Mulberry leaf aqueous fractions inhibit TNF-alpha-induced nuclear factor kappaB (NF-kappaB) 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-alpha (TNF-alpha), lipopolysaccharide (LPS), and transforming growth factor-beta (TGF-beta). 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-alpha- 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-beta-induced LOX-1 expression. Furthermore, mulberry leaf aqueous fractions inhibited TNF-alpha-induced activation of nuclear factor-kappaB (NF-kappaB) and phosphorylation of inhibitory factor of NF-kappaB-alpha (IkappaB-alpha) in a time- and concentration-dependent fashion. Thus, mulberry leaf aqueous fractions suppress TNF-alpha- and LPS-induced LOX-1 gene expression, by inhibiting NF-kappaB activation.
Shibata
Yusuke
Y
Department of Applied Biology, Graduate School of Science and Technology, Kyoto Institute of Technology, Matsugasaki, Kyoto 606-8585, Japan.
Kume
Noriaki
N
Arai
Hidenori
H
Hayashida
Kazutaka
K
Inui-Hayashida
Atsuko
A
Minami
Manabu
M
Mukai
Eri
E
Toyohara
Masako
M
Harauma
Akiko
A
Murayama
Toshinori
T
Kita
Toru
T
Hara
Saburo
S
Kamei
Kaeko
K
Yokode
Masayuki
M
D000818:Animals; D001483:Base Sequence; D002417:Cattle; D002478:Cells, Cultured; D004247:DNA / Q000235:genetics; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D031625:Morus / Q000737:chemistry*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology; D018515:Plant Leaves / Q000737:chemistry; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D051127:Scavenger Receptors, Class E / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D010936:Plant Extracts; D012333:RNA, Messenger; D011994:Recombinant Proteins; D051127:Scavenger Receptors, Class E; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D004247:DNA