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Garlic and onion oils inhibit proliferation and induce differentiation of HL-60 cells.

Phytochemicals present in the genus Allium have potential pharmacological effects, such as antimicrobial, antithrombotic, antitumor, hypolipidaemic and hypoglycemic activities. In this present study, we examined the effects of garlic and onion oils on human promyelocytic leukemia cells, HL-60. Incubation of HL-60 with garlic or onion oil (20 microg/ml) caused a marked suppression of HL-60 proliferation; the suppression was almost identical with those obtained by all-trans-retinoic acid (ATRA) or dimethyl sulfoxide (DMSO) used as positive controls. These oils induced the generation of nitroblue tetrazolium (NBT)-reducing activity, and about 20% of the HL-60 cells became NBT positive. CD11b, another marker of the differentiation of these cells, was also significantly induced by garlic oil or onion oil. The combination of garlic or onion oil with ATRA was more effective than either alone. These data suggest that garlic and onion oils have the ability to induce differentiation of HL-60 cells into those of the granulocytic lineage.

Cell Count↗

Endothelium-dependent and -independent effect of aqueous extract of garlic on vascular reactivity on diabetic rats.

Garlic has been well known for its protective effects against cardiovascular disease. In this study, the effect of aqueous extract of garlic on the vascular reactivity of thoracic aorta from streptozotocin (STZ)-diabetic rats was investigated in the presence and absence of endothelium. Although, 8-weeks of treatment with garlic extract had no significant effect on the concentration of serum glucose, but it significantly attenuated the abnormality in vascular reactivity to noradrenaline (NA) and acetylcholine (Ach). In addition, the endothelium-independent relaxation response to isosorbide dinitrate (ISD) was not affected by diabetes or garlic treatment. The results suggest that garlic treatment of STZ-diabetic rats can prevent the development of abnormal contractility through an endothelium-dependent and -independent mechanism.

Acetylcholine↗

Effect of garlic (Allium sativum L.) extract on tissue lead level in rats.

The prophylactic efficacy of garlic (Allium sativum L.) extract to reduce tissue lead (Pb) concentration was evaluated experimentally in rats. Thirty female rats were divided into five groups, keeping group A as a healthy control. Rats of groups B, C, D and E received lead acetate orally at the rate of 5 mg per kg body weight daily for 6 weeks. The garlic extract was tried in three doses, viz. 100 (low), 200 (medium) and 400 mg (high) per kg body weight orally and given simultaneously with lead salt to the rats of group C, D and E, respectively. Mean blood lead concentrations in lead-exposed rats ranged between 0.13+/-0.02 and 0.96+/-0.06 microg/ml, whereas in garlic-treated rats, the range was between 0.16+/-0.01 and 0.80+/-0.05; 0.13+/-0.01 and 0.71+/-0.06 and 0.14+/-0.01 and 0.60+/-0.05 microg per ml in low, medium and high dose groups, respectively. The mean lead concentration in liver, kidneys, brain and bone of lead exposed rats was 2.943+/-0.206, 4.780+/-0.609, 1.019+/-0.100 and 44.075+/-2.60 microg per ml, respectively. Concomitant use of garlic extract at the three different doses was found to reduce lead concentration considerably indicating the potential therapeutic activity of garlic against lead.

Animals↗

The antihypertensive effect of garlic (Allium sativum) in the rat two-kidney--one-clip Goldblatt model.

A study was designed to elucidate the antihypertensive effect of garlic in the two-kidney--one-clip (2K-1C) Goldblatt model. Since the hypertension in this model depends largely on the increasing concentrations of vasopressor agents (prostaglandins and angiotensin II) there is a strong indication that reducing these factors could contribute in controlling the pathological rise in blood pressure. In this study, single or multiple doses of 0.5 ml of aqueous extract of garlic were given orally to 2K-1C rats. The data shows that the single dose of garlic used had a maximum antihypertensive effect 2-6 h after administration. The residual effect of this single dose continued for up to 24 h. The multiple dose of garlic appeared to be effective in restraining the expected rise in blood pressure that normally occurs in 2K-1C rats. Switching multiple-dose treatments halfway through the experiment further strengthened the findings. The study suggests that garlic does have an effective antihypertensive ability, and may be used as a supplementary and natural remedy in cases of unilateral renovascular hypertension.

