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Cardiovascular benefits of garlic (Allium sativum L).

Although garlic is believed to have health-promoting benefits, many of the claimed benefits are not supported by good scientific studies. This review critically examined current scientific literature concerning claims of cardiovascular benefits from regular consumption of garlic or garlic preparations. The vast majority of recent randomized, placebo-controlled studies do not support a role for garlic in lowering blood lipids. There also is insufficient evidence to support a role in reducing blood pressure. While there have been indications of antiatherosclerotic effects associated with garlic consumption, there are insufficient data in humans. Investigation of antithrombotic effects of garlic consumption appears to hold promise, but too few data exist to draw firm conclusions.

Antioxidants↗

Tomato and garlic can modulate azoxymethane-induced colon carcinogenesis in rats.

Tomato (Lycopersicon esculentum) and garlic (Allium cepa) are important constituents of the human diet. Compounds like diallyl sulfides, diallyl disulfides and quercetin, which are active components of garlic, have known anti-inflammatory, antimutagenic activities. Similarly, active components in tomato, such as kaempferol and chlorogenic acid, have antimutagenic activities and lycopene is the most active oxygen quencher with potential chemopreventive activities. In view of this, an endeavour was made to evaluate the anticarcinogenic effect, if any, of tomato and garlic consumption individually and in combination on azoxymethane-induced colonic precancerous lesion, the aberrant crypt foci in animal model. Sprague-Dawley rats (4-5 weeks old) were injected with azoxymethane (15 mg/kg b.w.) and orally administered with 2% (w/v) of tomato, garlic and a combination of both. After 12 weeks of first azoxymethane injection, colons were assessed for aberrant crypt foci and compared with the carcinogen control group. Lipid peroxidation level and glutathione-S-transferase (GST) activity were assessed in liver as well as in colon. Furthermore, in situ cell proliferation and apoptosis were estimated using the Brdu incorporation method and TUNEL method respectively. It was observed that aberrant crypt foci were reduced in all treated groups (by 32.11% in garlic, by 76.14% in tomato and by 55.96% in the combination group). Among treated groups, GST activity was found to be induced in both liver and colon, whereas considerable reduction in lipid peroxidation level was observed in liver as well as in colon with respect to the carcinogen control group. Significant reduction in Brdu labelling index and increase in apoptotic index in colon was noted in the treated groups. These results suggest that tomato and garlic suspensions have a protective effect on colon carcinogenesis, which is mediated by modulation of different biological pathways during carcinogenesis.

Animals↗

Effects of garlic extract (Allium sativum) on neutrophil migration at the cellular level.

Studies of the effects of garlic extract on oxidative and lipoprotein levels have yielded widely different findings. Leukocytes play an important role during many processes, including inflammation. They migrate from intravascular spaces into tissues and attack microorganisms. In a recent study, the inhibitory effects of the nonsteroidal antiinflammatory drug, ibuprofen, on leukocyte transmigration were demonstrated using an in vitro assay. Little is known about the cellular effects of garlic extracts (Allium sativum). The aim of the current study was to investigate the influence of garlic extract on leukocyte migration through endothelial cell monolayers and thereby evaluate a possible role in inflammatory processes. Human umbilical endothelial cells were cultured on microporous membranes to make an endothelial cell monolayer (ECM). Freshly isolated neutrophils were used in a recently described migration assay. The amount of untreated neutrophils migrating through the untreated ECM was used as control and set at 100%. Neutrophils and/or ECM were pretreated with garlic extract using moderate, higher, and lower concentrations. Moderate plasma concentrations of garlic extract inhibited neutrophil migration through ECM significantly (64 +/- 5.8% standard deviation [SD]; P < 0.05) when both cell types were treated, (a situation that may have clinical relevance). Treating either neutrophils or ECM alone showed significant reductions in migratory rate (neutrophils treated alone: 81 +/- 7.7% SD, P < 0.05; ECM alone: 70 +/- 6.7%, P < 0.05). Thus, garlic extract is identified as a potent inhibitor of leukocyte migration through endothelial cell monolayers. Treatment of both cell types has an additive effect. Endothelial cells seem to be more affected than neutrophils. Further investigations are necessary to understand the potential clinical consequences.

