1: Cell Mol Biol (Noisy-le-grand) 2000 Feb;46(1):199-214
Programmed cell death (apoptosis), a form of cell death, described by Kerr and Wyllie some 20 years ago, has generated considerable interest in recent years. The mechanisms by which this mode of cell death (seen both in animal and plant cells), takes place have been examined in detail. Extracellular signals and intracellular events have been elaborated. Of interest to the clinician, is the concentrated effort to study pharmacological modulation of programmed cell death. The attempt to influence the natural phenomenon of programmed cell death stems from the fact that it is reduced (like in cancer) or increased (like in neurodegenerative diseases) in several clinical situations. Thus, chemicals that can modify programmed cell death are likely to be potentially useful drugs. From foxglove, which gave digitalis to the Pacific Yew from which came taxol, plants have been a source of research material for useful drugs. Recently, a variety of plant extracts have been investigated for their ability to influence the apoptotic process. This article discusses some of the interesting data. The ability of plants to influence programmed cell death in cancerous cells in an attempt to arrest their proliferation has been the topic of much research. Various cell-lines like HL60, human hepatocellular carcinoma cell line (KIM-1), a cholangiocarcinoma cell-line (KMC-1), B-cell hybridomas, U937 a monocytic cell-line, HeLa cells, human lymphoid leukemia (MOLT-4B) cells and K562 cells have been studied. The agents found to induce programmed cell death (measured either morphologically or flow cytometrically) included extracts of plants like mistletoe and Semicarpus anacardium. Isolated compounds like bryonolic acid (from Trichosanthes kirilowii var. Japonica, crocin (from saffron) and allicin (from Allium sativum) have also been found to induce programmed cell death and therefore arrest proliferation. Even Chinese herbal medicine "Sho-saiko-to" induces programmed cell death in selected cancerous cell lines. Of considerable interest is the finding that Panax ginseng prevents irradiation-induced programmed cell death in hair follicles, suggesting important therapeutic implications. Nutraceuticals (dietary plants) like soya bean, garlic, ginger, green tea, etc. which have been suggested, in epidemiological studies, to reduce the incidence of cancer may do so by inducing programmed cell death. Soy bean extracts have been shown to prevent development of diseases like polycystic kidneys, while Artemisia asiatica attenuates cerulein-induced pancreatitis in rats. Interestingly enough, a number of food items as well as herbal medicines have been reported to produce toxic effects by inducing programmed cell death. For example, programmed cell death in isolated rat hepatocytes has been implicated in the hepatitis induced by a herbal medicine containing diterpinoids from germander. Other studies suggest that rapid progression of the betel- and tobacco-related oral squamous cell carcinomas may be associated with a simultaneous involvement of p53 and c-myc leading to inhibition of programmed cell death. Several mechanisms have been identified to underlie the modulation of programmed cell death by plants including endonuclease activation, induction of p53, activation of caspase 3 protease via a Bcl-2-insensitive pathway, potentiate free-radical formation and accumulation of sphinganine. Programmed cell death is a highly conserved mechanism of self-defense, also found to occur in plants. Hence, it is natural to assume that chemicals must exist in them to regulate programmed cell death in them. Thus, plants are likely to prove to be important sources of agents that will modulate programmed cell death.
Publication Types: Review Review, tutorial
PMID: 10726985, UI: 20189519
2: J Cell Biochem 2000;77(S34):125
Shu Zheng, Hua Yang, Suzhan Zhang, Xianping Wang, Linlin Yu, Jieqing Lu, and Jun Li. 1997. Initial study on naturally occurring products from traditional Chinese herbs and vegetables for chemoprevention. J Cell Biochem Suppl 27:106-112. The sulfur compound of garlic in this study should read "allitridi (diallyl trisulfide)" instead of "allicin (diallyl sulfide, DAS)." The authors acknowledge the error.
3: Am J Gastroenterol 2000 Feb;95(2):563-4
PMID: 10685782, UI: 20148218
4: Biochim Biophys Acta 2000 Jan 15;1463(1):20-30
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Allicin (diallyl thiosulfinate) is the main biologically active component of the freshly crushed garlic extracts. In the present work the ability of allicin to cross through membranes (artificial and biological) was studied. Partition coefficients of allicin in water/octanol, water/hexadecane and water/phospholipids mixtures were determined. Using phospholipid vesicles loaded with hydrophilic thiols (reduced glutathione or 2-nitro-5-thiobenzoate), we observed that allicin freely permeates through phospholipid bilayers and interacts with the SH groups. The reaction rate of allicin with SH containing molecules after crossing the membrane was the same as in solution. Fast diffusion and permeation of allicin across human red blood cell membranes was also demonstrated. Allicin does not induce leakage, fusion or aggregation of membrane. The high permeability of allicin through membranes may greatly enhance the intracellular interaction with thiols.
5: Arch Environ Contam Toxicol 2000 Feb;38(2):182-90
Effect of sublethal treatment (20% and 60% of LC(50)/24 h) of plant-derived molluscicides, viz. Polianthes tuberosa, Trachyspermum ammi, Allium sativum powder; Azadirachta indica oil; oleoresin of Zingiber officinale; and their active molluscicidal component in combination (1:5) with MGK-264 or piperonyl butoxide on the reproduction of snail Lymnaea acuminata have been studied. It was observed that the combination of plant derived molluscicide and their active molluscicidal components, viz. tigogenin, hecogenin, azadirachtin, allicin, thymol, and -gingerol combination with MGK-264 or piperonyl butoxide caused a significant reduction in fecundity, hatchability, and survival of young snails. Withdrawal of snails to fresh water after the above treatment caused a significant recovery in the fecundity of L. acuminata.
PMID: 10629280, UI: 20096501
6: Microbes Infect 1999 Feb;1(2):125-129
[Record supplied by publisher]
Allicin, one of the active principles of freshly crushed garlic homogenates, has a variety of antimicrobial activities. Allicin in its pure form was found to exhibit i) antibacterial activity against a wide range of Gram-negative and Gram-positive bacteria, including multidrug-resistant enterotoxicogenic strains of Escherichia coli; ii) antifungal activity, particularly against Candida albicans; iii) antiparasitic activity, including some major human intestinal protozoan parasites such as Entamoeba histolytica and Giardia lamblia; and iv) antiviral activity. The main antimicrobial effect of allicin is due to its chemical reaction with thiol groups of various enzymes, e.g. alcohol dehydrogenase, thioredoxin reductase, and RNA polymerase, which can affect essential metabolism of cysteine proteinase activity involved in the virulence of E. histolytica.
7: Coron Artery Dis 1999 Oct;10(7):515-9
BACKGROUND: Garlic (Allium sativum) has been considered to exhibit therapeutic features for many years. The effects of garlic on levels of serum lipids and on atherosclerosis have been investigated extensively. We have previously demonstrated that allicin, an active component of garlic, exerts a beneficial effect on lipid profile in hyperlipidemic rabbits. OBJECTIVE: To investigate the effects of allicin on formation of fatty streaks (atherosclerosis) and lipid profile in mice. METHODS: Allicin was extracted from garlic and kept in a buffer citrate solution at 4 degrees C. Sixty C57BL/6 mice were fed Paigen diet (17% fat, 1.25% cholesterol) for 15 weeks. Thirty randomly selected animals were administered allicin solution (9 mg/kg) and 30 were administered placebo. Blood lipid profile was evaluated five times during the study. At the end of the 15-week period, the animals were killed and the aortic sinus was evaluated for formation of fatty streaks (atherosclerosis). RESULTS: We observed no statistically significant differences between blood lipid profiles of groups. Microscopic evaluation of aortic sinus formation of fatty streaks (atherosclerosis), however, showed that values for mice in the allicin-treated group were significantly lower: areas of formation of fatty streaks (atherosclerosis) were 13,440 +/- 3310 and 23,410 +/- 3723 micron 2, respectively, for allicin-treated and control mice (means +/- SEM; P = 0.023). CONCLUSIONS: These results indicate that allicin reduces formation of fatty streaks (atherosclerosis) in hyperlipidemic mice. These changes do not seem to occur through an alteration in blood lipid profile.
PMID: 10562920, UI: 20028660
8: Arch Dis Child 1999 Sep;81(3):278
PMID: 10532926, UI: 99460064
9: J Antimicrob Chemother 1999 Jun;43(6):837-9
The antibacterial effect of a home-made raw garlic extract and commercial garlic tablets alone and in combination with antibiotics or omeprazole was determined against clinical isolates of Helicobacter pylori. MIC values of raw garlic extract and three types of commercial garlic tablets ranged from 10,000 to 17,500 mg/L. When MIC values of the commercial tablets were based on the allicin content, no differences between the three types were observed. The combination of garlic and omeprazole, studied with killing curves, showed a synergic effect which was concentration dependent. Further clinical evaluation of garlic in combination with the conventional agents for H. pylori treatment seems warranted.
PMID: 10404325, UI: 99332396
10: Drug Metab Dispos 1999 Jul;27(7):835-41
The metabolism of diallyl disulfide (DADS), a garlic sulfur compound, was investigated in human liver microsomes. Diallyl thiosulfinate (allicin) was the only metabolite observed and its formation followed Michaelis-Menten kinetics with a Km = 0.61 +/- 0.2 mM and a Vmax = 18.5 +/- 4.2 nmol/min/mg protein, respectively (mean +/- S.E. M., n = 4). Both flavin-containing monooxygenase and the cytochrome P-450 monooxygenases (CYP) were involved in DADS oxidation, but the contribution of CYP was predominant. The cytochrome P-450 isoforms involved in this metabolism were investigated using selective chemical inhibitors, microsomes from cells expressing recombinant CYP isoenzymes, and studying the correlation of the rate of DADS oxidation with specific monooxygenase activities of human liver microsomes. Diethyldithiocarbamate and tranylcypromine inhibited allicin formation, whereas other specific inhibitors had low or no effect. Most of the different human microsomes from cells expressing CYP were able to catalyze this reaction, but CYP2E1 showed the highest affinity with a substantial activity. Furthermore, allicin formation by human liver microsomes was correlated with p-nitrophenol hydroxylase activity, a marker of CYP2E1, and tolbutamide hydroxylase activity, a marker of CYP2C9. Among these approaches only CYP2E1 was identified in each case, which suggested that DADS is preferentially metabolized to allicin by CYP2E1 in human liver. However the minor participation of other CYP forms and flavin-containing monooxygenases is likely.
