Ulva conglobata, a marine algae, has neuroprotective and anti-inflammatory effects in murine hippocampal and microglial cells

It has been reported that inflammatory processes are associated with the pathophysiology of Alzheimer's disease (AD), and the treatment of AD using anti-inflammatory agents slows the progress of AD. Marine algae have been utilized in food products as well as in medicine products for a variety of purposes. In this study, we investigated the neuroprotective effects of methanol extracts of Ulva conglobata (U. conglobata), a marine algae, on glutamate-induced neurotoxicity in the murine hippocampal HT22 cell line and the anti-inflammatory effects on interferon gamma (IFN-gamma)-induced microglial activation in BV2 cells. U. conglobata methanol extracts significantly attenuated the neurotoxicity induced by glutamate in HT22 cells and inhibited nitric oxide production induced by IFN-gamma in BV2 cells. U. conglobata methanol extract treatments were also examined and it was found that they almost completely suppressed the expression of the proinflammatory enzyme cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS). These results suggest that U. conglobata possesses therapeutic potential for combating neurodegenerative diseases associated with neuroinflammation.

[1]  E. Uemura,et al.  Microglial release of nitric oxide by the synergistic action of β-amyloid and IFN-γ , 1995, Brain Research.

[2]  J. Buxbaum,et al.  Neuronal cyclooxygenase 2 expression in the hippocampal formation as a function of the clinical progression of Alzheimer disease. , 2001, Archives of neurology.

[3]  L. Ignarro,et al.  Inducible Nitric-oxide Synthase and Nitric Oxide Production in Human Fetal Astrocytes and Microglia , 1997, The Journal of Biological Chemistry.

[4]  Stichtenoth Do,et al.  COX-2 and the kidneys. , 2000 .

[5]  Y. Ichimori,et al.  β-Amyloid protein-dependent nitric oxide production from microglial cells and neurotoxicity , 1996, Brain Research.

[6]  Patrick L. McGeer,et al.  Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer's disease , 1996, Neurology.

[7]  J. Vane,et al.  Nonsteroid drug selectivities for cyclo-oxygenase-1 rather than cyclo-oxygenase-2 are associated with human gastrointestinal toxicity: a full in vitro analysis. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[8]  M. Ball,et al.  Gene expression profiling of 12633 genes in Alzheimer hippocampal CA1: Transcription and neurotrophic factor down‐regulation and up‐regulation of apoptotic and pro‐inflammatory signaling , 2002, Journal of neuroscience research.

[9]  P. Worley,et al.  COX-2, a synaptically induced enzyme, is expressed by excitatory neurons at postsynaptic sites in rat cerebral cortex. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[10]  J. Rodrigo,et al.  Expression of nitric oxide system in clinically evaluated cases of Alzheimer's disease , 2004, Neurobiology of Disease.

[11]  D. Dewitt,et al.  Characterization of inducible cyclooxygenase in rat brain , 1995, The Journal of comparative neurology.

[12]  N. Awad Biologically active steroid from the green alga Ulva lactuca , 2000, Phytotherapy research : PTR.

[13]  Patrick L. McGeer,et al.  Inflammatory processes in Alzheimer's disease , 2003, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[14]  D. Carter,et al.  Ibuprofen: effect on inducible nitric oxide synthase. , 1997, Brain research. Molecular brain research.

[15]  M. Colasanti,et al.  Inhibition of inducible nitric oxide synthase mRNA expression by basic fibroblast growth factor in human microglial cells , 1995, Neuroscience Letters.

[16]  J. Calleja,et al.  Antiinflammatory, analgesic and free radical scavenging activities of the marine microalgaeChlorella stigmatophora andPhaeodactylum tricornutum , 2001, Phytotherapy research : PTR.

[17]  H. Manev,et al.  New anti-inflammatory treatment strategy in Alzheimer's disease. , 2000, Japanese journal of pharmacology.

[18]  G. Landreth,et al.  Inflammatory Mechanisms in Alzheimer's Disease: Inhibition of β-Amyloid-Stimulated Proinflammatory Responses and Neurotoxicity by PPARγ Agonists , 2000, The Journal of Neuroscience.

[19]  A. Hofman,et al.  Nonsteroidal antiinflammatory drugs and the risk of Alzheimer's disease. , 2001, The New England journal of medicine.

[20]  D. Dickson,et al.  Inducible nitric oxide synthase immunoreactivity in the Alzheimer disease hippocampus: association with Hirano bodies, neurofibrillary tangles, and senile plaques. , 1999, Journal of neuropathology and experimental neurology.

[21]  Carol A. Barnes,et al.  Expression of a mitogen-inducible cyclooxygenase in brain neurons: Regulation by synaptic activity and glucocorticoids , 1993, Neuron.

[22]  Jae-Kwan Hwang,et al.  Anti-oxidant and anti-inflammatory activities of macelignan in murine hippocampal cell line and primary culture of rat microglial cells. , 2005, Biochemical and biophysical research communications.

[23]  W F Stewart,et al.  Risk of Alzheimer's disease and duration of NSAID use , 1997, Neurology.

[24]  J. Rodés,et al.  Cyclooxygenase‐derived products modulate the increased intrahepatic resistance of cirrhotic rat livers , 2003, Hepatology.

[25]  D. Selkoe,et al.  Relationship of microglia and astrocytes to amyloid deposits of Alzheimer disease , 1989, Journal of Neuroimmunology.

[26]  M. T. Saçan,et al.  A case study on algal response to raw and treated effluents from an aluminum plating plant and a pharmaceutical plant. , 2006 .

[27]  D. Ferrari,et al.  Activation of microglial cells by β-amyloid protein and interferon-γ , 1995, Nature.

[28]  C. Cotman,et al.  β-Amyloid stimulates glial cells in vitro to produce growth factors that accumulate in senile plaques in Alzheimer's disease , 1992, Brain Research.

[29]  D. Casper,et al.  Ibuprofen protects dopaminergic neurons against glutamate toxicity in vitro , 2000, Neuroscience Letters.