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PubMed1996

Therapeutic actions of garlic constituents.

Most studies on garlic during the past 15 years have been primarily in the fields of cardiovascular and cancer research. Cardiovascular studies have been mainly related to atherosclerosis, where effects were examined on serum cholesterol, LDL, HDL, and triglycerides. Although the studies were not consistent in relation to the dosage, standardization of garlic preparations, and period of treatment, most findings suggest that garlic decreases cholesterol and triglycerides levels in patients with increased levels of these lipids. Lowering of serum lipids by garlic ingestion may decrease the atherosclerosis process. The other major beneficial effect of garlic is due to its antithrombotic actions. This field of garlic research has been extensively studied. Garlic extracts and several garlic constituents demonstrate significant antithrombotic actions both in vitro and in vivo systems. Allicin and adenosine are the most potent antiplatelet constituents of garlic because of their in vitro effects. Since both allicin and adenosine are rapidly metabolized in human blood and other tissues, it is doubtful that these compounds contribute to any antithrombotic actions in the body. In addition, ajoene also seems not to be an active antiplatelet principle, because it is not naturally present in garlic, garlic powders, or other commercial garlic preparations. Only a small amount of ajoene can be found in garlic oil-macerates; however, ajoene is being developed as a drug for treatment of thromboembolic disorders. Recent findings on the identification of potent enzyme inhibiting activities of adenosine deaminase and cyclic AMP phosphodiesterase in garlic extracts are interesting, and may have a significant role in the pharmacological actions in the body. Presence of such enzyme inhibitors in garlic may perhaps explain several clinical effects in the body, including the antithrombotic, vasodilatory, and anticancer actions. Epidemiological studies have suggested that garlic plays a significant role in the reduction of deaths caused by malignant diseases. This had led many investigators to examine garlic and garlic constituents for their antitumor and cytotoxic actions both in vitro and in laboratory animals. The data from these investigations suggest that garlic contains several potentially important agents that possess antitumor and anticarcinogenic properties. In summary, the epidemiological, clinical, and laboratory data have proved that garlic contains many biologically and pharmacologically important compounds, which are beneficial to human health from cardiovascular, neoplastic, and several other diseases. Numerous studies are in progress all over the world to develop effective and odorless garlic preparations, as well as to isolate the active principles that may be therapeutically useful.

Animals↗
PubMed2001

[In vivo and in vitro effects of selenium-enriched garlic on growth of human gastric carcinoma cells].

OBJECTIVE: To compare the effects of selenium-enriched garlic (Se-garlic), garlic, Na2SeO3, and garlic + Na2SeO3 on growth of human gastric carcinoma cells. METHODS: In vivo and in vitro assays were carried out in the cultured human gastric carcinoma cell line MGC803 transplanted in the nude mice by cell count, flow cytometry, Western blot and neoplasm volume measurement. RESULTS: The inhibition effect of garlic was similar to that of Se-garlic, but Na2SeO3 was weaker than Se-garlic. Combination of garlic and Na2SeO3 was stronger than Se-garlic. In flow cytometry assay, the proportion of G1 phase was increased after 24 hour treatment of Se-garlic, garlic and Na2SeO3 in the non-synchronized cells. However, the proportion of S phase was increased in the synchronized cells. The proportion of G2 + M phase was increased both in non-synchronized and synchronized cells on treatment with the combination of garlic and Na2SeO3. The amount of Cdk2-CyclinE complex and Cdk4-CyclinD1 complex was decreased in all treated synchronized cells in immunoprecipitation and immunoblot assays. The growth of MGC803 tumor in male Balb/c nude mice was inhibited by administration of 1.67% of Se-garlic (Se 2 micrograms/g) in diet with an inhibition rate of 29.92% in tumor weight. Treatment of either 0.83% of Se-garlic or 1.67% of garlic or 4.38 micrograms/g of Na2SeO3 (Se 2 micrograms/g) could not appreciably inhibit the growth of tumor. Wrapping of a number of monocytes around the tumor was induced in 62.50% of tumors in 0.83% of the Se-garlic group. CONCLUSION: In vitro, Se-garlic is able to inhibit the growth of MGC803 cell through action of garlic. In vivo, Segarlic is able to inhibit growth of MGC803 tumor in nude mice by being better than garlic and selenite.

