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Garlic oil extract ameliorates the severity of copper deficiency.

This study was undertaken to determine whether a reduction in hepatic lipogenesis would be beneficial in the amelioration of copper (Cu) deficiency when fructose is fed. Garlic was chosen as the agent for reducing hepatic lipogenesis. Forty-eight weanling rats were fed Cu-deficient or adequate diets containing fructose or starch with or without garlic for 5 weeks. Garlic ameliorated the signs associated with Cu deficiency, although hepatic lipogenesis was not affected. Administration of garlic reduced the activity of the lipogenic enzyme glucose-6-phosphate dehydrogenase only in Cu-adequate rats. Consumption of garlic resulted in increased epididymal fat pad and pancrease sizes, and higher hematocrits, insulin and thyroxine concentrations. Mechanisms other than lipogenesis that could be responsible for this phenomenon are discussed.

Allyl Compounds↗

Antimicrobial effects of garlic, clove and red hot chilli on Listeria monocytogenes in broth model systems and soft cheese.

Antimicrobial activity of 1% (w/v) fresh garlic, ground clove and red dried chilli on Listeria monocytogenes was tested in broth systems at 37 degrees C and at 4 degrees C for 7 h. The initial cell concentration in the broth systems was between 2 x 10(6) and 4 x 10(6) CFU/ml. At 37 degrees C, growth to viable numbers of 3 x 10(8) CFU/ml in 7 h was measured. Clove had bacteriocidal activity and reduced the count to 1 CFU/ml. Garlic displayed bacteriostatic properties, and a count of 4 x 10(6) CFU/ml was maintained. Red chilli displayed an inhibitory effect and resulted in 50% lower counts than the control. L. monocytogenes had a slow growth rate at 4 degrees C and increased from an initial value of 3 x 10(6) to 5 x 10(6) CFU/ml during 7 h. The addition of garlic resulted in 3 x 10(6) CFU/ml, and clove reduced the viable cell concentration to 1 x 10(3) CFU/ml after 7 h. Two batches of soft cheese were produced in the laboratory using milk that was supplemented with L. monocytogenes. The final cheese containing L. monocytogenes with about 1 x 10(5) CFU/g. Half of each cheese batch was supplemented with either 1% garlic or 1% clove, whereby the other half served as a control. After 7 or 11 days incubation at 4 degrees C, the cheese was incubated at abuse temperature of 25 degrees C for 7 or 3 days, respectively. No antimicrobial effects of 1% (w/w) fresh garlic or clove powder on L. monocytogenes were observed in cheese after 1 or 2 weeks at the lower or higher temperature.

Bacteriological Techniques↗

A double-blind crossover study in moderately hypercholesterolemic men that compared the effect of aged garlic extract and placebo administration on blood lipids.

A double-blind crossover study comparing the effect of aged garlic extract with a placebo on blood lipids was performed in a group of 41 moderately hypercholesterolemic men [cholesterol concentrations 5.7-7.5 mmol/L (220-290 mg/dL)]. After a 4-wk baseline period, during which the subjects were advised to adhere to a National Cholesterol Education Program Step I diet, they were started on 7.2 g aged garlic extract per day or an equivalent amount of placebo as a dietary supplement for a period of 6 mo, then switched to the other supplement for an additional 4 mo. Blood lipids, blood counts, thyroid and liver function measures, body weight, and blood pressure were followed over the entire study period. The major findings were a maximal reduction in total serum cholesterol of 6.1% or 7.0% in comparison with the average concentration during the placebo administration or baseline evaluation period, respectively. Low-density-lipoprotein cholesterol was also decreased by aged garlic extract, 4% when compared with average baseline values and 4.6% in comparison with placebo period concentrations. In addition, there was a 5.5% decrease in systolic blood pressure and a modest reduction of diastolic blood pressure in response to aged garlic extract. We conclude that dietary supplementation with aged garlic extract has beneficial effects on the lipid profile and blood pressure of moderately hypercholesterolemic subjects.

Adult↗

Effect of garlic powder on C-reactive protein and plasma lipids in overweight and smoking subjects.