Animals↗

Garlic ameliorates gentamicin nephrotoxicity: relation to antioxidant enzymes.

Reactive oxygen species are involved in gentamicin (GM) nephrotoxicity, and garlic is effective in preventing or ameliorating oxidative stress. Therefore, the effect of garlic on GM nephrotoxicity was investigated in this work. Four groups of rats were studied: (i) fed normal diet (CT), (ii) treated with GM (GM), (iii) fed 2% garlic diet (GA), and (iv) treated with GM and 2% garlic diet (GM + GA). Rats were placed in metabolic cages and GM nephrotoxicity was induced by injections of GM (75 mg/kg every 12 h) for 6 d. Lipoperoxidation and enzyme determinations were made in renal cortex on day 7. GM nephrotoxicity was made evident on day 7 by (i) tubular histological damage, (ii) enhanced BUN and urinary excretion of N-acetyl-beta-D-glucosaminidase, and (iii) decreased creatinine clearance. These alterations were prevented or ameliorated in GM + GA group. The rise in lipoperoxidation and the decrease in Mn-SOD and glutathione peroxidase (GPx) activities observed in the GM group, were prevented in the GM + GA group. Cu, Zn-SOD activity and Mn-SOD and Cu,Zn-SOD content did not change. CAT activity and content decreased in the GM, GA, and GM + GA groups. CAT mRNA levels decreased in the GM group. The protective effect of garlic is associated with the prevention of the decrease of Mn-SOD and GPx activities and with the rise of lipoperoxidation in renal cortex.

Acetylglucosaminidase↗

[Ajoene the main active compound of garlic (Allium sativum): a new antifungal agent].

The curative properties of garlic in medicine have been known for a long time. But, it was only in the last three decades when garlic properties were seriously investigated confirming its potential as therapeutic agent. Allicin, ajoene, thiosulfinates and a wide range of other organosulphurate compounds, are known to be the constituents linked to the garlic properties. Regarding the biochemical properties of these compounds, ajoene [(E,Z)-4,5,9 Trithiadodeca 1,6,11 Triene 9-oxide] is stable in water, and it can be obtained by chemical synthesis. There is evidence that some of the garlic constituents exert a wide variety of effects on different biological systems. However, ajoene is the garlic compound related to more biological activities, as showed in in vitro and in vivo systems. Those studies found that ajoene has antithrombotic, anti-tumoral,antifungal, and antiparasitic effects. This study deals with a recently described antifungal property of ajoene, and its potential use in clinical trails to treat several fungal infections.

Animals↗

Garlic and aging: new insights into an old remedy.

There has been an impressive gain in individual life expectancy with parallel increases in age-related chronic diseases of the cardiovascular, brain and immune systems. These can cause loss of autonomy, dependence and high social costs for individuals and society. It is now accepted that aging and age-related diseases are in part caused by free radical reactions. The arrest of aging and stimulation of rejuvenation of the human body is also being sought. Over the last 20 years the use of herbs and natural products has gained popularity and these are being consumed backed by epidemiological evidence. One such herb is garlic, which has been used throughout the history of civilization for treating a wide variety of ailments associated with aging. The role of garlic in preventing age-related diseases has been investigated extensively over the last 10-15 years. Garlic has strong antioxidant properties and it has been suggested that garlic can prevent cardiovascular disease, inhibit platelet aggregation, thrombus formation, prevent cancer, diseases associated with cerebral aging, arthritis, cataract formation, and rejuvenate skin, improve blood circulation and energy levels. This review provides an insight in to garlic's antioxidant properties and presents evidence that it may either prevent or delay chronic diseases associated with aging.

Aging↗

Thermal degradation of allicin in garlic extracts and its implication on the inhibition of the in-vitro growth of Helicobacter pylori.

