Aged garlic extract supplemented with B vitamins, folic acid and l-arginine retards the progression of subclinical atherosclerosis: A randomized clinical trial

Budoff, Matthew J.; Ahmadi, Naser; Gul, Khawar; Liu, Sandy T.; Flores, Ferdinand; Tiano, Jima; Takasu, Junichiro; Miller, Elizabeth R.; Tsimikas, Sotirios

doi:10.1016/j.ypmed.2009.06.018

Cited by 127 publications

(120 citation statements)

References 45 publications

(54 reference statements)

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“…LEVA-induced IgG and IgM elevation provided evidence for the immunostimulatory effect of LEVA, and is in agreement with its effect on calves (32). The normalizing effects of GO on LEVA-induced IgG and IgM elevation indicated its immunomodulatory effect, and is in agreement with its lowering effect on IgG and IgM in human patients (33). The effects of LEVA on the upregulation of peripheral leukocytes is in line with its effects on serum cytokine and Ig levels, and coincided with its effect in rats (34).…”

Section: A B C D E F G H I Discussionsupporting

confidence: 76%

Modulatory effects of levamisole and garlic oil on the immune response of Wistar rats: Biochemical, immunohistochemical, molecular and immunological study

et al. 2016

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Abstract. Levamisole (LEVA) and garlic are prevalent immunomodulators in humans and animals. Therefore, the present study aimed to examine the immunomodulatory effects of LEVA and garlic oil (GO) alone or in combination on the immune response of Wistar rats. A total of 24 male Wistar rats were allocated into four equal groups: Control group, which was given ad libitum access to food and water; and groups 2-4, which were orally administered LEVA [2.5 mg/kg body weight (BW) every 2 days], GO, (5 ml/kg BW daily), or LEVA plus GO, respectively for 4 consecutive weeks. Serum immunoglobulin (Ig)G and IgM levels were measured using a radial immunodiffusion assay. Serum cytokine levels, including interferon (IFN)-γ, interleukin (IL)-5 and tumor necrosis factor (TNF)-α, were measured using enzyme-linked immunosorbent assay kits. Total blood counts were measured automatically using a cell counter. Serum lysozyme enzymatic activity was determined by measuring the diameters of the zones of clearance relative to lysozyme. Immunohistochemical detection of CD4 and CD8 was carried out using the streptavidin-biotinperoxidase method. Furthermore, the mRNA expression levels of IL-4, IL-5 and IL-12 were measured in the leukocytes and thymus gland by semi-quantitative polymerase chain reaction. The results revealed that LEVA increased serum levels of IFN-γ, IL-5 and TNF-α cytokines, whereas co-administration of LEVA and GO decreased the stimulatory action of LEVA alone. LEVA and GO alone increased the serum levels of IgG, IgM and total blood cell counts, and co-administration of GO and LEVA inhibited the effects of LEVA. At the cellular level, in the spleen, LEVA increased immunoreactivity of CD4 and CD8, whereas co-administration of GO with LEVA decreased this strong expression. At the molecular level, in leukocytes, LEVA upregulated the mRNA expression levels of IL-2, IL-4 and IL-5, whereas GO alone downregulated mRNA expression. Co-administration of GO with LEVA inhibited the LEVA-induced upregulation of IL-2, IL-4 and IL-5 mRNA expression. In the thymus, both LEVA and GO upregulated the mRNA expression levels of IL-4 and IL-5, whereas LEVA alone did not affect IL-12 mRNA expression. Co-administration of GO with LEVA inhibited LEVA-induced upregulation of IL-4 and GO-induced upregulation of IL-12 expression, and had an additive upregulatory effect on IL-5 expression. In conclusion, LEVA stimulated T-helper (Th)1 cytokines, whereas GO stimulated a Th2 response, and co-administration of GO with LEVA inhibited the stimulatory effects of LEVA and balanced the Th1/Th2 response.

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Section: A B C D E F G H I Discussionsupporting

confidence: 76%

Modulatory effects of levamisole and garlic oil on the immune response of Wistar rats: Biochemical, immunohistochemical, molecular and immunological study

et al. 2016

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“…These insights may help explain positive cardiovascular outcomes of several smaller, randomized controlled trials that utilized garlic or garlic extracts. Results were largely independent of any effects on standard risk factors (222,223,247,939).…”

Section: E Hydrogen Sulfide Signalingmentioning

confidence: 86%

Molecular Biology of Atherosclerosis

Hopkins

2013

Physiological Reviews

382

344

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At least 468 individual genes have been manipulated by molecular methods to study their effects on the initiation, promotion, and progression of atherosclerosis. Most clinicians and many investigators, even in related disciplines, find many of these genes and the related pathways entirely foreign. Medical schools generally do not attempt to incorporate the relevant molecular biology into their curriculum. A number of key signaling pathways are highly relevant to atherogenesis and are presented to provide a context for the gene manipulations summarized herein. The pathways include the following: the insulin receptor (and other receptor tyrosine kinases); Ras and MAPK activation; TNF-␣ and related family members leading to activation of NF-B; effects of reactive oxygen species (ROS) on signaling; endothelial adaptations to flow including G protein-coupled receptor (GPCR) and integrin-related signaling; activation of endothelial and other cells by modified lipoproteins; purinergic signaling; control of leukocyte adhesion to endothelium, migration, and further activation; foam cell formation; and macrophage and vascular smooth muscle cell signaling related to proliferation, efferocytosis, and apoptosis. This review is intended primarily as an introduction to these key signaling pathways. They have become the focus of modern atherosclerosis research and will undoubtedly provide a rich resource for future innovation toward intervention and prevention of the number one cause of death in the modern world.

