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The present results suggest that icariin regulates PRMT/ADMA/DDAH pathway to improve endothelial function.

Osteopontin (OPN), also called cytokine Eta-1, is a pro-inflammatory cytokine. Recent studies have shown that aldosterone increases OPN gene expression in endothelial cells. As a flavonoid compound, kaempferol has potent anti-inflammatory properties, but whether kaempferol regulates aldosterone signaling and aldosterone-induced gene expression is still unknown. Human umbilical vein endothelial cells (HUVECs) were pretreated with kaempferol (0, 1, 3, or 10 μmol/L) for 1 h prior to exposure to aldosterone (10(-6) mol/L) for 24 h. Aldosterone induced generation of reactive oxygen species; OPN and cluster of differentiation 44 gene expression; phospho-p38 MAPK and NF-κB binding activity. The effect of aldosterone was abrogated by kaempferol and spironolactone (10(-6) mol/L). The present results suggest that kaempferol exerts its anti-inflammatory properties via its inhibition of aldosterone signaling and aldosterone-induced gene expression in HUVECs.

In the present study, we tested the hypothesis that aldosterone regulates osteopontin (OPN)-related signaling pathways to promote nuclear factor κB (NF-κB) activation in primary human umbilical vein endothelial cells (HUVECs) and that kaempferol, a flavonoid compound, blocks those changes. Aldosterone induced productions of reactive oxygen species (ROS), OPN, interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) and expression of nicotinamide adenine dinucleotide phosphate-oxidase 4 (Nox4), NF-κB, OPN, alphavbeta3 (αvβ3) integrin, and inhibitor of NF-κB alpha phosphorylation (P-IκBα) in HUVEC. HUVECs were pretreated with kaempferol (0, 1, 3, or 10 μM) for 1 h and exposed to aldosterone (10(-6) M) for 24 h. Kaempferol reduced ROS, OPN, NF-κB, IL-6, and TNF-α levels; Nox4, αvβ3 integrin; and P-IκBα expressions. The effect of aldosterone was also abrogated by spironolactone (10(-6) M). In addition, vitamin C (20 mmol/L) reduced ROS production. Vitamin C and LM609 (10 μg/mL) treatment decreased expressions of OPN, αvβ3 integrin, and NF-κB (P < 0.05 or P < 0.01). The present results suggest that kaempferol may modulate OPN-αvβ3 integrin pathway to inhibit NF-κB activation in HUVECs.

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