New lupeol esters as active substances in the treatment of skin damage

PLoS One. 2019 Mar 28;14(3):e0214216. doi: 10.1371/journal.pone.0214216. eCollection 2019.

Abstract

The purpose of the research was to obtain new derivatives of natural triterpene lupeol and to evaluate their potential as active substances in the treatment of skin damage. Four new lupeol esters (propionate, succinate, isonicotinate and acetylsalicylate) and lupeol acetate were obtained using an eco-friendly synthesis method. In the esterification process, the commonly used hazardous reagents in this type of synthesis were replaced by safe ones. This unconventional, eco-friendly, method is particularly important because the compounds obtained are potentially active substances in skin care formulations. Even trace amounts of hazardous reagents can have a toxic effect on damaged or irritated tissues. The molecular structure of the esters were confirmed by 1H NMR, 13C NMR and IR spectroscopy methods. Their crystal structures were determined using XRD method. To complete the analysis of their characteristics, physicochemical properties (melting point, lipophilicity, water solubility) and biological activity of the lupeol derivatives were studied. Results of an irritant potential test, carried out on Reconstructed Human Epidermis (RHE), confirmed that the synthesized lupeol derivatives are not cytotoxic and they stimulate a process of human cell proliferation. The safety of use for tested compounds was determined in a cell viability test (cytotoxicity detection kit based on the measurement of lactate dehydrogenase activity) for keratinocytes and fibroblasts. The results obtained showed that the modification of lupeol structure improve its bioavailability and activity. All of the esters penetrate the stratum corneum and the upper layers of the dermis better than the maternal lupeol. Lupeol isonicotinate, acetate and propionate were the most effective compounds in a stimulation of the human skin cell proliferation process. This combination resulted in an increase in the concentration of cells of more than 30% in comparison to control samples. The results indicate that the chemical modification of lupeol allows to obtain promising active substances for treatment of skin damage, including thermal, chemical and radiation burns.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Burns / drug therapy*
  • Burns / metabolism
  • Burns / pathology
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dermis / injuries*
  • Dermis / metabolism
  • Dermis / pathology
  • Epidermis / injuries*
  • Epidermis / metabolism
  • Epidermis / pathology
  • Esters / chemical synthesis
  • Esters / chemistry
  • Esters / pharmacology
  • Fibroblasts / metabolism*
  • Fibroblasts / pathology
  • Humans
  • Keratinocytes / metabolism*
  • Keratinocytes / pathology
  • Pentacyclic Triterpenes* / chemistry
  • Pentacyclic Triterpenes* / pharmacology

Substances

  • Esters
  • Pentacyclic Triterpenes
  • lupeol

Grants and funding

The research was carried out with the equipment purchased thanks to the financial support of the European Regional Development Fund in the framework of the Operational Program Development of Eastern Poland 2007-2013 (Contract No. POPW.01.03.00-06-009/11-00, Equipping the laboratories of the Faculties of Biology and Biotechnology, Mathematics, Physics and Informatics, and Chemistry for studies of biologically active substances and environmental samples). The calculations in Discovery Studio (BIOVIA) were supported by PL-Grid Infrastructure (AGH CYFRONET). Calculator Plugins of Chemicalize was used for structure property prediction and calculation 01.2019 https://chemicalize.com/ developed by ChemAxon (http://www.chemaxon.com) The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.