Prunellate A: An Unprecedented Lignan Lactone with a 6/7/6/5-Fused Tetracycle Skeleton by C-2-C-2' and C-7-C-8' Linkage from the Chinese Medicinal Plant Prunella vulgaris Inhibiting the Activation of Hepatic Stellate Cells by Targeting FXR.

Prunellate A (1), an unprecedented lignan lactone bearing a 6/7/6/5 tetracyclic system with C-2-C-2' and C-7-C-8' single bond linkage, probably derived from the rearrangement of methyl rosmarinate (2), has been isolated from the medicinal plant Prunella vulgaris. An extensive interpretation of multispectroscopic data including HRMS, IR, 1D, and 2D NMR elucidated its structure. The stereochemical assignment was conclusively established through electronic circular dichroism (ECD) experiments. The possible biosynthetic routes for the rearrangement from 2 to 1 were deduced. The antifibrosis activity was tested according to the traditional application of raw materials. Prunellate A exhibited a significant inhibition effect against TGFβ1-induced activation on LX-2 cells by targeting the Farnesoid X Receptor (FXR). These results indicated that prunellate A has great potential for use in the treatment of liver fibrosis.