Animals↗
PubMedDate not supplied

An in vitro evaluation of human cytochrome P450 3A4 and P-glycoprotein inhibition by garlic.

PURPOSE: Garlic has been used as a flavouring agent, traditional medicine, and functional food to improve physical or mental well-being. Garlic and garlic products generally have been regarded as safe but a number of conflicting reports in the literature and confounding factors make it difficult to unequivocally establish the clinical efficacy and safety of these products either alone or in the presence of therapeutic products. A preliminary study was undertaken with fresh garlic and garlic products using the major cDNA-expressed human cytochrome P-450 isozymes associated with the metabolism of HIV/AIDS drugs, and purified P-glycoprotein (P-gp) cell membranes to ascertain the risk potential for generating interactions with therapeutic products. METHODS: A broad screening was undertaken with 10 garlic products (aged, odourless, oil, freeze-dried) and 3 varieties of fresh garlic bulbs (common, Elephant and Chinese), all purchased from local outlets, to examine their potential to affect human cytochrome P-450 2C9*1, 2C9*2, 2C19, 2D6, 3A4, 3A5 and 3A7 mediated-metabolism of marker substrates using an in vitro fluorometric microtiter plate assay. Four garlic products were screened for their potential to interact with P-gp using an in vitro colourmetric ATPase assay. RESULTS: Extracts of fresh garlic, different brands and lots of odourless garlic and representative samples of garlic oil, freeze dried garlic, and aged garlic exhibited an inhibitory effect on cytochrome P450 2C9*1, 2C19, 3A4, 3A5 and 3A7 mediated metabolism of a marker substrate. The activity of 2D6 mediated-metabolism was generally unaffected by garlic. Extracts of the fresh garlic stimulated CYP2C9*2 metabolism of the marker substrate. With the extracts tested, garlic had very low to moderate P-gp interaction as compared with the positive control verapamil. CONCLUSIONS: Our in vitro findings demonstrate that garlic components can affect cytochrome P-450 2C, 2D and 3A mediated-metabolism of the isoforms studied. The safety and efficacy of conventional therapeutic products metabolized by the affected isozymes, particularly those with a narrow therapeutic index, taken concomitantly with garlic needs to be examined further under clinical settings.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

Raw and boiled garlic enhances plasma antioxidant activity and improves plasma lipid metabolism in cholesterol-fed rats.

UNLABELLED: In the present study the effect of garlic, in a form more similar to how most people eat garlic, on lipid and antioxidant metabolism in rats was investigated. The antioxidant activity was determined by the efficacy to scavenge 2, 2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) derived radicals in garlic samples. The highest results were estimated in aqueous fraction in comparison with other extracts divided on the basis of polarity. Wistar male rats were randomly divided into 10 diet groups, each with seven animals. The groups were named: Control, RG (raw garlic), BG (boiled garlic for 20 min), AERG (aqueous extract of raw garlic), AEBG (aqueous extract of boiled garlic), Ch (Cholesterol), Ch/RG, Ch/BG, Ch/AERG and Ch/AEBG. All experimental diets were supplemented with 25 mg of lyophilized garlic/kg body weight obtained from raw, boiled and their aqueous extracts over a period of 30 days. Serum lipid (total cholesterol, LDL-cholesterol and triglycerides) concentrations were higher in all groups fed cholesterol (Ch); however, the increase was significant only in Ch group, without garlic supplementation. In groups of rats fed diets with cholesterol, garlic samples significantly hindered the rise of TC and LDL-C (P < 0.05). A significant increase (P < 0.05) in the plasma antioxidant activity was registered in experimental groups of rats fed cholesterol-free diets supplemented with garlic; oppositely, a significant decrease was only in group of rats given food containing cholesterol without garlic. The protein spectra has shown that during short boiling some proteins change their functional properties such as solubility and mobility, resulting in a number of protein bands in SDS-electrophoresis. CONCLUSIONS: Raw and boiled garlic improved plasma lipid metabolism and plasma antioxidant activity in an experiment on rats. Thus, dietary hypolipidemic garlic was effective in reducing the oxidant stress, which was indicated by an increase of antioxidant activity and a decrease of lipids in the rats' blood. It was found that garlic boiled for 20 min has the same bioactivity as raw garlic in its antioxidant and protein spectra. Therefore it should be added at this time to foods. The selenium and copper content of raw garlic is not altered by boiling. The protein electrophoretic pattern of raw garlic is altered by boiling.

