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Effect of the essential oils of garlic and onion on alimentary hyperlipemia.

SUMMARY: The effect of garlic and onion on alimentary hyperlipemia, induced by feeding 100 g butter, has been studied in 10 healthy subjects. The freshly extracted juice of 50 g of garlic or onion, as well as an equivalent amount of their ether-extracted essential oils, was administered randomly on four different days during a one-week period. Garlic and onion have a significant protective action against fat-induced increases in serum cholesterol and plasma fibrinogen and decreases in coagulation time and fibrinolytic activity. The essential oil fraction, which contains all the taste and odour, exactly duplicated the beneficial effects of whole garlic and onion. It is, therefore, concluded that the active principle of garlic and onion is the essential oil, which chemically is a combination of sulphur-containing compounds, mainly allyl propyl disulphide and diallyl disulphide.

Adult↗

Characterization of a potent inhibitor of platelet aggregation and release reaction isolated from allium sativum (garlic).

When added to platelet-rich plasma, aqueous extracts of garlic inhibited platelet aggregation and the release reaction. Subsequent experiments designed to characterize the inhibitory component revealed that the inhibitory activity was i) associated with small molecular-weight components, ii) the inhibitory component possessed the typical garlic odor and contained an abundance of sulfur, iii) the inhibitory activity could be extracted with organic solvents, and iv) temperatures above 56 degrees C and alkaline pH above 8.5 quickly destroyed the inhibitory activity. The Rf value of the major inhibitory component after thin-layer chromatographic separation was similar to that of allicin, an unique thiosulfinate in garlic previously shown to possess strong antibiotic and antifungal properties. Allicin was synthesized. On thin-layer chromatographic plates, allicin co-migrated with the inhibitory component in garlic. At 10 microM concentration, allicin inhibited completely platelet aggregation and the release reaction. Comparative studies suggest that the major platelet aggregation and release inhibitor in garlic may be allicin.

Adult↗

Garlic: a review of its relationship to malignant disease.

Garlic (Allium sativum) has had an important dietary and medicinal role for centuries. It is now known that garlic contains chemical constituents with antibiotic, lipid-lowering, detoxification, and other medicinal effects in the body. This article reviews some of the physiological characteristics of garlic and examines the relationship between garlic and cancer prevention and treatment. Hypotheses regarding the possible role of garlic in modulating mechanisms that may alter the carcinogenic process are discussed.

Animals↗

Allium sativum (garlic)--a natural antibiotic.

Allium sativum (garlic) has been recognized not only as a spice but also as a substance which exerts a control on microorganisms. Recent publications indicate that garlic extract has broad-spectrum antimicrobial activity against many genera of bacteria and fungi. The active component (allicin) has been isolated and characterized. Because many of the microorganisms susceptible to garlic extract are medically significant, garlic holds a promising position as a broad-spectrum therapeutic agent. Furthermore, garlic plants may also play an important role in the ecological control of pathogenic microorganisms in nature.

Animals↗

How does garlic exert its hypocholesterolaemic action? The tellurium hypothesis.

The efficacy of garlic as a lipid-lowering agent is being increasingly recognized, but the biochemical mechanisms underlying this action are currently unknown. It is proposed that organic tellurium compounds, which are found in high concentration in fresh garlic buds, may contribute to this action by inhibiting squalene epoxidase, the penultimate enzyme in the synthetic pathway of cholesterol. Weanling rats fed a diet rich in tellurium develop a demyelinating polyneuropathy due to inhibition of this enzyme in peripheral nerves. Chronic exposure to small amounts of tellurium found in garlic might reduce endogenous cholesterol production through inhibition of hepatic squalene epoxidase and so reduce cholesterol levels. Tellurium may also contribute to the characteristic odour of garlic since the most obvious clinical sign of tellurium poisoning is a garlic-like odour.

Animals↗

Alterations in hepatic phase I and phase II biotransformation enzymes by garlic oil in rats.

