title: Protective effects of diosmetin extracted from Galium verum L. on the thymus of U14-bearing mice.
abstract: Diosmetin (DGVL) extracted from the traditional Chinese herb Galium verum L. has been found to have anticancer activity. In this study, the effects of DGVL on the thymus of U14-bearing mice were investigated. Using flow cytometry, peripheral blood lymphocytes were characterized based on the expression of surface markers for T helper cells (CD4(+)) and T suppressor cells (CD8(+)). Serum levels of tumor necrosis factor α (TNF-α), interleukin-2 (IL-2), IL-10, and transforming growth factor β1 (TGF-β1) and a cell proliferation assay were determined with an enzyme-linked immunosorbent assay. The expression of Fas and Fas ligand (FasL) on the thymus was determined by Western blotting. Our results showed that DGVL inhibited tumor growth and significantly increased the thymus weight compared with the control. Also, DGVL elevated serum levels of IL-2 and significantly reduced levels of TNF-α, TGF-β1, and IL-10 in a dose-dependent manner. Histological study and terminal dUTP nick end labeling staining results showed that DGVL protected thymus tissue against the onslaught of tumor growth by inhibiting thymus lymphocyte apoptosis. The cell proliferation assay revealed that DGVL might promote more thymus lymphocytes towards proliferation. Furthermore, the ratio of CD4(+)/CD8(+) T lymphocytes was significantly increased from 0.69 to 2.29 by treatment with DGVL. Immunoblotting analyses revealed that the expression of Fas and FasL on the thymus was lower in mice in the DGVL treatment group than in the control mice. In conclusion, DGVL can inhibit tumor growth and protect tumor-induced apoptosis of the thymus, and the mechanism is closely associated with reduced cell death in the thymus and a Fas-FasL-dependent pathway.
authors.affiliation: Department of Pharmaceutical Engineering, College of Life Science and Biotechnology, Heilongjiang August First Land Reclamation University, Daqing High-Tech Industrial Development Zone, P.R. China. zhaorui2010@hotmail.com
authors.forename: Rui
authors.initials: R
authors.lastname: Zhao
authors.forename: Zhibao
authors.initials: Z
authors.lastname: Chen
authors.forename: Guiyan
authors.initials: G
authors.lastname: Jia
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Yaping
authors.initials: Y
authors.lastname: Cai
authors.forename: Xingyue
authors.initials: X
authors.lastname: Shao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D053222:Fas Ligand Protein / Q000378:metabolism; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D032061:Galium / Q000737:chemistry; D020287:In Situ Nick-End Labeling / Q000379:methods; D016753:Interleukin-10 / Q000097:blood / Q000378:metabolism; D007376:Interleukin-2 / Q000097:blood / Q000378:metabolism; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D051379:Mice; D013950:Thymus Gland / Q000187:drug effects* / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000097:blood / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
chemical_list: D004365:Drugs, Chinese Herbal; D053222:Fas Ligand Protein; C491899:Fas protein, mouse; C505658:Fasl protein, mouse; D005419:Flavonoids; D007376:Interleukin-2; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D016753:Interleukin-10; C039602:diosmetin