Animals↗
PubMedDate not supplied

Effects of wild versus cultivated garlic on blood pressure and other parameters in hypertensive rats.

Two separate studies were performed on hypertensive rats to assess the effects of wild, uncultivated garlic on elevated systolic blood pressure (SBP) and other cardiovascular parameters. Also, effects of wild garlic and cultivated garlic preparations were compared and the mechanisms behind pressure-lowering abilities of different garlic preparations were examined. The initial study determined that wild garlic lowers blood pressure. In the second study, cardiovascular effects of three different concentrations of wild garlic and two different cultivated garlics, i.e., a preparation low in allicin and one high in allicin, were compared. All three garlic preparations decreased SBP significantly. Wild garlic produced the greatest pressure-lowering effects, and the least pressure-lowering effects were seen with low-allicin garlic. Compared with control rats, circulating angiotensin II levels were significantly lower in all garlic-eating rats. Losartan decreased blood pressure significantly less and Nw-nitro-L arginine-methyl ester hydrochloride (LNAME) increased blood pressure significantly more in garlic-eating rats than in control rats, suggesting that the renin-angiotensin system (RAS) was less active and the nitric oxide system more active in garlic-consuming hypertensive rats. Accordingly, different garlic preparations, especially wild garlic, favorably influenced high SBP in hypertensive rats. These results suggest that both the RAS and the nitric oxide system are involved in the antihypertensive effects of garlic in hypertensive rats.

Animals↗
PubMed1999

Volatile sulfur compounds in human expiration after eating raw or heat-treated garlic.

Volatile sulfur compounds arising from grated raw or heat-treated garlic in both in-vitro and in-vivo tests were gas-chromatographically analyzed. In in-vitro tests, the head-space vapor gas from garlic in a vial was analyzed. It was clarified that allyl mercaptan arising from raw garlic decreased with the passage of time and other volatile low-molecular sulfur compounds (LMSC) did not show remarkable changes. The change of LMSC from heat-treated garlic was also studied. Methyl mercaptan and allyl mercaptan from heat-treated garlic gradually increased to some extent. On the other hand, the quantities of somewhat high-molecular sulfur compounds (HMSC) were much less in heat-treated garlic compared to those of raw garlic. These compounds increased till approx. 60 min and then decreased gradually. In in-vivo tests, human expiration after eating garlic was analyzed. Allyl mercaptan, methyl mercaptan and allyl methyl sulfide in LMSC were detected in significant amounts. The quantities of these compounds arising from heat-treated garlic were smaller than those from raw garlic. These compounds had the tendency of decreasing with the passage of time. On the other hand, almost no HMSC was detected in both raw and heat-treated garlic. By sensory testing, raw garlic showed a stronger smell than heat-treated garlic in both in-vitro and in-vivo tests. GC analysis exhibited higher values of volatile sulfur compounds in raw garlic. That is, the higher the volatile sulfur compound level, the stronger the garlic flavor or malodor.

Allyl Compounds↗
PubMed2003

Does regular garlic intake affect the prevalence of Helicobacter pylori in asymptomatic subjects?

