Discovery of artemargyins A-E: rare 9'-nor-dibenzylbutane lignans and a lignan-coumarin hybrid with anti-hepatic fibrosis activities from Artemisia argyi var. gracilis.

Artemargyins A-E (1-5), along with three known compounds (6-8), were isolated from Artemisia argyi var. gracilis. Their structures and absolute configurations were elucidated using comprehensive spectroscopic data, theoretical ECD calculations and NMR computations. The structure of compound 1 was unambiguously determined by single-crystal X-ray diffraction. Structurally, compounds 1-4 are rare 9'-nor-dibenzylbutane lignans. Compound 5 is an unprecedented lignan-coumarin hybrid. Assays of anti-hepatic fibrosis activity demonstrated that compounds 1-4 at a concentration of 50 μM suppressed transforming growth factor-β1 (TGF-β1)-induced expression of fibronectin (FN) in human hepatic stellate LX-2 cells. Importantly, compound 1 suppressed the expression of FN with an inhibitory ratio of 60.7% at 50 μM, which was comparable to that for pirfenidone (PFD, 61.5%, 400 μM). Moreover, compound 1 downregulated collagen I in LX-2 cells. This research provided compound 1 as a promising anti-hepatic fibrosis compound with inhibition of FN and downregulation of collagen I.