BACKGROUND: Epidemiologic studies suggest that garlic may have beneficial effects on risk factors associated with cardiovascular disease (CVD). However, these findings are not unambiguously supported by randomized placebo-controlled clinical trials. OBJECTIVE: We sought to investigate the effects of a chemically well-characterized garlic preparation on biomarkers for inflammation, endothelial function, and lipid metabolism in subjects with risk factors for CVD. DESIGN: This was a double-blind, randomized, placebo-controlled trial in 90 overweight [body mass index (in kg/m2) > 24.5] subjects aged 40-75 y who smoked >10 cigarettes/d. The subjects were randomly assigned to 3 parallel treatment groups: garlic powder (2.1 g/d), atorvastatin (40 mg/d), or placebo. Duplicate measurements were performed at baseline and after 1 and 3 mo of treatment. Treatments were compared with analysis of covariance with baseline as the covariate, and differences between the treatments were reported as mean percentage difference and corresponding 97.5% CI. RESULTS: None of the variables showed significant differences between the garlic-treated and the placebo groups. In contrast, compared with the placebo group, atorvastatin treatment resulted in significantly lower plasma concentrations of C-reactive protein (20.2%; 1.7%, 35.3%), total cholesterol (37.2%; 33.1%, 41.1%), LDL cholesterol (52.7%; 47.9%, 57.1%), triacylglycerols (31.9%; 20.8%, 41.5%), and tumor necrosis factor alpha (TNF-alpha; 41.9%; 19.0%, 58.3%) and increased the ratio of ex vivo whole blood lipopolysaccharide-stimulated to nonstimulated TNF-alpha concentrations (109.7%; 37.9%, 218.9%). CONCLUSION: We conclude that a chemically well-characterized garlic preparation has no significant effect on inflammatory biomarkers, endothelial function, or lipid profile in normolipidemic subjects with risk factors for CVD.

Adult↗

A novel anticancer effect of garlic derivatives: inhibition of cancer cell invasion through restoration of E-cadherin expression.

Metastatic cancer is one of the main causes of cancer-related death since they rarely respond to available treatments. Recently, certain compounds isolated from the dietary supplement, garlic, have shown anti-proliferation effect on cancer cells. The aim of this study was to investigate whether certain garlic derivatives had any effect on the potentially invasive androgen-independent prostate cancer (PCa) cells. Using colony-forming, wound-closure as well as matrigel-invasion assays, we found that two main water-soluble constituents of the garlic, S-allylcysteine (SAC) and S-allylmercaptocysteine (SAMC), were able to suppress PCa cell proliferation and invasive abilities. This inhibitory effect was associated with induction of mesenchymal to epithelial transition. Most importantly, the SAC and SAMC treatment led to restoration of E-cadherin expression at transcription and protein levels. In contrast, the expression of E-cadherin repressor, Snail, was reduced in the SAC- and SAMC-treated cells. Furthermore, examination of cell lines from other types of cancer (ovarian, nasopharyngeal and esophageal carcinomas) also confirmed that the effect of SAC and SAMC on activation of E-cadherin might be a general effect on human cancer cells. Our results demonstrate a novel anticancer effect of garlic and suggest that certain garlic-derived compounds may be potential agents for suppression of invasive growth through restoration of E-cadherin expression in cancer cells.

Antineoplastic Agents↗

Garlic ingestion by pregnant women alters the odor of amniotic fluid.

Amniotic fluid samples were obtained from 10 pregnant women undergoing routine amniocentesis procedure. Approximately 45 min prior to the procedure, five of the women ingested placebo capsules, whereas the remaining five ingested capsules containing the essential oil of garlic. Randomly selected pairs of samples, one from a woman who ingested garlic and the other from a woman who ingested placebo capsules, were then evaluated by a sensory panel of adults. The odor of the amniotic fluid obtained from four of the five women who had ingested the garlic capsules was judged to be stronger or more like garlic than the paired samples collected from the women consuming placebo capsules. Thus, garlic ingestion by pregnant women significantly alters the odor of their amniotic fluid.

Adult↗

Aged garlic extract may be safe for patients on warfarin therapy.

Garlic has been known to have antiplatelet properties. Because of the lack of major clinical data regarding the safety of concomitant use of garlic supplements and anticoagulants, we decided to evaluate the safety of using garlic extract along with oral anticoagulation therapy. During this project we tested aged garlic extract (AGE), a commercial garlic preparation, with warfarin (Coumadin). Sixty-six (66) patients were screened for a double-blind, randomized, placebo-controlled pilot study. Fifty-two (52) patients were randomized for the project. Forty-eight patients (30 men and 18 women, with a mean age of 56+/-10 years) completed the study. Eighteen patients (14 before randomization, 4 after randomization) were dropped from the study. The study medication (AGE or placebo) was administered at a dose of 5 mL twice a day for 12 wk. Potential bleeding and thromboembolic episodes were monitored. There was no evidence of increased hemorrhage in either the placebo or the AGE group. Adverse events included headache, fatigue, colds, and dizziness. However, no significant difference was found in the incidence of these minor adverse events between the groups. Thus, the adverse events are unlikely to be attributable to AGE. The results suggest that AGE is relatively safe and poses no serious hemorrhagic risk for closely monitored patients on warfarin oral anticoagulation therapy. Although the risk-benefit ratio of AGE use needs to be considered carefully when warfarin therapy is necessary, its positive effects may be beneficial to people with a high-risk background or who are taking cardiovascular medications.

