genkwanin and Disease-Models--Animal

Genkwanin is a biologically active O-methylated flavone extracted from. Forty C57BL/6 male mice were orally administered dextran sulfate sodium (DSS) to generate the colitis model, and genkwanin was orally administered at the indicated concentrations. Body weight, disease activity index, colon length, and H&E staining were used to evaluate colitis. Oxidative stress and antioxidant levels were measured by detecting ROS generation and malondialdehyde, superoxide dismutase and glutathione levels. The levels of proinflammatory cytokines (TNF-α, IL-1β, IFNγ and IL-6) were measured using ELISAs. Cell viability was determined using the CCK-8 assay. Mitochondrial function was evaluated by measuring the oxygen consumption rate, mtDNA content, and activities of electron transfer chain (ETC) complexes I, II, and IV. The expression of SIRT1, Nrf2 and its target genes was determined using qRT-PCR and western blotting. SIRT1 was depleted by lentivirus-mediated knockdown.. In this study, oral administration of genkwanin alleviated colitis induced by oral administration of DSS in mice, as evidenced by reduced weight loss, colon length shortening and histopathology scores. Furthermore, genkwanin relieved oxidative stress and reduced the production of proinflammatory cytokines.. Findings from our murine model and cell culture experiments provide a promising basis for genkwanin to be studied as a treatment for IBD in clinical trials.

Topics: Animals; Antioxidants; Colitis; Colon; Cytokines; Dextran Sulfate; Disease Models, Animal; Flavones; Male; Mice; Mice, Inbred C57BL; Mitochondria; Oxidative Stress; Reactive Oxygen Species; Sirtuin 1

Bioassay-guided fractionation of the combined fruits, leaves, and twigs (fruiting branches) of Callicarpa americana, collected from a plot in a forested area in southern Florida, led to the isolation of six new clerodane diterpenes (1-6) and eight known compounds. The structures of 1-6 [12(S),16xi-dihydroxycleroda-3,13-dien-15,16-olide (1), 12(S)-hydroxy-16xi-methoxycleroda-3,13-dien-15,16-olide (2), 12(S)-hydroxycleroda-3,13-dien-15,16-olide (3), 16xi-hydroxycleroda-3,11(E),13-trien-15,16-olide (4), 3beta,12(S)-dihydroxycleroda-4(18),13-dien-15,16-olide (5), and 12(S)-hydroxycleroda-3,13-dien-16,15-olide (6)] were elucidated by interpretation of spectroscopic data and chemical methods. The absolute configuration at C-12 in 1 and 3 was ascertained using the Mosher ester technique. The cytotoxicity of all isolates was tested against a panel of human cancer cell lines, and compounds 1, 4, and 6, and the known compounds genkwanin, 16xi-hydroxycleroda-3,13-dien-15,16-olide, and 2-formyl-16xi-hydroxy-3-A-norcleroda-2,13-dien-15,16-olide were active (ED50 <5 microg/mL). However, 1 was found to be inactive against human cancer cells implanted in mice using a hollow-fiber tumor model.

Topics: Animals; Antineoplastic Agents, Phytogenic; Callicarpa; Disease Models, Animal; Diterpenes, Clerodane; Drug Screening Assays, Antitumor; Florida; Fruit; Humans; Mice; Molecular Structure; Plant Leaves; Plant Stems; Plants, Medicinal