Sulforaphane prevents and reverses allergic airways disease in mice via anti-inflammatory, antioxidant, and epigenetic mechanisms.

Simon G Royce; Paul V Licciardi; Raymond C Beh; Jane E Bourke; Chantal Donovan; Andrew Hung; Ishant Khurana; Julia J Liang; Scott Maxwell; Nadia Mazarakis; Eleni Pitsillou; Ya Yun Siow; Kenneth J Snibson; Mark J Tobin; Katherine Ververis; Jitraporn Vongsvivut; Mark Ziemann; Chrishan S Samuel; Mimi L K Tang; Assam El-Osta; Tom C Karagiannis
Sulforaphane has been investigated in human pathologies and preclinical models of airway diseases. To provide further mechanistic insights, we explored L-sulforaphane (LSF) in the ovalbumin (OVA)-induced chronic allergic airways murine model, with key hallmarks of asthma. Histological analysis indicated that LSF prevented or reversed OVA-induced epithelial thickening, collagen deposition, goblet cell metaplasia, and inflammation. Well-known antioxidant and anti-inflammatory mechanisms contribute to the beneficial effects of LSF. Fourier transform infrared microspectroscopy revealed altered composition of macromolecules, following OVA sensitization, which were restored by LSF. RNA sequencing in human peripheral blood mononuclear cells highlighted the anti-inflammatory signature of LSF. Findings indicated that LSF may alter gene expression via an epigenetic mechanism which involves regulation of protein acetylation status. LSF resulted in histone and α-tubulin hyperacetylation in vivo, and cellular and enzymatic assays indicated decreased expression and modest histone deacetylase (HDAC) inhibition activity, in comparison with the well-known pan-HDAC inhibitor suberoylanilide hydroxamic acid (SAHA). Molecular modeling confirmed interaction of LSF and LSF metabolites with the catalytic domain of metal-dependent HDAC enzymes. More generally, this study confirmed known mechanisms and identified potential epigenetic pathways accounting for the protective effects and provide support for the potential clinical utility of LSF in allergic airways disease.
ISSN 1420-9071
Published 01 Nov 2022
Volume 79
Issue 11
Pages 579
DOI 10.1007/s00018-022-04609-3
Type Journal Article