Adult↗

Redox-sensitive proteins are potential targets of garlic-derived mercaptocysteine derivatives.

Molecular investigations support existing clinical and epidemiological data that garlic-derived allylsulfides reduce cancer risk. Various allylsulfides can diminish progression of cancer cells at either the G1/S or G2/M phase. Allylsulfide derivatives modify redox-sensitive signal pathways and cause growth inhibition, mitotic arrest, and apoptosis induction. Whether allylsulfides modify intracellular redox potentials by affecting the ratio of glutathione:glutathione disulfide and/or by interacting directly with sulfhydryl domains on regulatory or catalytic-signal proteins requires further investigation. To understand the possible biochemical mechanisms contributing to the protective effects of allylsulfides, we investigated the ability of these compounds to undergo enzyme-catalyzed transformations. In addition to catalyzing gamma-elimination reactions, gamma-cystathionase can perform beta-elimination reactions with cysteinyl S-conjugates derived from garlic extracts when the S-alkyl group (R) is larger than ethyl. The reaction products are pyruvate, ammonium, and a sulfur-containing fragment (RSH). beta-Lyase substrates of gamma-cystathionase thus far identified from garlic include: S-allyl-L-cysteine (R=CH2=CHCH2-), S-allylmercapto-L-cysteine (R=CH2=CHCH2S-), and S-propylmercapto-L-cysteine (R=CH3CH2CH2S-). Mercapto derivatives yield persulfide products (RSSH) that are potential sources of sulfane sulfur, which may modify protein function by reacting at important cysteinyl domains. Thus, beta-elimination reactions with cysteine S-conjugates in garlic may modify cancer-cell growth by targeting redox-sensitive signal proteins at sulfhydryl sites, thereby regulating cell proliferation and/or apoptotic responses. These interactions may be useful in identifying efficacy of garlic-derived compounds and/or developing other novel organosulfur compounds that may modify intracellular redox potentials or interact with thiols associated within cysteine domains in regulatory, catalytic, signal, or structural proteins.

Animals↗

The microaerophilic flagellate Giardia intestinalis: Allium sativum (garlic) is an effective antigiardial.

Whole garlic (Allium sativum L.) extract and some of its components were assayed for antigiardial activity. Whole garlic extract gave an IC(50) at 24 h of 0.3 mg ml(-1). Most of the components assayed were inhibitory to the organism, especially allyl alcohol and allyl mercaptan, with IC(50) values of 7 microg ml(-1) and 37 microg ml(-1) respectively. Studies with calcofluor white indicated that whole garlic and allyl alcohol collapse the transmembrane electrochemical membrane potential (Deltapsi) of the organism, as indicated by uptake of the fluorochrome. Electron microscopy allowed the morphological changes that occur with garlic inhibition to be recorded. Both the surface topography and internal architecture of the organism changed during incubation with the biocides. Both whole garlic and allyl alcohol resulted in fragmentation of the disc and an overexpression of disc microribbons, internalization of flagella, vacuole formation and an increase in distended vesicles. Allyl mercaptan, however, only gave an increase in distended vesicles, suggesting that this biocide has a different mode of action.

Animals↗

Antidermatophytic activity of garlic (Allium sativum) in vitro.

BACKGROUND: Interest in herbal medicine is enjoying a renaissance at present. Garlic (Allium sativum) is an intriguing herb with a long history of medicinal use for a variety of diseases including ringworm infections. METHODS: Antidermatophytic activity of the aqueous extract of garlic (A. sativum) was investigated against 88 clinical isolates of dermatophytes by an agar dilution technique. The isolates included Microsporum canis (50), M. audouinii (5), Trichophyton rubrum (6), T. mentagrophytes (5), T. violaceum (12), T. simii (5), T. verrucosum (1), T. erinacei (1), and Epidermophyton floccosum (2). The results were compared with the minimal inhibitory concentrations of ketoconazole. RESULTS: The aqueous extract of garlic, diluted 1:150 and 1:100, had inhibited 50 and 90% of the isolates tested, whereas the respective values for ketoconazole were 1 and 2.5 micrograms/mL. CONCLUSIONS: Garlic (A. sativum) could be used as an effective antidermatophytic agent. Further purification and extraction of the active principle of garlic would give a true antidermatophytic activity comparable to standard antifungal drugs.