Studies were conducted to examine the effect of a single and repeated administrations of garlic oil (diallyl sulfide) on Phase I and Phase II biotransformation enzymes in rats. Adult, male Sprague-Dawley rats treated with a single dose of garlic oil (500 mg/kg i.p.) showed a significant depression of hepatic cytochrome P-450, aminopyrine N-demethylase and aniline hydroxylase while microsomal protein content, cytochrome b5, NADPH-cytochrome c reductase, benzphetamine N-demethylase and cytosolic glutathione, S-transferase remained unaffected 24 h following the treatment. Although certain microsomal enzymes were depressed, there was no liver damage caused by garlic oil as judged by the putative serum enzyme test. On the other hand, daily administration of garlic oil (50 mg/kg i.p. for 5 days) produced a significant increase in hepatic cytochrome P-450, aminopyrine N-demethylase and benzphetamine N-demethylase activities, but not in the rest of the aforementioned parameters of biotransformation reactions. These data indicate that the effect of garlic oil on the hepatic drug-metabolizing enzyme system is dose-dependent.

Allyl Compounds↗

Direct relaxant effects of garlic juice on smooth and cardiac muscles.

The effects of garlic juice on smooth and cardiac muscles of rabbit and guinea pig were tested in vitro using isolated segments of aorta, trachea and intestines and isolated rabbit hearts. Garlic juice inhibited the contractions of rabbit and guinea pig aortic rings induced by norepinephrine in Ca(2+)-free and Ca(2+)-containing Krebs-Henseleit solutions. Also, garlic juice inhibited the contractions of rabbit and guinea pig tracheal smooth muscles induced by acetylcholine and histamine, respectively, in both Ca(2+)-free and Ca(2+)-containing Krebs-Henseleit solutions. Furthermore, garlic juice inhibited the spontaneous movements of rabbit jejunum and guinea pig ileum and inhibited the force of contraction of isolated rabbit hearts in a concentration-dependent manner. All inhibitions were reversible. These data suggest that the hypotensive action of garlic juice may be due, at least in part, to a direct relaxant effect on smooth muscles.

Acetylcholine↗

Experimental cardiovascular depressant effects of garlic (Allium sativum) dialysate.

The objectives of this work were to investigate the effects of a garlic dialysate on diastolic blood pressure (DBP), heart rate (HR) and electrocardiogram (ECG) of anaesthetized dogs and its effects on frequency and tension of isolated rat atria. Garlic dialysate led to a drop in DBP (from 112.5 +/- 3.67 to 70 +/- 3.16 mmHg) and a decrease in HR (from 198 +/- 9.81 to 164 +/- 16.59 beats/min) in a dose-dependent manner. The ECG showed a regular sinus bradycardic rhythm. The addition of garlic dialysate to isolated left rat atria evoked a decrease in tension development. Frequency, measured by spontaneous beating of the right atria, was also reduced. Both effects were dose-dependent. In addition to these effects, the positive inotropism and chronotropism induced by addition of isoproterenol 10(-9) M, were partially antagonized by preincubation of the rat atria with the garlic dialysate. The above findings can be explained by a depressant effect on automaticity and tension development in the heart, suggesting a beta-adrenoceptor blocking action produced by the garlic dialysate.

Anesthesia↗

Absence of an atheroprotective effect of the garlic powder printanor in APOE*3-Leiden transgenic mice.

Numerous animal studies have reported that garlic can protect against atherosclerosis. However, a comparable number of studies do not support this observation. This contradiction may result from differences in study design, use of different animal models, and use of different garlic formulations and preparations. Here, we investigated the effect of the chemically well-characterized and production-controlled garlic powder printanor on atherosclerosis in the APOE*3-Leiden transgenic mouse, a mouse model well suited for evaluating anti-atherosclerotic properties of drugs and food components under human-like conditions. APOE*3-Leiden mice were fed a Western diet supplemented with either 5 or 50 g kg(-1) printanor. As a reference, the commercially available fermented garlic kyolic was included (1.6 g kg(-1) diet). Treatment with printanor demonstrated reduced body weight, coinciding with increased feces production and fecal fatty acids excretion. Printanor and kyolic treatment did not affect plasma lipids, markers of inflammation (serum amyloid A, serum-soluble intercellular adhesion molecule-1, and blood-leukocytes tumor necrosis factor-alpha (TNFalpha) production) and vascular activation (plasma von Willebrand factor (vWF)). As analyzed after 28 weeks of treatment, printanor and kyolic did not affect atherosclerotic lesion type, area or composition. Under conditions relevant to the human situation, the well-characterized and production-controlled garlic powder printanor does not display hypolipidemic, anti-inflammatory or anti-atherosclerotic properties.

Animals↗

Cancer chemoprevention with garlic and its constituents.