Allicin, the main active principle related to Allium sativum chemistry, is considered to be responsible for the bacteriostatic properties of garlic. The work described here has demonstrated the direct implication of the allicin present in solvent-free garlic extracts obtained with ethanol (ethanolic garlic extract, EGE) and acetone (acetonic garlic extract, AGE) in the inhibition of the in-vitro growth of Helicobacter pylori (Hp), the bacterium responsible for serious gastric diseases such as ulcers and even gastric cancer. The evolution of allicin concentration as a function of time and temperature has been the subject of a kinetic study. The reaction order, activation energy, and preexponential factor (in accordance with Arrhenius theory) have been determined for the decomposition process of allicin in these organic media. First-order decomposition, an activation energy of 97.4 kJ/mol, and an Arrhenius preexponential factor of 8.9 x 10(10) s(-1) have been determined for allicin in EGE. For allicin in AGE the kinetic order determined was 1.5, the activation energy 184.5 kJ/mol, and the preexponential factor 3.1 x 10(24) s(-1) (mg/L)(-0.5). The presence or absence of allicin in these garlic products was found to be crucial for the inhibition of the in-vitro growth of Hp, as demonstrated by microbiological analysis for AGE. A relationship has been identified between the effectiveness and durability of the anti-Hp properties shown by AGE and the allicin content of these products. The bacteriostatic properties were active for up to 10 months if the samples were maintained at 6 degrees C.

Anti-Bacterial Agents↗

Allyl-thiosulfinates, the bacteriostatic compounds of garlic against Helicobacter pylori.

Allicin and allyl-methyl plus methyl-allyl thiosulfinate from acetonic garlic extracts (AGE) have been isolated by high-performance liquid chromatography. These compounds have shown inhibition of the in vitro growth of Helicobacter pylori (Hp), the bacterium responsible for serious gastric diseases such as ulcers and even gastric cancer. A chromatographic method was optimized and used to isolate these thiosulfinates. The method developed has allowed the isolation of natural thiosulfinates extracted from garlic by organic solvents and is an easy and cheap methodology that avoids complex synthesis and purification procedures. The capacity and effectiveness of isolated natural thiosulfinates have been tested, and this has enabled the identification of the main compounds responsible for the bacteriostatic activity shown by AGE origin of these kinds of organosulfur compounds along with ethanolic garlic extracts (EGE). Additionally, microbiological analyses have suggested that these compounds show a synergic effect on the inhibition of the in vitro growth of Hp. The results described here facilitate the process of obtaining garlic extracts with optimal bacteriostatic properties. The product is obtained in a way that avoids expensive purification methods and will allow the design of live tests with the aim of investigating the potential for the use of these garlic derivatives in the treatment of patients with Hp infections.

Anti-Bacterial Agents↗

Effects of allyl sulfur compounds and garlic extract on the expression of Bcl-2, Bax, and p53 in non small cell lung cancer cell lines.

Allyl sulfur compounds play a major role in the chemoprevention against carcinogenesis. The present study compared the antiproliferative effects of diallyl sulfide (DAS), diallyl disulfide (DADS) and garlic extract on p53-wild type H460 and p53-null type H1299 non small cell lung cancer cells (NSCLC). The DAS and DADS treatment of both H460 and H1299 cells resulted in the highest numbers of cells in apoptotic state as measured by acridine orange staining, however, garlic extract treatment did not induce any significant apoptotic cells by MTT assay. DADS was found to be more effective in inducing apoptosis on NSCLC. The level of p53 protein in H460 cell was increased following DADS treatment. DAS and garlic extract treatment of H460 cells induced a rise in the level of Bax and a fall of Bcl-2 level. These results demonstrate that DAS, DADS and garlic extract are effective in reduction of anti-proliferative gene in NSCLC and suggest that modulation of apoptosis-associated cellular proteins by DAS, DADS and garlic extract may be the mechanism for apoptosis which merit further investigation as potential chemoprevention agents.

Allyl Compounds↗

A pilot study to determine the effectiveness of garlic oil capsules in the treatment of dyspeptic patients with Helicobacter pylori.

BACKGROUND: Resistance of Helicobacter pylori to clarithromycin and metronidazole is now found worldwide. Steam-distilled garlic oil has in vitro activity against H. pylori and may be a useful alternative treatment strategy. MATERIALS AND METHODS: In this pilot study dyspeptic patients with positive serology for H. pylori confirmed by 13C urea breath test (UBT), at 0 and 2 weeks, were enrolled. Treatment consisted of one 4 mg garlic oil capsule with a meal four times per day for 14 days. H. pylori eradication was defined as a negative UBT at both follow-up appointments. Suppression was defined as a 50% fall in 13C excess between baseline and follow-up 1. RESULTS: Five patients completed the study. There was no evidence of either eradication or suppression of H. pylori or symptom improvement whilst taking garlic oil. CONCLUSION: These negative results show that, within the gastric milieu, garlic oil at this dose does not inhibit H. pylori. A higher dose administered for a longer time-period may be effective. Antibiotics are usually combined with a proton-pump inhibitor or bismuth salt, as the only antibiotic with any in vivo activity against H. pylori in monotherapy is clarithromycin. A proton pump inhibitor raises gastric pH and, by increasing bacterial division, may increase the in vivo activity of garlic oil. This may be worth pursuing in a future trial.

