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ARS Home » Pacific West Area » Davis, California » Western Human Nutrition Research Center » Immunity and Disease Prevention Research » Research » Publications at this Location » Publication #212787
Title: Garlic (Allium sativum) Extracts Inhibits Lipopolysaccharide-Induced Toll-Like Receptor 4 Dimerization

Author
item YOUN, HYUNG-SUN
item LIM, HYO JIN
item LEE, HWA JIN
item Hwang, Daniel
item YANG, MIHI
item JEON, RAOK
item RYU, JAE-HA

Submitted to: Bioscience Biotechnology and Biochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/8/2007
Publication Date: 2/7/2008
Citation: Youn, H., Lim, H., Lee, H., Hwang, D.H., Yang, M., Jeon, R., Ryu, J. 2008. Garlic (Allium sativum) Extracts Inhibits Lipopolysaccharide-Induced Toll-Like Receptor 4 Dimerization. Bioscience Biotechnology and Biochemistry 72(2):368-375, 2008.

Interpretive Summary: Garlic has long been used as a folk medicine. Numerous studies have demonstrated that a garlic extract and its sulfur-containing compounds inhibited nuclear factor kappa B (NF-'B) activation induced by various receptor agonists including lipopolysaccharide (LPS). Toll-like receptors (TLRs) play a key role in sensing diverse microbial products and inducing innate immune responses. The dimerization of TLR4 is required for the activation of downstream signaling pathways, including NF-'B. Therefore, TLR4 dimerization may be one of the first lines of regulation in activating LPS-induced signaling pathways. We report here biochemical evidence that the ethyl acetate fraction of garlic inhibited the LPS-induced dimerization of TLR4, resulting in the inhibition of NF-'B activation and the expression of cyclooxygenase 2 and inducible nitric oxide synthase. Our results demonstrate for the first time that a garlic extract can directly inhibit the TLRs-mediated signaling pathway at the receptor level. These results shed a new insight into understanding how garlic modulates the immune responses that could modify the risk of many chronic diseases.

Technical Abstract: Garlic has been used as a folk medicine for a long history. Numerous studies demonstrated that garlic extracts and its sulfur-containing compounds inhibit nuclear factor-kappa B (NF-kB) activation induced by various receptor agonist including lipopolysaccharide (LPS). These effects suggest that garlic extracts have anti-cancer and anti-inflammatory effects. However, the mechanism as to how garlic extracts mediate the health effects is largely unknown. Toll-like receptors (TLRs) play a key role in sensing diverse microbial products and inducing innate immune responses. The LPS-induced dimerization of TLR4 is required for the activation of NF-kB that is the central mediator of the immune responses. Therefore, TLR4 dimerization may be one of the first lines of regulation in activating LPS-induced signaling pathways. Here, we report biochemical evidence that ethyl acetate fraction of garlic inhibits the LPS-induced dimerization of TLR4 resulting in the inhibition of NF-kB activation and expression of cyclooxygenase 2 and inducible nitric oxide synthase. Our results first demonstrate that garlic extracts can directly inhibit TLRs-mediated signaling pathway at the receptor level. These results shed a new insight in understanding how garlic modulates the immune responses that could modify the risk of many diseases.