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Olive leaf‐derived PPAR agonist complex induces collagen IV synthesis in human skin models
INTRODUCTION: Peroxisome proliferator‐activated receptor (PPAR) agonists are known to modulate the synthesis of dermal lipids and proteins including collagens. Olive (Olea europaea) leaves have been reported to contain PPAR‐binding ligands. Collagen IV, a major dermal‐epidermal junction (DEJ) protei...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9298265/ https://www.ncbi.nlm.nih.gov/pubmed/34661292 http://dx.doi.org/10.1111/ics.12742 |
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author | Majewski, George P. Singh, Smrita Bojanowski, Krzysztof |
author_facet | Majewski, George P. Singh, Smrita Bojanowski, Krzysztof |
author_sort | Majewski, George P. |
collection | PubMed |
description | INTRODUCTION: Peroxisome proliferator‐activated receptor (PPAR) agonists are known to modulate the synthesis of dermal lipids and proteins including collagens. Olive (Olea europaea) leaves have been reported to contain PPAR‐binding ligands. Collagen IV, a major dermal‐epidermal junction (DEJ) protein, degrades with both age and disease. Here, we report the formulation of a novel multi‐ligand complex, Linefade, and its effects on collagen IV synthesis. METHODS: Linefade prepared from the leaves of Olea europaea contains 2% w/w plant extract solids dissolved in a mixture of glyceryl monoricinoleate and dimethyl isosorbide. In silico docking was performed with PPAR‐α (PDB ID: 2P54). Linefade was evaluated for PPAR‐α‐dependent transcription in a luciferase reporter assay system. Cell viability and collagen IV levels in human dermal fibroblast cultures were measured using the MTT method and ELISA assay, respectively. Transcriptome analysis was conducted on a full‐thickness reconstituted human skin (EpiDermFT) model. Ex vivo cell viability and collagen IV immunostaining were performed on human skin explants. RESULTS: In silico docking model of the major constituents (oleanolic acid and glyceryl monoricinoleate) produced a co‐binding affinity of −6.7 Kcal/mole. Linefade significantly increased PPAR‐α transcriptional activity in CHO cells and collagen IV synthesis in adult human dermal fibroblasts. Transcriptome analysis revealed that 1% Linefade modulated the expression of 280 genes with some related to epidermal differentiation, DEJ, PPAR, Nrf2 and retinoid pathways. An ex vivo human explant study showed that 1% Linefade, delivered via a triglycerides excipient, increased collagen IV levels along the dermal–epidermal junction by 52%. CONCLUSION: In silico modelling and in vitro and ex vivo analyses confirmed Linefade‐mediated activation of PPAR‐α and stimulation of collagen IV synthesis. |
format | Online Article Text |
id | pubmed-9298265 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92982652022-07-21 Olive leaf‐derived PPAR agonist complex induces collagen IV synthesis in human skin models Majewski, George P. Singh, Smrita Bojanowski, Krzysztof Int J Cosmet Sci Original Articles INTRODUCTION: Peroxisome proliferator‐activated receptor (PPAR) agonists are known to modulate the synthesis of dermal lipids and proteins including collagens. Olive (Olea europaea) leaves have been reported to contain PPAR‐binding ligands. Collagen IV, a major dermal‐epidermal junction (DEJ) protein, degrades with both age and disease. Here, we report the formulation of a novel multi‐ligand complex, Linefade, and its effects on collagen IV synthesis. METHODS: Linefade prepared from the leaves of Olea europaea contains 2% w/w plant extract solids dissolved in a mixture of glyceryl monoricinoleate and dimethyl isosorbide. In silico docking was performed with PPAR‐α (PDB ID: 2P54). Linefade was evaluated for PPAR‐α‐dependent transcription in a luciferase reporter assay system. Cell viability and collagen IV levels in human dermal fibroblast cultures were measured using the MTT method and ELISA assay, respectively. Transcriptome analysis was conducted on a full‐thickness reconstituted human skin (EpiDermFT) model. Ex vivo cell viability and collagen IV immunostaining were performed on human skin explants. RESULTS: In silico docking model of the major constituents (oleanolic acid and glyceryl monoricinoleate) produced a co‐binding affinity of −6.7 Kcal/mole. Linefade significantly increased PPAR‐α transcriptional activity in CHO cells and collagen IV synthesis in adult human dermal fibroblasts. Transcriptome analysis revealed that 1% Linefade modulated the expression of 280 genes with some related to epidermal differentiation, DEJ, PPAR, Nrf2 and retinoid pathways. An ex vivo human explant study showed that 1% Linefade, delivered via a triglycerides excipient, increased collagen IV levels along the dermal–epidermal junction by 52%. CONCLUSION: In silico modelling and in vitro and ex vivo analyses confirmed Linefade‐mediated activation of PPAR‐α and stimulation of collagen IV synthesis. John Wiley and Sons Inc. 2021-11-04 2021-12 /pmc/articles/PMC9298265/ /pubmed/34661292 http://dx.doi.org/10.1111/ics.12742 Text en © 2021 Contrast Product Development, LLC. International Journal of Cosmetic Science published by John Wiley & Sons Ltd on behalf of Society of Cosmetic Scientists and Societe Francaise de Cosmetologie. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Majewski, George P. Singh, Smrita Bojanowski, Krzysztof Olive leaf‐derived PPAR agonist complex induces collagen IV synthesis in human skin models |
title | Olive leaf‐derived PPAR agonist complex induces collagen IV synthesis in human skin models |
title_full | Olive leaf‐derived PPAR agonist complex induces collagen IV synthesis in human skin models |
title_fullStr | Olive leaf‐derived PPAR agonist complex induces collagen IV synthesis in human skin models |
title_full_unstemmed | Olive leaf‐derived PPAR agonist complex induces collagen IV synthesis in human skin models |
title_short | Olive leaf‐derived PPAR agonist complex induces collagen IV synthesis in human skin models |
title_sort | olive leaf‐derived ppar agonist complex induces collagen iv synthesis in human skin models |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9298265/ https://www.ncbi.nlm.nih.gov/pubmed/34661292 http://dx.doi.org/10.1111/ics.12742 |
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