PMID: 10383929, UI: 99315504
11: Prostaglandins Leukot Essent Fatty Acids 1999 Jan;60(1):43-7
The effects of aqueous extracts of raw and boiled garlic and onions were studied in vitro on the collagen-induced platelet aggregation using rabbit and human platelet-rich plasma. A dose dependant inhibition of rabbit platelet aggregation was observed with garlic. Onion also showed dose-dependent inhibitory effects on the collagen-induced platelet aggregation but this inhibition was of a lesser magnitude compared to garlic when related to dose. The concentration required for 50% inhibition of the platelet aggregation for garlic was calculated to be approximately 6.6 mg ml(-1) plasma, whereas the concentration for onion was 90 mg ml(-1) plasma. Boiled garlic and onion extracts showed a reduced inhibitory effect on platelet aggregation. Garlic but not onion significantly inhibits human platelet aggregation in a dose-dependent fashion. The potency of garlic in inhibiting the collagen-induced platelet aggregation is approximately similar to that of rabbit platelets (8.8 mg ml(-1) produced 50% inhibition of platelet aggregation). The results of this study show that garlic is about 13 times more potent than onion in inhibiting platelet aggregation and suggest that garlic and onion could be more potent inhibitors of blood platelet aggregation if consumed in raw than in cooked or boiled form.
PMID: 10319916, UI: 99251634
12: Pharmazie 1999 Apr;54(4):289-93
In recent years, numerous clinical trials were undertaken in order to elucidate the active principle of garlic (Allium sativum L., Alliaceae). The most prominent effect of garlic preparations is a contribution to the prevention of stroke and arteriosclerosis. Allicin[(2-propenyl)-2-propenethiosulfinate] and other sulfur containing compounds were suggested as active compounds. The extremely unstable allicin itself is liberated from the more stable alliin [S-(+)-2-propenyl-L-cysteine sulfoxide] by the enzyme alliinase (EC 184.108.40.206) if fresh garlic is crunched or garlic powder is moistened. Therefore, an active enzyme is required in alliin containing remedies like those prepared from garlic powder. In order to investigate enzyme stability, alliinase was isolated from garlic powder. The partially purified enzyme could be stabilized over several months by addition of sodium chloride, sucrose, and pyridoxal-5'-phosphate. Alliinase may also be freeze-dried. This allows combinations of synthetic alliin and purified alliinase as components of an acid resistant tablet or capsule. In the intestine, the pro-drug alliin would be enzymatically converted to allicin. In clinical trials, highly dosed preparations of this kind should yield a precise information about the physiological effects of allicin. In addition, alliin-homologues substances which bear a modified alkyl side chain and do not occur in nature may be tested.
PMID: 10234740, UI: 99251048
13: Phytomedicine 1999 Mar;6(1):13-6
Sulfur containing constituents of garlic are considered responsible for conveying the antioxidative properties of garlic preparations. The radical scavenging properties of garlic preparations against oxygen radicals, specifically their ability to inhibit the formation of superoxide anions, were investigated using human granulocytes activated with 10 nM phorbol myristyl acetate (PMA). A garlic powder preparation inhibited the production of superoxide with a calculated IC50 of 390 micrograms/ml. An 8-10% alliin enriched garlic extract (alliinase inactivated) did not inhibit superoxide production even at concentrations as high as 1000 micrograms/ml. When the extract was mixed with garlic powder (90% garlic powder, 10% garlic extract), there was a clear inhibition of superoxide production with an IC50 value of 295 micrograms/ml. An even stronger inhibitory effect could be achieved when garlic powder was added to garlic extract (10% garlic powder, 90% extract, IC50 = 160 micrograms/ml). These experimental results suggest that the alliin metabolite allicin may be responsible for the oxygen radical scavenging properties of garlic.
PMID: 10228606, UI: 99245290
14: Phytomedicine 1999 Mar;6(1):7-11
Epidemiological studies in China provide reason to suspect that a rich garlic content in the diet might reduce the proliferation of tumors in humans. We conducted experiments on human tumor cell lines and determined the influence of a garlic powder preparation, a garlic extract (reported as 8-10% L(+)-alliin enriched), and a combination thereof, on cellular proliferation in cell cultures, employing the widely used indirect neutral red procedure. Garlic powder failed to inhibit the growth of human hepatoma HepG2 or human colorectal carcinoma Caco2 cells at concentrations of up to 1000 micrograms/ml. Garlic extract, in which the alliin content was highly enriched was also unable to inhibit the growth of these cells. However, when the garlic extract was supplemented with garlic powder (to 10% final concentration) there was a concentration-dependent clear inhibition of tumor cell growth (IC50 values of 330 micrograms/ml for HepG2 and 480 micrograms/ml for Caco-2 cells). The growth of the human lymphatic leukemia cell line CCRF CEM was significantly inhibited in a dose-dependent manner by both garlic powder and garlic extract at concentrations as low as 30 micrograms/ml. However, no potentiation of this effect occurred upon mixing of the two preparations. Our results suggest that the antiproliferative effects of garlic may be due to breakdown products of alliin, such as allicin or polysulfides, rather than alliin itself, since the addition of an alliinase system (garlic powder) to an alliin enriched preparation without alliinase (garlic extract) potentiated the effects observed with the two preparations alone.
PMID: 10228605, UI: 99245289
15: Biosci Biotechnol Biochem 1999 Mar;63(3):591-4
Three thiosulfinates were isolated from oil-macerated garlic extract, and their structures were identified as 2-propene-1-sulfinothioic acid S-(Z,E)-1-propenyl ester [AllS(O)SPn-(Z,E)], 2-propenesulfinothioic acid S-methyl ester [AllS(O)SMe], and methanesulfinothioic acid S-(Z,E)-1-propenyl ester [MeS(O)SPn-(Z,E)]. This is the first report of isolating these thiosulfinates from oil-macerated garlic extract. Antimicrobial activities of AllS(O)SPn-(Z,E) and AllS(O)SMe against Gram-positive and negative bacteria and yeasts were compared with 2-propene-1-sulfinothioic acid S-2-propenyl ester [AllS(O)SAll, allicin] which is well-known as the major thiosulfinate in garlic. Antimicrobial activity of AllS(O)SMe and AllS(O)SPn-(Z,E) were comparable and inferior to that of allicin, respectively. This result suggested that the antimicrobial activity of 2-propene sulfinothioic acid S-alk(en)yl esters were affected by alk(en)yl groups. The order for antimicrobial activity was: allyl > or = methyl > propenyl.
PMID: 10227150, UI: 99243737
16: Planta Med 1999 Mar;65(2):139-43
Alliinase (EC 220.127.116.11) has been isolated from commercially available garlic (Allium sativum L., Alliaceae) powder and was investigated with respect to its use as ingredient of herbal remedies. The enzyme was purified to apparent homogeneity and results were compared with those obtained from a sample of fresh A. sativum var. pekinense. The purification of the enzyme involved a gel filtration step as well as affinity chromatography on concanavalin-A agarose. Vmax using L-(+)-alliin as substrate (252 mumol min-1 mg-1) was at the lower range of data given in the literature (214-390 mumol min-1 mg-1). L-(-)-Alliin was also accepted as substrate (54 mumol min-1 mg-1). Vmax for alliinase from A. sativum var. pekinense was at 332 mumol min-1 mg-1 and 90 mumol min-1 mg-1 for L-(+)- and L-(-)-alliin, respectively. The Km values for alliinase from garlic powder were estimated to be 1.6 mM for L-(+)-alliin and 2.8 mM for L-(-)-alliin. In contrast to literature values, both temperature and pH optima were somewhat higher (36 degrees C and pH 7.0 versus 33 degrees C and pH 6.5, respectively). The enzyme was found to be active in a range from pH 5 to pH 10. Gel electrophoresis gave evidence that the alliinase obtained from garlic powder consisted of two slightly different subunits with molecular weights of 53 and 54 kDa whereas alliinase obtained from fresh garlic consists of two identical subunits. It is assumed that the alliinase gets significantly altered during the drying process of garlic powder but is still capable to convert alliin to allicin.
PMID: 10193205, UI: 99209285
17: Anal Biochem 1998 Dec 15;265(2):317-25
Allicin (diallylthiosulfinate) is the main biologically active component of freshly crushed garlic cloves. It is produced upon the interaction of the nonprotein amino acid alliin with the enzyme alliinase (alliin lyase, EC 18.104.22.168). A simple and rapid spectrophotometric procedure for determination of allicin and alliinase activity, based on the reaction between 2-nitro-5-thiobenzoate (NTB) and allicin, is described. NTB reacts with the activated disulfide bond --S(O)-S--; of allicin, forming the mixed-disulfide allylmercapto-NTB, as characterized by NMR. The method can be used for determination of allicin and total thiosulfinates in garlic preparations and garlic-derived products. The method was applied for determination of pure alliinase activity and for the activity of the enzyme in crude garlic extracts. Copyright 1998 Academic Press.
PMID: 9882409, UI: 99102750
18: Phytochemistry 1998 Sep;49(2):359-64
Supercritical fluid (SF) extracts of homogenized ramp (Allium tricoccum Ait.) were separated and characterized with liquid chromatography coupled with atmospheric pressure chemical ionization mass spectrometric identification. The profiles of SF extracts of aqueous homogenates of ramp bulbs from three different seasons and growing regions revealed that the thiosulfinates were major components. In addition, some of the cepaenes (alpha-sulfinyldisulfides) found in extracts of onion juice, as well as allyl containing cepaenes (2-propenyl l-(2-propenylsulfinyl)propyl disulfide), are present in the ramp extracts. The amount of allicin in ramp bulb homogenates ranged from approximately 10% to 50% of that found in extracts of aqueous garlic homogenates. The greater amount of the methyl 1-propenyl thiosulfinates in the ramp extracts relative to that found in the garlic extracts correlates with the flavor characteristics of ramp bulbs.
PMID: 9747536, UI: 98419673
19: Atherosclerosis 1998 Aug;139(2):333-9
Inducible nitric oxide synthase (iNOS) has recently been shown to be present in human atherosclerotic lesions and to promote the formation of deleterious peroxynitrite. Allicin and ajoene are discussed as active compounds with regard to the beneficial effects of garlic in atherosclerosis. The aim of this study was to investigate the effect of allicin and ajoene on the iNOS system in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Ajoene (IC50 2.5-5 microM) and allicin (IC50 15-20 microM) dose dependently reduced nitrite accumulation, a parameter for NO synthesis, in supernatants of LPS-stimulated (1 microg/ml, 20 h) macrophages. Accordingly, reduced iNOS enzyme activities were measured by conversion of L-[3H]arginine to L-[3H]citrulline in homogenates of LPS-activated cells treated with ajoene or allicin. None of these compounds, however, showed a direct effect on the catalytic-activity of iNOS. Consequently, iNOS protein and mRNA expression in ajoene (10 microM) or allicin (50 microM) treated cells were evaluated by Western blot and Northern blot analysis, respectively. Markedly reduced iNOS protein as well as mRNA levels were demonstrated. These observations indicate that allicin and ajoene inhibit the expression of iNOS in activated macrophages. The possible link of this effect to the beneficial features attributed to garlic is discussed.
