Efficacy of allicin, the reactive molecule of garlic, in inhibiting Aspergillus spp. in vitro, and in a murine model of disseminated aspergillosis.
OBJECTIVE
The evaluation of allicin, the biologically active compound responsible for the antimicrobial activities of freshly crushed garlic cloves, in inhibiting Aspergillus spp. in vitro and in a murine model of disseminated aspergillosis.


METHODS
Pure allicin was prepared by reacting synthetic alliin with a stabilized preparation of the garlic enzyme alliinase. We tested the in vitro efficacy of pure allicin against 31 clinical isolates of Aspergillus spp. using a microdilution broth method and following the NCCLS guidelines (document M-38P). Subsequently, the in vivo efficacy of allicin was tested in immunocompetent mice infected intravenously (iv) with Aspergillus fumigatus conidia. Allicin (5 mg/kg body weight) was administered iv once daily for 5 days post-infection or orally (po) (9 mg/kg body weight) for 5 days pre-infection and 10 days post-infection. No ill effects were observed in allicin-treated uninfected mice.


RESULTS
The in vitro MICs and MFCs of allicin were between 8 and 32 mg/L, indicating that allicin in its pure form may be an effective fungicide in vitro. Time-kill studies indicate that allicin exerts its fungicidal activity within 2-12 h of administration in vitro. Allicin treatment significantly prolonged survival of infected mice (P < 0.01) from mean survival time (MST) = 7.7 days in untreated mice to MST = 21.3 and 13.9 days for allicin iv and po treated mice, respectively. Allicin iv treatment led to a significant (P < 0.001) 10-fold reduction in fungal burden in A. fumigatus infected mice as evaluated by quantitative fungal cultures of kidney tissue samples.


CONCLUSIONS
These favourable results, despite the short half-life of this compound in vivo, support further studies of controlled sustained release or more prolonged administration of allicin as a treatment for aspergillosis.
Shadkchan
Yona
Y
Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Shemesh
Einav
E
Mirelman
David
D
Miron
Talia
T
Rabinkov
Aharon
A
Wilchek
Meir
M
Osherov
Nir
N
D000284:Administration, Oral; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D001228:Aspergillosis / Q000188:drug therapy* / Q000382:microbiology; D001230:Aspergillus / Q000187:drug effects*; D004220:Disulfides; D005260:Female; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D051379:Mice; D008813:Mice, Inbred ICR; D013441:Sulfinic Acids / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D016019:Survival Analysis
D000890:Anti-Infective Agents; D004220:Disulfides; D013441:Sulfinic Acids; C006452:allicin