Cell Adhesion↗

A garlic extract protects from ultraviolet B (280-320 nm) radiation-induced suppression of contact hypersensitivity.

Lyophilized aged garlic extract has been incorporated at concentrations of 0.1%, 1% and 4% by weight into semipurified powdered diets and fed to hairless mice. Under moderate UVB exposure conditions resulting in 58% suppression of the systemic contact hypersensitivity response in control-fed mice, a dose-responsive protection was observed in the garlic-fed mice; contact hypersensitivity in the UVB-exposed mice fed 4% garlic extract was suppressed by only 19%. If the UVB exposure was replaced by topical application of one of a series of lotions containing increasing concentrations of cis-urocanic acid, a dose-responsive suppression of contact hypersensitivity was demonstrated in control-fed mice (urocanic acid at 25, 50, 100 and 200 micrograms per mouse resulting in 22-46% suppression). Mice fed a diet containing 1% aged garlic extract were partially protected from cis-urocanic acid-induced suppression of contact hypersensitivity, with greater protection from the lower concentrations of urocanic acid. Mice fed a diet containing 4% aged garlic extract were protected from all concentrations of urocanic acid. The results indicate that aged garlic extract contains ingredient(s) that protect from UVB-induced suppression of contact hypersensitivity and suggest that the mechanism of protection is by antagonism of the cis-urocanic acid mediation of this form of immunosuppression.

Administration, Oral↗

Construction of a garlic BAC library and chromosomal assignment of BAC clones using the FISH technique.

For molecular and cytogenetic studies, two partial bacterial artificial chromosome (BAC) libraries of the garlic cultivar Allium sativum L. 'Danyang' were constructed using high molecular weight (HMW) garlic DNA, the pBAC1-SACB1 vector, and the pIndigoBAC536 vector. The average insert size of the BAC library was about 90 kb. The sequence compositions of the BAC clones were characterized by Southern hybridization with garlic genomic DNA and a repetitive sequence clone of garlic. Two BAC clones with weak signals (thus implying mostly unique sequences), GBC2-5e and GBC2-4d, were selected for FISH analysis. FISH analysis localized the GBC2-5e (approximately 100 kb) BAC clone on the long arm of garlic chromosome 7. The other BAC clone, GBC2-4d (approximately 110 kb), gave rise to discrete FISH signals on a mid-size early metaphase chromosome. The FISH screening with BAC clones proved to be a useful resource for molecular cytogenetic studies of garlic, and will be useful for further mapping and sequencing studies of important genes of this plant.

Blotting, Southern↗

Allicin in garlic protects against coronary endothelial dysfunction and right heart hypertrophy in pulmonary hypertensive rats.

We recently reported that coronary endothelial cell (CEC) dysfunction may contribute to the development of right ventricular (RV) hypertrophy (RVH) in monocrotaline (MCT)-induced pulmonary hypertensive rats. This present study investigated whether preservation of CEC function with garlic and its active metabolite allicin could abrogate RVH. Rats were fed with 1% raw garlic (RG)-supplemented diet 1 day or 3 wk before and 1 day after MCT injection, and changes in RV pressure (RVP), RVH, and CEC function were assessed 3 wk after MCT administration. In all cases, RG feeding significantly inhibited the development of RVP and RVH in these MCT rats. However, similar treatments with either boiled garlic (BG) or aged garlic (AG), which do not contain the active allicin metabolite, were ineffective. CEC function, assessed with acetylcholine-induced dilation as well as N(omega)-nitro-l-arginine methyl ester-induced constriction, revealed marked attenuation in right, but not left, coronary arteries of the MCT rats. This is consistent with our earlier report. Feeding of RG, but not BG or AG, preserved the CEC function and prevented the exaggerated vasoconstrictory responses of the MCT coronary arteries. There was no change in the coronary dilatory responses to a nitric oxide donor sodium nitroprusside. Further testings of vasoactivity to garlic extracts showed that only RG, but not BG or AG, elicited a potent, dose-dependent dilation on the isolated coronaries. Taken together, these findings show that the protective effect of garlic against the development of RVP and RVH in MCT-treated rats is probably mediated via its active metabolite allicin action on coronary endothelial function and vasoreactivity.