OBJECTIVE: The in vitro antibacterial activity of garlic against Helicobacter pylori (H.pylori) is well documented and the potential for its use in vivo was suggested. Garlic intake, a traditional habit by the Taskopru population in Turkey for decades, was examined for its effect on the prevalence of H. pylori and compared with the non garlic consuming group. METHODS: Eighty-one garlic consuming asymptomatic subjects in Kastamonu province in Turkey (68 males, 13 females) of 23-82 years of age (average 46) were selected on a very restricted bases in regards to the garlic intake (raw or cooked, or both), amount, duration and other criteria. Control group (non-garlic consuming) of 81 asymptomatic subjects (66 males, 15 females) of 23-90 years of age (average 43) were enrolled for comparison with the garlic consuming group. Serum samples were collected from both groups during the period from September 2001 through to April 2002 and examined by the enzyme linked immunoassay test for anti H.pylori antibodies. RESULTS: An overall H.pylori prevalence of 79% and 81% was detected in the garlic and non garlic consuming groups. A significantly lower average antibody titer was detected in the garlic consuming group than that of the control group and similarly in those who consumed mixture of raw plus cooked garlic as compared to those who consumed raw or cooked garlic alone. CONCLUSION: Garlic intake for long durations (years) did not appear to have an effect on the prevalence of H.pylori infection. Garlic consuming subjects had a significantly lower average antibody titer than non garlic consuming groups, which might suggest an indirect inhibitory effect on the reproduction of H.pylori and possibly progression to more serious peptic ulcer diseases.

Adult↗
PubMed1996

Urinary excretion of N-acetyl-S-allyl-L-cysteine upon garlic consumption by human volunteers.

N-Acetyl-S-allyl-L-cysteine (allylmercapturic acid, ALMA) was previously detected in urine from humans consuming garlic. Exposure of rats to allyl halides is also known to lead to excretion of ALMA in urine. ALMA is a potential biomarker for exposure assessment of workers exposed to allyl halides. It is not known whether garlic consumption can lead to urinary concentrations of ALMA which may interfere with biological monitoring of exposure to allyl halides by determination of urinary ALMA. Therefore, this study was undertaken to determine the cumulative excretion and the excretion kinetics of ALMA in urine of humans consuming garlic. Six human volunteers were given orally two garlic tablets, each containing 100 mg garlic extract (each representing 300 mg fresh garlic). Three of the volunteers consumed additional garlic after the garlic tablet intake. Urine samples were collected up to 24 h after the intake of the garlic tablets. ALMA was identified in the urine using gas chromatography-mass spectrometry (GC-MS) and determined quantitatively with a limit of detection of 0.10 microgram/ml with gas chromatography with sulphur selective detection. The total amount of ALMA found in urine of volunteers who consumed two garlic tablets was 0.43 +/- 0.14 mg (n = 3). In the urine of the three volunteers who consumed not only two garlic tablets but also additional fresh garlic, a significantly higher amount of ALMA was excreted in the urine, 1.4 +/- 0.2 mg (n = 3). The elimination half-life of ALMA, estimated from urinary excretion rate versus time curves, was 6.0 +/- 1.3 h (n = 5). One volunteer, who ate additional garlic, showed an irregular elimination profile and was excluded from this estimation. The highest urinary concentration of ALMA found in this study was 2.2 micrograms/ml. In a preliminary biological monitoring study of exposure in workers with potential exposure to allyl chloride (AC) up to the occupational exposure limit of 1 ppm (8-h TWA), we recently found urinary ALMA concentrations up to 4 micrograms/ml. Based on the results presented here, we conclude that garlic consumption is a potential confounder when monitoring human exposure to allylhalides and other chemicals leading to ALMA excretion when ALMA is used as a biomarker of exposure.

Acetylcysteine↗
PubMed1997

Occupational asthma induced by garlic dust.

