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

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 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.