J Ethnopharmacol: Yuxuebi tablet inhibits angiogenesis in experimental rheumatoid arthritis by inhibiting LOX/Ras/Raf-1 signaling

Background: Yuxuebi Tablet (YXB) is mainly used for the syndrome of arthralgia due to blood stasis blocking collateral.

OBJECTIVE: To evaluate the anti-angiogenic activity of YXB and explore its mechanism of action in collagen-induced arthritis (CIA) rats and VEGF-induced HUVE.

Methods: Transcriptional regulatory network analysis and network pharmacology were used to explore the mechanism of YXB in RA angiogenesi.

The antiarthritic effect of YXB was assessed by determining the incidence of arthritis, scoring and micro-CT analysi.

The in vitro anti-angiogenic effects of YXB were evaluated by wound healing, cell migration, cell invasion and angiogenesis assay.

Results: YXB reduced disease severity and improved pathological features in CIA rat.

In vitro, YXB effectively inhibited HUVEC migration, invasion and angiogenesi.

After determining the transcriptional expression profile, the interaction network of "YXB putative target known RA-related genes and genes associated with YXB treatment effect" was constructed and analyze.

In the experimental verification, YXB dose-dependently reduced the expression levels of LOX, Ras and Raf-1, as well as the phosphorylation of MEK and ERK in CIA rats, and these effects were superior to the inhibitory effect of methotrexate (MTX.

Furthermore, YXB may be a potent angiogenesis inhibitor and significantly inhibit VEGF-induced activation of LOX/Ras/Raf-1 signaling in vitr.

Conclusion: YXB may inhibit angiogenesis by inhibiting LOX/Ras/Raf-1 signaling, thereby reducing disease severity and bone erosion in R.

Source:

Su X, Yuan B, Tao X, et a.