Cell experiment:

Primary HUVECs are seeded at 60 000 cells per well and incubated at 37℃ for 14 to 16 hours to allow tube formation. Cells are then cultured in the presence of either TNF-α (10 ng/mL) alone, with both TNF-α (10 ng/mL) and Sofalcone 50 μM, or control media for 8 to 12 hours. Tube formation is assessed, and images are captured using microscope at ×4 magnification[1].

Sofalcone, a gastric antiulcer agent in clinical use, is known to induce the expression of Heme oxygenase-1 (HO-1) in gastric epithelium.

Sofalcone (50 μmol/L) significantly increases HO-1 mRNA expression compare with the control group in both trophoblasts and HUVECs (P<0.05 for both). Western blot analysis demonstrates that Sofalcone potently increases HO-1 protein expression in primary HUVECs treated for 24 hours. Western blot analysis also reveals a significant increase in the amount of Nrf2 in the nuclear fraction of HUVECs with Sofalcone treatment (50 μmol/L) for 6 hours. In primary HUVECs, expression of NQO1, TXN, and GCLC are increased in a dose dependently manner with Sofalcone treatment for 24 hours. Sofalcone significantly decreases the sFlt-1 concentrations in the culture media and dose dependently decreases the amount of THP-1 monocyte adherence to HUVECs[1].

[1]. Onda K, et al. Sofalcone upregulates the nuclear factor (erythroid-derived 2)-like 2/heme oxygenase-1 pathway, reduces soluble fms-like tyrosine kinase-1, and quenches endothelial dysfunction: potential therapeutic for preeclampsia. Hypertension. 2015 Apr;65(4):855-62.