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26 février 2011 6 26 /02 /février /2011 10:25

FEMS Microbiol Lett. 2011 Feb;315(2):87-93. doi: 10.1111/j.1574-6968.2010.02170.x. Epub 2011 Jan 10.

Comparison between efficacy of allicin and fluconazole against Candida albicans in vitro and in a systemic candidiasis mouse model.

Khodavandi AAlizadeh FHarmal NSSidik SMOthman FSekawi ZJahromi MANg KPChong PP.

Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Selangor, Malaysia.


The efficacy of allicin compared with fluconazole in alleviating systemic Candida albicans infections was evaluated both in vitro and in vivo through a systemic candidiasis mouse model. Determination of in vitro minimum inhibitory concentrations (MICs) for different C. albicans isolates revealed that both allicin and fluconazole showed different MICs that ranged from 0.05 to 12.5 μg mL(-1) and 0.25 to 16 μg mL(-1) , respectively. A time-kill study showed a significant effect of allicin (P<0.01) against C. albicans, comparable to that of fluconazole. Scanning electron microscopy observation revealed that, similar to fluconazole, allicin produced structural destruction of C. albicans cell surface at low MIC and lysis or puncture at high MIC concentrations. Treatment of BALB/c mice systemically infected with C. albicans showed that although the allicin treatment (at 5 mg kg(-1) day(-1) ) was slightly less efficacious than fluconazole treatment in terms of the fungal load reduction and host survival time, it was still effective against C. albicans in terms of mean survival time, which increased from 8.4 to 15.8 days. These results demonstrate the efficacy of anticandidal effects of allicin both in vitro and in an animal model of candidiasis and affirm the potential of allicin as an adjuvant therapy to fluconazole.

© 2010 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

PMID: 21204918 [PubMed - in process]

 

 

 

 

 

J Antibiot (Tokyo). 2010 Dec;63(12):689-92. Epub 2010 Oct 13.

Dependence of vacuole disruption and independence of potassium ion efflux in fungicidal activity induced by combination of amphotericin B and allicin against Saccharomyces cerevisiae.


Ogita AYutani MFujita KTanaka T.

Department of Biology and Geosciences, Graduate School of Science, Osaka City University, Osaka, Japan.


Allicin selectively enhances the fungicidal activity of amphotericin B (AmB). It also accelerates AmB-induced vacuole disruption but does not affect AmB-induced potassium ion efflux in Saccharomyces cerevisiae and Candida albicans. The fungicidal activity of AmB alone or combined with allicin was further evaluated based on the relationship among cell viability, vacuole disruption and potassium ion efflux in S. cerevisiae. Lethality and vacuole disruption caused by AmB alone were completely restricted when K(+) and Mg(2+) were added to the growth medium. On the other hand, in identical conditions, the combination of AmB and allicin induced both lethality and vacuole disruption. S. cerevisiae Δerg6 cells, which lack ergosterol in plasma membrane, were mostly resistant to AmB as well as the combination of AmB and allicin against both lethality and vacuole disruption. The incorporation of AmB into the cytoplasm of Δerg6 cells was significantly reduced in comparison with that in parent cells, regardless of the presence of allicin. Our results suggest that the fungicidal activity of AmB combined with allicin is involved in vacuole disruption but not in potassium ion efflux, and that the expression of allicin-mediated activity of AmB requires the presence of ergosterol in the plasma membrane.

PMID: 20940723 [PubMed - indexed for MEDLINE]


 

 

Free Radic Biol Med. 2010 Dec 15;49(12):1916-24. Epub 2010 Sep 27.

Allicin disrupts the cell's electrochemical potential and induces apoptosis in yeast.

Gruhlke MCPortz DStitz MAnwar ASchneider TJacob CSchlaich NLSlusarenko AJ.

Department of Plant Physiology (Bio III), RWTH Aachen University, Aachen, Germany.


