Ajoene, the antiplatelet compound derived from garlic, specifically inhibits platelet release reaction by affecting the plasma membrane internal microviscosity

Rendu, Francine; Daveloose, Denis; Debouzy, Jean‐Claude; Bourdeau, Nathalie; Lévy-Toledano, S; Jain, Mahendra Kumar; Apitz‐Castro, Rafael

doi:10.1016/0006-2952(89)90339-0

Cited by 51 publications

(26 citation statements)

References 17 publications

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“…The experimental data described here do not provide information on the possible mechanism of action of ajoene against P. berghei. However, studies on the interaction of ajoene with platelet membranes have shown that this molecule localizes deep in the layer, inducing a disordering effect on the deep part of the membrane (9). Ajoene may alter protein and lipid trafficking in the parasite and host cell membranes (5), leading to irreversible damage of parasites.…”

Section: Discussionmentioning

confidence: 99%

In vivo activity of ajoene against rodent malaria

Pérez

Rosa

Apitz

1994

Antimicrob Agents Chemother

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Ajoene (4,5,9-trithiadodeca-1,6,11-triene 9-oxide), a product initially isolated from extracts of garlic (Alium sativum), was tested for its antimalarial activity in vivo in a well-characterized murine model. A single ajoene dose of 50 mg/kg, on the day of infection, suppressed the development of parasitemia; there were no obvious acute toxic effects from the tested dose. The combination of ajoene (50 mg/kg) and chloroquine (4.5 mg/kg), given as a single dose on the day of the infection, completely prevented the subsequent development of parasitemia in treated mice.Malaria parasites resistant to various drugs are widespread in South America, Asia, and Africa (15). In particular, the chloroquine (CQ)-resistant strains of Plasmodium falciparum have become a major public health problem around the world (11,15). Hence, the search for new antimalarial therapies is a high-priority task for the control of the disease. Ajoene (4,5,9-trithiadodeca-1,6,11-triene 9-oxide), an organosulfur compound derived from garlic (Allium sativum) (1, 7), is a well-known inhibitor of platelet activation (2-4) and also has significant antifungal (10, 12, 16), antitrypanosomal (14), and antiviral (13) activities.We investigated the potential anti-Plasmodium berghei activity of ajoene in vivo. The results show that when used alone, ajoene displays a moderate anti-P. berghei activity. However, when used in combination with a noneffective dose of CQ, ajoene synergistically enhances the susceptibility of the parasite to this drug. MATERUILS AND METHODSAjoene. Synthetic ajoene (Mr, 234) was prepared as previously described (1, la, 3), dissolved in ethanol, and diluted eightfold with Intralipid (200 g of fractionated soybean, 12 g of fractionated egg phospholipids, 22 g of glycerol USP, 1,000 ml of water q.s.p) (Kavi Vitrum, Stockholm, Sweden). The final concentration of ethanol was less than 1% (vol/vol Animal experiments. All experimental mice were infected at random before being divided into groups of 7 to 10. Mice were treated by intraperitoneal injection of ajoene given on the day of inoculation (day 0). The time between the inoculation of parasites and drug injection was 60 min. The effectiveness of CQ alone at a dose of 4.5 mg/kg (8) or in combination with various concentrations of ajoene was studied by using the same experimental protocol described for ajoene. CQ diphosphate (CQ; Sigma Chemical Co.) was diluted in 0.9% (wt/vol) NaCl to give the dose required in 0.1 ml for 10 g of mouse and was administered intraperitoneally. Experiments were repeated at least three times. Data from a representative experiment are given. RESULTSDrug toxicity. On the basis of the results of a set of preliminary experiments, ajoene doses of up to 50 mg/kg were used. No signs of toxicity were observed in 30 days.Inhibition of parasite growth by ajoene. In BALB/c mice infected with 105 parasitized erythrocytes, systemic parasitemia became apparent (1%) on day 2 and increased to 24 ± 2.8% infected cells on day 6 after the inoculation. Ajoene (50 mg/kg) given ...

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Section: Discussionmentioning

confidence: 99%

In vivo activity of ajoene against rodent malaria

Pérez

Rosa

Apitz

1994

Antimicrob Agents Chemother

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“…Ajoene is formed from allicin during steam or water distillation of the essential oil from garlic cloves, or during storage in ethanol (Block et al, 1986, Iberl et al, 1990. The presence of vinyl groups attached by a disulfide bond makes ajoene a highly reactive molecule which can inhibit the release of both dense granules and α-granules (Rendu et al, 1989). Ajoene can reduce platelet aggregation induced by 0.1 U/mL thrombin by 94.7% after a pre-stimulation incubation time for one minute at a dose of 25 µM (Villar et al, 1997).…”

