CASTICIN INHIBITS LIPOPOLYSACCHARIDE-INDUCED ACTIVATION OF SIGNALING PATHWAYS IN MICROGLIAL CELLS IN VITRO

Microglia are primary immune cells residing in the central nervous system.The play key rolesin homeostasis, inflammatory responses and tissue repair in brain. Microglial activation isclosely associated with neuroinflammation which plays an important role in theneurodegenerative diseases [1,2]. Mitogen activated protein kinases (MAPKs) and IκBsignaling pathways are involved in the production of inflammatory cytokines. Activation ofmicroglia results in the induction of these intracellular signalling pathways leading to changesof genes that are related to inflammation. Flavonoids are naturally occurring polyphenoliccompounds that are known to have neuroprotective effects. Casticin is an active componentof Vitex agnus-castus. It is a polymethylflavone which has been shown to have anticancer andantioxidant activities [3-5]. In the present study, we investigated the effect of casticin on thelipopolysaccharide (LPS)-activated activation of p38 MAPK and IκB pathways in microglial cellsin vitro. N9 mouse microglial cells were used in the study. The cells were treated with 0.1, 0.5and 1 μM of casticin for 24 h and the viability of cells was determined using WST-1 assay. N9cells were pretreated with 0.1 and 0.5 μM of casticin for 1 h and then incubated with 1 μg/mLof LPS for 4, 8 and 24h. LPS-induced phosphorylation levels of p38 MAPK and of IκB-α wereanalyzed by Western blotting. The viability of cells incubated with 0.1 and 0.5 μM of casticindid not show significant differences compared to untreated cells, whereas 1 μM of casticindecreased cell viability to 89.3% at 24 h. Phosphorylation of p38 MAPK and of IκB-α wereinduced after LPS incubation at 2, 4 and 8 h compared to control cells. Casticin decreased LPSinduced phosphorylation of p38 MAPK at concentrations of 0.1 and 0.5 μM at 4 h and at theconcentration of 0.5 μM at 8 h. Casticin also inhibited LPS-induced phosphorylation of IκB-αat concentrations of 0.1 and 0.5 μM at 4 h. Our results demonstrate that casticin couldregulate inflammation by inhibiting phosphorylation of p38 MAPK and IκB-α in a time- anddose-depent manner. These findings suggest a neuroprotective effect and promisingtherapeutic potential of casticin for neuroinflammation.</p

Erythropoietin signaling and neuroprotection

Erythropoietin (Epo) plays an essential role in the regulation of erythropoiesis by stimulating growth, preventing apoptosis, and promoting terminal differentiation of erythroid progenitors. The Epo receptor belongs to the cytokine receptor superfamily. Epo and its receptor have been localized to several nonhematopoietic tissues and cells, including the central and peripheral nervous systems, endothelial cells and heart. Epo exerts neuronal, vascular and cardiac protection through multiple signaling pathways in different models of tissue and cell injury in vitro and in vivo, such as ischemia, hypoxia. inflammation and oxidative stress. As a result, Epo has been suggested as a possible candidate in the treatment of neurological and cardiac disorders. A better understanding of cellular pathways and molecules modulated by Epo signaling is crucial in determining the potential therapeutic application of recombinant human Epo and may provide further insights in the development of both better synergistic therapies as well as new molecular targets. In this review, we summarize the current knowledge on the signaling pathways by which Epo offers neuroprotection and cytoprotection, signal transduction systems modulated by Epo and negative regulation of Epo signaling in the nervous system

Inverted Polymer Solar Cells Using CdS Thin Film Grown by Successive Ionic Layer Adsorption and Reaction Method as Electron Transport Layer

In this work, CdS thin films were coated by Successive Ionic Layer Adsorption and Reaction (SILAR) technique with various immersion cycles and used as electron transport layer (ETL). The effects of number of immersion cycle on the optical, structural and morphological properties of as prepared and annealed CdS films were investigated. The inverted type geometry hybrid solar cells were fabricated by using CdS films as electron transport layer (ETL), blend of P3HT(poly(3-hexyl) thiophene) and PCBM([6,6]-phenylC61 butyric acid methyl ester) as photoactive layer, and PEDOT:PSS:IPA and V2O5 films as hole transport layers (HTL). The power conversion efficiencies of the inverted hybrid solar cells were significantly enhanced by improved morphology, chemical composition of surface, optical properties of ETL and type of HTL