Antifungal Agents↗

Self-inflicted garlic burns: our experience and literature review.

BACKGROUND: Throughout history, garlic has been used to treat a large variety of illnesses. One of garlic's adverse local effects is contact dermatitis. METHODS: We present three patients treated in the Department of Plastic Surgery for suspected self-inflicted lower extremity burns. RESULTS: The burns had unique features, not consistent with the etiology first claimed by the patients. All were soldiers with low motivation who confessed to using garlic to cause the burns. CONCLUSIONS: Garlic application usually results in local inflammation, but, if applied under a pressure bandage, or if there is poor wound care or a secondary infection, it can cause a severe dermal reaction and a deep chemical burn. We present these cases to increase physician awareness of the characteristics of self-inflicted garlic burns, and review the dermatotoxic effect.

Adult↗

Antifungal effects of Allium sativum (garlic) extract against the Aspergillus species involved in otomycosis.

Otomycosis due to saprophytic keratolytic fungi represents a small percentage of clinical external otitis. Although there are certain antibacterial and antifungal agents available, they usually are very caustic, potentially ototoxic and cannot be used if the ear drum is perforated. Garlic is utilized as a folk medicine in many countries for its antimicrobial and other beneficial properties. In response to a lack of otic preparations, the authors studied the efficacy of garlic extracts against the fungi belonging to the genus Aspergillus which are the most common cause of this infection. Aqueous garlic extract (AGE) and concentrated garlic oil (CGO) along with various commercial garlic supplements and pharmaceutical prescriptions were used in an in-vitro study. AGE and especially CGO were found to have antifungal activity. These agents showed similar or better inhibitory effects than the pharmaceutical preparations and demonstrated similar minimum inhibitory concentrations.

Aspergillus fumigatus↗

Chronic garlic administration protects rat heart against oxidative stress induced by ischemic reperfusion injury.

BACKGROUND: Oxidative stress plays a major role in the biochemical and pathological changes associated with myocardial ischemic-reperfusion injury (IRI). The need to identify agents with a potential for preventing such damage has assumed great importance. Chronic oral administration of raw garlic has been previously reported to augment myocardial endogenous antioxidants. In the present study, the effect of chronic oral administration of raw garlic homogenate on oxidative stress induced by ischemic-reperfusion injury in isolated rat heart was investigated. RESULTS: Raw garlic homogenate (125, 250 and 500 mg/kg once daily for 30 days) was administered orally in Wistar albino rats. Thereafter, hearts were isolated and subjected to IRI (9 min. of global ischemia, followed by 12 min of reperfusion; perfusion with K-H buffer solution; 37 degrees C, 60 mm Hg.). Significant myocyte injury and rise in myocardial TBARS along with reduction in myocardial SOD, catalase, GSH and GPx were observed following IRI. Depletion of myocardial endogenous antioxidants and rise in TBARS were significantly less in the garlic-treated rat hearts. Oxidative stress induced cellular damage as indicated by ultrastructural changes, like disruption of myofilament, Z-band architecture along with mitochondrial changes were significantly less. CONCLUSIONS: The study strongly suggests that chronic garlic administration prevents oxidative stress and associated ultrastructural changes, induced by myocardial ischemic-reperfusion injury.

Animals↗

Cell cycle arrest and differential gene expression in HT-29 cells exposed to an aqueous garlic extract.

Epidemiological data show an inverse correlation between garlic consumption and the risk for colon cancer. To examine this relationship, HT-29 human adenocarcinoma cells were cultured in the presence and absence of an aqueous garlic extract. Garlic treatment resulted in a fraction of cells detaching from the culture flasks. These cells remained viable. Flow cell cytometry showed that untreated cells exhibited a normal distribution among phases of the cell cycle, with 12% of cells at the G2/M boundary. Of the garlic-treated cells remaining attached to the flask, 27% were present at the G2/M boundary. Treated cells that detached from the flask were found almost exclusively (89%) at the G2/M boundary. RNA fingerprinting and microarray analysis showed that expression of the gene for menin was twice as high in control cells as in detached treated cells. In contrast, expression of genes for epidermal growth factor receptor and integrin-alpha6 was nearly twice as high in detached treated cells as in control cells. These changes in gene expression were consistent with an arrest of the cell cycle at the G2/M boundary. Garlic's arrest of the cell cycle in human adenocarcinoma cells may explain in part its anticarcinogenic properties.