The volatile substance allicin gives crushed garlic (Allium sativum) its characteristic odor and is a pro-oxidant that undergoes thiol-disulfide exchange reactions with -SH groups in proteins and glutathione. The antimicrobial activity of allicin is suspected to be due to the oxidative inactivation of essential thiol-containing enzymes. We investigated the hypothesis that at threshold inhibitory levels allicin can shunt yeast cells into apoptosis by altering their overall redox status. Yeast cells were treated either with chemically synthesized, pure allicin or with allicin in garlic juice. Allicin-dependent cell oxidation was demonstrated with a redox-sensitive GFP construct and the shift in cellular electrochemical potential (E(hc)) from less than -215 to -181mV was calculated using the Nernst equation after the glutathione/glutathione disulfide couple (2GSH/GSSG) in the cell was quantified. Caspase activation occurred after allicin treatment, and yeast expressing a human antiapoptotic Bcl-XL construct was rendered more resistant to allicin. Also, a yeast apoptosis-inducing factor deletion mutant was more resistant to allicin than wild-type cells. We conclude that allicin in garlic juice can activate apoptosis in yeast cells through its oxidizing properties and that this presents an alternative cell-killing mechanism to the previously proposed specific oxidative inactivation of essential enzymes.

Copyright © 2010 Elsevier Inc. All rights reserved.

PMID: 20883774 [PubMed - in process]

 

 

 

 

 

Planta Med. 2010 Nov;76(16):1864-6. Epub 2010 May 19.

The cyclic organosulfur compound zwiebelane A from onion (Allium cepa) functions as an enhancer of polymyxin B in fungal vacuole disruption.

 

Borjihan BOgita AFujita KDoe MTanaka T.

Department of Bio- and Geosciences, Graduate School of Science, Osaka City University, Sumiyoshi-ku, Osaka, Japan.


Zwiebelane A ( CIS-2,3-dimethyl-5,6-dithiabicyclo[2.1.1]hexane 5-oxide), a natural product of onion bulbs (Allium cepa L.), is found to enhance the potential fungicidal activity of polymyxin B (PMB). As is the case with allicin, an allyl sulfur compound from garlic, zwiebelane A amplifies the disruptive effect of PMB on the vacuole of Saccharomyces cerevisiae, which has been found to represent a target for antifungal agents.

© Georg Thieme Verlag KG Stuttgart · New York.

PMID: 20486078 [PubMed - in process]


 

 

 Antimicrob Agents Chemother. 2010 Feb;54(2):898-906. Epub 2009 Nov 30.

Therapy of murine pulmonary aspergillosis with antibody-alliinase conjugates and alliin.

Appel EVallon-Eberhard ARabinkov ABrenner OShin ISasson KShadkchan YOsherov NJung SMirelman D.

Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel.


Aspergillus fumigatus is an opportunistic fungal pathogen responsible for invasive aspergillosis in immunocompromised individuals. The high morbidity and mortality rates as well as the poor efficacy of antifungal agents remain major clinical concerns. Allicin (diallyl-dithiosulfinate), which is produced by the garlic enzyme alliinase from the harmless substrate alliin, has been shown to have wide-range antifungal specificity. A monoclonal antibody (MAb) against A. fumigatus was produced and chemically ligated to the enzyme alliinase. The purified antibody-alliinase conjugate bound to conidia and hyphae of A. fumigatus at nanomolar concentrations. In the presence of alliin, the conjugate produced cytotoxic allicin molecules, which killed the fungus. In vivo testing of the therapeutical potential of the conjugate was carried out in immunosuppressed mice infected intranasally with conidia of A. fumigatus. Intratracheal (i.t.) instillation of the conjugate and alliin (four treatments) resulted in 80 to 85% animal survival (36 days), with almost complete fungal clearance. Repetitive intratracheal administration of the conjugate and alliin was also effective when treatments were initiated at a more advanced stage of infection (50 h). The fungi were killed specifically without causing damage to the lung tissue or overt discomfort to the animals. Intratracheal instillation of the conjugate without alliin or of the unconjugated monoclonal antibody significantly delayed the death of the infected mice, but only 20% of the animals survived. A limitation of this study is that the demonstration was achieved in a constrained setting. Other routes of drug delivery will be investigated for the treatment of pulmonary and extrapulmonary aspergillosis.

 

 

 

Mycopathologia. 2010 Apr;169(4):287-95. Epub 2009 Nov 19.

In vitro investigation of antifungal activity of allicin alone and in combination with azoles against Candida species.

Khodavandi AAlizadeh FAala FSekawi ZChong PP.

Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia.