Animals↗

Effect of oral administration of crude aqueous extract of garlic on pharmacokinetic parameters of isoniazid and rifampicin in rabbits.

AIM: To study the effect of oral administration of crude aqueous extract of garlic for 14 days on pharmacokinetic parameters of isoniazid and rifampicin. MATERIALS AND METHODS: Crude extract was prepared according to the method described by Fromtling and Bulmer. The study was done on 16 New Zealand white rabbits, divided into two groups of 8 animals each for two drugs. Baseline pharmacokinetic parameters for single-dose isoniazid and rifampicin were calculated from plasma drug concentrations obtained at various time intervals after dosing. The animals were given garlic extract orally for 14 days. Pharmacokinetic parameters were calculated again as done previously. OBSERVATIONS: Administration of crude aqueous extract of garlic significantly altered the pharmacokinetic parameters for isoniazid. C(max) was reduced from 15.4 +/- 5.6 to 5.4 +/- 3.3 microg/ml. AUC((0-24)) was reduced from 76.7 +/- 25.0 to 34.3 +/- 19.2 microg/ml.h. No significant change in T(max), k(el) and AUC((0-)(alpha)) was seen. Pharmacokinetic parameters of rifampicin were not significantly altered by administration of garlic extract. CONCLUSIONS: Oral administration of garlic extract decreased the bioavailability of isoniazid significantly with no change in rate of elimination. Bioavailability of rifampicin is not significantly altered by garlic extract.

Administration, Oral↗

Antioxidant activity of thiosulfinates derived from garlic.

Garlic extract significantly inhibited the oxidation of methyl linoleate in homogeneous acetonitrile solution, whereas the antioxidant effect of allicin-free garlic extract, prepared by removing allicin by prepared by removing allicin by preparative HPLC, was much lower than that of the garlic extract. These results suggest that the antioxidant properties are mostly attributed to the presence of allicin in the garlic extract. Allicin a major component of the thiosulfinates in garlic extract, was found to be effective for inhibiting methyl linoleate oxidation, but its efficiency was less than that of alpha-tocopherol. Next, the reactivity of allicin toward the peroxyl radical, which is a chain-propagating species, was investigated by direct ESR detection. The addition allicin to 2,2'-azobis(2,4-dimethylvaleronitrile)-peroxyl radical solution caused the signal intensity of the peroxyl radical to dose-dependently decrease, indicating that allicin is capable of scavenging the the peroxyl radical and acting as an antioxidant. Finally, we studied the structure-anioxidant activity relationship for thiosulfinates and suggested that the combination of the allyl group (-CH2CH=CH2) and the -S(O)S- group is necessary for the antioxidant action of thiosulfinates in the garlic extract. In addition, one of the two possible combinations, -S(O)S-CH2CH=CH2, was found to make a much larger contribution to the antioxidant activity of the thiosulfinates than the other, CH2=CH-CH2-S(O)S-.

Acetonitriles↗

Potent activation of nitric oxide synthase by garlic: a basis for its therapeutic applications.

Garlic (Allium sativum L.) is thought to have a variety of therapeutic applications including inhibition of platelet aggregation. Many of the therapeutic actions of garlic parallel the physiological effects of nitric oxide and may be explained by its ability to increase nitric oxide synthase activity intracellularly. Our studies showed that both water and alcoholic extracts of garlic are very potent inhibitors of platelet aggregation induced by epinephrine and ADP. Similar dilutions of garlic extract also activated nitric oxide synthase activity in isolated platelets in vitro. The same extract was also very effective in activating nitric oxide synthase activity in placental villous tissue. The addition of garlic extracts increased nitric oxide synthase activity in a dose-dependent manner. Nitrite levels in the supernatants of incubated placental villous tissue were similarly increased. Activation of calcium-dependent nitric oxide synthase and the subsequent production of nitric oxide is probably the most novel mechanism yet claimed by which garlic can exert its therapeutic properties.

