CI-III

The aim of this study was to investigate the antidepressive effects of timosaponin B-III (TB-III) and the underlying mechanism. A postpartum depression (PPD) mouse model was established by the administration of dexamethasone sodium phosphate during pregnancy. Mice with PPD were assigned to the following groups: Model, fluoxetine and high, medium and low doses of TB-III. Post-parturient mice without PPD served as a normal control group. To examine the effect of TB-III, mice were treated with TB-III, then forced swimming tests (FSTs) and tail suspension tests (TSTs) were performed to evaluate depression. Serum and hippocampal cytokines, namely tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and IL-10, were quantified using ELISAs and protein levels of hippocampal brain-derived neurotrophic factor (BDNF), glucagon synthase kinase (GSK)-3β, glutamate receptor subunit 1 (GluR1), postsynaptic density protein 95 (PSD95) and synapsin I were quantified using western blot analysis. Compared with those in the control group, immobility time in the FST and TST, serum and hippocampal TNF-α, IL-1β and IL-6 levels and hippocampal IL-10 levels were increased significantly in the model group (P<0.01). Serum IL-10 levels and hippocampal levels of BDNF, GSK-3β, GluR1, PSD95 and synapsin I decreased significantly in the model group compared with the control group (P<0.01). Fluoxetine or TB-III (10, 20 or 40 mg/kg) treatment significantly decreased immobility times in the FST and TST (P<0.01) and significantly reversed the aforementioned alterations in cytokine and protein levels (P<0.01). Thus, TB-III exhibited a protective effect against depression in PPD and such effects may have been mediated via the regulation of inflammatory cytokines, the BNDF signaling pathway and synaptic plasticity-related proteins.

Targeted tumor therapy is a perspective procedure to specifically destroy the cancer tissues with eliminating or at least decreasing the side effects of anticancer drugs. For this purpose the drug molecule is attached to a targeting moiety (e.g. peptide hormones) that recognizes tumor specific or overexpressed receptors on cancer cells. The in vitro cytostatic or cytotoxic assays do not give proper information whether the tumor growth inhibitory effect of the conjugate is better than the activity of the free drug. Only in vivo studies are adequate to answer this question. However, the selection of the appropriate tumor model is important to eliminate the false positive results. In our studies a gonadotropin-releasing hormone analog (GnRH-III) was applied as targeting moiety in drug conjugates. The in vivo antitumor activity of these conjugates was investigated on mice bearing subcutaneously or orthotopically szigdeveloped tumors. The subcutaneously implanted tumor model which is isolated from its surroundings may provide false results in tumor growth inhibition. In contrast, the orthotopically developed tumor is a better model representing appropriate anatomical and clinical status of cancer. Therefore, the orthotopical colon cancer developed in our laboratory is a suitable model for the study of the antitumor activity of the conjugates prepared for targeted tumor therapy.