S-Allyl Cysteine Inhibits Activation of Nuclear Factor Kappa B in Human T Cells

Geng, Zhi-Hui; Rong, Yongqi; Lau, Benjamin H.S.

doi:10.1016/s0891-5849(97)00006-3

Cited by 153 publications

(74 citation statements)

References 24 publications

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“…Garlic and its sulfurcontaining compounds are known to inhibit the NF-B activation induced by various agonists (LPS, TNF, and H 2 O 2 ) in macrophages. [13][14][15] EAG inhibited the LPSinduced activation of NF-B and the expression of COX-2 and iNOS in RAW 264.7 cells (Fig. 1A and B).…”

Section: Inhibition Of Lps-induced Nf-b Activation and Expression Of mentioning

confidence: 81%

“…Many studies have demonstrated that a garlic extract and its sulfurcontaining compounds inhibited NF-B activation induced by various receptor agonists, including TNF and LPS. 13,14) However, the direct molecular targets of garlic to exert an anti-inflammatory effect have not been fully identified. We have demonstrated here that the garlic extract inhibited the LPS-induced dimerization of TLR4 (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…[4][5][6][7][8][9] The mechanisms of garlic for its biological activities have been ascribed to its potent antioxidative, 10) antithrombotic 1) and lipid-lowering 11) activities, and to its stimulating ability for immunological responses. 12) Numerous studies have demonstrated that a garlic extract and its related compounds with anti-inflammatory effects inhibited the nuclear factor kappa B (NF-B) activation induced by various receptor agonists, including tumor necrosis factor (TNF) and lipopolysaccharide (LPS), 13,14) and the expression of inducible nitric oxide synthase (iNOS) in activated macrophages. 15,16) NF-B is a central transcription factor for pro-inflammatory gene expression.…”

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confidence: 99%

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Garlic (Allium sativum) Extract Inhibits Lipopolysaccharide-Induced Toll-Like Receptor 4 Dimerization

Youn

Lim

Lee

et al. 2008

Bioscience, Biotechnology, and Biochemistry

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Section: Inhibition Of Lps-induced Nf-b Activation and Expression Of mentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Garlic (Allium sativum) Extract Inhibits Lipopolysaccharide-Induced Toll-Like Receptor 4 Dimerization

Youn

Lim

Lee

et al. 2008

Bioscience, Biotechnology, and Biochemistry

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“…Induction of glutathione S-transferase-␣ and glutathione S-transferase-was observed when SAC (1.8 mmol/kg/ day) was administered to rats for 3 days (Hatono et al, 1996) and may be one mechanism by which SAC exerts its chemoprotective effects. SAC has also been shown to have antioxidant properties and to inhibit nuclear factor kappa B in human T cells (Geng et al, 1997). However, the roles of SAC metabolites in these biological effects of SAC are presently unknown.…”

Section: Discussionmentioning

confidence: 99%

Sulfoxides as Urinary Metabolites ofS-Allyl-l-Cysteine in Rats: Evidence for the Involvement of Flavin-Containing Monooxygenases

Krause¹,

Glocke²,

Elfarra³

2002

Drug Metab Dispos

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ABSTRACT:S-Allyl-L-cysteine (SAC), a component of garlic and a metabolite of allyl halides, is a known substrate for multiple flavin-containing monooxygenases (FMOs). In the current study, we characterize the in vivo SAC metabolism by investigating the presence of SAC, N-acetyl-S-allyl-L-cysteine (NASAC), and their corresponding sulfoxides in the urine of rats given SAC (200 or 400 mg/kg i.p.). In some experiments, rats were given aminooxyacetic acid (AOAA), an inhibitor of cysteine conjugate ␤-lyase, or methimazole, an alternative FMO substrate, 30 min prior to treatment with 200 mg/kg SAC. Nearly 40 to 50% of the dose was recovered in the 24-h collection period. In all treatment groups, the majority of the metabolites were excreted within 8 h. The major metabolites detected were NASAC and NASAC sulfoxide (NASACS; nearly 30-40% and 5-10% of the dose, respectively). Only small amounts of the dose (approximately 1.5%) were recovered as SAC and SAC sulfoxide (SACS). Methimazole pretreatment significantly reduced amounts of both SACS and NASACS detected in the urine when compared with rats given SAC only, whereas AOAA pretreatment had no effect. In vitro assays using rat liver microsomes were also carried out to compare the sulfoxidation rates of SAC and NASAC. The results showed that SAC was much more readily oxidized than NASAC. Collectively, the results provide evidence for the involvement of FMOs in the in vivo metabolism of SAC and that SAC is a much better substrate for FMOs than its corresponding mercapturic acid. (SAC 1 ) is a significant water-soluble allyl sulfur component in garlic preparations (Weinberg et al., 1993), a component which has been shown to have antioxidant and anticancer properties in animals (Sumiyoshi and Wargovich, 1990;Hatono et al., 1996;Ho et al., 2001). SAC has been shown to have antiproliferative effects on neuroblastoma (Welch et al., 1992), melanoma (Takeyama et al., 1993), and prostate carcinoma cells (Pinto et al., 1997). However, the mechanisms of the anticancer properties of SAC are unclear. S-Allyl-L-cysteineSAC is also a known metabolite of allyl halides and allyl esters, including allyl chloride, allyl bromide, sodium allyl sulfate, and allyl nitrate (Kaye et al., 1972;Kaye, 1973). It results from the formation of the glutathione conjugate of the allyl halide or ester. The glutamate and glycine moieties of S-allyl-glutathione are then cleaved by ␥-glutamyl transpeptidase and dipeptidases to yield SAC.Our laboratory has previously shown that SAC is a substrate for multiple rabbit and human flavin-containing monooxygenases (FMOs). FMOs are microsomal enzymes that catalyze the NADPHdependent oxidation of many compounds that contain sulfur, nitrogen, selenium, and phosphorus (Ziegler, 1993). Previously, we have shown that SAC is metabolized to the greatest extent by cDNA-expressed rabbit FMO3 followed by FMO1 and then FMO2, but SAC showed no activity with rabbit FMO5 (Ripp et al., 1997). More recently and using cDNA-expressed human FMOs, SAC has been shown to be a good substr...

