Identification and screening of novel diterpenoids from roasted arabica coffee in the regulation of lipid content in white adipocytes

Abstract

Previous studies have shown that coffee has a role in regulating lipid metabolism. However, the active compounds and pharmacological mechanism(s) are still unclear. Here, four new coffee diterpenoids (1–4) were identified from roasted arabica coffee (Coffea arabica L.) beans, and together with 31 known coffee diterpenoids (5–35), their bioactivities in the regulation of lipid content in white adipocytes were evaluated. Based on their structures and correlated bioactivities, we proposed that the α,β-unsaturated-γ-lactone moiety and hydroxyl group at C-3 are required for the bioactivity. Furthermore, the pharmacological approaches revealed that the active new diterpenoid, dehydrocaffarolide B, inhibited the Akt/mTOR/GSK3β pathway and arrested cells in the G0/G1 phase of the mitotic clonal expansion process during the adipocyte differentiation and maturation, eventually resulting in the blunting of lipid accumulation in the adipocytes. Collectively, our findings identified four new diterpenoids of arabica coffee and elucidated a mechanism of an active lactone-type diterpenoid in the regulation of lipid content in white adipocytes.