losartan-potassium and epigallocatechin-gallate

Inhibition of microglial over-activation is an important strategy to counter balance neurodegenerative progression. We previously demonstrated that the adenosine monophosphate-activated protein kinase (AMPK) may be a therapeutic target in mediating anti-neuroinflammatory responses in microglia. Brain-derived neurotrophic factor (BDNF) is one of the major neurotrophic factors produced by astrocytes to maintain the development and survival of neurons in the brain, and have recently been shown to modulate homeostasis of neuroinflammation. Therefore, the present study focused on BDNF-mediated neuroinflammatory responses and may provide an endogenous regulation of neuroinflammation. Among the tested neuroinflammation, epigallocatechin gallate (EGCG) and minocycline exerted BDNF upregulation to inhibit COX-2 and proinflammatory mediator expressions. Furthermore, both EGCG and minocycline upregulated BDNF expression in microglia through AMPK signaling. In addition, minocycline and EGCG also increased expressions of erythropoietin (EPO) and sonic hedgehog (Shh). In the endogenous modulation of neuroinflammation, astrocyte-conditioned medium (AgCM) also decreased the expression of COX-2 and upregulated BDNF expression in microglia. The anti-inflammatory effects of BDNF were mediated through EPO/Shh in microglia. Our results indicated that the BDNF-EPO-Shh novel-signaling pathway underlies the regulation of inflammatory responses and may be regarded as a potential therapeutic target in neurodegenerative diseases. This study also reveals a better understanding of an endogenous crosstalk between astrocytes and microglia to regulate anti-inflammatory actions, which could provide a novel strategy for the treatment of neuroinflammation and neurodegenerative diseases.

Topics: Animals; Anti-Inflammatory Agents; Astrocytes; Brain-Derived Neurotrophic Factor; Catechin; Cell Line; Culture Media, Conditioned; Cyclooxygenase 2; Erythropoietin; Hedgehog Proteins; Humans; Inflammation; Inflammation Mediators; Lipopolysaccharides; Mice; Microglia; Minocycline; Models, Biological; Neuroprotective Agents; Signal Transduction

Epigallocatechin-3-gallate (EGCg) is widely recognised as a powerful antioxidant and free radical scavenger. This study examined the radioprotective effects of EGCg on human granulopoiesis and erythropoiesis. Highly purified human CD34(+) haematopoietic stem/progenitor cells were prepared from human placental/umbilical cord blood. The cells were exposed to X rays at a dose rate of ∼1 Gy min(-1) and then cultured in a medium supplemented with either granulocyte colony-stimulating factor (G-CSF) or erythropoietin (EPO). EGCg (100 nM) was added to the culture immediately before or after X-irradiation. The concentration of 100-nM EGCg was determined in the authors' previous study. The number of granulocyte and erythrocyte colonies generated by X-irradiated CD34(+) cells decreased in a dose-dependent manner. Although EGCg addition yielded an ∼2-fold increase in the proliferation of each haematopoietic progenitor, no significant protective effect was observed in the surviving fraction of granulocyte progenitors (G-CSF alone: D(0)=1.06 Gy, n=1.14). However, EGCg addition before or after irradiation conferred a significantly higher protective effect on erythrocyte colony formation compared with the control (EPO alone: D(0)=0.66 Gy, n=1.56; EGCg (before): D(0)=0.43 Gy, n=5.48). EGCg addition before irradiation significantly improved the survival of erythroid progenitors subjected to radiation of <1 Gy. These results suggest that EGCg is more protective of erythropoiesis than granulopoiesis from radiation damage.

Topics: Antigens, CD34; Catechin; Cell Lineage; Erythrocytes; Erythropoietin; Female; Granulocyte Colony-Stimulating Factor; Granulocytes; Hematopoietic Stem Cells; Humans; Placenta; Pregnancy; Radiation-Protective Agents; Recombinant Proteins; Stem Cells; Umbilical Cord; X-Rays