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“…AGE has been shown to attenuate the inflammatory cascade. Geng and coworkers (140) demonstrated that SAC dose-dependently inhibited the NFB activation induced by TNF␣ in Jurkat cells. Kim and coworkers (141) supported this finding by examining the effect of AGE on NFB activation, NO production, and free radical formation in LPS-stimulated RAW264.7 cells.…”

Section: Aged Garlic Extractmentioning

confidence: 99%

Membrane dynamics, cholesterol homeostasis, and Alzheimer's disease

Chauhan

2003

Journal of Lipid Research

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Alzheimer's disease (AD) is characterized by the deposition of ␤ -amyloid (A ␤ ) plaques derived from the amyloidogenic processing; of a transmembrane protein called ␤ -amyloid precursor protein (APP). In addition to the known genetic/sporadic factors that promote the formation of A ␤ , the composition and structural dynamics of the membrane are also thought to play a significant role in the amyloidogenic processing of APP that promotes seeding of A ␤ . This minireview reinforces the roles played by membrane dynamics, membrane microdomains, and cholesterol homeostasis in relation to amyloidogenesis, and reviews current strategies of lowering cholesterol in treating AD. -N STRUCTURE OF CELL MEMBRANEBiological membranes play a critical role in carrying out almost all physiological functions of the cell. The molecular organization of the cell membrane forms an infrastructural basis for all specialized function(s) carried out by the cell membrane. Many model membranes of varying molecular organization have been hypothesized and proposed to justify membrane functions (1-4). Among these, a dynamic fluid mosaic model (5) that evolved after several hypothetical modifications (6-8) has become a widely accepted model applicable to most biological membranes. Fluid mosaic model of cell membraneAccording to this classic model, membrane is composed of a bulk of phospholipid organized as a bilayer, with globular integral proteins embedded within the phospholipid texture. Phospholipids are arranged with their ionic and polar head groups in direct contact with the aqueous phase at the exterior and interior surfaces of the bilayer ( Fig. 1 , black gradient-filled circles), thereby maximizing hydrophilic interactions at the aqueous surfaces, while the nonpolar saturated fatty acid chains interdigitate within the interior of the membrane bilayer, forming a matrix (5). Voids and spaces between these chain aggregates are filled with lipids, of which cholesterol constitutes a major component (9, 10). The lipid matrix of the model membrane exists in three different phases, i.e., gel, liquid-ordered, and liquid-disordered states, in order of increasing fluidity (11). In the gel state, lipids are semifrozen; in the liquid-ordered state, lipids are viscous; and in the liquid-disordered state, lipids exist as fluids. This liquid-disordered fluid phase is essential for protein functions (12). The liquid-disordered fluid phase can be transformed to the liquid-ordered or gel state by tight packing of phospholipids and hydrocarbon chains with cholesterol intercalations in order of increasing rigidity (9). Thus, the amount of cholesterol present in the membrane determines the fluid/rigid state of the membrane.Integral membrane proteins [membrane anchor proteins, i.e., glycophosphatidylinositol (GPI), Src -family proteins, receptor ligands, signaling molecules, transmembrane proteins] are embedded within the phospholipid bilayer with their ionic and highly polar groups protruding to the exterior surface, and nonpolar groups largely bur...

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S-Allyl Cysteine Inhibits Activation of Nuclear Factor Kappa B in Human T Cells

Cited by 153 publications

References 24 publications

Garlic (Allium sativum) Extract Inhibits Lipopolysaccharide-Induced Toll-Like Receptor 4 Dimerization

Garlic (Allium sativum) Extract Inhibits Lipopolysaccharide-Induced Toll-Like Receptor 4 Dimerization

Sulfoxides as Urinary Metabolites ofS-Allyl-l-Cysteine in Rats: Evidence for the Involvement of Flavin-Containing Monooxygenases

Membrane dynamics, cholesterol homeostasis, and Alzheimer's disease

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