title: Curcumin enhances the activity of fluconazole against Cryptococcus gattii-induced cryptococcosis infection in mice.
abstract: OBJECTIVE
  The aim of this study was to investigate the in vitro and in vivo activities of pure curcumin, as well as its combination with fluconazole, against Cryptococcus gattii.
  
  
  RESULTS
  The minimal inhibitory concentrations (MIC) of curcumin and its interactions with fluconazole against C. gattii were assessed in vitro using standard methods. This same combination was used to treat C. gattii-induced cryptococcosis in mice. The behavioural and functional assessment of the mice during treatment was also performed. The average MIC for curcumin was 19·8 μg ml(-1) . Its combination with fluconazole resulted in FICΣ (fractional inhibitory concentration index) values between 0·79 and 2·29. Curcumin (alone or combined with fluconazole) significantly reduced pulmonary damage and fungal burden in the brain. No colonies were found in the brain following combination treatment, which was also confirmed by the improved behaviour of mice.
  
  
  CONCLUSIONS
  The combination therapy with curcumin and fluconazole was the most effective among the treatments tested, as in addition to reducing the fungal burden and damage on lung tissues, it was able to eliminate the fungal burden in the brain, enhancing the survival of mice.
  
  
  CONCLUSIONS
  This study points to the possibility of using curcumin in combination with fluconazole as a clinical treatment of cryptococcosis.
authors.affiliation: Departamento de Microbiologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: D L
authors.initials: DL
authors.lastname: da Silva
authors.affiliation: Departamento de Microbiologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: T F F
authors.initials: TF
authors.lastname: Magalhães
authors.affiliation: Departamento de Microbiologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: J R A
authors.initials: JR
authors.lastname: Dos Santos
authors.affiliation: Departamento de Microbiologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: T P
authors.initials: TP
authors.lastname: de Paula
authors.affiliation: Departamento de Botânica, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: L V
authors.initials: LV
authors.lastname: Modolo
authors.affiliation: Departamento de Química, ICEx, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: A
authors.initials: A
authors.lastname: de Fátima
authors.affiliation: Centro de Engenharias e Ciências Exatas, Universidade Estadual do Oeste do Paraná, Toledo, PR, Brazil.
authors.forename: C V
authors.initials: CV
authors.lastname: Buzanello Martins
authors.affiliation: Departamento de Microbiologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: D A
authors.initials: DA
authors.lastname: Santos
authors.affiliation: Departamento de Microbiologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: M A
authors.initials: MA
authors.lastname: de Resende-Stoianoff
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage*; D003453:Cryptococcosis / Q000188:drug therapy* / Q000382:microbiology; D056285:Cryptococcus gattii / Q000187:drug effects* / Q000254:growth & development; D003474:Curcumin / Q000008:administration & dosage*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D015725:Fluconazole / Q000008:administration & dosage*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D000935:Antifungal Agents; D015725:Fluconazole; D003474:Curcumin
keywords: SHIRPA protocol; bioenhancer; brain and lung protector; combination therapy; cryptococcosis; curcumin; fluconazole