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

Area of Science:

• Biochemistry
• Dermatology
• Pharmacology

Background:

• Hypertrophic scarring results in pain, disfigurement, and mobility issues.
• Excessive transforming growth factor-beta 1 (TGF-β1) signaling, leading to SMAD3 phosphorylation, is a key factor in hypertrophic scar development.
• Tomentosenol A is a novel compound isolated from Australian stingless bee propolis (Tetragonula carbonaria).

Purpose of the Study:

• To investigate the mechanism of action of tomentosenol A.
• To determine if tomentosenol A can inhibit TGF-β1/SMAD3 signaling and downstream profibrotic responses.
• To evaluate the potential of tomentosenol A as a therapeutic agent for hypertrophic scarring.

Main Methods:

• Cultured human dermal fibroblasts and HEK293 cells were stimulated with TGF-β1, with or without tomentosenol A.
• SMADs 2/3 phosphorylation was assessed using Western blot and AlphaLISA assays.
• SMAD signalling, profibrotic gene transcription (ACTA2, COL1A1, COL3A1, CCN2, FN1), fibronectin protein expression, and smooth muscle α-actin formation were evaluated.

Main Results:

• TGF-β1 significantly increased SMAD3 phosphorylation (44.3-fold), an effect dose-dependently inhibited by tomentosenol A (IC50, 99.0 nM).
• Tomentosenol A (6.25 μM) inhibited TGF-β1-induced SMAD3 reporter gene expression, profibrotic gene transcription, fibronectin protein production, and smooth muscle α-actin assembly.
• These findings demonstrate tomentosenol A's ability to counteract key molecular events in TGF-β1 signaling.

Conclusions:

• Tomentosenol A effectively inhibits the TGF-β1/SMAD3 signaling pathway.
• The compound suppresses downstream profibrotic gene transcription and protein expression implicated in scar formation.
• Tomentosenol A holds potential as a novel therapeutic for managing hypertrophic scars from deep dermal injuries.