNY were investigated and verified through RNA sequencing (RNA-seq), network pharmacology, molecular docking analysis, and web-lab experiments.

RESULTS AND

CONCLUSION

RA serum-treated HUVECs displayed hallmark inflammaging features, including abnormal proliferation, increased apoptosis, elevated ROS and higher SA-β-gal levels. GCNY medicated serum reduced ROS, SA-β-gal, P53 and P21 levels, while improving angiogenesis. RNA-seq analysis revealed that GCNY lowered the transcriptional expression of adhesion molecules and chemokines. LC-MS/MS identified 72 compounds, and network pharmacology analysis linked these compounds to the phosphatidylinositol 3-kinase/protein kinase B signaling pathway (PI3K/AKT pathway). Western blot assay verified that GCNY downregulated the phosphorylated protein levels of PI3K/AKT pathway. The molecular docking analysis suggested coactions between the PI3K-related proteins and the components of GCNY. In conclusion, the RA serum induced inflammaging HUVECs model, and GCNY demonstrated therapeutic potential by mitigating these effects. This study offers a promising approach for preventing cardiovascular complications in RA patients.