PMID: 9712340, UI: 98376185
20: Harv Health Lett 1998 Jun;23(8):7
21: Planta Med 1998 May;64(4):303-8
Farnesyl protein transferase (FPT) catalyzes the posttranslational farnesylation of the cysteine residue located in the carboxyl-terminal tetrapeptide of the Ras oncoprotein. Prenylation of this residue is essential for membrane association and cell transforming activities of Ras. Inhibitors of FPT have been demonstrated to inhibit Ras-dependent cell transformation and thus represent a potential therapeutic strategy for the treatment of human cancers (1). In the present study, the inhibitory principles for protein prenyltransferases were isolated and identified from Ganoderma lucidum and garlic. The inhibitors from Ganoderma lucidum were identified as ganoderic acid A and ganoderic acid C by comparison with the reported spectral data. Ganoderic acid A has an IC50 value of 100 microM against FPT and its methyl ester (methyl ganoderate A) has an IC50 value of 38 microM for the same enzyme. These inhibitors appear to be competitive with farnesyl pyrophosphate (FPP), and Ki values of ganoderic acid A and methyl ganoderate A are 54 microM and 20 microM, respectively. The inhibitors from garlic were identified as diallyl thiosulfinate (allicin), methyl allyl thiosulfinate, and allyl methyl thiosulfinate. These inhibitors are more effective against geranylgeranyl protein transferase (GGPT) than FPT and IC50 values of allicin, methyl allyl thiosulfinate, and allyl methyl thiosulfinate for GGPT were 43 microM, 57 microM, and 53 microM, respectively. Methyl allyl thiosulfinate appears to be competitive with geranylgeranyl pyrophosphate (GGPP) and its Ki was determined to be 15 microM. The molecular structures of triterpenes and thiosulfinates are expected to be useful in designing lead compounds for new potent antitumour agents.
PMID: 9619109, UI: 98282868
22: J Cell Biochem Suppl 1997;27:106-12
A number of naturally occurring products from vegetables and herbs exert chemopreventive properties against carcinogenesis. In this paper, two such compounds, isolated from garlic and from a traditional Chinese medicinal herb, are described for review. Elemene, isolated from the Chinese medicinal herb Rhizoma zedoariae, was shown to exhibit antitumor activity in human and murine tumor cells in vitro and in vivo. This novel antineoplastic agent has substantial clinical activity against various tumors. The in vitro effect of elemene on the growth of leukemia cells was evaluated by MTT assay. The IC50 values of elemene for promyelocytic leukemia HL-60 cells and erythroleukemia K562 cells were 27.5 micrograms/mL and 81 micrograms/mL, respectively, while IC50 for peripheral blood leukocytes (PBL) was 254.3 micrograms/mL. The inhibitory effect of elemene on proliferation of HL-60 cells was associated with cell cycle arrest from S to G2M phase transition and with induction of apoptosis. The apoptosis of tumor cells was confirmed by DNA ladder formation on gel electrophoresis and characteristic ultrastructural alterations. The results also demonstrated that inhibitory effects of allicin, a natural organosulfide from garlic, on proliferation of tumor cells were associated with the cell cycle blockage of S/G2M boundary phase and induction of apoptosis. These findings suggest that induction of apoptosis may contribute to the mechanisms of antitumor activity of elemene and allicin, which merit investigation as potential chemoprevention agents in humans.
PMID: 9591200, UI: 98253425
23: J Am Vet Med Assoc 1998 Apr 1;212(7):987-90
OBJECTIVE: To evaluate effectiveness of an allicin-based product in neonatal calves inoculated with Cryptosporidium parvum. DESIGN: Randomized controlled study. ANIMALS: 43 neonatal calves. PROCEDURE: Calves were inoculated with 1.5 x 10(8) or 7.5 x 10(5) C parvum oocysts within 2 days after birth. Calves were given an allicin-based product once after inoculation or daily for 7 days after inoculation or were not treated. Calves that developed diarrhea were treated by administration of the product. Fecal consistency scores and weight gains were statistically evaluated. RESULTS: Mean daily weight gain and severity of diarrhea in calves 4 to 21 days old were unaffected by prophylactic use of the product. However, intensive prophylactic administration may have delayed onset of C parvum-induced diarrhea in calves inoculated with the lower dose of oocysts. CLINICAL IMPLICATIONS: Administration of an allicin-based product did not alter duration of C parvum-induced diarrhea or enhance weight gain in neonatal calves. However, intensive prophylactic administration of an allicin-based product may delay onset of diarrhea in calves exposed to C parvum oocysts.
Publication Types: Clinical trial Randomized controlled trial
PMID: 9540869, UI: 98201746
24: Biochim Biophys Acta 1998 Feb 2;1379(2):233-44
Allicin (thio-2-propene-1-sulfinic acid S-allyl ester) is the main biologically active component of garlic clove extracts. Its biological activity was attributed to either antioxidant activity or thiol disulfide exchange. Antioxidant properties of both allicin and its precursor, alliin (+S-allyl-L-cysteine sulfoxide), were investigated in the Fenton oxygen-radical generating system [H2O2-Fe(II)]. Using the spin trapping technique and ESR, it was found that both compounds possessed significant antioxidant activity. The reaction between allicin and L-cysteine was studied by 1H and 13C-NMR, and a S-thiolation product, S-allylmercaptocysteine, was identified. Allicin irreversibly inhibited SH-protease papain, NADP(+)-dependent alcohol dehydrogenase from Thermoanaerobium brockii (TBAD), and the NAD(+)-dependent alcohol dehydrogenase from horse liver (HLAD). All the three enzymes could be reactivated with thiol containing compounds. Papain could be reactivated with glutathione, TBAD with dithiothreitol or 2-mercaptoethanol (2-ME) but not by glutathione, while HLAD could be reactivated only with 2-ME. This study demonstrates that in addition to its antioxidant activity, the major biological effect of allicin should be attributed to its rapid reaction with thiol containing proteins.
PMID: 9528659, UI: 98189237
25: Antimicrob Agents Chemother 1997 Oct;41(10):2286-8
The ability of Entamoeba histolytica trophozoites to destroy monolayers of baby hamster kidney cells is inhibited by allicin, one of the active principles of garlic. Cysteine proteinases, an important contributor to amebic virulence, as well as alcohol dehydrogenase, are strongly inhibited by allicin.
PMID: 9333064, UI: 97472194
26: Brain Res 1997 Apr 4;753(1):47-55
It is well established that extracellular choline is transported into central cholinergic nerve terminals by 'high' and 'low' affinity processes to form the neurotransmitter acetylcholine (ACh). The intent of the present investigation was to ascertain whether extracellular acetate might also be transported into central cholinergic nerve terminals to form ACh. To test this possibility, rat hippocampal tissue was incubated with varying concentrations of extracellular [1-(14)C]acetate (0.1-100 microM) and the uptake of [1-(14)C]acetate and the amount of [14C]ACh formed by the tissue determined. The results indicated that the uptake of extracellular [1-(14)C]acetate was temperature-dependent and saturable having an apparent Michaelis constant (Km) of 22 microM. The formation of [14C]ACh in the tissue as a function of extracellular [1-(14)C]acetate appeared to occur by both 'high' and 'low' affinity processes with apparent Km values of 0.5 and 19.6 microM, respectively. In other experiments, three inhibitors (lithium, allicin and sodium) of acetyl CoA synthetase (EC 22.214.171.124 acetate: CoA ligase), the enzyme which converts acetate to acetyl CoA when ATP and CoA are present, inhibited [1-(14)C]acetate uptake and the amount of [14C]ACh formed from that [1-(14)C]acetate. Additionally, vesamicol, an inhibitor of ACh transport into synaptic vesicles, blocked the filling of a synaptic vesicle-enriched fraction of hippocampal tissue with newly synthesized [14C]ACh formed from extracellular [1-(14)C]acetate. High K+ depolarization of hippocampal tissue loaded with extracellular [1-(14)C]acetate not only increased the synthesis but also the release of [14C]ACh. These results suggest that extracellular acetate is recycled by rat hippocampal cholinergic nerve terminals for the formation and release of ACh. They also suggest that the enzyme acetyl CoA synthetase mediates extracellular acetate uptake into hippocampal cholinergic nerve terminals by metabolizing it to acetyl CoA and thereby creating a diffusion gradient for it to follow.
PMID: 9125430, UI: 97270347
27: Nutrition 1997 Apr;13(4):379-80
PMID: 9178295, UI: 97321585
28: Klin Med (Mosk) 1997;75(3):39-41
Department of Common Therapy, RGMU.
PMID: 9229613, UI: 97314590
29: Lipids 1996 Dec;31(12):1269-76
Using primary rat hepatocyte cultures, the potency of several garlic-derived organosulfur compounds to inhibit cholesterol biosynthesis in toto as well as at early and late steps of this metabolic pathway was compared. Concerning early steps, allicin significantly inhibited incorporation of [14C]acetate into nonsaponifiable neutral lipids already at concentrations as low as 10 microM, while diallyl disulfide and allyl mercaptan were effective above 100 microM only. Likewise, inhibition in response to the two vinyl-dithiins started at 500 microM. If [14C]acetate was replaced by [14C]mevalonate, inhibition due to allicin, diallyl disulfide, and allyl mercaptan disappeared suggesting that HMGCoA-reductase was the target of inhibition. In contrast, for the vinyl-dithiins a stimulation of mevalonate incorporation was found. Concerning the late step, the potency to exert accumulation of lanosterol presumably by inhibiting lanosterol 14 alpha-demethylase decreased in the order allicin > diallyl disulfide > allyl mercaptan = 1,3-vinyl-dithiin >> 1,2-vinyldithiin, the effect of the latter compound being close to zero. With respect to the total inhibition of [14C]acetate labeling of cholesterol, the half-maximal effective concentration-value of allicin was determined to be 17 +/- 2 microM compared to 64 +/- 7 microM for diallyl disulfide and to 450 +/- 20 microM for allyl mercaptan. Cytotoxicity as determined by the lactate dehydrogenase leakage assay was slightly higher for the two vinyl-dithiins than for diallyl disulfide and allyl mercaptan, but was apparent only at concentrations higher than 10 mM and, consequently, was irrelevant for the effects described. These results demonstrate that different garlic-derived organosulfur compounds interfere differently with cholesterol biosynthesis and, thus, may provoke multiple inhibition of this metabolic pathway in response to garlic consumption. The fact that allicin was the most effective inhibitor argues against the possibility that its degradation products, namely diallyl disulfide or allyl mercapatan, might mediate its effects, a possibility that might be true, however, in the case of the vinyl-dithiins.