Adenocarcinoma↗

Inhibition by allyl sulfides and crushed garlic of O6-methylguanine formation in liver DNA of dimethylnitrosamine-treated rats.

Garlic consumption is linked with lower incidences of certain cancers perhaps because garlic-derived allyl sulfides inhibit nitrosamine activation by cytochrome P450s. To help evaluate this view, effects of allyl sulfides on O6-methylguanine (O6MG) levels were examined in liver of rats injected with 20 mg/kg of liver carcinogen dimethylnitrosamine (DMN) and killed 3 h later. DNA was isolated and hydrolyzed, and O6MG/guanine ratios were determined by HPLC-fluorescence. Mean inhibition of O6MG formation fell from 89% for 200 to 33% for 12 mg diallyl sulfide (DAS) per kilogram gavaged 18 h before DMN injection. Gavage of DAS 3 or 6 h (instead of 18 h) before DMN injection significantly reduced inhibitions. Mean inhibitions for diallyl disulfide, diallyl sulfoxide, and diallyl sulfone (75-100 mg/kg) gavaged 18 h before DMN were 39%, 72%, and 82%. In lung and kidney, DAS produced mean inhibitions of 98% and 74% compared with 89% in liver. When methylnitrosourea was injected instead of DMN, neither DAS nor DADS inhibited O6MG formation in liver DNA. Feeding 2.5% garlic for 7 days inhibited DMN-induced O6MG formation in liver DNA by 46%, similar to that expected from the estimated yield of allyl sulfides from garlic. Hence, dosing with DAS or feeding garlic may be useful chemopreventive strategies against nitrosamine-induced cancers.

Allyl Compounds↗

Allixin accumulation with long-term storage of garlic.

Extremely high accumulation of allxiin, a phytoalexin derived from garlic, was observed in necrotic tissue areas after long-term storage. The allixin produced recrystallized on the surface of the garlic clove. The amount of allixin produced in raw garlic with necrotic tissue areas was 1400 ng/mg wet garlic, which exceeds the minimum exhibitory concentration of allixin. After approximately 2 years of storage, amount of allixin accumulated reached slightly less than 1% of the dry weight of garlic cloves.

Chromatography, High Pressure Liquid↗

[Garlic compounds protect vascular endothelial cells from oxidant injury].

Oxygen radical injury and lipid peroxidation have been suggested as major causes of cancer, atherosclerosis and the aging process. We examined in vitro the effect of garlic on H2O2-induced oxidant injury in bovine pulmonary artery endothelial cells (PAEC). After overnight preincubation with Aged Garlic Extract (AGE, from Wakunaga Pharmaceutical Co., Ltd., Japan) or S-allyl cysteine (SAC), PAEC monolayers were exposed to H2O2 for 3 h. Cell viability (MTT assay), lactate dehydrogenase (LDH) release, and lipid peroxidation (TBA-RS) were measured to assess oxidant injury. AGE (1-4 mg/ml) pretreatment significantly reduced the loss of cell viability induced by 50-100 microM of H2O2. AGE and SAC exhibited dose dependent inhibition of both LDH release and TBA-RS production induced by 50 microM of H2O2. The results show that AGE and SAC can protect vascular endothelial cells from oxidant injury. Numerous garlic compounds could be involved in the antioxidant properties of garlic, while there could be some prooxidant compounds derived from garlic. It is important to keep an array of antioxidant compounds to develop good herbal preparation, like AGE.

Animals↗

Antithrombotic effects of odorless garlic powder both in vitro and in vivo.

Antithrombotic activities of odorless garlic powder were demonstrated in blood fibrinolytic and coagulation systems. Though the odorless garlic preparation did not influence tissue-type plasminogen activator (t-PA) or its inhibitor secretions from human umbilical vein endothelial cells, it enhanced plasmin generation by t-PA on fibrin film and in chromogenic assays by 1.8-fold and 8.7-fold respectively. The coagulation system was considerably reduced after the administration of the garlic in a rat in situ loop model, indicating that increased levels of thrombin-antithrombin III (TAT) complex in the control group were significantly reduced to normal (sham) in the garlic group (p<0.05), which was associated with decreasing tendencies towards prolonged or increased values of coagulation parameters in the control group. These findings suggest that odorless garlic not only activates fibrinolytic activity by accelerating t-PA-mediated plasminogen activation, but also suppresses the coagulation system by downregulating thrombin formation, suggesting a beneficial role in preventing pathological thrombus formation in such cardiovascular disorders.

Animal Feed↗