Propolis compound inhibits profibrotic TGF-β1/SMAD signalling in human fibroblasts

Lisa J. Randall; Sarah Bajan; Trong D. Tran; Robert J. Harvey; Fraser D. Russell

doi:10.1038/s41598-025-07918-2

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Propolis compound inhibits profibrotic TGF-β1/SMAD signalling in human fibroblasts

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Propolis compound inhibits profibrotic TGF-β1/SMAD signalling in human fibroblasts

Lisa J. Randall, Sarah Bajan, Trong D. Tran, Robert J. Harvey and Fraser D. Russell

Scientific Reports, Vol.15, pp.1-14

2025

DOI: https://doi.org/10.1038/s41598-025-07918-2

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Abstract

propolis

transforming growth factor-beta1 (TGF-B1)

small mothers against decapentaplegic (SMAD)

hypertrophic scarring

fibrosis

wound healing

UniSC Diversity Area - Life Stages

Hypertrophic scarring of the skin is a cause of pain, disfigurement, and restricted mobility. Excessive TGF-β1 signalling leads to SMAD3 phosphorylation, which is implicated in hypertrophic scarring. In this study, we examined the mechanism of action of tomentosenol A, a small compound that we isolated from the propolis of the Australian stingless bee Tetragonula carbonaria. Cultured adult human dermal fibroblasts and HEK293 cells were stimulated with TGF-β1, with or without tomentosenol A, and were assessed for phosphorylation of SMADs 2/3 (Western blot, AlphaLISA assay), SMAD signalling (HEK293 cells expressing a SMAD3 reporter gene), and profibrotic gene transcription using RTqPCR for ACTA2 (smooth muscle α-actin), COL1A1 and COL3A (collagens), CCN2 (connective tissue growth factor) and FN1 (fibronectin). Protein expression was measured using ELISA (fibronectin) and visualised via confocal microscopy (smooth muscle α-actin). TGF-β1 increased SMAD3 phosphorylation by 44.3-fold above baseline levels, and this effect was inhibited by tomentosenol A in a concentration-dependent manner (IC50, 99.0 nM). TGF-β1 stimulated SMAD3 reporter gene expression and upregulated ACTA2, COL1A1, COL3A1, FN1 and CCN2 transcription; fibronectin protein expression; and smooth muscle α-actin filament formation in fibroblasts. These responses were inhibited by 6.25 μM tomentosenol A. These findings indicate that tomentosenol A inhibits TGF-β1/SMAD3 signalling and downstream profibrotic gene transcription and protein expression. As this pathway is implicated in hypertrophic scarring of the skin, tomentosenol A can be developed as a novel therapy for the management of scars caused by deep dermal injuries that are associated with surgery, trauma and burns.

Details

Title: Propolis compound inhibits profibrotic TGF-β1/SMAD signalling in human fibroblasts
Authors: Lisa J. Randall - University of the Sunshine Coast, Queensland, School of Science, Technology and Engineering
Sarah Bajan - University of the Sunshine Coast, Queensland, School of Health - Biomedicine
Trong D. Tran - University of the Sunshine Coast, Queensland, School of Science, Technology and Engineering
Robert J. Harvey - University of the Sunshine Coast, Queensland, School of Health
Fraser D. Russell (Corresponding Author) - University of the Sunshine Coast, Queensland, School of Health - Biomedicine
Publication details: Scientific Reports, Vol.15, pp.1-14
Publisher: Nature Publishing Group
Date published: 2025
DOI: 10.1038/s41598-025-07918-2
ISSN: 2045-2322
Copyright note: This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
Data Availability: Raw data is available on Figshare. https://doi.org/10.6084/m9.figshare.27850359.
Grant note: This research is supported by an Australian Government Research Training Program (RTP) Scholarship.
Organisation Unit: School of Health - Biomedicine; Healthy Ageing Research Cluster; School of Health; School of Science, Technology and Engineering; Centre for Bioinnovation
Language: English
Record Identifier: 991147037802621
Output Type: Journal article

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