PMID: 8972460, UI: 97127709
30: Biull Eksp Biol Med 1996 Nov;122(11):502-4
31: Comp Biochem Physiol C Pharmacol Toxicol Endocrinol 1996 Sep;115(1):89-94
A previous study has shown that allicin produces changes in aqueous humor dynamics, and this study was conducted to examine possible cellular mechanisms. In rabbit nonpigmented ciliary epithelial cells, basal levels of [Ca2+]i were determined to be 164 +/- 34 nM. Allicin, a sulfhydryl-reactive agent, induced Ca2+ transients at 0.01 mM and at 0.2 mM, the Ca2+ transient peaked at 732 +/- 35 nM. Allicin-induced Ca2+ transients were prevented by pretreatment with dithiothreitol which did not affect the basal Ca2+ levels. Allicin had only a slight, insignificant, effect on L-type Ca2+ currents, and allicin-induced Ca2+ transients were also present under extracellular Ca(2+)-free conditions. These data suggest that intracellular Ca2+ stores are the most probable source of allicin's effect. Pretreatment of cells with ryanodine, an inhibitor of Ca(2+)-induced-Ca(2+)-release, inhibited allicin-induced Ca2+ transients, but the basal Ca2+ levels were unaffected by ryanodine. Thus, allicin-induced Ca2+ transients are most likely mediated through ryanodine-sensitive intracellular Ca2+ stores.
PMID: 8983172, UI: 97137835
32: Nippon Shokakibyo Gakkai Zasshi 1996 Sep;93(9):688
PMID: 8905979, UI: 97062135
33: Indian J Med Sci 1996 Jul;50(7):231-3
S-allyl cysteine sulphoxide (SACS), a sulphur containing aminoacid of garlic is the precursor of allicin and garlic oil, and has been found to show significant radio protective effect in albino rats which were whole body irradiated with 400 rads of irradiation by Cobalt 60 source. It markedly reduced the radiation induced mortality and showed significant protection against the tissue damaging effects of irradiation in histopathological sections of liver and lung.
PMID: 8979540, UI: 97134160
34: J R Coll Physicians Lond 1996 Jul-Aug;30(4):329-34
OBJECTIVE: To determine the effect of 900 mg/day of dried garlic powder (standardised to 1.3% allicin) in reducing total cholesterol. DESIGN: Double-blind, randomised six-month parallel trial. SUBJECTS: 115 individuals with a repeat total cholesterol concentration of 6.0-8.5 mmol/l and low-density lipoprotein (LDL) cholesterol of 3.5 mmol/l or above after six weeks of dietary advice. INTERVENTION: The active treatment group received dried garlic tablets (standardised to 1.3% allicin) at a dosage of 300 mg three times daily. The control group received a matching placebo. OUTCOME MEASURES: Primary end-point: total cholesterol concentration; secondary end-points: concentrations of LDL and high-density lipoprotein cholesterol, apolipoproteins (apo) A1 and B, and triglycerides. RESULTS: There were no significant differences between the groups receiving garlic and placebo in the mean concentrations of serum lipids, lipoproteins or apo A1 or B, by analysis either on intention-to-treat or treatment received. In a meta-analysis which included the results from this trial, garlic was associated with a mean reduction in total cholesterol of -0.65 mmol/l (95% confidence intervals: -0.53 to -0.76). CONCLUSIONS: In this trial, garlic was less effective in reducing total cholesterol than suggested by previous meta-analyses. Possible explanations are publication bias, overestimation of treatment effects in trials with inadequate concealment of treatment allocation, or a type 2 error. We conclude that meta-analyses should be interpreted critically and with particular caution if the constituent trials are small.
Publication Types: Clinical trial Randomized controlled trial
PMID: 8875379, UI: 97029368
35: Med Res Rev 1996 Jan;16(1):111-24
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.
Publication Types: Review Review, tutorial
PMID: 8788216, UI: 96380203
36: Coron Artery Dis 1995 Dec;6(12):985-90
BACKGROUND: The effect of garlic on the serum lipid profile has been the subject of controversy. This study was therefore designed to examine the effects of allicin, an active constituent of garlic, on the lipid profile in a rabbit model. METHODS: Allicin was produced by reacting alliin, synthesized in our laboratory, with purified alliinase. Nineteen New Zealand White rabbits were fed a cholesterol-rich diet (0.25% cholesterol) for 18 weeks. Ten rabbits received freshly produced allicin (3 mg/kg orally) starting at 8 weeks, and nine received placebo. There was no significant difference between the lipid profiles of the two groups at baseline up to 8 weeks. RESULTS: From day 28 of allicin supplementation a significant difference was found between the allicin and placebo groups in the graph regression lines describing the influence of allicin on serum cholesterol: Y = 41.39 + 8.69 multiplied by day (control) versus Y = -877.24 + 17.67 multiplied by day (allicin). The same trend was found for low-density lipoprotein concentrations: Y = 10.3 + 8.4 multiplied by (control) versus Y = -750.4 + 15.7 multiplied by day (allicin). The serum high-density lipoprotein levels also differed significantly between the groups: Y = 20.29 + 0.24 multiplied by day (control) versus Y = -109.9 + 1.65 multiplied by day (allicin). CONCLUSIONS: Our results indicate that allicin has a beneficial effect on the serum lipid profile in hyperlipidemic rabbits, and should be further tested clinically.
PMID: 8723021, UI: 96303195
37: Glycoconj J 1995 Oct;12(5):690-8
Alliinase (EC 126.96.36.199) catalyses the production of allicin (thio-2-propene-1-sulfinic acid S-allyl ester), a biologically active compound which is also responsible for the characteristic smell of garlic. It was demonstrated that alliinase which contains 5.5-6% of neutral sugars, gives clear PAS-staining, binds to Con A and can form a complex with garlic mannose-specific lectin (ASA). Evidence that the formation of such a complex is mediated by the interaction of the carbohydrate of the glycoprotein enzyme with the lectin was obtained from a radioligand assay which demonstrated the binding of alliinase to ASA and competitive inhibition of this binding by methyl alpha-D-mannoside. ASA I was shown as the lectin mainly present in the complex with alliinase. The results of this study also demonstrate that alliinase is glycosylated at Asn146 in the sequence Asn146-Met147-Thr148.
PMID: 8595261, UI: 96121432
38: J Cell Biochem 1995 Aug;58(4):481-9
Garlic is known as a potent spice and a medicine with broad therapeutic properties ranging from antibacterial to anticancer, antidiabetic, and anticoagulant. Two major proteins of 40 KD and 14 KD constituting approximately 96% of total garlic proteins have been recently purified at our Institute. This immunocytochemical and ultrastructural study revealed that the 40 KD protein was localized in the parenchyma sheath cells (PSC) of garlic bulbs, whereas the 14 KD protein was present in the cortical cells (CC). Immunogold electron microscopy study indicated that the 40 KD protein was specifically localized in the globular granules of the cytoplasmic area of PSC. Each globular granule was amorphous and homogenous with membrane limiting its outermost layer. The yellowish color of PSC in freshly cut slices of garlic bulb suggested that PSC may have sulfur-containing compounds such as allicin, the primary contributor of the pungency and medicinal properties of garlic. Ellman's reagent test quantitatively revealed that there were 17.8 n moles sulfhydryl (SH)/ml of 40 KD garlic protein. Microtubule tubulin in mitotic figures from PHA-stimulated human short-term whole blood cultures reacted strongly with antitubulin antibody but reacted negatively with anti-40 KD garlic protein antibodies and therefore was not related to the 40 KD garlic protein immunocytochemically.
PMID: 7593270, UI: 96026763
39: Mol Cell Biochem 1995 Jul 19;148(2):183-9
Garlic has been claimed to be effective against diseases, in the pathophysiology of which oxygen free radicals (OFRs) have been implicated. Effectiveness of garlic could be due to its ability to scavenge OFRs. However, its antioxidant activity is not known. We investigated the ability of allicin (active ingredient of garlic) contained in the commercial preparation Garlicin to scavenge hydroxyl radicals (.OH) using high pressure liquid chromatographic (HPLC) method. .OH was generated by photolysis of H2O2 (1.25-10 mumoles/ml) with ultraviolet light and was trapped with salicylic acid which is hydroxylated to produce .OH adduct products 2,3- and 2,5-dihydroxybenzoic acid (DHBA). H2O2 produced a concentration-dependent .OH as estimated by .OH adduct products 2,3-DHBA and 2,5-DHBA. Allicin equivalent in Garlicin (1.8, 3.6, 7.2, 14.4, 21.6, 28.8 and 36 micrograms) produced concentration-dependent decreases in the formation of 2,3-DHBA and 2,5-DHBA. The inhibition of formation of 2,3-DHBA and 2,5-DHBA with 1.8 micrograms/ml was 32.36% and 43.2% respectively while with 36.0 micrograms/ml the inhibition was approximately 94.0% and 90.0% respectively. The decrease in .OH adduct products was due to scavenging of .OH and not by scavenging of formed .OH adduct products. Allicin prevented the lipid peroxidation of liver homogenate in a concentration-dependent manner. These results suggest that allicin scavenges .OH and Garlicin has antioxidant activity.
PMID: 8594422, UI: 96064292
40: Pharmazie 1995 May;50(5):359-61
Aqueous extracts of fresh garlic (Allium sativum L.) inhibited efficiently the activity of adenosine deaminase (ADA) of cultivated endothelial cells. The IC50 value (range between 6 and 120 micrograms per ml) depended on the origin and storage time of the fresh garlic. The aqueous extraction of dried garlic powder showed also an inhibition if ADA activity, but the IC50 value was in the range of 2.5 mg per ml indicating that parts of the active principle were lost during the preparation of the garlic powder. The inhibition of endothelial ADA by garlic extracts seems to contribute to the hypotensive activity and vessel protective effects of A. sativum L.
PMID: 7604070, UI: 95327724
41: Eur J Pharmacol 1995 Mar 24;276(1-2):21-6
Allicin, diallyl disulfide-oxide, an active ingredient released from garlic is a systemic vasodilator that acts by an unknown mechanism. In the present experiments, pulmonary vascular responses to allicin (0.1-1.0 mg) were studied in the intact-chest anesthetized cat and in the isolated lung of the rat under constant flow conditions. When baseline tone in the pulmonary vascular bed of the cat was raised with U46619 (11 alpha,9 alpha-epoxymethano-9 alpha,11 beta-dideoxyprostaglandin F2 alpha), intralobar injections of allicin produced dose-related decreases in pulmonary arterial pressure without changing left atrial pressure indicating that allicin had significant vasodilator activity in the pulmonary vascular bed when tone was increased experimentally. Allicin also decreased systemic arterial pressure in a dose-related manner. In terms of relative vasodilator activity in the cat, allicin was 100-fold less potent than sodium nitroprusside and many orders of magnitude less potent than isoproterenol. In the cat, vasodilator responses to allicin were unchanged by methylene blue or N omega-nitro-L-arginine methyl ester. Allicin also significantly diminished the pulmonary pressor response to ventilatory hypoxia in the isolated perfused rat lung. These data show that allicin has significant vasodilator activity in the pulmonary vascular bed of the cat and the rat. The present data suggest that pulmonary vasodilator responses to allicin are independent of the synthesis of endothelial-derived relaxing factor or the activation of soluble guanylate cyclase.
