Lignan glucosides from Gentiana macrophylla with potential anti-arthritis and hepatoprotective activities

Ten lignans, including six previously undescribed phenolic ester glycosyl lignans (1-6), were isolated from a well-known traditional Chinese medicine, Qin-Jiao, which is the dry root of Gentiana macrophylla Pall. (Gen-tianaceae). Their structures were determined by spectroscopic and chemical methods, especially 2D NMR techniques. Quantum chemical calculations of theoretical ECD spectra allowed the determination of their ab-solute configurations. Refer to its traditional applications for the treatment of rheumatic arthralgia and hepat-opathy, these compounds were evaluated on a TNF-alpha induced MH7A human synoviocyte inflammation model and a D-GalN induced AML12 hepatocyte injury model. Compounds 1, 2, 5, and 6 significantly reduced the release of proinflammatory cytokine IL-1 beta in MH7A cells at 15 mu M and they also could strongly protect AML12 cells against D-GalN injury at 30 mu M. Flow cytometry and Western blot analysis showed that compound 5 ameliorated D-GalN induced AML12 cell apoptosis by upregulating the expression of anti-apoptotic Bcl-2 protein and down-regulating the expression of pro-apoptotic Bax protein.