Anti-Fibrotic Potential of Tomentosenol A, a Constituent of Cerumen from the Australian Native Stingless Bee, Tetragonula carbonaria

Karina D Hamilton; Daniel Czajkowski; Nicolas J Kong; Trong D Tran; Kirk R Gustafson; Gary Pauly; Glen M Boyle; Jacinta L Simmons; Robert Steadman; Ryan Moseley; Peter R Brooks; Steven M Ogbourne; Fraser D Russell

doi:10.3390/antiox11081604

Anti-Fibrotic Potential of Tomentosenol A, a Constituent of Cerumen from the Australian Native Stingless Bee, Tetragonula carbonaria

Antioxidants (Basel). 2022 Aug 19;11(8):1604. doi: 10.3390/antiox11081604.

Authors

Karina D Hamilton^{1

2}, Daniel Czajkowski^{1

2}, Nicolas J Kong^{1

2}, Trong D Tran^{1

3}, Kirk R Gustafson⁴, Gary Pauly⁵, Glen M Boyle⁶, Jacinta L Simmons⁶, Robert Steadman⁷, Ryan Moseley⁸, Peter R Brooks^{1

3}, Steven M Ogbourne^{1

3}, Fraser D Russell^{1

2}

Affiliations

¹ Centre for Bioinnovation, University of the Sunshine Coast, Maroochydore DC, QLD 4558, Australia.
² School of Health and Behavioural Sciences, University of the Sunshine Coast, Maroochydore DC, QLD 4558, Australia.
³ School of Science, Technology and Engineering, University of the Sunshine Coast, Maroochydore DC, QLD 4558, Australia.
⁴ Molecular Targets Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702-1201, USA.
⁵ Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702-1201, USA.
⁶ QIMR Berghofer Medical Research Institute, Locked Bag 2000, PO Royal Brisbane Hospital, Brisbane, QLD 4029, Australia.
⁷ Wales Kidney Research Unit, School of Medicine, Cardiff Institute of Tissue Engineering and Repair (CITER), Cardiff University, Cardiff CF14 4XN, UK.
⁸ Regenerative Biology Group, School of Dentistry, Cardiff Institute of Tissue Engineering and Repair (CITER), Cardiff University, Cardiff CF14 4XY, UK.

Abstract

Bioactivity-guided fractionation was used to isolate two compounds, tomentosenol A (1) and torellianone A (2), from a cerumen extract from Tetragonula carbonaria. The anti-fibrotic activity of these compounds was examined using human cultured neonatal foreskin fibroblasts (NFF) and immortalised keratinocytes (HaCaTs). Tomentosenol A (1), inhibited NFF and HaCaT cell proliferation and prevented NFF and HaCaT scratch wound repopulation at 12.5-25 µM concentrations. These inhibitory effects were associated with reduced cell viability, determined by tetrazolium dye (MTT) and sulforhodamine B (SRB) assays. Compound 1 further inhibited transforming growth factor-β₁ (TGF-β₁)-stimulated, NFF-myofibroblast differentiation and soluble collagen production; and was an effective scavenger of the model oxidant, 2,2-diphenyl-1-picrylhydrazyl (DPPH·), with an EC₅₀ value of 44.7 ± 3.1 µM. These findings reveal significant anti-fibrotic potential for cerumen-derived tomentosenol A (1).

Keywords: antioxidant; cerumen; fibroblasts; hypertrophic scars; keratinocytes; proliferation; propolis; stingless bee.

Grants and funding

This research received no external funding.