PMID: 7781691, UI: 95300875
42: Anal Biochem 1995 Feb 10;225(1):157-60
PMID: 7778769, UI: 95297682
43: Chung Kuo Chung Hsi I Chieh Ho Tsa Chih 1995 Feb;15(2):124-6
PMID: 7787391, UI: 95307049
44: Planta Med 1994 Dec;60(6):546-9
Allium sativum (garlic) derived preparations are used alone or with amphotericin B in Asia to treat human systemic fungal infections and cryptococcal meningitis. To evaluate the scientific merit of using allicin-derived compounds as an anti-fungal drug, we prepared a concentrated A. sativum extract that contained 34% allicin, 44% total thiosulfinates, and 20% vinyldithiins. We found that the concentrated extract possessed potent in vitro fungistatic and fungicidal activity against 3 different isolates of Cryptococcus neoformans. The minimum inhibitory concentration of the concentrated garlic extract against 1 x 10(5) organisms of C. neoformans ranged from 6 to 12 micrograms/ml. In addition, in vitro synergistic fungistatic activity with amphotericin B was demonstrated against all isolates of C. neoformans. This study lends laboratory support for the treatment of cryptococcal infections with concentrated garlic extracts.
PMID: 7809209, UI: 95108136
45: Appl Biochem Biotechnol 1994 Sep;48(3):149-71
The garlic plant (Allium sativum) alliinase (EC 188.8.131.52), which catalyzes the synthesis of allicin, was purified to homogeneity from bulbs using various steps, including hydrophobic chromatography. Molecular and biochemical studies showed that the enzyme is a dimer of two subunits of MW 51.5 kDa each. Its Km using synthetic S-allylcysteine sulfoxide (+ isomer) as substrate was 1.1 mM, its pH optimum 6.5, and its isoelectric point 6.35. The enzyme is a glycoprotein containing 6% carbohydrate. N-terminal sequences of the intact polypeptide chain as well as of a number of peptides obtained after cyanogen bromide cleavage were obtained. Cloning of the cDNAs encoding alliinase was performed by a two-step strategy. In the first, a cDNA fragment (pAli-1-450 bp) was obtained by PCR using a mixed oligonucleotide primer synthesized according to a 6-amino acid segment near the N-terminal of the intact polypeptide. The second step involved screening of garlic lambda gt11 and lambda ZAPII cDNA libraries with pAli-1, which yielded two clones; one was nearly full length and the second was full length. These clones exhibited some degree of DNA sequence divergence, especially in their 3' noncoding regions, suggesting that they were encoded by separate genes. The nearly full length cDNA was fused in frame to a DNA encoding a signal peptide from alpha wheat gliadin, and expressed in Xenopus oocytes. This yielded a 50 kDa protein that interacted with the antibodies against natural bulb alliinase. Northern and Western blot analyses showed that the bulb alliinase was highly expressed in bulbs, whereas a lower expression level was found in leaves, and no expression was detected in roots. Strikingly, the roots exhibited an abundant alliinase activity, suggesting that this tissue expressed a distinct alliinase isozyme with very low homology to the bulb enzyme.
PMID: 7979352, UI: 95070098
46: Chung Kuo Chung Hsi I Chieh Ho Tsa Chih 1994 Aug;14(8):478-81
It was shown that the cerebral ischemia-reperfusion produced free radicals are the main factor that causes irreversible cerebral injury. The mechanism of Naoxin Sutong (NXST) treated acute cerebral infarction was elucidated. It is compared with Ligustrazine (LT), which has been proved to be an effective drug for cerebral infarction. The curative effect and the changes of serum malondialdehyde (MDA) levels, blood rheology, blood lipid, etc. of 41 patients with acute cerebral infarction within 3 days, who were confirmed by CT. The therapeutic result showed that after 4 weeks of treatment the points of progress for central nervous system deficit scoring of NXST and LT group were 10.67 +/- 5.02 and 6.85 +/- 4.49 respectively. The difference between these two groups was significant. MDA levels of the patients and the healthy subjects were 6.46 +/- 1.70 and 3.87 +/- 0.67 nmol/ml respectively, the difference was also significant (P < 0.01). After 2 weeks of treatment, MDA content of NXST was less than before (P < 0.05). However the level of LT group did not reduce, while after 3 weeks of treatment, MDA content of NXST group was 4.34 nmol/ml. It was much less than that of LT group and approached that of healthy subjects. Results also showed that blood rheology improved, blood lipid reduced after NXST treatment. All these indicated that the effect of NXST in treating acute cerebral infarction was good, and the mechanism as that NXST could scavenge free radicals, ameliorate cerebral ischemia-reperfusion injury, improve blood rheology and reduce blood lipid.
Publication Types: Clinical trial Controlled clinical trial
PMID: 7841756, UI: 95143902
47: Biochim Biophys Acta 1994 Jun 23;1213(1):57-62
Exposure of primary rat hepatocytes and human HepG2 cells to allicin and ajoene resulted in the concentration-dependent inhibition of cholesterol biosynthesis at different steps of this metabolic pathway. At low concentrations of ajoene sterol biosynthesis from [14C]acetate in rat hepatocytes was decreased by 18% with an IC50-value of 15 microM, while allicin was almost uneffective. In HepG2 cells, both compounds significantly inhibited sterol biosynthesis by 14% and 19% with IC50-values of 7 and 9 microM for allicin and ajoene, respectively. This inhibition was exerted at the level of HMG-CoA-reductase as revealed by the absence of inhibition, if [14C]acetate was replaced by [14C]mevalonate as a precursor, and by direct determination of enzyme activity. At somewhat higher concentrations inhibition of cholesterol biosynthesis by both, allicin and ajoene, was also observed at late steps resulting in the accumulation of the precursor lanosterol. Alliin instead was completely inactive. In the case of allicin, small amounts of dihydrolanosterol and 7-dehydrocholesterol were formed at intermediate concentrations of 5-10 microM. From these results it is concluded that a major point of inhibition at the late steps occurs at the level of lanosterol 14 alpha-demethylase.
PMID: 8011681, UI: 94281263
48: Arzneimittelforschung 1994 Jun;44(6):734-43
Three groups of 3 rats received oral doses (8 mg/kg) of garlic constituents (alliin, allicin and vinyldithiines (2-vinyl-[4H]-1,3-dithiine and 3-vinyl-[4H]-1,2-dithiine)) in the form of an oil macerate of the 35S-labeled substance. The measured activity was referred to 35S-alliin (35S-alliin equivalents). The blood activity levels in each group were monitored for 72 h. For 35S-allicin and the labeled vinyldithiines the excretion with the urine, feces, and exhaled air was also measured. The distribution among the organs (whole-body autoradiography) and the urinary metabolite pattern (thin-layer chromatography) were also determined. For 35S-alliin the blood activity profile differed considerably from those of 35S-allicin and the labeled vinyldithiines: both the absorption and the elimination of the radioactivity were distinctly faster than for the other garlic constituents, maximum blood levels being reached within the first 10 min and elimination from the blood being almost complete after 6 h. For the other garlic constituents the maximum blood levels were not reached until 30-60 min (35S-allicin) or 120 min (vinyldithiines) p.a. and blood levels > 1000 ng-Eq/ml were still present at the end of the study after 72 h. The mean total urinary and fecal excretion after 72 h was 85.5% (35S-allicin) or 92.3% (labeled vinyldithiines) of the dose. The urinary excretion indicates a minimum absorption rate of 65% (35S-allicin) or 73% (vinyldithiines). It is uncertain whether the 19-21% recovered in the feces was unabsorbed substance or had been excreted via the bile or intestinal mucosa. The exhaled air showed only traces of activity although the whole-body autoradiographs, after fairly long exposure (96 h), showed distinct enrichment of activity in the mucosa of the airways and pharynx. The activity is deposite mainly in the cartilage of the vertebral column and ribs. There was no detectable difference in organ distribution between 35S-allicin and the labeled vinyldithiines. All that could be established from the urinary metabolite pattern was that unchanged 35S-allicin and unchanged labeled vinyldithiines are absent. There is therefore extensive metabolization. The metabolites must have a very polar structure with acid functional groups since satisfactory separation was achievable only with acid solvent systems. Conjugates with sulfuric or glucuronic acid were not detectable. These results reveal no differences in pharmacokinetic behavior between 35S-allicin and the labeled vinyldithiines. A final verdict as to whether the metabolites, which may be pharmacologically active, are identical must await further studies designed to identify the metabolites.
PMID: 8053972, UI: 94331045
49: J Chromatogr Sci 1994 Mar;32(3):93-6
Supercritical fluid chromatography-mass spectrometry has been used successfully to identify allicin (2-propene-1-sulfinothioic acid S-2-propenyl ester), the predominant thiosulfinate in freshly cut garlic (Allium sativum). A low oven temperature (50 degrees C) and low restrictor tip temperature (115 degrees C) were needed in order to obtain a chemical ionization (CI) mass spectrum of allicin with the protonated molecular ion, m/z 163, as the major ion. The effects of tip temperature on the CI mass spectrum of allicin are presented.
PMID: 8200919, UI: 94259729
50: Ann Soc Belg Med Trop 1994 Mar;74(1):51-9
Garlic (Allium sativum L.) and one of its major components, allicin, have been known to have antibacterial and antifungal activity for a long time. Diallyl trisulfide is a chemically stable final transformation product of allicin which was synthesized in 1981 in China and used for treatment of bacterial, fungal and parasitic infections in man. The activity of diallyl trisulfide was investigated in several important protozoan parasites in vitro. The IC50 (concentration which inhibits metabolism or growth of parasites by 50%) for Trypanosoma brucei brucei, T.b. rhodesiense, T.b. gambiense, T. evansi, T. congolense and T. equiperdum was in the range of 0.8-5.5 micrograms/ml. IC50 values were 59 micrograms/ml for Entamoeba histolytica and 14 micrograms/ml for Giardia lamblia. The cytotoxicity of the compound was evaluated on two fibroblast cell lines (MASEF, Mastomys natalensis embryo fibroblast and HEFL-12, human embryo fibroblast) in vitro. The maximum tolerated concentration for both cell lines was 25 micrograms/ml. The results indicate that the compound has potential to be used for treatment of several human and animal parasitic diseases.
