Antimalarial and analgesic activities of root extract of Panicum maximum

Background: Panicum maximum is used as malarial remedy traditionally and the leaf extract has been found to possess antimalarial, analgesic and anticancer properties. Objective: The ethanol root extract of Panicum maximum were evaluated for antiplasmodial and analgesic activities in rodents. Methods: The crude root extract (137 – 547mg/kg) of Panicum maximum were investigated for antiplasmodial activity against chloroquine sensitive Plasmodium berghei infections in mice. The antiplasmodial activity during early and established infections as well as prophylactic were investigated. Artesunate 5mg/kg and pyrimethamine 1.2mg/kg were used as positive controls. Analgesic activity of the crude extract/fractions was also evaluated against acetic acid, formalin and heat-induced pains. Results: The extract dose-dependently reduced parasitaemia induced by chloroquine sensitive Plasmodium berghei infection in prophylactic, suppressive and curative models in mice. These reductions were statistically significant (p<0.001). They also improved the mean survival time (MST) from 13 to 28 days relative to control (p<0.001).  The activity of extract was weak compared to that of the standard drugs used (artesunate and pyrimethamine). On chemically and thermally- induced pains, the extract inhibited acetic acid and formalin-induced inflammation as well as hot plate-induced pain in mice. These inhibitions were statistically significant (p<0.001) and in a dose-dependent fashion. Conclusion: Panicum maximum root extract has antiplasmodial and analgesic activities which may in part be mediated through the chemical constituents of the plant. Key words: Panicum maximum, analgesic, antimalaria

Stat3 Mediates Expression of Autotaxin in Breast Cancer

We determined that signal transducer and activator of transcription 3 (Stat3) is tyrosine phosphorylated in 37% of primary breast tumors and 63% of paired metastatic axillary lymph nodes. Examination of the distribution of tyrosine phosphorylated (pStat3) in primary tumors revealed heterogenous expression within the tumor with the highest levels found in cells on the edge of tumors with relatively lower levels in the central portion of tumors. In order to determine Stat3 target genes that may be involved in migration and metastasis, we identified those genes that were differentially expressed in primary breast cancer samples as a function of pStat3 levels. In addition to known Stat3 transcriptional targets (Twist, Snail, Tenascin-C and IL-8), we identified ENPP2 as a novel Stat3 regulated gene, which encodes autotaxin (ATX), a secreted lysophospholipase which mediates mammary tumorigenesis and cancer cell migration. A positive correlation between nuclear pStat3 and ATX was determined by immunohistochemical analysis of primary breast cancer samples and matched axillary lymph nodes and in several breast cancer derived cell lines. Inhibition of pStat3 or reducing Stat3 expression led to a decrease in ATX levels and cell migration. An association between Stat3 and the ATX promoter, which contains a number of putative Stat3 binding sites, was determined by chromatin immunoprecipitation. These observations suggest that activated Stat3 may regulate the migration of breast cancer cells through the regulation of ATX