Protective effects of diosmetin extracted from Galium verum L. on the thymus of U14-bearing mice

Can J Physiol Pharmacol. 2011 Sep;89(9):665-73. doi: 10.1139/y11-058. Epub 2011 Aug 18.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drugs, Chinese Herbal / pharmacology
  • Fas Ligand Protein / metabolism
  • Female
  • Flavonoids / pharmacology*
  • Galium / chemistry
  • In Situ Nick-End Labeling / methods
  • Interleukin-10 / blood
  • Interleukin-10 / metabolism
  • Interleukin-2 / blood
  • Interleukin-2 / metabolism
  • Kidney / drug effects
  • Liver / drug effects
  • Mice
  • Thymus Gland / drug effects*
  • Thymus Gland / metabolism
  • Transforming Growth Factor beta1 / blood
  • Transforming Growth Factor beta1 / metabolism
  • Tumor Necrosis Factor-alpha / blood
  • Tumor Necrosis Factor-alpha / metabolism
  • Uterine Cervical Neoplasms / drug therapy*
  • Uterine Cervical Neoplasms / metabolism
  • fas Receptor / metabolism

Substances

  • Drugs, Chinese Herbal
  • Fas Ligand Protein
  • Fas protein, mouse
  • Fasl protein, mouse
  • Flavonoids
  • Interleukin-2
  • Transforming Growth Factor beta1
  • Tumor Necrosis Factor-alpha
  • fas Receptor
  • Interleukin-10
  • diosmetin