Development and Sequential Analysis of a New Multi-Agent, Anti-Acne Formulation Based on Plant-Derived Antimicrobial and Anti-Inflammatory Compounds

Int J Mol Sci. 2017 Jan 17;18(1):175. doi: 10.3390/ijms18010175.


The antibacterial and anti-inflammatory potential of natural, plant-derived compounds has been reported in many studies. Emerging evidence indicates that plant-derived essential oils and/or their major compounds may represent a plausible alternative treatment for acne, a prevalent skin disorder in both adolescent and adult populations. Therefore, the purpose of this study was to develop and subsequently analyze the antimicrobial activity of a new multi-agent, synergic formulation based on plant-derived antimicrobial compounds (i.e., eugenol, β-pinene, eucalyptol, and limonene) and anti-inflammatory agents for potential use in the topical treatment of acne and other skin infections. The optimal antimicrobial combinations selected in this study were eugenol/β-pinene/salicylic acid and eugenol/β-pinene/2-phenoxyethanol/potassium sorbate. The possible mechanisms of action revealed by flow cytometry were cellular permeabilization and inhibition of efflux pumps activity induced by concentrations corresponding to sub-minimal inhibitory (sub-MIC) values. The most active antimicrobial combination represented by salycilic acid/eugenol/β-pinene/2-phenoxyethanol/potassium sorbate was included in a cream base, which demonstrated thermodynamic stability and optimum microbiological characteristics.

Keywords: acne; antimicrobial; eucalyptol; eugenol; limonene; plant-derived compounds; β-pinene.

MeSH terms

  • Acne Vulgaris / microbiology
  • Acne Vulgaris / prevention & control*
  • Adolescent
  • Adult
  • Anti-Infective Agents / therapeutic use*
  • Anti-Inflammatory Agents / therapeutic use*
  • Bicyclic Monoterpenes
  • Bridged Bicyclo Compounds / therapeutic use
  • Cyclohexanols / therapeutic use
  • Cyclohexenes / therapeutic use
  • Eucalyptol
  • Eugenol / therapeutic use
  • Flow Cytometry
  • Host-Pathogen Interactions / drug effects
  • Humans
  • Limonene
  • Microbial Sensitivity Tests
  • Monoterpenes / therapeutic use
  • Phytotherapy / methods
  • Plants / chemistry*
  • Pseudomonas aeruginosa / drug effects
  • Pseudomonas aeruginosa / physiology
  • Skin / drug effects*
  • Skin / microbiology
  • Skin / pathology
  • Skin Cream / therapeutic use
  • Staphylococcus aureus / drug effects
  • Staphylococcus aureus / physiology
  • Terpenes / therapeutic use
  • Young Adult


  • Anti-Infective Agents
  • Anti-Inflammatory Agents
  • Bicyclic Monoterpenes
  • Bridged Bicyclo Compounds
  • Cyclohexanols
  • Cyclohexenes
  • Monoterpenes
  • Terpenes
  • Eugenol
  • beta-pinene
  • Limonene
  • Eucalyptol