Hinokione: an abietene diterpene with pancreatic β cells regeneration and hypoglycemic activity, and other derivatives with novel structures from the woods of Agathis dammara

J Nat Med. 2024 Sep;78(4):849-862. doi: 10.1007/s11418-024-01816-z. Epub 2024 May 9.

Abstract

In this study, 14 abietene and pimarene diterpenoids were isolated from the woods of Agathis dammara. Among them, 4 new compounds, dammarone A-C and dammaric acid A (1-4), were firstly reported, respectively. The structure of the new compounds was determined by HR ESI-MS and 1D/2D NMR spectroscopy, and their absolute configuration was determined by electronic circular dichroism (ECD) exciton chirality method. The hypoglycemic effect of all compounds was evaluated by transgenic zebrafish model, and the structure-activity relationship was discussed. Hinokione (7, HO) has low toxicity and significant hypoglycemic effects on zebrafish, the mechanism is mainly by promoting the differentiation of zebrafish pancreatic endocrine precursor cells (PEP cells) into β cells, thereby promoting the regeneration of pancreatic β cells.

Keywords: Agathis dammara; Diterpenes; Hypoglycemic; Pancreatic β Cells.

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Diterpenes* / chemistry
  • Diterpenes* / isolation & purification
  • Diterpenes* / pharmacology
  • Hypoglycemic Agents* / chemistry
  • Hypoglycemic Agents* / isolation & purification
  • Hypoglycemic Agents* / pharmacology
  • Insulin-Secreting Cells* / drug effects
  • Insulin-Secreting Cells* / metabolism
  • Molecular Structure
  • Regeneration* / drug effects
  • Structure-Activity Relationship
  • Thymelaeaceae / chemistry
  • Wood / chemistry
  • Zebrafish*

Substances

  • Diterpenes
  • Hypoglycemic Agents