Effect of enoxaparin and onion extract on human skin fibroblast cell line - therapeutic implications for the treatment of keloids

Pharm Biol. 2014 Feb;52(2):262-7. doi: 10.3109/13880209.2013.826246. Epub 2013 Sep 30.


Context: Keloids and hypertrophic scars are hyperproliferative skin disorders resulting in abnormal wound healing. In the prevention and treatment of keloids and hypertrophic scars, ointments containing heparin and onion extract are very popular. Their therapeutic effects, however, are still controversial and the mechanism of action is not fully understood.

Objective: The aim of this study was to assess the effect of enoxaparin and dry onion extract on proliferation, apoptosis and β1 integrin expression in human fibroblasts.

Materials and methods: Fibroblast human cell lines (46 BR.1 N) were treated for 48 h with various concentrations of enoxaparin sodium (20, 100, 500 µg/mL) and/or onion [Allium cepa L. (Alliaceae)] extract (50, 250, 1000 µg/mL). The cell proliferation was evaluated by [(3)H]-thymidine incorporation assay. Furthermore, the expression of β1 integrin and apoptosis was determined by flow cytometry.

Results and discussion: The results demonstrate that enoxaparin and onion extract inhibited the proliferation of human fibroblasts. Almost complete inhibition of cell proliferation was achieved by enoxaparin in 500 µg/mL concentration (91.5% reduction). The onion extract at a concentration of 250 µg/mL also strongly inhibited the proliferation of cells (50.8% reduction). Depending on concentration, enoxaparin and onion extract induced apoptosis (500 and 1000 µg/mL, respectively) and, depending on concentration, downregulated the expression of β1 integrin on human fibroblasts.

Conclusion: This work points at possible mechanism of action of enoxaparin and onion extract, when administered in the treatment of patients with keloids and hypertrophic scars.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Cell Line
  • Cell Proliferation / drug effects
  • Cicatrix, Hypertrophic / drug therapy
  • Cicatrix, Hypertrophic / pathology
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects
  • Drug Therapy, Combination
  • Enoxaparin / administration & dosage
  • Enoxaparin / pharmacology*
  • Fibrinolytic Agents / administration & dosage
  • Fibrinolytic Agents / pharmacology
  • Fibroblasts / drug effects*
  • Fibroblasts / metabolism
  • Flow Cytometry
  • Humans
  • Integrin beta1 / genetics
  • Keloid / drug therapy
  • Keloid / pathology
  • Onions / chemistry*
  • Plant Extracts / administration & dosage
  • Plant Extracts / pharmacology*


  • Enoxaparin
  • Fibrinolytic Agents
  • Integrin beta1
  • Plant Extracts