Adult↗

Thromboxane-B2, prostaglandin-E2 and hypertension in the rat 2-kidney 1-clip model: a possible mechanism of the garlic induced hypotension.

Serum collected from unilaterally clipped and unclipped rats before and after treatment with water, garlic or cilazapril and subsequent to measuring blood pressure was assayed for thromboxane-B2 and prostaglandin-E2. The unclipped rats' thromboxane-B2 and prostaglandin-E2 levels were about 23 ng/ml and 2 ng/ml, respectively, and blood pressure was 126+/-3 mmHg. These values were not affected by either water or garlic administration. The clipped rats' thromboxane-B2 and prostaglandin-E2 concentrations were close to 34 ng/ml and 4 ng/ml, respectively, and declined only in response to garlic (by 15 ng/ml and 3 ng/ml) and cilazapril (by 12 ng/ml and 1.5 ng/ml). The blood pressure of these rats was 196+/-7 mmHg and again was reduced only by garlic to 169+/-14 mmHg and cilazapril to 137+/-5 mmHg. The no-treatment and water-treatment readings were significantly higher in the clipped rats. The data suggest that prostanoid system activity in the 2-kidney 1-clip rat is enhanced and mostly toward maintaining the hypertension. Furthermore, the blood pressure lowering effects of garlic and cilazapril might have been induced partially by a greater reduction in the synthesis of vasoconstrictor prostanoids.

Animals↗

Protection of liver microsomal membranes from lipid peroxidation by garlic extract.

Garlic extract, the ethanol-soluble fraction of garlic, prevented formation of thiobarbituric-acid-reactive substances and fluorescent substances during lipid peroxidation of rat liver microsomes. Lipid peroxidation increased the fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene labelled to the microsomes while this increase was prevented by the garlic extract. It thus seems probable that the garlic extract serves to maintain membrane fluidity. These effects were dependent on its concentration and particularly prominent on exceeding a certain concentration of garlic extract. These results suggest its possible role of protecting the membranes from lipid peroxidation.

Animals↗

Chemoprotection of garlic extract toward cyclophosphamide toxicity in mice.

The effect of the administration of an extract of garlic (Allium sativum) was studied in mice that were treated with a chronic lethal dose of cyclophosphamide (50 mg/kg body wt, 14 days). The intraperitoneal administration of garlic (50 mg/animal, 14 days) along with cyclophosphamide reduced the toxicity of the latter considerably with an increase in life span of more than 70%. The administration of garlic extract did not improve the lymphopenia produced by cyclophosphamide or liver alkaline phosphatase, but there was a significant reduction in liver glutamic-pyruvic transaminase. Moreover, garlic extract reduced the level of lipid peroxidation induced in the liver by cyclophosphamide administration. Administration of garlic extract did not interfere with the tumor-reducing activity of cyclophosphamide.

Alanine Transaminase↗

Inhibition of experimental carcinogenesis by painting with garlic extract.

The inhibitory effect of topical garlic extract on 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in Syrian hamsters was studied to define the local anticarcinogenicity of garlic. Two other chemicals, benzo[a]pyrene (BP) and 5-nitroso-2,4,6-triaminopyrimidine (NTP), were also testing materials. All chemicals were applied topically to the cheek pouches of hamsters. The tumorigenesis and architecture of blood vessels on pouch mucosa were examined periodically. The amount of DNA synthesis and gamma-glutamyl transpeptidase activity of the pouch mucosa was detected when the animals were killed. The anticarcinogenicity of garlic and other chemicals was determined by comparing the data obtained from all the examinations with each other and with those shown in the control animals. The apparent local inhibitory effect of garlic on DMBA-induced carcinogenesis was demonstrated, which was even stronger than those of BP and NTP. It suggests that garlic could be developed as a potential chemopreventive agent for oral cancer. This study also disclosed that the examination parameters used were reliable and reproducible. Therefore, they might be utilized for screening the anticarcinogenicity of materials or for early diagnosis of carcinogenesis. The animal model could also be adopted appropriately in evaluating the inhibitory effect of other materials on experimental carcinogenesis because of its comparability.

