Neuroprotection and enhanced neurogenesis by extract from the tropical plant Knema laurina after inflammatory damage in living brain tissue.
Inflammatory reactions in the CNS, resulting from a loss of control and involving a network of non-neuronal and neuronal cells, are major contributors to the onset and progress of several major neurodegenerative diseases. Therapeutic strategies should therefore keep or restore the well-controlled and finely-tuned balance of immune reactions, and protect neurons from inflammatory damage. In our study, we selected plants of the Malaysian rain forest by an ethnobotanic survey, and investigated them in cell-based-assay-systems and in living brain tissue cultures in order to identify anti-inflammatory and neuroprotective effects. We found that alcoholic extracts from the tropical plant Knema laurina (Black wild nutmeg) exhibited highly anti-inflammatory and neuroprotective effects in cell culture experiments, reduced NO- and IL-6-release from activated microglia cells dose-dependently, and protected living brain tissue from microglia-mediated inflammatory damage at a concentration of 30 microg/ml. On the intracellular level, the extract inhibited ERK-1/2-phosphorylation, IkB-phosphorylation and subsequently NF-kB-translocation in microglia cells. K. laurina belongs to the family of Myristicaceae, which have been used for centuries for treatment of digestive and inflammatory diseases and is also a major food plant of the Giant Hornbill. Moreover, extract from K. laurina promotes also neurogenesis in living brain tissue after oxygen-glucose deprivation. In conclusion, extract from K. laurina not only controls and limits inflammatory reaction after primary neuronal damage, it promotes moreover neurogenesis if given hours until days after stroke-like injury.
Häke
Ines
I
Institute of Immunology, Medical Faculty, Otto-von-Guericke-University Magdeburg, Germany.
Schönenberger
Silvia
S
Neumann
Jens
J
Franke
Katrin
K
Paulsen-Merker
Katrin
K
Reymann
Klaus
K
Ismail
Ghazally
G
Bin Din
Laily
L
Said
Ikram M
IM
Latiff
A
A
Wessjohann
Ludger
L
Zipp
Frauke
F
Ullrich
Oliver
O
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001973:Bromodeoxyuridine / Q000378:metabolism; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000089622:Doublecortin Domain Proteins; D004660:Encephalitis / Q000188:drug therapy* / Q000209:etiology; D005947:Glucose / Q000172:deficiency; D018698:Glutamic Acid / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D000860:Hypoxia / Q000188:drug therapy; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D008070:Lipopolysaccharides / Q000494:pharmacology; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000187:drug effects; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D026324:Myristicaceae / Q000737:chemistry*; D055495:Neurogenesis / Q000187:drug effects*; D009479:Neuropeptides / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009924:Organ Culture Techniques; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000627:therapeutic use*
D000089622:Doublecortin Domain Proteins; D008070:Lipopolysaccharides; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D018696:Neuroprotective Agents; D010936:Plant Extracts; D018698:Glutamic Acid; D020930:MAP Kinase Kinase Kinases; D001973:Bromodeoxyuridine; D005947:Glucose