lignans and triptolide

Natural products have been used as medicinal agents for many years. In addition, these compounds have also served as the starting points for semisynthetic analogs with improved properties. This review focuses on recent advances in the pharmacological studies on natural products mainly performed and published in China. Emphasis will be placed on those compounds that show the greatest promise clinically such as huperzine A (9-amino-13-ethylidene-11-methyl-4-azatricyclo[7.3.1.0(3.8)]trideca-3(8),6,11-trien-5-one), s-(-)-3-n-butylphthalide (s-(-)-3-butyl-1(3H)-isobenzofuranone), (-)-clausenamide (3-hydroxy-4-phenyl-5a-hydroxybenzyl-N-methyl-gamma-lactam) and Ginkgo biloba extract and its active components.

Topics: Alkaloids; Animals; Benzofurans; Berberine; China; Cholinesterase Inhibitors; Diterpenes; Dopamine Agonists; Dopamine Antagonists; Drugs, Chinese Herbal; Epoxy Compounds; Ginkgo biloba; Humans; Immunosuppressive Agents; Lactams; Lignans; Neuroprotective Agents; Phenanthrenes; Rutaceae; Sesquiterpenes

To investigate the inhibitory activity of HIF-1 by triptolide and manasaantin A, two cell-based models with luciferase report gene assay were established.. Two cell-based models of HIF-1 were used to evaluate HIF-1 inhibition activity of triptolide and manasaantin A. Secreted VEGF expression induced by hypoxia was detected by ELISA with two compounds. The growth inhibition of different solid tumor cell lines was measured by the MTT assay.. The expression of firefly luciferase was induced by hypoxia in U251-HRE and T47D-HRE cells. U251-HRE model was suitable for the detection of HIF-1 inhibition activity of triptolide. The IC50 of triptolide on HIF-1 activity was (3.4 +/- 0.5) x 10(-8) mol x L(-1). The report gene assay using T47D cells co-transfected with pGL2-TK-HRE and pRL-CMV showed more sensitive inhibition activity of HIF-1 on manassantin A than that of detected by U251-HRE model. The IC50 of manassantin A on HIF-1 activity was (2.4 +/- 0.6) x 10(-8) mol x L(-1). HIF-1 target gene VEGF was also inhibited by test compounds on protein level in T47D cells. Manasaantin A showed selective inhibition on the growth of human solid cancer cell lines, especially on breast cancer and pancreatic cancer cells. Meanwhile, triplotide showed strong proliferation inhibition activity on all tested cell lines.. It is very important to select a suitable cell-based report gene assay of HIF-1 for screening of different kinds of inhibitor.

Topics: Cell Line, Tumor; Cell Proliferation; Diterpenes; Drug Evaluation, Preclinical; Epoxy Compounds; Humans; Hypoxia-Inducible Factor 1; Lignans; Luciferases; Models, Biological; Neoplasms; Phenanthrenes