Adenosine Diphosphate↗

Effect of purified allicin, the major ingredient of freshly crushed garlic, on cancer cell proliferation.

The diverse health benefit effects of garlic include its anticancer activity. However, very little is known about such activity of isolated garlic compounds, among which allicin (the major ingredient of crushed garlic) has been the least studied. The aim of this work was to determine whether pure allicin exhibits the antiproliferative effect reported for garlic in in vitro models. Allicin, but not its precursor alliin, inhibited proliferation of human mammary (MCF-7), endometrial (Ishikawa), and colon (HT-29) cancer cells (50% inhibitory concentration = 10-25 microM). Two of three tested primary lines of human fibroblasts displayed a similar response to allicin (50% inhibitory concentration = 16-40 microM), whereas the third line was almost unaffected by this compound. The pure allicin and water extract of garlic powder with equivalent allicin concentrations displayed a similar potency, suggesting that allicin is responsible for the antiproliferative effect of the extract. The growth inhibition was accompanied by accumulation of cells in the G0/G1 and G2/M phases of the cell cycle (MCF-7 cells) and not by a significant increase in cell death. Allicin caused a transient drop in the intracellular glutathione (GSH) level, the magnitude and kinetics of which significantly varied depending on cell type. The extent of the decrease in GSH levels correlated well (r = 0.75) with the growth inhibitory activity of allicin. On the basis of these findings, we suggest that allicin plays a major role in the antiproliferative effect of water-soluble garlic preparations and that this effect may be attributed to the ability of allicin to transiently deplete the intracellular GSH level.

Antineoplastic Agents, Phytogenic↗

Toxic effect of garlic extracts on the eggs of Aedes aegypti (Diptera: Culicidae): a scanning electron microscopic study.

The surface features of the eggs of Aedes aegypti (L.) and the effect of garlic extracts on their hatching were studied by scanning electron microscopy. The exochorion and endochorion layers of the eggshells display an essentially pentagonal reticulation. The exochorion meshwork exhibits large and small papillae interconnected by horizontal struts. At higher magnification, the large papillae show aeropyles on their rough surface. Eggs hatched in deionized water undergo complete fracture near the anterior poles producing free shell caps. In contrast, eggs placed in 6% reconstituted Kyolic garlic extract are only partially fractured, display attached shell caps, and the larvae remain trapped within the shells. In the natural garlic bulb extract, the eggs show no fracture lines in their shells. No larvae were observed either alive or dead in the garlic extracts, suggesting the embryos were disabled before they could escape from their eggshells as viable larvae. It is concluded that aqueous extracts of garlic inhibit hatching of Aedes eggs. Thus, compounds in garlic may be beneficial in the control of mosquitoes.

Aedes↗

Garlic preserves patency and delays hyperthermia-induced thrombosis in pial microcirculation.

Three trials were carried out to study the effect of garlic on thrombus formation and patency in the mouse pial microcirculation in response to hyperthermia. Two different hyperthermic exposures, at 43 degrees C for 60 min and at 44 degrees C for 45 min, were applied to the brain surface of anaesthetized mice by heated artificial cerebrospinal fluid (ACSF). Garlic solutions were prepared 24 h prior to their injection, i.p., from a finely-ground powder in saline (pH 7.3) to deliver doses of 25, 50 and 75 mg/kg. Control groups of the three trials were injected with saline, pH 7.3. Garlic and vehicle solution injections were made 60 min prior to the intended hyperthermic exposure. Microvascular responses were monitored and were recorded by intravital videomicroscopy. With core body temperature kept at 37 degrees C and at the elevated ACSF temperatures, the first observed intravascular response was in the form of either passing emboli or as visible thrombosis in either arterioles or venules. Further thromboembolic events continued and throughout such exposures higher arteriolar patency was evident in the garlic-treated mice. Collectively, garlic significantly delayed the appearance of the first observable thrombo/embolic response. Data of this study evidenced that garlic delayed hyperthermia-induced platelet aggregation, in vivo. Such results could prove beneficial to those adversely affected by antithrombotic drugs, like aspirin.