PMID: 8024350, UI: 94296162
51: J R Coll Physicians Lond 1994 Jan-Feb;28(1):39-45
Garlic supplements may have an important role to play in the treatment of hypercholesterolaemia. To determine the effect of garlic on serum lipids and lipoproteins relative to placebo and other lipid lowering agents, a systematic review, including meta-analysis, was undertaken of published and unpublished randomised controlled trials of garlic preparations of at least four weeks' duration. Studies were identified by a search of MEDLINE and the ALTERNATIVE MEDICINE electronic databases, from references listed in primary and review articles, and through direct contact with garlic manufacturers. Sixteen trials, with data from 952 subjects, were included in the analyses. Many of the trials had methodological shortcomings. The pooled mean difference in the absolute change (from baseline to final measurement in mmol/l) of total serum cholesterol, triglycerides, and high-density lipoprotein (HDL)-cholesterol was compared between subjects treated with garlic therapy against those treated with placebo or other agents. The mean difference in reduction of total cholesterol between garlic-treated subjects and those receiving placebo (or avoiding garlic in their diet) was -0.77 mmol/l (95% CI: -0.65, -0.89 mmol/l). These changes represent a 12% reduction with garlic therapy beyond the final levels achieved with placebo alone. The reduction was evident after one month of therapy and persisted for at least six months. In the dried garlic powders, in which the allicin content is standardised, there was no significant difference in the size of the reduction across the dose range of 600-900 mg daily. Dried garlic powder preparations also significantly lowered serum triglyceride by 0.31 mmol/l compared to placebo (95% CI: -0.14, -0.49).
Publication Types: Meta-analysis
PMID: 8169881, UI: 94223605
52: Dermatology 1994;189(4):337-9
Today it is generally accepted that every drug that possesses an active thiol group in its molecule is capable of inducing pemphigus. Some plants, in particular those belonging to the Allium group, contain several active compounds with stable disulfide and thiol groups in their molecule. The Allium group contains many important vegetables like onion, leek and garlic. Examples of molecules with an active thiol group are: CH2 = CH-CH2-S-S-CH2-CH = CH2 (diallyl disulfide) or CH2 = CH-CH2-S(O)S-CH2-CH = CH2 (allicin). It is suggested that some foods, in particular vegetables of the Allium group that contain active thiol groups in their molecule, could contribute to the induction of pemphigus. In general, nutritional factors should be added to the list of exogenous factors that are capable of inducing pemphigus.
Publication Types: Review Review, tutorial
PMID: 7873815, UI: 95178771
53: Biochem Mol Biol Int 1993 Dec;31(6):1007-15
The activity of chicken liver fructose 1,6-bisphosphatase increases dramatically after incubation with allicin, a major biologically active compound produced by garlic. Activation is more pronounced when the enzyme is assayed with Mn2+ than Mg2+. Maximum activation is accompanied by the disappearance of 4 highly reactive sulfhydryl groups per molecule of enzyme. This modification also leads to loss of activation by K+, and reduced sensitivity to inhibition by AMP, fructose 2,6-bisphosphate, and high concentration of fructose 1,6-bisphosphate. All the altered properties induced by allicin can be reversed by dithiothreitol or tris(2-carboxyethyl)phosphine, the latter being much more effective.
PMID: 8193584, UI: 94251164
54: Prostaglandins Leukot Essent Fatty Acids 1993 Aug;49(2):587-95
When garlic cloves are chopped or crushed several dialkyl thiosulfinates are rapidly formed by the action of the enzyme alliin lyase or alliinase (EC 184.108.40.206) on S(+)-alkyl-L-cysteine sulfoxides. Allicin (diallyl thiosulfinate or allyl 2-propene thiosulfinate) is the dominant thiosulfinate released. A variety of sulfur containing compounds are formed from allicin and other thiosulfinates depending on the way in which garlic is handled. One such compound identified recently is ajoene which has been reported to possess antithrombotic properties. We present here data on the antiplatelet properties of ajoene together with its effects on the metabolism of arachidonic acid (AA) in intact platelets. Thus, ajoene was found to inhibit platelet aggregation induced by AA, adrenaline, collagen, adenosine diphosphate (ADP) and calcium ionophore A23187; the nature of the inhibition was irreversible. In washed platelets stimulated by labelled arachidonate, ajoene inhibited the formation of thromboxane A2; 12-lipoxygenase product(s) were reduced at higher ajoene concentrations. This garlic-derived substance inhibited the incorporation of labelled AA into platelet phospholipids at higher concentration. In labelled platelets, on stimulation with either calcium ionophore A23187 or collagen, reduced amounts of thromboxane and 12-HETE (12-hydroxyeicosatetraenoic acid) were produced in ajoene-treated platelets compared to control platelets. This substance had no effect on the deacylation of platelet phospholipids. The results suggest that at least one of the mechanisms by which ajoene shows antiplatelet effects could be related to altered metabolism of AA. PMID: 8415808, UI: 94022496
55: Lipids 1993 Jul;28(7):613-9
Exposure of primary rat hepatocytes and human HepG2 cells to water-soluble garlic extracts resulted in the concentration-dependent inhibition of cholesterol biosynthesis at several different enzymatic steps. At low concentrations, sterol biosynthesis from [14C]acetate was decreased in rat hepatocytes by 23% with an IC50 (half-maximal inhibition) value of 90 micrograms/mL and in HepG2 cells by 28% with an IC50 value of 35 micrograms/mL. This inhibition was exerted at the level of hydroxymethylglutaryl-CoA reductase (HMG-CoA reductase) as indicated by direct enzymatic measurements and the absence of inhibition if [14C]mevalonate was used as a precursor. At high concentrations (above 0.5 mg/mL), inhibition of cholesterol biosynthesis was not only seen at an early step where it increased considerably with dose, but also at later steps resulting in the accumulation of the precursors lanosterol and 7-dehydrocholesterol. No desmosterol was formed which, however, was a major precursor accumulating in the presence of triparanol. Thus, the accumulation of sterol precursors seems to be of less therapeutic significance during consumption of garlic, because it requires concentrations one or two orders of magnitude above those affecting HMG-CoA reductase. Alliin, the main sulfur-containing compound of garlic, was without effect itself. If converted to allicin, it resulted in similar changes of the sterol pattern. This suggested that the latter compound might contribute to the inhibition at the late steps. In contrast, nicotinic acid and particularly adenosine caused moderate inhibition of HMG-CoA reductase activity and of cholesterol biosynthesis suggesting that these compounds participate, at least in part, in the early inhibition of sterol synthesis by garlic extracts.
PMID: 8394977, UI: 93360788
56: Pharmacotherapy 1993 Jul-Aug;13(4):406-7
A popular garlic preparation containing 1.3% allicin at a large dose (2400 mg) was evaluated in this open-label study in nine patients with rather severe hypertension (diastolic blood pressure > or = 115 mm Hg). Sitting blood pressure fell 7/16 (+/- 3/2 SD) mm Hg at peak effect approximately 5 hours after the dose, with a significant decrease in diastolic blood pressure (p < 0.05) from 5-14 hours after the dose. No significant side effects were reported. Our results indicate that this garlic preparation can reduce blood pressure. Further controlled studies are needed, particularly with more conventional doses (e.g., < or = 900 mg/day), in patients with mild to moderate hypertension and under placebo-controlled, double-blind conditions.
PMID: 8361870, UI: 93369094
57: Pediatr Infect Dis J 1993 Jul;12(7):613-4
PMID: 8346006, UI: 93347940
58: J Ocul Pharmacol 1993 Fall;9(3):201-9
The intent of this work was to examine the actions of allicin on 1) intraocular pressure (IOP) in normal and unilaterally sympathectomized (SX) rabbits; 2) cAMP accumulation in the rabbit iris-ciliary body (ICB) and cultured nonpigmented epithelial (NPE) ciliary body cells; and 3) 3H-norepinephrine (NE) release by calculating fractional tritium overflow in response to electrical field stimulation (EFS, 5 Hz, 12 V/cm) in isolated, perfused rabbit ICBs. Allicin, one of the active compounds produced by garlic, was evaluated on IOP and it was determined that allicin (1, 2.5, or 10 micrograms), topically, but not the precursor, alliin (10 micrograms), lowered the IOP unilaterally in normal rabbits. Allicin (10 micrograms) reduced the IOP by 6 +/- 1 mmHg (n = 4) in normal rabbits at 2 hrs (maximum response) whereas no change occurred in sympathectomized rabbit eyes. Moreover, allicin (0.01, 0.1, or 1 microM) caused 40, 40, or 52% inhibition, respectively, of 3H-NE overflow in response to EFS. Isoproterenol (ISO, 1 microM) stimulated cAMP accumulation by 3.6 and 9 fold in isolated rabbit ICB and cultured NPE cells, respectively. Allicin (1 microM) had no effect on basal cAMP level while it inhibited ISO-stimulated cAMP accumulation by 40% and 23% in ICB and NPE cells, respectively. This study suggests that allicin lowered IOP, in part, by dual actions at the neuroeffector junction.
PMID: 8228529, UI: 94045135
59: J Clin Gastroenterol 1992 Oct;15(3):248-50
Hypoxia in the setting of liver disease is often multifactorial. Obstructive or restrictive lung disease, pleural effusions, and tense ascites are common underlying disorders. Less often observed and frequently unrecognized is hypoxia related to diffuse intrapulmonary shunting--the hepatopulmonary syndrome. Its etiology is unknown but may result from disordered gut peptide metabolism. Symptoms may be ameliorated by somatostatin and reversed by successful liver transplantation. Here we report a patient with severe hepatopulmonary syndrome who failed somatostatin therapy and declined liver transplantation. On her own the patient took large daily doses of powdered garlic (Allium sativum). She has experienced partial palliation of her symptoms and some objective signs of improvement over 18 months of continuous self-medication. The possible effects of garlic's main physiologically active compound, allicin, on gut peptide metabolism and pulmonary vasculature are unknown. This innocuous compound may deserve further investigation given the limited therapeutic options for this disorder.
PMID: 1479173, UI: 93123682
60: Planta Med 1992 Oct;58(5):417-23
Garlic (Allium sativum) has been shown to have antiviral activity, but the compounds responsible have not been identified. Using direct pre-infection incubation assays, we determined the in vitro virucidal effects of fresh garlic extract, its polar fraction, and the following garlic associated compounds: diallyl thiosulfinate (allicin), allyl methyl thiosulfinate, methyl allyl thiosulfinate, ajoene, alliin, deoxyalliin, diallyl disulfide, and diallyl trisulfide. Activity was determined against selected viruses including, herpes simplex virus type 1, herpes simplex virus type 2, parainfluenza virus type 3, vaccinia virus, vesicular stomatitis virus, and human rhinovirus type 2. The order for virucidal activity generally was: ajoene > allicin > allyl methyl thiosulfinate > methyl allyl thiosulfinate. Ajoene was found in oil-macerates of garlic but not in fresh garlic extracts. No activity was found for the garlic polar fraction, alliin, deoxyalliin, diallyl disulfide, or diallyl trisulfide. Fresh garlic extract, in which thiosulfinates appeared to be the active components, was virucidal to each virus tested. The predominant thiosulfinate in fresh garlic extract was allicin. Lack of reduction in yields of infectious virus indicated undetectable levels of intracellular antiviral activity for either allicin or fresh garlic extract. Furthermore, concentrations that were virucidal were also toxic to HeLa and Vero cells. Virucidal assay results were not influenced by cytotoxicity since the compounds were diluted below toxic levels prior to assaying for infectious virus. These results indicate that virucidal activity and cytotoxicity may have depended upon the viral envelope and cell membrane, respectively. However, activity against non-enveloped virus may have been due to inhibition of viral adsorption or penetration.
