Garlic (Allium sativum) extract inhibits lipopolysaccharide-induced Toll-like receptor 4 dimerization.
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-kappaB) 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-kappaB. 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-kappaB 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.
Youn
Hyung-Sun
HS
Department of Biomedical Laboratory Science, College of Medical Sciences, Soonchunhyang University, Asan-Si, Chungnam 336-745, Korea.
Lim
Hyo Jin
HJ
Lee
Hwa Jin
HJ
Hwang
Daniel
D
Yang
Mihi
M
Jeon
Raok
R
Ryu
Jae-Ha
JH
D000818:Animals; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism; D019281:Dimerization; D005737:Garlic; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000819:agonists / Q000737:chemistry / Q000378:metabolism*
D008070:Lipopolysaccharides; D016328:NF-kappa B; D051197:Toll-Like Receptor 4; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2