1-1-diphenyl-2-picrylhydrazyl and xanthohumol

Seven naturally derived components from hop plant (Humulus lupulus L.) extracts were tested for evaluation of biological activities affecting acne vulgaris. Five strains, Propionibacterium acnes, Staphylococcus epidermidis, Staphylococcus aureus, Kocuria rhizophila and, Staphylococcus pyogenes, were selected as the main acne-causing bacteria. Hop extracts xanthohumol and the lupulones showed strong inhibitory activities against all of the strains. Although hydrogenated derivatives did not show the same level of activity, naturally occurring xanthohumol, humulones, and lupulones all showed moderate to strong anticollagenase inhibitory activities. Antioxidant capacity was also evaluated with seven different methods based on different reactive oxygen species. Xanthohumol showed the highest activity in total oxygen radical absorbance capacity as well as singlet oxygen absorbance capacity.

Topics: Acne Vulgaris; Actinobacteria; Anti-Bacterial Agents; Antioxidants; Bacteria; Biphenyl Compounds; Cyclohexenes; Flavonoids; Humans; Humulus; Matrix Metalloproteinase 1; Matrix Metalloproteinase 8; Matrix Metalloproteinase Inhibitors; Microbial Sensitivity Tests; Phytotherapy; Picrates; Plant Extracts; Propionibacterium acnes; Propiophenones; Staphylococcus; Terpenes

The female parts of hops (Humulus lupulus L.) show estrogenic effects as well as cancer chemopreventive potential. We analyzed the chemopreventive mechanism of hops by studying its antioxidative activities and its effect on the detoxification of a potentially toxic quinone (menadione). The detoxification enzyme quinone reductase [(NAD(P)H:quinone oxidoreductase, QR] protects against quinone-induced toxicity and has been used as a marker in cancer chemoprevention studies. Although the hop extract was only a weak quencher of free radicals formed from 1,1-diphenyl-2-picrylhydrazyl, it demonstrated strong QR induction in Hepa 1c1c7 cells. In addition, compounds isolated from hops including xanthohumol (XH) and 8-prenylnaringenin were tested for QR induction. Among these, XH was the most effective at inducing QR with a concentration required to double the specific activity of QR (CD value) of 1.7 +/- 0.7 microM. In addition, pretreatment of Hepa1c1c7 cells with XH significantly inhibited menadione-induced DNA single-strand breaks. The QR inhibitor dicumarol reversed the protective effect of XH against menadione-induced DNA damage. Because the expression of QR and other detoxifying enzymes is known to be upregulated by binding of the transcription factor Nrf2 to the antioxidant response element (ARE), the reporter activity mediated by ARE in HepG2-ARE-C8 cells was investigated after incubation with XH for 24 h. Under these conditions, XH increased ARE reporter activity in a dose-dependent manner. One mechanism by which XH might induce QR could be through interaction with Keap1, which sequesters Nrf2 in the cytoplasm, so that it cannot activate the ARE. Using LC-MS-MS, we demonstrated that XH alkylates human Keap1 protein, most likely on a subset of the 27 cysteines of Keap1. This suggests that XH induces QR by covalently modifying the Keap1 protein. Therefore, XH and hops dietary supplements might function as chemopreventive agents, through induction of detoxification enzymes such as QR.

Topics: Adaptor Proteins, Signal Transducing; Alkylation; Animals; Antioxidants; Biphenyl Compounds; Cell Line, Tumor; Cell Survival; Cytoskeletal Proteins; Dicumarol; DNA Damage; Enzyme Induction; Flavonoids; Genes, Reporter; Humulus; Hydrazines; Kelch-Like ECH-Associated Protein 1; Luciferases; Mice; NAD(P)H Dehydrogenase (Quinone); Picrates; Plant Extracts; Propiophenones; Protein Prenylation; Response Elements; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Vitamin K 3