2,3-Seco and 3-nor guaianolides fromAchillea alpina with antidiabetic activity

In this study, we presented the isolation and characterization of eight novel seco-guaianolide sesquiterpenoids (1–8) and two known guaianolide derivatives (9 and 10), from the aerial part of Achillea alpina L.. Compounds 1–3 were identified as guaianolides bearing an oxygen insertion at the 2, 3 position, while compounds 4–8 belonged to a group of special 3-nor guaianolide sesquiterpenoids. The structural elucidation of 1–8, including their absolute configurations, were accomplished by a combination of spectroscopic data analysis and quantum electronic circular dichroism (ECD) calculations. To evaluate the potential antidiabetic activity of compounds 1–10, we investigated their effects on glucose consumption in palmitic acid (PA)-mediated HepG2-insulin resistance (IR) cells. Among the tested compounds, compound 7 demonstrated the most pronounced ability to reverse IR. Moreover, a mechanistic investigation revealed that compound 7 exerted its antidiabetic effect by reducing the production of the pro-inflammatory cytokine IL-1β, which was achieved through the suppression of the NLRP3 pathway.