The Effects of the Alkaloid Tambjamine J on Mice Implanted with Sarcoma 180 Tumor Cells.

The tambjamines are a small group of bipyrrolic alkaloids that, collectively, display a significant range of biological activities including antitumor, antimicrobial and immunosuppressive properties. The key objective of the present study was to undertake preclinical assessments of tambjamine J (T-J) so as to determine its in vivo antitumor effects. To that end, sarcoma 180 cells were transplanted in mice and the impacts of the title compound then evaluated using a range of protocols including hematological, biochemical, histopathological, genotoxic and clastogenic assays. As a result it was established that this alkaloid has a significant therapeutic window and effectively reduces tumor growth (by 40 % and 79 % at doses of 10 and 20 mg/kg/day, respectively). In this regard it displays similar antitumor activity to the anticancer agent cyclophosphamide and alters animal weight in an analogous manner.

Improvement of in vivo anticancer and antiangiogenic potential of thalidomide derivatives.

The strategy of antiangiogenic drugs is based on inhibiting formation of new blood vessels as alternative to limit cancer progression. In this work, we investigated the antitumor and antiangiogenic potential of eight thalidomide derivatives. Most of the molecules was not cytotoxic but 2a, 2d and 3d revealed weak antiproliferative activity on HL-60, Sarcoma 180 (S180) and normal peripheral blood mononuclear cells. Thalidomide, 2a and 2b were able to inhibit tumor growth (53.5%, 67.9% and 67.4%, respectively) in S180-bearing mice and presented moderate and reversible toxicity on liver, kidneys and spleens. Both analogs (2a and 2b) inhibited cell migration of endothelial (HUVEC) and melanoma cells (MDA/MB-435) at 50µg/mL. Immunohistochemistry labeling assays with CD-31 (PECAM-1) antibody showed microvascular density (MVD) was significantly reduced in thalidomide, 2a and 2b groups (30±4.9, 64.6±1.8 and 46.5±19.5%, respectively) (p<0.05). Neovascularization evaluated by Chorioallantoic Membrane Assay (CAM) with compounds 2a and 2b showed reduction of vessels' number (12. 9±2.3 and 14.8±3.3%), neovascularization area (13.1±1.7 and 14.3±1.7%) and total length of vessels (9.2±1.5 and 9.9±1.9%). On the other hand, thalidomide did not alter vascularization parameters. Consequently, addition of thiosemicarbazone pharmacophore group into the phthalimidic ring improved the in vivo antitumor and antiangiogenic potential of the analogs 2a and 2b.

Mangiferin ameliorates the intestinal inflammatory response and the impaired gastrointestinal motility in mouse model of postoperative ileus.

Our previous study has shown that mangiferin (MGF), a glucosylxanthone from Mangifera indica, exerts gastrointestinal prokinetic action involving a cholinergic mechanism. Postoperative ileus (POI) is a temporary disturbance in gastrointestinal motility following surgery, and intestinal inflammatory response plays a critical role in the pathogenesis of POI. The present study investigated to know whether MGF having anti-inflammatory and prokinetic actions can ameliorate the intestinal inflammation and impaired gastrointestinal transit seen in the mouse model of POI. Experimental POI was induced in adult male Swiss mice by standardized small intestinal manipulation (IM). Twenty-four hours later, gastrointestinal transit was assessed by charcoal transport. MGF was administered orally 1 h before the measurement of GIT. To evaluate the inflammatory response, plasma levels of proinflammatory cytokines TNF-α, IL-1ß, IL-6, and chemokine MCP-1, and the myeloperoxidase activity, nitrate/nitrite level, and histological changes of ileum were determined in mice treated or not with MGF. Experimental POI in mice was characterized by decreased gastrointestinal transit and marked intestinal and systemic inflammatory response. MGF treatment led to recovery of the delayed intestinal transit induced by IM. MGF in ileum significantly inhibited the myeloperoxidase activity, a marker of neutrophil infiltration, and nitrate/nitrite level and reduced the plasma levels of TNF-α, IL-1ß, IL-6, and MCP-1 as well. MGF treatment ameliorates the intestinal inflammatory response and the impaired gastrointestinal motility in the mouse model of POI.