Advance metastasized cancers are generally incurable; hence an effort to prolong the process of carcinogenesis through chemoprevention has emerged consistent with this notion. In recent years, a considerable attention has been placed to identify naturally occurring chemopreventive substances capable of inhibiting, retarding or reversing the process of carcinogenesis. A number of phenolic substances, particularly those present in dietary and medicinal plants, have been shown to possess substantial anticarcinogenic and antimutagenic activities. Epidemiological observations and laboratory studies, both in cell culture and animal models have indicated anticarcinogenic potential of garlic and its constituents, which has been traditionally used for varied human ailments around the world. Chemical analysis has indicated that protective effects of garlic appear to be related to the presence of organosulfur compounds mainly allyl derivatives. Several mechanisms have been presented to explain cancer chemopreventive effects of garlic-derived products. These include modulation in activity of several metabolizing enzymes that activate and detoxify carcinogens and inhibit DNA adduct formation, antioxidative and free radicals scavenging properties and regulation of cell proliferation, apoptosis and immune responses. Recent data show that garlic-derived products modulate cell-signaling pathways in a fashion that controls the unwanted proliferation of cells thereby imparting strong cancer chemopreventive as well as cancer therapeutic effects. This review discusses mechanistic basis of cancer chemopreventive effects of garlic-derived products, their implication in cancer management and ways and means to take these agents from bench to real life situations.

Garlic↗

Enhancement of peritoneal macrophage phagocytic activity against Leishmania major by garlic (Allium sativum) treatment.

It has been shown that garlic (Allium sativum) extract modulates immune responses. Macrophage activation is required to establish control of the intracellular infection and progressive disease of leishmaniasis. In this study, we consider the effect of a garlic extract and a fraction isolated from it on the engulfment and destruction of Leishmania major by resident peritoneal macrophages of Balb/c mice. In regard to this study, the infiltration of macrophages in the peritoneal cavity after garlic treatment and the rate of amastigotes per macrophage were determined. The results show that a single dose of 20 mg/kg garlic extract intraperitoneally (i.p.) alters the number of peritoneal macrophages for at least 2 weeks. Intraperitoneal injection of garlic extract (20 mg/kg) or its protein fraction (0.04 mg/kg) augments parasite engulfment and destruction of intracellular amastigotes by macrophages.

Animals↗

Effects of garlic extract consumption on plasma and erythrocyte antioxidant parameters in atherosclerotic patients.

Effects of ingesting garlic extract on plasma and erythrocyte antioxidant parameters of atherosclerotic patients were investigated in this study. Eleven patients with atherosclerosis participated in the study. They ingested a dose of 1 ml/kg body weight of garlic extract daily for 6 months (study period). Before and after this period, fasting blood samples were obtained, and oxidant (malondialdehyde, MDA and xanthine oxidase, XO) and antioxidant (superoxide dismutase, SOD and glutathione peroxidase, GSH-Px) parameters were studied in plasma and erythrocytes obtained from the patients. Blood samples obtained from 11 healthy subjects served as the controls. Plasma XO activity and MDA levels were higher, but plasma and erythrocyte GSH-Px activities were lower, in patients with atherosclerosis relative to those of the control group. Our results showed that ingestion of garlic extract leads to significantly lowered plasma and erythrocyte MDA levels in the patients even in the absence of changes in antioxidant enzyme activities. Our results also demonstrated the presence of oxidant stress in blood samples from patients with atherosclerosis, but ingesting garlic extract prevented oxidation reactions by eliminating this oxidant stress. Thus, it is possible that reduced peroxidation processes may play a part in some of the beneficial effects of garlic in atherosclerotic diseases.

Aged↗

Combinatorial antigenotoxic and anticarcinogenic effects of tomato and garlic through modulation of xenobiotic-metabolizing enzymes during hamster buccal pouch carcinogenesis.

