Details

Autor(en) / Beteiligte

• Mazzotta, Sarah
• Governa, Paolo
• Borgonetti, Vittoria
• Marcolongo, Paola
• Nanni, Claudio
• Gamberucci, Alessandra
• Manetti, Fabrizio
• Pessina, Federica
• Carullo, Gabriele
• Brizzi, Antonella
• Aiello, Francesca

Titel

Pinocembrin and its linolenoyl ester derivative induce wound healing activity in HaCaT cell line potentially involving a GPR120/FFA4 mediated pathway

Ist Teil von

• Bioorganic chemistry, 2021-03, Vol.108, p.104657, Article 104657

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2021

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• [Display omitted] •Pinocembrin was hybridized with fatty acids by using pancreatic porcine lipase.•Pinocembrin and its linolenoyl derivative promoted wound closure in HaCaT cells.•Wound healing activity was mediated by GPR120/β-arrestin complexation.•Wound healing was limited by pre-treatment with GPR120 antagonist AH7614.•Pinocembrin and its linolenoyl derivative share the same binding pocket of TUG-891. Wound healing represents an urgent need from the clinical point of view. Several diseases result in wound conditions which are difficult to treat, such as in the case of diabetic foot ulcer. Starting from there, the medicinal research has focused on various targets over the years, including GPCRs as new wound healing drug targets. In line with this, GPR120, known to be an attractive target in type 2 diabetes drug discovery, was studied to finalize the development of new wound healing agents. Pinocembrin (HW0) was evaluated as a suitable compound for interacting with GPR120, and was hybridized with fatty acids, which are known endogenous GPR120 ligands, to enhance the wound healing potential and GPR120 interactions. HW0 and its 7-linolenoyl derivative (HW3) were found to be innovative wound healing agents. Immunofluorescence and functional assays suggested that their activity was mediated by GPR120, and docking simulations showed that the compounds could share the same pocket occupied by the known GPR120 agonist, TUG-891.