In vitro structure-toxicity relationship of chalcones in human hepatic stellate cells. (2nd October 2015)

• Record Type: Journal Article
• Authors: Zenger, Katharina; Dutta, Subhajit; Wolff, Horst; Genton, Marc G.; Kraus, Birgit
• Is Part Of: Toxicology. Volume 336(2015)
• Page Start: 26
• Page End: 33
• Publication Date: 2015-10-02
• Subjects: 3OH-Heli 3-hydroxy-helichrysetin -- 3OH-XNH 3-hydroxy-xanthohumol H -- 3OMe-XNH 3-methoxy-xanthohumol H -- 4Ac-XN 4-O-acetyl-xanthohumol -- 4Me-XN 4-O-methyl-xanthohumol -- 4′Me-XN 4′-O-methyl-xanthohumol -- C cardamonin -- dhFKC dihydro-flavokawain C -- dhHeli dihydro-helichrysetin -- dhXNC 1″, 2″-dihydro-xanthohumol C -- FKA flavokawain A -- FKB flavokawain B -- FKC flavokawain C -- HCA high-content analysis -- Heli helichrysetin -- HSC hepatic stellate cells -- P pinostrobin chalcone -- PBS phosphate buffered saline -- PFA paraformaldehyde -- thXNC dihydro-1″, 2″-dihydro-xanthohumol C -- XN xanthohumol -- XNC xanthohumol C -- XNH xanthohumol H; Chalcones -- Structure activity relationship -- Xanthohumol -- Hepatic stellate cell; Toxicology -- Periodicals; Chemicals -- Physiological effect -- Periodicals; 615.9005
• DOI: 10.1016/j.tox.2015.07.012
• Languages: English
• ISSNs: 0300-483X

Abstract

Abstract: Xanthohumol (XN), the major prenylated chalcone from hops ( Humulus lupulus L.), has received much attention within the last years, due to its multiple pharmacological activities including anti-proliferative, anti-inflammatory, antioxidant, pro-apoptotic, anti-bacterial and anti-adhesive effects. However, there exists a huge number of metabolites and structurally-related chalcones, which can be expected, or are already known, to exhibit various effects on cells. We have therefore analyzed the effects of XN and 18 other chalcones in a panel, consisting of multiple cell-based assays. Readouts of these assays addressed distinct aspects of cell-toxicity, like proliferation, mitochondrial health, cell cycle and other cellular features. Besides known active structural elements of chalcones, like the Michael system, we have identified several moieties that seem to have an impact on specific effects and toxicity in human liver cells in vitro. Based on these observations, we present a structure-toxicity model, which will be crucial to understand the molecular mechanisms of wanted effects and unwanted side-effects of chalcones.