ABSTRACT
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.
Subject(s)
Encephalitis/drug therapy , Myristicaceae/chemistry , Neurogenesis/drug effects , Neuroprotective Agents/therapeutic use , Phytotherapy , Plant Extracts/therapeutic use , Analysis of Variance , Animals , Animals, Newborn , Bromodeoxyuridine/metabolism , Cell Line, Transformed , Cell Survival/drug effects , Disease Models, Animal , Dose-Response Relationship, Drug , Doublecortin Domain Proteins , Encephalitis/etiology , Glucose/deficiency , Glutamic Acid/pharmacology , Hippocampus/drug effects , Hippocampus/pathology , Hypoxia/drug therapy , Infarction, Middle Cerebral Artery/complications , Lipopolysaccharides/pharmacology , MAP Kinase Kinase Kinases/metabolism , Mice , Microglia/drug effects , Microtubule-Associated Proteins/metabolism , Neuropeptides/metabolism , Organ Culture Techniques , Plant Extracts/chemistryABSTRACT
A new modified stilbene dimer, diptoindonesin D (1), was isolated from the acetone extract of the tree bark of Hopea dryobalanoides, together with seven known compounds, parviflorol (2), (-)-balanocarpol (3), heimiol A (4), hopeafuran (5), (+)-alpha-viniferin (6), vaticanol B (7) and (-)-hopeaphenol (8). Cytotoxic properties of compounds 1-8 were evaluated against murine leukemia P-388 cells. Compound 8 was found to be the most active with IC50 of 5.7 microM.