OBJECTIVE: Combination chemoprevention by dietary agents is a promising approach toward cancer control. Many dietary agents are known to prevent experimental mutagenesis and carcinogenesis by modulating xenobiotic-metabolizing enzymes. The present study evaluated the combinatorial chemopreventive effects of tomato and garlic on hamster buccal pouch carcinogenesis induced by 7,12-dimethylbenz[a]anthracene (DMBA). METHODS: Hamsters were assigned to one of four groups. The right buccal pouches of animals in group 1 were painted with 0.5% DMBA three times a week. The right buccal pouches of animals in group 2 were painted with DMBA and received intragastric administration of a combined dose of tomato and garlic on days alternate to DMBA application. Animals in group 3 were given chemopreventive agents alone. Animals in group 4 served as controls. Levels of phase I and II enzymes and the frequency of bone marrow micronuclei were used as biomarkers of chemoprevention. RESULTS: All the hamsters painted with DMBA alone developed buccal pouch carcinomas that exhibited increased activities of xenobiotic-metabolizing enzymes associated with increased frequencies of bone marrow micronuclei. In the liver, an increase in phase I enzymes was accompanied by compromised phase II detoxification activities. Combined administration of tomato and garlic effectively suppressed the incidence and mean tumor burden of hamster buccal pouch carcinomas. In addition, tomato and garlic combination significantly decreased phase I enzymes and increased phase II enzyme activities in the pouch and liver with a decreased incidence of bone marrow micronuclei. CONCLUSION: From these results, we suggest that modulation of xenobiotic-metabolizing enzymes exerted by tomato and garlic combination plays a key role in mitigating the mutagenic and carcinogenic effects of DMBA.

Animals↗

A pilot study of garlic consumption shows no significant effect on markers of oxidation or sub-fraction composition of low-density lipoprotein including lipoprotein(a) after allowance for non-compliance and the placebo effect.

Our aim was to define any effects of confirmed garlic supplementation on the resistance of low density lipoprotein (LDL) to oxidation, on LDL sub-fraction composition including levels of lipoprotein(a), and on levels of circulating antibody to oxidised LDL, variables of interest in relation to cardiovascular risk. Additional tests were performed on samples collected from a double blind, randomised 6-month parallel trial in which 900 mg Kwai garlic or placebo was taken by moderately hypercholesterolaemic volunteers. Final data was analysed for 20 garlic and 11 placebo subjects with compliance of at least 75% as determined by repeat tablet counting. EDTA plasma stabilised by sucrose was stored at -70 degrees C for up to 12 months. Lipids and apolipoproteins were determined by standard methods, lipoprotein(a) by an ELISA method and LDL fraction composition by non-gradient gel electrophoresis. Oxidative resistance of LDL purified after isolation by density gradient centrifugation was assessed from oxidative resistance to copper ions determined spectrophotometrically, antibodies to oxidised LDL were determined by a microtitre plate assay and vitamin E content of plasma by HPLC. Overall lipid/lipoprotein profiles including lipoprotein(a) were unchanged as with the parent group. LDL composition showed a trend to less dense material in both placebo and garlic groups, all differences not significant. Lag time as a marker of oxidative resistance also increased in both groups, without change in vitamin E content, all differences not significant and consistent with a placebo effect. Levels of antibodies to oxidised LDL were unchanged. The results of this study do not support the hypothesis that dietary garlic supplementation decreases the susceptibility of isolated LDL to oxidation and that patterns of LDL tractions in plasma might be involved. Levels of lipoprotein(a) in plasma were also not changed. Other mechanisms of cardiovascular benefit are however not excluded.

Double-Blind Method↗

High-performance ion-pair chromatography method for simultaneous analysis of alliin, deoxyalliin, allicin and dipeptide precursors in garlic products using multiple mass spectrometry and UV detection.

The quality of garlic and garlic products is usually related to their alliin content and allicin release potential. Until now no analytical method was able to quantify simultaneously allicin, its direct precursor alliin (S-allyl-L-cysteine sulfoxide), SAC (S-allyl-L-cysteine) as well as various dipeptides that apparently serve as storage compounds in garlic. It is well known that all these intermediates are involved in the allicin biosynthetic pathway. A simple and rapid HPLC method suitable for routine analysis was developed using eluents containing an ion-pairing reagent. Particularly, heptanesulfonate as ion-pairing reagent guarantees a sufficient separation between alliin and the more retained dipeptides at very low pH. Allicin was eluted after 18 min on a 150 x 3 mm column. Synthetic reference compounds were characterized by the same chromatographic method using a diode-array UV detector and an ion trap mass spectrometer (electrospray ionization) in the multiple MS mode. In routine analysis of garlic bulbs, powders and other products, the diode-array detector is sufficient for a relevant quantification. Our method has been used in studies to improve the quality of garlic and its derived products.

Carbon-Sulfur Lyases↗

Dose-dependent induction of endogenous antioxidants in rat heart by chronic administration of garlic.