PMID: 1470664, UI: 93110023
61: Planta Med 1992 Aug;58(4):301-5
The metabolic and kinetic behaviour of different garlic (Allium sativum L., Alliaceae) constituents were investigated in the isolated perfused rat liver, using aqueous extracts of garlic powder as well as isolated allicin, the main product of the enzymatic degradation of alliin. Allicin (allyl thiosulfinate) showed a remarkable first pass effect and passed the liver unmetabolized only at high concentrations which caused considerable cell injuries. Diallyl disulfide and allyl mercaptan were identified as metabolites of allicin, whereby diallyl disulfide probably is the metabolic precursor of allyl mercaptan as shown by perfusion with diallyl disulfide alone. The metabolites diallyl disulfide and allyl mercaptan could be determined in the perfusion medium as well as in the bile and the liver tissue. Other degradation products of garlic were also investigated in this model. Ajoenes and vinyldithiins were detected in perfusion medium after liver passage but no metabolites of them could be identified up to now.
PMID: 1438588, UI: 93066765
62: Indian J Exp Biol 1992 Jun;30(6):523-6
S-allyl cysteine sulphoxide (SACS), a sulphur containing amino acid of garlic which is the precursor of allicin and garlic oil, has been found to show significant antidiabetic effects in alloxan diabetic rats. Administration of it at a dose of 200 mg/kg body weight decreased significantly the concentration of serum lipids, blood glucose and activities of serum enzymes like alkaline phosphatase, acid phosphatase and lactate dehydrogenase and liver glucose-6-phosphatase. It increased significantly liver and intestinal HMG CoA reductase activity and liver hexokinase activity.
PMID: 1506036, UI: 92372124
63: Atherosclerosis 1992 May;94(1):79-85
Using a modified liver homogenate model to assay for the inhibition of cholesterol biosynthesis, different garlic and wild garlic extracts as well as pure compounds isolated from them were investigated for their influence on cholesterol synthesis. Chloroform and acetone/chloroform extracts of garlic and wild garlic inhibited cholesterol synthesis 44-52% at a concentration of 166 micrograms/ml, while the 5 individual sulfur-containing compounds ajoene, methylajoene, allicin, 2-vinyl-4H-1,3-dithiin and diallydisulfide inhibited cholesterol synthesis by 37-72% (10(-3) M corresponding to 234, 208, 162, 144, 146 micrograms/ml, respectively). Ajoene, 2-vinyl-4H-1,3-dithiin and allicin show IC50 values of 6.4, 7.2 and 9.4 x 10(-4) M, respectively. The results demonstrate that garlic and wild garlic may reduce serum cholesterol levels primarily by inhibiting cholesterol synthesis if taken in sufficient amount and that this effect arises from a mixture of multiple compounds from the sulfur-containing class of thiosulfinates, ajoenes and dithiines. Wild garlic extracts showed nearly identical efficiency to garlic extracts.
PMID: 1632861, UI: 92337763
64: Planta Med 1992 Feb;58(1):8-13
The pharmacokinetic behaviour of vinyldithiins, the main constituents of oily preparations of garlic (Allium sativum L.), was investigated after oral administration of 27 mg 2-vinyl-4H-1,3-dithiin and 9 mg 3-vinyl-4H-1,2-dithiin to rats. In serum, kidney, and fat tissue, both vinyldithiins could be detected by GC-MS over a period of 24 h, whereas in liver only 1,3-vinyldithiin was found. Pharmacokinetic parameters (t1/2, ke, Cltot, AUC, and Vd) were determined using compartment models, elucidating the different pharmacokinetic behaviour of both vinyldithiins. 1,3-Vinyldithiin seems to be less lipophilic and is rapidly eliminated from serum, kidney, and fat tissue, whereas 1,2-vinyldithiin is more lipophilic and shows a tendency to accumulate in fat tissue. Experiments with liver homogenate confirmed the in vivo findings on the different degradation rates of both vinyldithiins. Allicin, the precursor of the vinyldithiins, is metabolized more rapidly in liver homogenate than the vinyldithiins.
PMID: 1620748, UI: 92319848
65: Thromb Res 1992 Jan 15;65(2):141-56
The inhibitory effects of adenosine and 16 quantitatively determined organosulfur compounds derived from garlic cloves or commercial garlic preparations on collagen stimulated in vitro platelet aggregation in whole blood were determined. An estimation of the anti-aggregatory activity of several brands of the major types of commercial garlic preparations was determined from the activities of the individual compounds present in each sample. In platelet rich plasma (PRP) most of the anti-aggregatory activity of garlic clove homogenates was due to adenosine; however, in whole blood neither adenosine nor the polar fraction had any effect and all of the anti-aggregatory activity was due to allicin and other thiosulfinates. Allicin was equally active in whole blood and PRP. Among brands there was a several-fold variation in content of the organosulfur compounds and activity for all types of garlic products tested. The best garlic powder tablets were equally as active as clove homogenates whereas steam-distilled oils were 35% as active and oil-macerates (due to low content) only 12% as active. A garlic product aged many months in aqueous alcohol had no activity. For steam-distilled oils, most of the activity was due to diallyl trisulfide. For the oil-macerates, most of the activity was due largely to the vinyl dithiins. Ajoene, an exclusive component of the oil-macerates, had highest specific activity of all the compounds tested but, because of its low concentration, had only 13% of the activity of diallyl trisulfide and 3% of the activity of allicin. Compounds which may be active in vivo are discussed.
PMID: 1579891, UI: 92254117
66: Chung Kuo Chung Hsi I Chieh Ho Tsa Chih 1992 Jan;12(1):28-9, 6
This article deals with the 0.06/1000 allicin and 2.5% sodium bicarbonate in order to look for effective drugs in preventing thrush. The results revealed: (1) The incidence of the disease of the two drugs in the less dangerous group was significantly decreased compared with that of the control (P less than 0.01); (2) In the more dangerous group, the incidence of the disease of the allium group was more significantly decreased than that of the control, but no significant decrease in sodium bicarbonate was observed. The two drugs are both effective in preventing thrush and the allium is more effective.
Publication Types: Clinical trial Controlled clinical trial PMID: 1320966, UI: 92330254
67: Arzneimittelforschung 1991 Aug;41(8):800-4
Cultured rat hepatocytes continually synthesize cholesterol form radiolabeled acetate during a 24 h incubation period and export it, presumably as VLDL (very low density lipoprotein) to the culture medium. Mevastatin inhibits cholesterol biosynthesis by 90%. Incubation of the cultures with water-soluble extracts of garlic powder (Kwai, Sapec) diminish cholesterol biosynthesis (20-25%) as well as its export into the medium (30-35%). The IC50-value is 90 micrograms/ml. Between about 0.25 and 10 mg/ml the average maximal inhibition amounts to about 23%. Cytotoxicity of the extracts is apparent at concentrations above 125 mg/ml only. Pure alliin alone, or after incubation with alliinase (conversion to allicin) in concentrations corresponding to its content in the extracts does not exert any inhibition. Replacement of 14C-acetate by 14C-mevalonate omits the inhibitory effect. The activity of HMGCoA (hydroxymethylglutaryl-CoA) reductase is significantly reduced by garlic extracts at 50 micrograms/ml. At higher concentrations fatty acid synthetase, cholesterol 7 alpha-hydroxylase and cholesterol acyltransferase are slightly inhibited. Fatty acid synthetase is the only one of these enzymes which is inhibited by alliin at very high concentrations. These results demonstrate that water-soluble garlic extracts diminish hepatic cholesterol biosynthesis, thus contributing to the reduction of blood cholesterol. The main target site seems to be HMGCoA-reductase. The actual active principle(s) is still unknown. Alliin, however, does not seem to be of major significance.
PMID: 1781801, UI: 92143868
68: Planta Med 1991 Aug;57(4):371-5
In garlic (Allium sativum L.) the enzyme alliin lyase catalyzes the cleavage of alliin into allicin which reacts further to furnish ajoene. A simultaneous determination of allicin and ajoene is introduced which, in contrast to the determination of alliin only, allows for the testing of the activity of alliin lyase. It can be demonstrated that at a pH value of less than 3 the enzyme produces only small amounts of allicin. For this reason preparations from garlic should be administered only as enteric-coated formulations.
PMID: 1775580, UI: 92131949
69: Planta Med 1991 Aug;57(4):363-70
The content of dialk(en)yl thiosulfinates, including allicin, and their degradation products has been determined by high performance liquid chromatography (HPLC), using the respective determined extinction coefficients, for a number of commercially available garlic products. Quantitation has been achieved for the thiosulfinates; diallyl, methyl allyl, and diethyl mono-, di-, tri-, tetra-, penta-, and hexasulfides; the vinyldithiins; and (E)- and (Z)-ajoene. The thiosulfinates were found to be released only from garlic cloves and garlic powder products. The vinyldithiins and ajoenes were found only in products containing garlic macerated in vegetable oil. The diallyl, methyl allyl, and dimethyl sulfide series were the exclusive constituents found in products containing the oil of steam-distilled garlic. Typical steam-distilled garlic oil products contained about the same amount of total sulfur compounds as total thiosulfinates released from freshly homogenized garlic cloves; however, oil-macerated products contained only 20% of that amount, while garlic powder products varied from 0 to 100%. Products containing garlic powder suspended in a a gel or garlic aged in aqueous alcohol did not contain detectable amounts of these non-ionic sulfur compounds. A comparison of several brands of each type of garlic product revealed a large range in content (4-fold for oil-macerates and 33-fold for steam-distilled garlic oils), indicating the importance of analysis before garlic products are used for clinical investigations or commercial distribution.