9,10-Dimethyl-1,2-benzanthracene↗

Organosulfur compounds of garlic modulate mutagenesis, metabolism, and DNA binding of aflatoxin B1.

The effects of two organosulfur compounds of garlic (ajoene and diallyl sulfide) and a crude garlic extract on aflatoxin B1 (AFB1)-induced mutagenesis were determined using rat liver 9,000 g supernatant (S-9) as the activation system and Salmonella typhimurium TA-100 as the tester strain. The effects of these compounds on AFB1 binding to calf thymus DNA were also measured. Metabolites of AFB1 were isolated and analyzed by reverse-phase high-performance liquid chromatography. All these compounds inhibited S-9-dependent mutagenesis induced by AFB1. They also inhibited AFB1 binding to DNA. A significant decrease in organo-soluble metabolites of AFB1 was observed with ajoene and garlic extract. An increase of glucuronide and glutathione conjugates was obtained with garlic extract. The results indicate that garlic compounds tested in this study are antimutagenic and, potentially, anticarcinogenic.

Aflatoxin B1↗

Modulation of rat hepatic cytochrome P-450 activity by garlic organosulfur compounds.

Garlic organosulfur compounds exert chemopreventive effects at several organ sites in rodents after administration of chemical carcinogens, possibly by inhibiting carcinogen activation via cytochrome P-450-mediated oxidative metabolism. It has been suggested that the variability in potency of tumor inhibition by garlic sulfur compounds is due to structural differences, such as the number of allyl and sulfur groups. In this study, diallyl sulfide (DAS), diallyl disulfide (DADS), and allyl methyl sulfide (AMS) were administered to acetone-treated adult male Sprague-Dawley rats by gastric gavage at a dose of 1.75 mmol/kg in cottonseed oil. After 15 hours, hepatic microsomal cytochrome P-450 activity and content were examined. The activity of p-nitrophenol (pNP) hydroxylase (E.C. 1.14.13.29) was significantly decreased by all garlic compounds, whereas benzphetamine N-demethylase and ethoxyresorufin O-deethylase activities were not changed. The activity of pNP hydroxylase was decreased to 31%, 54%, and 65% of control activity, and immunodetectable CYP2E1 protein levels were decreased in a similar manner by DAS, DADS, and AMS, respectively. Additional acetone-treated rats were given 4-methyl pyrazole, a ligand specific for CYP2E1, intraperitoneally five hours after garlic compound administration. Ten hours later, pNP hydroxylase activity was decreased to 73%, 78%, and 67% of control levels by DAS, DADS, and AMS, respectively. Further studies are needed to determine whether the variable potency of inhibition of CYP2E1 enzyme activity is related to chemopreventive efficacy of garlic sulfur compounds.

Allyl Compounds↗

Helicobacter pylori--in vitro susceptibility to garlic (Allium sativum) extract.

Gastric cancer is the major cancer in the developing world and one of the top two worldwide. Helicobacter pylori is a bacterium implicated in the etiology of stomach cancer. The incidence of stomach cancer is lower in individuals and populations with high Allium vegetable intakes. Allium vegetables, particularly garlic, have antibiotic activity. Standard antibiotic regimens against H. pylori are frequently ineffective in high-risk populations. As part of our study of the role of Allium vegetable intake on cancer prevention, we wished to investigate its antimicrobial activity against H. pylori. An aqueous extract of garlic cloves was standardized for its thiosulfinate concentration and tested for its antimicrobial activity on H. pylori grown on chocolate agar plates. Minimum inhibitory concentration was 40 micrograms thiosulfinate per milliliter. Staphylococcus aureus tested under the same conditions was not susceptible to garlic extract up to the maximum thiosulfinate concentration tested (160 micrograms/ml). To our knowledge, this is the first report of H. pylori's susceptibility to garlic extract of known thiosulfinate concentration. It is plausible that the sensitivity of H. pylori to garlic extract at such low concentration may be related to the reported lower risk of stomach cancer in those with a high Allium vegetable intake. Furthermore, it may identify a strategy for a low-cost intervention, with few side effects, in populations at high risk for stomach cancer, particularly where antibiotic resistance and the risk of reinfection are high.

Anti-Bacterial Agents↗