Beneficial Effects of the Genus Aloe on Wound Healing, Cell Proliferation, and Differentiation of Epidermal Keratinocytes

PLoS One. 2016 Oct 13;11(10):e0164799. doi: 10.1371/journal.pone.0164799. eCollection 2016.


Aloe has been used as a folk medicine because it has several important therapeutic properties. These include wound and burn healing, and Aloe is now used in a variety of commercially available topical medications for wound healing and skin care. However, its effects on epidermal keratinocytes remain largely unclear. Our data indicated that both Aloe vera gel (AVG) and Cape aloe extract (CAE) significantly improved wound healing in human primary epidermal keratinocytes (HPEKs) and a human skin equivalent model. In addition, flow cytometry analysis revealed that cell surface expressions of β1-, α6-, β4-integrin, and E-cadherin increased in HPEKs treated with AVG and CAE. These increases may contribute to cell migration and wound healing. Treatment with Aloe also resulted in significant changes in cell-cycle progression and in increases in cell number. Aloe increased gene expression of differentiation markers in HPEKs, suggesting roles for AVG and CAE in the improvement of keratinocyte function. Furthermore, human skin epidermal equivalents developed from HPEKs with medium containing Aloe were thicker than control equivalents, indicating the effectiveness of Aloe on enhancing epidermal development. Based on these results, both AVG and CAE have benefits in wound healing and in treatment of rough skin.

MeSH terms

  • Aloe / chemistry*
  • Aloe / metabolism
  • Cadherins / genetics
  • Cadherins / metabolism
  • Cell Differentiation / drug effects*
  • Cell Line
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects*
  • Cornified Envelope Proline-Rich Proteins / genetics
  • Cornified Envelope Proline-Rich Proteins / metabolism
  • Humans
  • Integrin alpha6 / genetics
  • Integrin alpha6 / metabolism
  • Integrin beta1 / genetics
  • Integrin beta1 / metabolism
  • Integrin beta4 / genetics
  • Integrin beta4 / metabolism
  • Keratinocytes / cytology
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism
  • Microscopy, Fluorescence
  • Models, Biological
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Wound Healing


  • Cadherins
  • Cornified Envelope Proline-Rich Proteins
  • Integrin alpha6
  • Integrin beta1
  • Integrin beta4
  • Plant Extracts
  • SPRR2A protein, human
  • SPRR1B protein, human

Grant support

This study was supported by the Ministry of Education, culture, sports, science, and technology (MEXT) KAKENHI grant ( 26461672 to MM. In addition, the study was supported in part by grants from Japan Agency for Medical Research and Development (AMED) ( The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. KOBAYASHI Pharmaceutical Co., Ltd provided support in the form of salaries for authors JA, IY, and NM, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.