The inhibitory property of garlic on free radical generation and lipid peroxidation has been reported in a number of in vitro studies. However, the in vivo effects of chronic garlic intake on the antioxidant milieu of heart has not been reported. Therefore, the present study was designed to investigate the effect of chronic garlic homogenate administration on myocardial endogenous antioxidants and lipid peroxidation at five different dosage levels (125, 250, 500, 1000 and 2000 mg/kg; B, C, D, E, F groups respectively). Garlic homogenate was administered orally to Wistar albino rats (150-200 gms) of either sex 6 days/week for 30 days. Myocardial TBARS (Thiobarbituric acid reactive substances) and antioxidants such as SOD (Superoxide Dismutase), catalase, GPx (glutathione peroxidase) and GSH (Reduced Glutathione) were estimated and histopathological changes were observed. Group F was excluded after 55% mortality occurred in 15 days. TBARS levels were significantly lower in groups B, C and D than that of control group (A). Catalase was increased significantly in groups C, D and E, whereas SOD increased significantly in groups B, C and D but decreased in group E. Significant increase in GSH in group E and significant reduction in GPx activity in group B were observed. Histopathological studies showed marked focal myocytolysis in group E. These results showed that chronic garlic intake dose dependently augmented endogenous antioxidants, which might have important direct cytoprotective effects on the heart, especially in the event of oxidant stress induced injury.

Animals↗

The potential application of Allium sativum (garlic) for the treatment of bladder cancer.

Additional studies are needed to identify the active ingredients in Allium Sativum (garlic) that are responsible for the observed antitumor activity and immune stimulation. Garlic seems to detoxify chemical carcinogens and prevent carcinogenesis and can also directly inhibit the growth of cancer cells. Current data suggest that low molecular weight sulfur compounds and protein F4 have immune-stimulation properties. Garlic is reported to stimulate immunity, including macrophage activity, natural killer and killer cells, and LAK cells, and to increase the production of IL-2, TNF, and interferon-gamma. These cytokines are associated with the beneficial Th1 antitumor response, which is characteristic of effective cancer immunotherapies. As is true of BCG, garlic stimulates the proliferation of macrophages and lymphocytes and protects against the suppression of immunity by chemotherapy and ultraviolet radiation. Garlic is clearly not a panacea for cancer, but its broad range of beneficial effects are worthy of serious consideration in clinical trials for the prevention and treatment of cancer.

Administration, Oral↗

Attenuation of iron-nitrilotriacetate (Fe-NTA)-mediated renal oxidative stress, toxicity and hyperproliferative response by the prophylactic treatment of rats with garlic oil.

Iron nitrilotriacetate (Fe-NTA) is a potent nephrotoxic agent. In this communication we show that Fe-NTA-mediated nephrotoxicity is diminished by 1 wk of oral daily pretreatment of male albino Wistar rats with garlic oil given by gavage at 50 or 100 mg/kg body weight/ml corn oil. Intraperitoneal Fe-NTA treatment at a dose level of 9 mg Fe/kg body weight/10 ml enhances renal microsomal lipid peroxidation and hydrogen peroxide generation which are accompanied by a decrease in the activities of renal antioxidant enzymes (e.g. catalase, glutathione peroxidase, glutathione reductase and glutathione S-transferase), and a depletion in the level of renal glutathione. Parallel to these changes, a sharp increase in blood urea nitrogen and serum creatinine has been observed. In addition, Fe-NTA treatment also enhances renal ornithine decarboxylase (ODC) activity and increases [3H]thymidine incorporation into renal DNA. Prophylactic treatment of animals with garlic oil before the administration of Fe-NTA resulted in the diminution of Fe-NTA mediated injury. The enhancement of renal lipid peroxidation and hydrogen peroxide generation was decreased. In addition, there was recovery of glutathione depletion and inhibition of the activities of antioxidant enzymes. Similarly, in animals given the higher dose of garlic oil (100 mg/kg body weight) the enhanced blood urea nitrogen and serum creatinine levels, which are indicative of renal injury, showed a reduction of about 30% and 40%, respectively, in comparison with the group treated with Fe-NTA alone. Pretreatment with garlic oil also ameliorated the Fe-NTA-mediated induction of ODC activity and enhancement of [3H]thymidine incorporation into DNA in a dose-dependent manner. Our data suggest that garlic oil is a potent chemopreventive agent and may suppress Fe-NTA-induced nephrotoxicity.

Administration, Oral↗