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“…[5][6][7][8] This extraction process leads to the reduction of odorous, acidic, and irritating compounds found in fresh garlic and the enrichment of water-soluble organosulfur components in AGE, such as S-allyl-L-cysteine (SAC),…”

Section: -4)mentioning

confidence: 99%

Evaluation of the Effects of S-Allyl-L-cysteine, S-Methyl-L-cysteine, trans-S-1-Propenyl-L-cysteine, and Their N-Acetylated and S-Oxidized Metabolites on Human CYP Activities

Amano

Kazamori

Itoh

2016

Biological & Pharmaceutical Bulletin

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Three major organosulfur compounds of aged garlic extract, S-allyl-L-cysteine (SAC), S-methyl-Lcysteine (SMC), and trans-S-1-propenyl-L-cysteine (S1PC), were examined for their effects on the activities of five major isoforms of human CYP enzymes: CYP1A2, 2C9, 2C19, 2D6, and 3A4. The metabolite formation from probe substrates for the CYP isoforms was examined in human liver microsomes in the presence of organosulfur compounds at 0.01-1 mM by using liquid chromatography-tandem mass spectrometry (LC-MS/ MS) analysis. Allicin, a major component of garlic, inhibited CYP1A2 and CYP3A4 activity by 21-45% at 0.03 mM. In contrast, a CYP2C9-catalyzed reaction was enhanced by up to 1.9 times in the presence of allicin at 0.003-0.3 mM. SAC, SMC, and S1PC had no effect on the activities of the five isoforms, except that S1PC inhibited CYP3A4-catalyzed midazolam 1′-hydroxylation by 31% at 1 mM. The N-acetylated metabolites of the three compounds inhibited the activities of several isoforms to a varying degree at 1 mM. N-Acetyl-Sallyl-L-cysteine and N-acetyl-S-methyl-L-cysteine inhibited the reactions catalyzed by CYP2D6 and CYP1A2, by 19 and 26%, respectively, whereas trans-N-acetyl-S-1-propenyl-L-cysteine showed weak to moderate inhibition (19-49%) of CYP1A2, 2C19, 2D6, and 3A4 activities. On the other hand, both the N-acetylated and Soxidized metabolites of SAC, SMC, and S1PC had little effect on the reactions catalyzed by the five isoforms. These results indicated that SAC, SMC, and S1PC have little potential to cause drug-drug interaction due to CYP inhibition or activation in vivo, as judged by their minimal effects (IC 50 >1 mM) on the activities of five major isoforms of human CYP in vitro.Key words organosulfur compound; cytochrome P450 inhibition; drug-drug interaction; garlic Garlic (Allium sativum L.) has been widely consumed since ancient times and its health benefits as a supplementary medicine have been well recognized.1) Recently, the increased use of herbal medicines has raised concerns about potential interactions with prescription medications. Of particular concern are drug-drug interactions (DDIs) caused by the inhibition or induction of drug-metabolizing enzymes, in particular, CYP enzymes. 2-4)Aged garlic extract (AGE) is a unique garlic product manufactured through a long extraction process from raw garlic and its multiple pharmacologic effects have been demonstrated in several clinical studies. [5][6][7][8] This extraction process leads to the reduction of odorous, acidic, and irritating compounds found in fresh garlic and the enrichment of water-soluble organosulfur components in AGE, such as S-allyl-L-cysteine (SAC), S-methyl-L-cysteine (SMC), and trans-S-1-propenyl-L-cysteine (S1PC)9) (Fig. 1). SAC is recognized as an active key component of AGE, and its favorable effects have been demonstrated, including a cholesterol-lowering effect, 10) an antioxidative effect, 11) and an anticancer effect. 12) There has been limited study on the biological and pharmacologic activities of S1PC; however, its immun...

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Aged garlic extract supplemented with B vitamins, folic acid and l-arginine retards the progression of subclinical atherosclerosis: A randomized clinical trial

Cited by 127 publications

References 45 publications

Modulatory effects of levamisole and garlic oil on the immune response of Wistar rats: Biochemical, immunohistochemical, molecular and immunological study

Modulatory effects of levamisole and garlic oil on the immune response of Wistar rats: Biochemical, immunohistochemical, molecular and immunological study

Molecular Biology of Atherosclerosis

Evaluation of the Effects of <i>S</i>-Allyl-L-cysteine, <i>S</i>-Methyl-L-cysteine, <i>trans</i>-<i>S</i>-1-Propenyl-L-cysteine, and Their <i>N</i>-Acetylated and <i>S</i>-Oxidized Metabolites on Human CYP Activities

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