Animals↗

Mechanisms of the preventive properties of some garlic components in the carbon tetrachloride-promoted oxidative stress. Diallyl sulfide; diallyl disulfide; allyl mercaptan and allyl methyl sulfide.

Previous studies evidenced that garlic extracts and/or garlic components were able to prevent against chemically induced tumors or acute toxic effects of chemicals (e.g. CCl4 induced liver injury). The chemopreventive potential of garlic has been attributed to the presence in it of several bioactive organosulfur compounds. Those components might act as antioxidants able to scavenge free radicals. In the present work we describe initial studies on the antioxidative-stress properties of some garlic components such as: diallyl disulfide (DDS), diallyl sulfide (DAS), allyl mercaptan (AMT) and allyl methyl sulfide (AMS). We found that DAS, DDS and AMT but not AMS were able to trap trichloromethyl and trichloromethylperoxyl free radicals. Further, DDS but not DAS or AMT also inhibited CCl4 promoted liver microsomal lipid peroxidation. DAS, but not DDS, AMT or AMS was able to react with free radicals arised during UVC activation of hydrogen peroxide or terbutyl hydroperoxide but not with those produced during UVC activation of terbutyl peroxide. However, all garlic components tested absorbed energy from UVC and became partially destroyed in the process. AMT, but not DDS, AMS or DAS was able to destroy 4-hydroxynonenal, a key reactive aldehyde produced during lipid peroxidation. AMT and DDS were also able to prevent UVC plus CCl4 promoted oxidation of albumin in vitro, but DAS and AMS failed to do so. Results suggest that the antioxidative stress properties of garlic might result from the contributions of its sulfur component in different steps and not necessarily from the contribution of only one of them.

Allyl Compounds↗

Crude extract of garlic induced caspase-3 gene expression leading to apoptosis in human colon cancer cells.

Garlic (Allium sativum) is a popular spice, a remedy for a variety of ailments and is also known for its medicinal uses as an antibiotic, antithrombotic and antineoplastic agent. Epidemiological and animal studies have shown that garlic consumption reduces the incidence of cancer e.g. in the stomach, colon, breast and cervix. The aim of this study was to investigate whether garlic extract has any influence on caspase-3 activity and gene expression and on the signal induction of apoptosis in vitro. As an assay system, the flow cytometry assay, Western blotting and cDNA microarray were applied in human colon cancer colo 205 cells. Our results indicated that garlic extract, when administered to the colo 205 cell cultures, reduced the percetange of viable cells, induced apoptosis, increased the levels of Bax, cytochrome c and caspase-3, but decreased the level of Bcl-2. The results also showed that raw extract of garlic decreased the mitochondrial membrane potential and increased the caspase-3 activity and gene expression. We conclude that crude extract of garlic can induce apoptosis in colo 205 cells through caspase -3 activity, by means of a mitochondrial-dependent mechanism.

Adenocarcinoma↗

[Studies on the contents of twenty elements in different parts of garlic by using ICP-OES, AAS and AFS combined with microwave decomposition method].

The garlic plants sampled in the suburbs of Suzhou were rinsed thoroughly with deionized water, and divided into six different parts: root, low stem, middle stem, high stem, tender leaves and old leaves. After decomposition in a microwave oven, the contents of Al, As, B, Ca, Cd, Cr, Cu, Fe, Hg, K, Mg, Mn, Na, Ni, P, Pb, S, Se, Sr and Zn in these parts were determined by using ICP-OES, AAS and AFS, and the contents of these 20 elements in garlic bulbs collected from the same location were also determined. It was found that the tender leaves or the bulbs of garlic should be chosen preferably for the extraction of active compounds, because they are much richer in Cu, Fe, Mn, S, Se and Zn elements and rather low in harmful As, Cd, Hg and Pb elements as compared with other parts of garlic. The contents of 20 elements are varied in six different parts of garlic, from which some useful conclusions can be drawn concerning either physiological properties of garlic or situations of atmosphere contamination.