PMID: 1775579, UI: 92131948
70: Indian J Med Res 1991 Jan;93:33-6
The aqueous extract of garlic (Allium sativum) and allicin both showed significant in vitro antibacterial activity against isolates of multiple drug-resistant Shigella dysenteriae 1, Sh. flexneri Y, Sh. sonnei and enterotoxigenic Escherichia coli. The minimum inhibitory concentrations of the aqueous extract and allicin against Sh. flexneri Y were 5 and 0.4 microliters/ml, respectively. The two agents also showed promising in vivo antibacterial activity against Sh. flexneri Y when tested in the rabbit model of experimental shigellosis, fully curing the infected rabbits within 3 days. On the contrary, 4 of the 5 rabbits in the control group died within 48 h. The rectal swab of rabbits of the experimental groups became free of the challenge bacteria on the second day of treatment. The antibacterial activity against the challenge strain was observed in the sera of the treated rabbits with 30-60 min of administration of the agents. The LD50 values of the aqueous extract and allicin in mice were 173.78 ml/kg and 204.17 microliters/kg of body weight, respectively. At the therapeutic dose, the two agents did not show any adverse effects on the standard biochemical profile of blood. PMID: 2022399, UI: 91216587
71: Cancer Lett 1990 Sep;53(2-3):103-8
The sulfur-containing compound ajoene (4,5,9-trithiadodeca-1,6,11-triene-9-oxide) which arises from alliin, a cysteine derivative stored in garlic bulbs, was produced synthetically by decomposition of allicin. Its cytotoxic effect was tested using human primary fibroblasts (FS4), a permanent, non-tumorgenic cell line derived from baby hamster kidney cells (BHK21) and a tumorgenic lymphoid cell line derived from a Burkitt lymphoma (BJA-B). The cytotoxic action was in the range 2-50 micrograms/ml depending on the cell density. ED50 values, estimated on the basis of fmol ajoene/cell, revealed slightly higher doses for the primary cell (FS4) than the permanent line (BHK), whereas the tumorgenic BJA-B cells were most sensitive.
PMID: 2208068, UI: 91003938
72: Agents Actions 1990 Mar;29(3-4):360-3
We have identified three main antiplatelet constituents, namely adenosine, allicin and paraffinic polysulfides in both garlic and onion. Adenosine and allicin both inhibited platelet aggregation without affecting cyclooxygenase and lipoxygenase metabolites of arachidonic acid. The trisulfides inhibited platelet aggregation as well as thromboxane synthesis along with induction of new lipoxygenase metabolites. The data indicate that the observed in vivo antiplatelet effects of ingesting onion and garlic are attributable more to the adenosine than to the allicin and paraffinic polysulfide constituents.
PMID: 2111084, UI: 90252692
73: FEBS Lett 1990 Feb 12;261(1):106-8
Allicin is shown to be a specific inhibitor of the acetyl-CoA synthetases from plants, yeast and mammals. The bacterial acetyl-CoA-forming system, consisting of acetate kinase and phosphotransacetylase, was inhibited too. Non-specific interaction with sulfhydryl-groups could be excluded in experiments with dithioerythritol and p-hydroxymercuribenzoate. Binding of allicin to the enzyme is non-covalent and reversible. [14C]-Acetate incorporation into fatty acids of isolated plastids was inhibited by allicin with an I50-value lower than 10 microM. Other enzymes of the fatty acid synthesis sequence were not affected, as was shown using precursors other than acetate.
PMID: 1968399, UI: 90169096
74: Biochem Pharmacol 1989 Apr 15;38(8):1321-8
Ajoene (E,Z-4,5,9-trithiadodeca-1,6,11-triene 9-oxide), a product of the rearrangement of allicin (a major component of raw garlic), has been shown to be a potent inhibitor of platelet aggregation in vitro through inhibition of granule release and fibrinogen binding. Our present study further elaborates on this inhibitory action, through studies of the effect of ajoene on the earliest steps of platelet activation. The transducing mechanism involved in thrombin-induced platelet activation was not modified by the drug as indicated by a normal breakdown of phosphatidylinositol 4,5,bisphosphate and normal production of phosphatidic acid. Likewise, the agonist-induced phosphorylation of myosin light chain (P20) and of the 43 kD protein (P43) were not impaired by ajoene. Under the same conditions, however, ajoene (100 microM) produced a strong inhibition of the thrombin-induced release of dense body and alpha-granule constituents. Electron spin resonance studies of the effect of ajoene on some physico-chemical properties of the platelet plasma membrane (intact platelets), as well as on artificial lipid membranes, indicated that ajoene increased mobility of the fatty acid spin label 16 nitroxide stearate. This suggests the existence of a decreased microviscosity of the most internal region within the lipid bilayer membrane, without affecting the outer hydrophilic moieties of the bilayer. As a whole, these results suggest that the effect of ajoene on the release reaction must be, in part, due to physical modification of the bilayer, which impairs the fusion of the granules and plasma membrane, a prerequisite for exocytosis.
PMID: 2539823, UI: 89206819
75: Environ Mol Mutagen 1989;13(4):357-65
Experiments with Salmonella tester strains indicated that aqueous garlic extract possesses antimutagenic properties toward ionizing radiation, peroxides, adriamycin, and N-methyl-N'-nitro-nitrosoguanidine. The assumption that radical scavenging garlic constituents, i.e., molecules with sulfur moieties, might be responsible for the inhibitory effect of aqueous extract toward mutagenesis induced by radiation and radiomimetic compounds was confirmed by the results of subsequent experiments; 1) garlic extract attenuated the lethal effects of gamma-rays on repair-deficient E. coli strains; 2) the garlic constituent allicin (thio-2-propene-1-sulfinic acid S-allyl ester) is partly responsible for the reduced radiation-induced mutagenesis in Salmonella typhimurium TA 102. No such inhibitory effects were detected with alliin (S-allyl-L-cysteine sulfoxide) or cysteine; 3) aqueous garlic extract inhibited hydrogen-peroxide-induced lipid peroxidation. Results obtained in preliminary experiments with Chinese hamster ovary cells suggest that the antimutagenic properties of garlic extract are not restricted to procaryotic cells.
PMID: 2661224, UI: 89289683
76: Prostaglandins 1989 Jan;37(1):135-48
We have reported that allicin, a constituent of garlic oil, has no effect on the activities of platelet cyclooxygenase or thromboxane synthase, or vascular PGI2 synthase. The effect of allicin on glutathione (GSH) dependent PGH2 to PGE2 isomerase is unknown. We therefore studied the effect of allicin on PGE2 biosynthesis in a murine mammary adenocarcinoma cell line (No 4526). Intact or sonicated cells were incubated with either 14C-arachidonic acid (AA) or 14C-PGH2, respectively. Following metabolism, products were extracted, separated by TLC and analyzed by radiochromatographic scan. PGE2 was predominantly formed with minimal amounts of PGF2 alpha and PGD2. Formation of 6-keto-PGF1 alpha or TXB2 was not detected indicating the absence of TXA2 and PGI2 synthase activity. Indomethacin and ibuprofen inhibited the PGE2 formation (p less than 0.05). The enzymatic PGE2 formation in sonicates was blocked by depletion of the cellular non-protein thiols by buthionine sulfoximine and was shown to be dependent on GSH. Allicin, over the range of 10-1000 microM, inhibited the formation of PGE2 in cells exposed to 2.0 microM 14C-AA for 20 min. and in sonicated cells incubated with 20.0 microM 14C-PGH2 for 2 min (p less than 0.05). Allicin did not alter cyclooxygenase-mediated oxygen utilization in ram seminal vessicle microsomes, suggesting that allicin selectively inhibits the GSH-dependent PGH2 to PGE2 isomerase in this adenocarcinoma cell line.
PMID: 2497497, UI: 89241378
77: Antimicrob Agents Chemother 1988 Dec;32(12):1763-8
Diallyl thiosulfinate (allicin) is the agent found in garlic which is responsible for the antibacterial and antifungal activity of extracts of this plant. The effect of bacteriostatic concentrations of allicin (0.2 to 0.5 mM) on the growth of Salmonella typhimurium revealed a pattern of inhibition characterized by: (i) a lag of approximately 15 min between addition of allicin and onset of inhibition, (ii) a transitory inhibition phase whose duration was proportional to allicin concentration and inversely proportional to culture density, (iii) a resumed growth phase which showed a lower rate of growth than in uninhibited controls, and (iv) an entry into stationary phase at a lower culture density. Whereas DNA and protein syntheses showed a delayed and partial inhibition by allicin, inhibition of RNA synthesis was immediate and total, suggesting that this is the primary target of allicin action.
PMID: 2469386, UI: 89227090
78: Agents Actions 1988 Aug;25(1-2):182-90
Garlic has been used in herbal medicine for thousands of years. While garlic oil contains many components and has been widely studied, the pharmacology of pure allicin, a constituent of garlic oil, is not well understood. We report that allicin inhibits human platelet aggregation in vitro without affecting cyclooxygenase or thromboxane synthase activity or cyclic adenosine monophosphate (AMP) levels. Allicin does not alter the activity of vascular prostacyclin synthase. However, it inhibits ionophore A23187-stimulated human neutrophil lysosomal enzyme release. In vivo allicin dilates the mesenteric circulation of the cat independent of prostaglandin release or a beta adrenergic mechanism.
PMID: 2847508, UI: 89046852
79: Pharmazie 1987 Oct;42(10):687-8
Garlic, onion and shallot were tested for antimicrobial activity against pathogenic aerobic and anaerobic bacteria. The MIC of aqueous and petroleum ether extracts were determined. Garlic showed the greater activity; the combination garlic-antibiotic is synergistic against Acinetobacter calcoaceticus and leads to indifference against anaerobic bacteria. The active constituent is not probably allicin alone.
PMID: 3438321, UI: 88144557
80: Diagn Microbiol Infect Dis 1987 Oct;8(2):79-85
Garlic extract inhibited the growth of four strains of Mycobacterium tuberculosis, three strains of Mycobacterium avium-intracellulare, and three strains of Mycobacterium kansasii in concentrations ranging from 0.98 mg/ml to 2.94 mg/ml. Synergism could not be demonstrated when garlic extract was added to various concentrations of four commonly used antituberculous drugs.
PMID: 3123123, UI: 88110372
81: J Infect Dis 1987 Jul;156(1):243-4
82: Appl Environ Microbiol 1987 Mar;53(3):615-7
83: Thromb Res 1986 Dec 15;44(6):793-806
84: Anaesth Intensive Care 1986 Feb;14(1):94
85: Sci Am 1985 Mar;252(3):114-9
86: Med Hypotheses 1983 Nov;12(3):227-37
Publication Types: Review
PMID: 6366484, UI: 84141400
87: Arch Dermatol Res 1983;275(4):229-34
PMID: 6625648, UI: 84022658
88: Chung Yao Tung Pao 1981 May;6(3):12-4
89: Taiwan I Hsueh Hui Tsa Chih 1981 Apr;80(4):385-93
90: Antimicrob Agents Chemother 1977 Apr;11(4):743-9
91: Experientia 1975 Nov 15;31(11):1263-5
PMID: 1204765, UI: 76092258
92: Gann 1975 Aug;66(4):417-9
PMID: 1183776, UI: 76044451
93: Jpn J Antibiot 1975 Aug;28(4):638-42
PMID: 1099271, UI: 76008286
94: Experientia 1975 Feb 15;31(2):148-9
95: Experientia 1974 May 15;30(5):468-70
96: Indian J Biochem Biophys 1973 Sep;10(3):209-12
97: Nippon Eiseigaku Zasshi 1973 Jun;28(2):261-9
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