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

Abstract

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 by comprehensive spectroscopic data, theoretical ECD calculations and NMR computations. Compound 1 was unambiguously determined by the single-crystal X-ray diffraction. Structurally, compounds 1–4 are rare 9'-nor-dibenzylbutane lignans. Compound 5 is an unprecedented lignan-coumarin hybrid. Antihepatic fibrosis activity assays 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 cells LX-2. Importantly, compound 1 suppressed the expression of FN with inhibitory ratios of 60.7% at 50 μM, which was comparable to pirfenidone (PFD, 61.5%, 400 μM). Moreover, compound 1 downregulated collagen Ⅰ in LX-2 cells. This research provided compound 1 as a promising antihepatic fibrotic candidate with inhibition of FN and downregulation of collagen Ⅰ.