Section: Essential Oils and Cardiovascular Diseases Atherosclerosismentioning

confidence: 99%

“…The mechanism of action of ajoene differs to that of other known inhibitors of platelet aggregation. Ajoene penetrates the membrane of intact platelets and reduces the viscosity of the inner part of the lipid bilayer (Rendu et al, 1989), thus interfering with the expression of the fibrinogen receptor α IIB β 3 at the cell surface, thereby inhibiting fibrinogen binding . Ajoene also inhibits platelet aggregation through inhibiting the formation of thromboxane A2 via altering arachidonic acid metabolism.…”

Section: Essential Oils and Cardiovascular Diseases Atherosclerosismentioning

confidence: 99%

Pharmaceutical and therapeutic Potentials of essential oils and their individual volatile constituents: a review

Edris

2007

Phytotherapy Research

1,095

688

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Essential oils and their volatile constituents are used widely to prevent and treat human disease. The possible role and mode of action of these natural products is discussed with regard to the prevention and treatment of cancer, cardiovascular diseases including atherosclerosis and thrombosis, as well as their bioactivity as antibacterial, antiviral, antioxidants and antidiabetic agents. Their application as natural skin penetration enhancers for transdermal drug delivery and the therapeutic properties of essential oils in aroma and massage therapy will also be outlined.

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“…Also, there is a report that AI was reduced due to the increased absorption of garlic, which in turn was possible by the generation of allithiamine when garlic was injected in combination with fermented soybean gemmule [6]. Ajoene, a type of allicin, of garlic decreased microviscosity of internal region within the lipid bilayer membrane of intact platelets as well as artificial lipid membrane, without affecting the outer hydrophilic properties of the bilayer [41]. Reportedly, effect of lipid improvement in garlic is due to an emulsion that is formed between lipid and components of garlic [1].…”

Section: Lipids Level In Serummentioning

confidence: 99%

Effects of the Red Garlic Extract for Anti-Obesity and Hypolipidemic in Obese Rats Induced High Fat Diet

Lee¹,

Kim²,

Ryu³

et al. 2011

Journal of Life Science

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This study tested the anti-obesity and hypolipidemic effects of red garlic extract in obese rats induced by a high fat diet over a period of 4 weeks. Red garlic extract of 15 brix was added in 1, 3, 5 and 7% ratios in diets. The obesity index and body fat content significantly decreased in rats fed a diet with over 3% red garlic extract compared to the control group. There was no significant difference in weight of visceral and epididymal fat in rats fed red garlic extract. Total lipid and triglyceride levels in serum were significantly decreased in a dose-dependent manner, and AI and CRF also fell. ALT and AST activities in groups fed red garlic extract were decreased compared to the control group. Total lipid level in liver tissue of the groups fed 5-7% red garlic extract exhibited a significant decrease compared to the control group. Total cholesterol and triglyceride levels in feces were significantly increased in rats fed a diet with over 5% red garlic extract. Lipid peroxide levels were significantly decreased in the groups fed diets with 5-7% red garlic and antioxidant activity in serum was significantly increased in the group fed a diet with 7% red garlic extract compared to the control group. Our results suggest that red garlic extract could have anti-obesity and hypolipidemic effects for suppressing obesity index and decreasing lipid profiles. IntroductionAs the choice for a high-calorie and high-fat diet increases due to the economic stability and affluence, so does the occurrence of metabolic disease caused by over-weight [27]. Obesity is the condition under which surplus energy is accumulated as lipids, which is attributable to the increase of energy intake and the decrease of consumption. From the balance is lost, obesity or hyperlipidemia develops, leading to a serious disease. In Korea, the social and economic cost incurred by the increase of obese population rises annually. Given that 40% of people who die by circulating system disease including atherosclerosis, cerebro-, cardio-vascular complications, hypertention, diabetes and functional depression of certain organs are obese, it is necessary to take a fundamental measure to improve the situation [47].Although the drug therapy proved to be effective as a behavior correction therapy used for the control of lipid metabolism in obese, it accompanies side-effects such as headaches, insomnia, and vomiting [29]. Thus, there is a growing attention on the way to improve obesity using phyto-nutrient that does not cause side-effects, among which garlic is known to effective for the control of lipid metabolism and obesity [1,16,24,31,51]. A major bioactive substances of garlic (Allium sativum L.) are an organic sulfur compounds containing allicin [11,18,22], which has the cardioprotective function among others [25]. Reportedly in Korea, the bioactive effect is elevated through the heat-treatment which turns fresh garlic into aged black garlic [22,46] supplemented with 5% red garlic extract, RG-7: supplemented with 7% red garlic extract. production of t...

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Ajoene, the antiplatelet compound derived from garlic, specifically inhibits platelet release reaction by affecting the plasma membrane internal microviscosity

Cited by 51 publications

References 17 publications

In vivo activity of ajoene against rodent malaria

In vivo activity of ajoene against rodent malaria

Pharmaceutical and therapeutic Potentials of essential oils and their individual volatile constituents: a review

Effects of the Red Garlic Extract for Anti-Obesity and Hypolipidemic in Obese Rats Induced High Fat Diet

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