Candidiasis is a term describing infections by yeasts from the genus Candida, and the type of infection encompassed by candidiasis ranges from superficial to systemic. Treatment of such infections often requires antifungals such as the azoles, but increased use of these drugs has led to selection of yeasts with increased resistance to these drugs. In this study, we used allicin, an allyl sulfur derivative of garlic, to demonstrate both its intrinsic antifungal activity and its synergy with the azoles, in the treatment of these yeasts in vitro. In this study, the MIC(50) and MIC(90) of allicin alone against six Candida spp. ranged from 0.05 to 25 microg/ml. However, when allicin was used in combination with fluconazole or ketoconazole, the MICs were decreased in some isolates. Our results demonstrated the existing synergistic effect between allicin and azoles in some of the Candida spp. such as C. albicans, C. glabrata and C. tropicalis, but synergy was not demonstrated in the majority of Candida spp. tested. Nonetheless, In vivo testing needs to be performed to support these findings.

PMID: 19924565 [PubMed - indexed for MEDLINE]

 

 

J Biomater Sci Polym Ed. 2009;20(1):21-31.

Anti-fungal efficacy of polybutylcyanoacrylate nanoparticles of allicin and comparison with pure allicin.


Luo DQGuo JHWang FJJin ZXCheng XLZhu JCPeng CQZhang C.

Taihe Hospital of YunYang Medical College, Shiyan, Hubei 442000, P. R. China.

Although garlic has been used in Chinese traditional medicine for its medical properties for thousands of years, investigations into its mode of action are relatively recent. The purpose of this study was to evaluate the in vitro anti-fungal efficacy of the active principle of garlic, pure allicin and polybutylcyanoacrylate (PBCA) nanoparticles (NPs) loaded with allicin. Pure allicin was prepared by reacting synthetic alliin with a stabilized process of the garlic enzyme alliinase. PBCA NPs were prepared by emulsion polymerization method and pure allicin was wrapped into it. The in vitro efficacy of pure allicin and PBCA-allicin NPs to Candida albicans, Cryputococcus neoformans, Trichophyton rubum, Microsporum gypseum, M. canis and Epidermophyton floccosum was examined and evaluated by MIC and MFC. The MIC of PBCA-allicin NPs to C. albicans (2.93 x 10(-2)mg/ml), T. rubum (1.46 x 10(-2)mg/ml) and E. floccosum (1.46 x 10(-2)mg/ml) was significantly lower than that of pure allicin (5.86 x 10(-2)mg/ml, 2.93 x 10(-2)mg/ml, 2.93 x 10(-2)mg/ml, respectively); accordingly, the MFC of PBCA-allicin NPs to C. albicans (5.86 x 10(-2)mg/ml), T. rubum (2.93 x 10(-2)mg/ml), E. floccosum (2.93 x 10(-2)mg/ml) and M. canis (2.93 x 10(-2)mg/ml) also decreased dramatically. These favourable results indicated that pure allicin has stronger in vitro anti-fungal efficacy to six tested fungi than alliinase and alliin.

Moreover, it has improved significantly after pure allicin being wrapped into PBCA NP, which may be due to the NP's good prolonged release effect and nano-scale dimensions.

PMID: 19105898 [PubMed - indexed for MEDLINE]

 

Int J Antimicrob Agents. 2009 Mar;33(3):258-63. Epub 2008 Dec 17.

Allicin enhances the oxidative damage effect of amphotericin B against Candida albicans.

An MShen HCao YZhang JCai YWang RJiang Y.

Department of Clinical Pharmacology, Chinese People's Liberation Army General Hospital, Beijing, PR China. maoan168@yahoo.com.cn

Amphotericin B (AmB) is the gold standard of antifungal treatment for the most severe invasive mycoses. In addition to the interaction of AmB with ergosterol in the fungi cell membrane, several studies have demonstrated oxidative damage involved in the fungicidal activity of AmB.

In this study, allicin, an allyl sulphur compound from garlic, was shown to enhance significantly the effect of AmB against Candida albicans in vitro and in vivo, although allicin did not exert a fungicidal effect.

Further study first demonstrated that allicin-mediated oxidative damage, such as phospholipid peroxidation in the plasma membrane, via influencing the defence of C. albicans against oxidative damage may be the cause of the synergistic interaction between allicin and AmB.

We envision that a combination of AmB with allicin may prove to be a promising strategy for the therapy of disseminated candidiasis.

PMID: 19095412 [PubMed - indexed for MEDLINE]

 


 


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