Mulberry leaf aqueous fractions inhibit TNF-ot-induced nuclear factor κB (NF-κB) activation and lectin-like oxidized LDL receptor-1 (LOX-1) expression in vascular endothelial cells

Mulberry (Morus Alba L., family Moraceae) leaf extracts have various biological effects including inhibition of oxidative modification of low-density lipoprotein (LDL), which is the major cause of atherosclerosis. Endothelial dysfunction elicited by oxidized LDL (Ox-LDL) has been implicated in atherogenesis. Lectin-like Ox-LDL receptor- I (LOX- 1), a cell-surface receptor for atherogenic Ox-LDL, appears to mediate Ox-LDL-induced inflammation, which may be crucial in atherogenesis. Previous studies revealed that expression of LOX- I is highly inducible by proinflammatory stimuli, including tumor necrosis factor-a TNF-alpha, lipopolysaccharide (LPS), and transforming growth factor-beta (TGF-beta). Therefore, we examined whether mulberry leaf aqueous fractions inhibit LOX- I expression induced by proinflammatory stimuli. Pretreatment of cultured bovine aortic endothelial cells (BAECs) with mulberry leaf aqueous fractions inhibited TNF-alpha- and LPS-induced expression of LOX-I at both protein and mRNA levels in a time- and concentration-dependent manner. In contrast, mulberry leaf aqueous fractions did not affect TGF-beta-induced LOX- I expression. Furthermore, mulberry leaf aqueous fractions inhibited TNF-alpha-induced activation of nuclear factor-kappa B (NF-kappa B) and phosphorylation of inhibitory factor of NF-kappa B-alpha (I kappa B-alpha) in a time- and concentration-dependent fashion. Thus, mulberry leaf aqueous fractions suppress TNF-a- and LPS-induced LOX- I gene expression, by inhibiting NF-kappa B activation. (c) 2006 Elsevier Ireland Ltd. All rights reserved.