title: Efficacy of allicin, the reactive molecule of garlic, in inhibiting Aspergillus spp. in vitro, and in a murine model of disseminated aspergillosis.
abstract: 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.
authors.affiliation: Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Yona
authors.initials: Y
authors.lastname: Shadkchan
authors.forename: Einav
authors.initials: E
authors.lastname: Shemesh
authors.forename: David
authors.initials: D
authors.lastname: Mirelman
authors.forename: Talia
authors.initials: T
authors.lastname: Miron
authors.forename: Aharon
authors.initials: A
authors.lastname: Rabinkov
authors.forename: Meir
authors.initials: M
authors.lastname: Wilchek
authors.forename: Nir
authors.initials: N
authors.lastname: Osherov
mesh_terms: 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
chemical_list: D000890:Anti-Infective Agents; D004220:Disulfides; D013441:Sulfinic Acids; C006452:allicin