Chinese Journal of Natural Medicines (English Ed.) 2023;21(8):610-618

doi:10.1016/S1875-5364(23)60411-X

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

Guimin XUE 1 2 ; Chenguang ZHAO 3 ; Jinfeng XUE 3 ; Jiangjing DUAN 3 ; Hao PAN 3 ; Xuan ZHAO 3 ; Zhikang YANG 3 ; Hui CHEN 3 ; Yanjun SUN 3 ; Weisheng FENG 4

Affiliations

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Keywords

Achillea alpina; Antidiabetic activity; Glucose consumption; Seco-guaianolide

Country

China

Language

English

Abstract

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.