BACKGROUND: Garlic dust has not been a frequently encountered cause of IgE-mediated disease. OBJECTIVE: We report on 12 patients (all of them garlic workers) with the clinical criteria for occupational asthma. METHODS: Skin prick tests and serum-specific IgE determinations were performed with common inhalants, garlic, and other members of the Liliaceae family (onion, leek, and asparagus). Bronchial challenge test with garlic powder was performed in all patients. Garlic and onion extract proteins were separated by sodium dodecylsulfate-polyacrylamide gel electrophoresis. Immunoblot and IgE immunoblot inhibition analyses were performed with patients' sera on extracts of garlic, onion, and pollens of Phleum pratense and Chenopodium album. RESULTS: Garlic sensitization was demonstrated by bronchial challenge test in seven patients (group 1) and ruled out in the remaining five (group 2). Clinical data were similar in both groups. The patients with garlic allergy had a mean age of 27 years, and all of them had pollen allergy; sensitization to other members of the Liliaceae family was also common. Electrophoresis of garlic extract revealed two major protein bands at approximately 12 and 54 kd. During IgE immunoblotting, the pool of sera reacted with garlic proteins mainly at 54 kd. Preincubation with onion, Phleum, and Chenopodium partially abolished the IgE binding to several allergens of garlic. CONCLUSION: We report on seven patients in whom an occupational garlic allergy was demonstrated. Garlic allergy is relatively rare but seems to affect young subjects with pollen allergy, and sensitization to other members of the Liliaceae family is common. The results of this study confirm the presence of some structurally similar allergens in garlic, onion, and certain pollens.

Administration, Inhalation↗
PubMed1997

[New pharmacological activities of garlic and its constituents].

According to the recent pharmacological findings, garlic is a preventive rather than therapeutic. Epidemiological studies in China, Italy and USA showed the inverse relationship between stomach and colon cancer incidences and dietary garlic intake. Anti-carcinogenic activities of garlic and its constituents including sulfides and S-allyl cysteine, have been demonstrated using several animal models. Garlic preparations has been also shown to lower serum cholesterol and triglyceride levels, which are major risk factors of cardiovascular diseases, through inhibition of their bio-synthesis in the liver, and to inhibit oxidation of low density lipoprotein. Furthermore, in vitro and in vivo studies have revealed that aged garlic extract stimulated immune functions, such as proliferation of lymphocyte, cytokine release, NK activity and phagocytosis. More recently, aged garlic extract has been demonstrated to prolong life span of senescence accelerated mice and prevent brain atrophy. Manufacturing processes significantly affect chemical constituents in garlic preparations. Different forms contain different phytochemicals and may have different effects and toxicities. For example, aged garlic extract inhibited t-BuOOH-induced oxidation, whereas raw garlic stimulated the oxidation. Although garlic has been used as a condiment and folklore for a long time, it has been noted to cause adverse reactions, such as stomach ulcer and anemia. Among the garlic preparations, only aged garlic extract has been proven to be safe through toxicological studies. Thus, aged garlic extract could be the most promising garlic preparation for disease prevention.

Adjuvants, Immunologic↗
PubMed2003

Garlic [Allium sativum]: a review of its potential use as an anti-cancer agent.

Garlic [Allium sativum] is among the oldest of all cultivated plants. It has been used as a medicinal agent for thousands of years. It is a remarkable plant, which has multiple beneficial effects such as antimicrobial, antithrombotic, hypolipidemic, antiarthritic, hypoglycemic and antitumor activity. In this review, we will discuss particularly the largely preclinical use of this agent in the treatment and prevention of cancer. A number of studies have demonstrated the chemopreventive activity of garlic by using different garlic preparations including fresh garlic extract, aged garlic, garlic oil and a number of organosulfur compounds derived from garlic. The chemopreventive activity has been attributed to the presence of organosulfur compounds in garlic. How this is achieved is not fully understood, but several modes of action have been proposed. These include its effect on drug metabolizing enzymes, antioxidant properties and tumor growth inhibition. Most of these studies were carried out in the animal models. Also, recent research has focused on the antimutagenic activity of garlic. Recently, it has been observed that aged garlic extract, but not the fresh garlic extract, exhibited radical scavenging activity. The two major compounds in aged garlic, S-allylcysteine and S-allylmercapto-L-cysteine, had the highest radical scavenging activity. In addition, some organosulfur compounds derived from garlic, including S-allylcysteine, have been found to retard the growth of chemically induced and transplantable tumors in several animal models. Therefore, the consumption of garlic may provide some kind of protection from cancer development.

Antineoplastic Agents, Phytogenic↗