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Panax notoginseng (PN) exerts cardiovascular-disease-protective effects, but the effect of PN on reducing vascular calcification (VC) is unknown. Under the VC process, however, endothelial bone morphogenetic protein-2 (BMP-2) signals connect endothelial and smooth muscle cells. To investigate the effects of PN water extract (PNWE) on BMP-2 expression, human EA.hy926 endothelial cells were pretreated with PNWE for 48 h, and BMP-2 expression was then induced using warfarin/β-glycerophosphate (W/BGP) for another 24 h. The expression of BMP-2, the degrees of oxidative stress and inflammation, and the activation of noncanonical NF-κB and Wnt/β-catenin signaling were analyzed. The results showed that the BMP-2 levels in EA.hy926 cells were reduced in the groups treated with 10, 50, or 100 μg/mL PNWE combined with W/BGP. PNWE combined with W/BGP significantly reduced thiobarbituric-acid-reactive substrate and reactive oxygen species levels as well as prostaglandin E2, IL-1β, IL-6, and TNF-α. PNWE (10, 50, and 100 μg/mL) reduced the p52 levels and p52/p100 protein ratio. Wnt and β-catenin protein expression was decreased in the groups treated with PNWE combined with W/BGP. These results showed that PNWE reduced BMP-2 expression in EA.hy926 cells by inhibiting the noncanonical NF-κB and Wnt/β-catenin signaling pathways.