Ginkgo biloba Extract Inhibits Endotoxin-Induced Human Aortic Smooth Muscle Cell Proliferation via Suppression of Toll-like Receptor 4 Expression and NADPH Oxidase Activation

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• 作者：Feng-Yen Lin ; Yung-Hsiang Chen ; Yuh-Lien Chen ; Tao-Cheng Wu ; Chi-Yuan Li ; Jaw-Wen Chen ; Shing-Jong Lin
• 刊名：Journal of Agricultural and Food Chemistry
• 出版年：2007
• 出版时间：March 7, 2007
• 年：2007
• 卷：55
• 期：5
• 页码：1977 - 1984
• 全文大小：417K
• 年卷期：v.55,no.5(March 7, 2007)
• ISSN：1520-5118

文摘

Toll-like receptor 4 (TLR4) initiates the inflammatory response in blood vessels in reaction to immunestimuli such as lipopolysaccharide (LPS) produced by Gram-negative bacteria. LPS-inducedproliferation and functional perturbation in vascular smooth muscle cells play important roles duringatherogenesis. Ginkgo biloba extract is an antiatherothrombotic Chinese herbal medicine with anti-inflammatory properties. The effects of G. biloba extract on LPS-induced proliferation and TLR4expression and the underlying mechanisms for these actions, in human aortic smooth muscle cells(HASMCs), were examined in vitro. LPS-induced proliferation was mediated by the expression ofTLR4 in HASMCs. LPS increased the expression of TLR4 in HASMCs, and this effect was mediatedby the activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, phosphorylationof intracellular mitogen-activated protein kinases (MAPKs), and increases in the cytoplasmic level ofHuR and TLR4 mRNA stability. G. biloba extract inhibited LPS-induced HASMC proliferation anddecreased the expression of TLR4 by inhibiting LPS-induced NADPH oxidase activation, mRNAstabilization, and MAPK signaling pathways. These results suggest that LPS-induced TLR4 expressioncontributes to HASMC proliferation and that G. biloba inhibits LPS-stimulated proliferation of HASMCsby decreasing TLR4 expression.