Elements↗

The effect of a garlic preparation on the composition of plasma lipoproteins and erythrocyte membranes in geriatric subjects.

This study evaluated the effect of a dried garlic powder preparation, standardised to 1.3% alliin, on the composition of plasma lipoproteins and erythrocyte membranes. Forty volunteers, aged 70 years and over, took 600 mg of garlic powder per day for three months. In participants with initially normal plasma cholesterol levels (CH less than 200 mg/dl; n = 11) after three months of garlic tablet administration, little or no change in CH values was registered, as for most of the other parameters. In contrast, in volunteers with initially elevated CH levels (CH greater than 200 mg/dl, n = 29), the CH levels were reduced by -7.7% (p less than 0.001). This reduction took place primarily in the esterified cholesterol fraction (-12%, p less than 0.001), whereas free cholesterol concentrations were not altered significantly. Triglycerides (-15.9%, p less than 0.05) and plasma choline phospholipids (-4.6%, p less than 0.01) were also reduced. No change of the plasma LDL-CH to HDL-CH ratio was observed in this group. Based on the weight of lyophilised, haemoglobin-free erythrocytes, the mean membrane concentration of phospholipids and cholesterol in the total cohort (n = 40) increased by 5.7% (p less than 0.001) and 6.1% (p less than 0.01), respectively. These increases were more pronounced the lower the body mass indices (kg/m2) were, and the longer the duration of garlic administration was. The molar ratio of membrane phospholipids to cholesterol remained unchanged. The results are discussed with regard to a possible role of the garlic-induced membrane effects in the plasma lipid-lowering potency of garlic and preparations made from it.

Aged↗

Effect of ginger & garlic on DNA content of gastric aspirate.

DNA content of gastric aspirates was studied before and after intragastric infusions of three doses of ginger (2, 4, 6 g) and four doses of garlic (0.3, 0.75, 1.5, 3 g) on different days in volunteers. Only one dose was administered on any day. The mean changes of DNA-p/min in gastric aspirates after intragastric infusions of 2 and 4 g ginger were -1.37 +/- 2.3 and 6.74 +/- 3.06 respectively, which were not significant statistically. However, 6 g ginger given intragastrically showed a mean significant increase in DNA-p/min of 3.23 +/- 1.02 (P less than 0.05). Intragastric infusion of 0.3 g uncooked garlic showed a non-significant increase in DNA-p/min of 0.307 +/- 0.59. On the other hand, infusion of 0.75, 1.5 and 3 g of uncooked garlic each caused significant increase in DNA-p/min of 5.47 +/- 1.63 (P less than 0.01), 10.42 +/- 3.46 (P less than 0.01) and 29.26 +/- 4.55 (P less than 0.001) respectively. Infusion of 3 g of cooked garlic also showed significant increase in DNA-p/min of 21.43 +/- 4.62 (P less than 0.001). There was no significant difference between the effect of cooked and uncooked (3 g) garlic. Ginger in quantities of 6 g or more and garlic in quantities of 0.75 g or more cause a significant increase in exfoliation of gastric surface epithelial cells in human subjects.

Cooking↗

[Paraffin treatment of garlic for long-term preservation].

The optimal conditions have been developed for garlic preservation by its treatment with a mixture of food paraffin and monoglyceride in the ratio of 95:5 at 80 degrees C, followed by the storage at 0-1 degrees C, and relative humidity 65-75%. When garlic is treated with plasticized paraffin, the main hydrocarbon components of paraffin - n-alkanes C20-C31 are accumulated in its pulp. Monocyclic aromatic hydrocarbons are practically absent in food paraffin and paraffined garlic. The quantitative parameters of the paraffined garlic characterizing high technological and economic effectiveness of the method, as well as insignificant increase in the p-alkanes content (1%) in the daily ration for humans, that contains paraffined garlic, have permitted the authors to recommend this method of garlic storage for using under industrial conditions, the technological regulations should be strictly kept to.

Food Preservation↗