Mulberry leaf aqueous fractions inhibit TNF-α-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-1 (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-1 is highly inducible by proinflammatory stimuli, including tumor necrosis factor-α (TNF-α), lipopolysaccharide (LPS), and transforming growth factor-β (TGF-β). Therefore, we examined whether mulberry leaf aqueous fractions inhibit LOX-1 expression induced by proinflammatory stimuli. Pretreatment of cultured bovine aortic endothelial cells (BAECs) with mulberry leaf aqueous fractions inhibited TNF-α- and LPS-induced expression of LOX-1 at both protein and mRNA levels in a time- and concentration-dependent manner. In contrast, mulberry leaf aqueous fractions did not affect TGF-β-induced LOX-1 expression. Furthermore, mulberry leaf aqueous fractions inhibited TNF-α-induced activation of nuclear factor-κB (NF-κB) and phosphorylation of inhibitory factor of NF-κB-alpha (IκB-α) in a time- and concentration-dependent fashion. Thus, mulberry leaf aqueous fractions suppress TNF-α- and LPS-induced LOX-1 gene expression, by inhibiting NF-κB activation.