Supplementation with tocotrienols from Bixa orellana improves the in vivo efficacy of daptomycin against methicillin-resistant Staphylococcus aureus in a mouse model of infected wound

Elisa Pierpaoli, Fiorenza Orlando, Oscar Cirioni, Oriana Simonetti, Andrea Giacometti, Mauro Provinciali

Research output: Contribution to journalArticle

Abstract

Background Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of skin and soft-tissue infection worldwide. An adequate immune response acts as a first line of defence against infections and therefore plays an essential role in the maintenance of health. Tocotrienols (T3s), the lesser known isomers of vitamin E, possess many biological properties and have been recognized as immunomodulators. Purpose The aim of this study was to investigate whether the in vivo supplementation with a mixture of 87.1% δ- and 12.9% γ-T3s extract from seeds of Bixa orellana, (T3s) could be effective in increasing the effect of daptomycin (DAP) in a mouse model of wound infection due to MRSA. Study design/methods Bacteria were inoculated onto full-thickness wound on the dorsal side of BALB/c mice at 5 × 106 CFU per mouse. Mice were randomized into five groups: an uninfected group, an infected-untreated group, a T3s-pretreated group with no antibiotics given after challenge, a T3s-pretreated group plus DAP given after challenge, a group only given DAP after challenge. Main outcome measures were: bacterial load on the wounds, analysis of Natural Killer (NK) cytotoxicity, immunological phenotype and markers of tissue repair. Results Our results showed that bacterial load in wounds from mice receiving T3s or DAP alone was 1- or 3-log10 lower, respectively, compared with the infected-untreated group. T3s plus daptomycin showed the highest efficacy, achieving a 4-log10 decrease in bacterial load. This higher antimicrobial effect was associated with increased levels of NK cytotoxicity and markers of wound repair. Conclusion These data suggest that treatment with T3s may be useful for the management of infected wounds as immune adjuvants in combination with DAP.

Original languageEnglish
Pages (from-to)50-53
Number of pages4
JournalPhytomedicine
Volume36
DOIs
Publication statusPublished - Dec 1 2017

Keywords

  • Animal model
  • Immunomodulation
  • MRSA
  • Tocotrienols
  • Wound healing

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine

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