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 µg/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.
Keywords
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References
- Methods to induce primary and secondary traumatic damage in organotypic hippocampal slice cultures.Brain Res. Brain. Res. Protoc. 2000; 5: 153-158
- Ismail G. Phytochemical Survey of Plants of Tawau Hills Park, Sabah in A Scientific Journey through Borneo — Tawau Hills Park. Pelanduk Publications, Kuala Lumpur1995: 139-150
- MEK1 protein kinase inhibition protects against damage resulting from focal cerebral ischemia.Proc. Natl. Acad. Sci. U. S. A. 1999; 96: 12866-12869
- N-methyl-d-aspartate receptor-mediated increase of neurogenesis in adult rat dentate gyrus following stroke.Eur. J. Neurosci. 2001; 14: 10-18
- Immortalization of murine microglial cells by a v-raf/v-myc carrying retrovirus.J. Neuroimmunol. 1990; 27: 229-237
- Microglial-produced nitric oxide and reactive nitrogen oxides mediate neuronal cell death.Brain Res. 1992; 587: 250-256
- Monoclonal antibody to the ICAM-1 adhesion site reduces neurological damage in a rabbit cerebral embolism stroke model.Exp. Neurol. 1993; 119: 215-219
- A Dictionary of the Economic Products of the Malay Peninsula, Crown Agents for the Colonies. London, U. K.1935
- Ethnobotany part 2.Sarawak Mus. J. 1978; 47: 243-270
- Ethnobotany part 1.Sarawak Mus. J. 1975; 44: 36-51
- Activated microglia mediate neuronal cell injury via a nitric oxide mechanism.J. Immunol. 1992; 149: 2736-2741
- Anti-inflammatory treatment in oxygen–glucose-deprived hippocampal slice cultures is neuroprotective and associated with reduced cell proliferation and intact neurogenesis.Neurobiol. Dis. 2006; 23: 247-259
- Statins induce angiogenesis, neurogenesis, and synaptogenesis after stroke.Ann. Neurol. 2003; 53: 743-751
- Cerebral protection in homozygous null ICAM-1 mice after middle cerebral artery occlusion. Role of neutrophil adhesion in the pathogenesis of stroke.J. Clin. Invest. 1996; 97: 209-216
- Antioxidant therapy: a new pharmacological approach in shock, inflammation, and ischemia/reperfusion injury.Pharmacol. Rev. 2001; 53: 135-159
- Pathobiology of ischaemic stroke: an integrated view.Trends Neurosci. 1999; 22: 391-397
- Medicinal plants used by Kedayan community in Sarawak.Sarawak Mus. J. 1993; 65: 45-57
- Medicinal plants used by various ethnic groups in Sabah, Malaysian Borneo.Sabah Parks Nat. J. 2000; 3: 99-108
- Medicinal plants of Sabah — part I.Pharm. Biol. 2003; 41: 340-346
- Antioxidants, oxidative stress, and degenerative neurological disorders.Proc. Soc. Exp. Biol. Med. 1999; 222: 236-245
- Inflammatory resolution: new opportunities for drug discovery.Nat. Rev. Drug. Discov. 2004; 3: 401-416
- Toward wisdom from failure: lessons from neuroprotective stroke trials and new therapeutic directions.Stroke. 2002; 33: 2123-2136
- Further alkyl and alkenylphenols of Knema laurina and Knema austrosiamensis: location of the double bond in the alkenyl side chains.Phytochem. 1996; 43: 1333-1337
- Analysis of nitrate, nitrite, and [15N] nitrate in biological fluids.Anal. Biochem. 1982; 126: 131-138
- Fluorescent dye prelabelled microglial cells migrate into organotypic hippocampal slice cultures and ramify.Eur. J. Neurosci. 1997; 9: 863-866
- Nuclear factor-kappa B and mitogen-activated protein kinases mediate nitric oxide-enhanced transcriptional expression of interferon-beta.J. Biol. Chem. 2003; 278: 8018-8027
- Constituents of Knema laurina and Knema tenuinervia ssp. setosa.Planta Med. 1991; 57: 575-577
- Neolignans from Piper futokadsura and their inhibition of nitric oxide production.Chem. Pharm. Bull. 2005; 53: 121-124
- Latiff A. An Annotated Checklist of Seed Plants of Fraser's Hill in Fraser's Hill: Physical, Biological and Socio-economic Environments. UKM Publications, 2001: 245-274
- Contribution of microglia/macrophages to expansion of infarction and response of oligodendrocytes after focal cerebral ischemia in rats.Stroke. 2000; 31: 1735-1743
- The role of monoamine metabolism in oxidative glutamate toxicity.J. Neurosci. 1996; 16: 6394-6401
- Role of cell adhesion molecules in brain injury after transient middle cerebral artery occlusion in the rat.Brain Res. 1994; 656: 344-352
- Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays.J. Immunol. Methods. 1983; 65: 55-63
- Intravenous administration of MEK inhibitor U0126 affords brain protection against forebrain ischemia and focal cerebral ischemia.Proc. Natl. Acad. Sci. U. S. A. 2001; 98: 11569-11574
- The Rat Brain in Stereotaxic Coordinates.4th edn. Academic Press, New York1998
- 7-Hydroxylated epiandrosterone (7-OH-EPIA) reduces ischaemia-induced neuronal damage both in vivo and in vitro.Eur. J. Neurosci. 2003; 18: 117-124
- Cashew nut dermatitis.South Med. J. 1994; 87: 542-546
- Characterisation of an experimental model of stroke produced by intracerebral microinjection of endothelin-1 adjacent to the rat middle cerebral artery.J. Neurosci. Methods. 1995; 60: 125-131
- Alkyl and phenylalkyl anacardic acids from Knema elegans seed oil.J. Nat. Prod. 1980; 43: 724-730
- Inflammation and glial responses in ischemic brain lesions.Prog. Neurobiol. 1998; 56: 149-171
- Anti-inflammatory treatment with the p38 mitogen-activated protein kinase inhibitor SB239063 is neuroprotective, decreases the number of activated microglia and facilitates neurogenesis in oxygen–glucose-deprived hippocampal slice cultures.Eur. J. Pharmacol. 2008; 592: 55-61
- Neuronal nitric oxide synthase and ischemia-induced neurogenesis.J. Cereb. Blood Flow Metab. 2005; 25: 485-492
- Anacardic acid (6-nonadecyl salicylic acid), an inhibitor of histone acetyltransferase, suppresses expression of nuclear factor-kappaB-regulated gene products involved in cell survival, proliferation, invasion, and inflammation through inhibition of the inhibitory subunit of nuclear factor-kappaBalpha kinase, leading to potentiation of apoptosis.Blood. 2008; 111: 4880-4891
- Potential immunosuppressive and antiinflammatory activities of Malaysian medicinal plants characterized by reduced cell surface expression of cell adhesion molecules.Phytother. Res. 2001; 15: 681-686
- Regulation of microglial expression of integrins by poly(ADP-ribose)polymerase-1.Nat. Cell. Biol. 2001; 3: 1035-1042
- Neuroprotection in cerebral ischaemia: facts and fancies — the need for new approaches.Cerebrovasc. Dis. 2004; 17: 153-166
- Neurotrophic effects of taulaumidine, a neolignane from Aristolochia arcuata, in primary cultured rat cortical cells.Planta Med. 2004; 70: 598-602
- Anti-ICAM-1 antibody reduces ischemic cell damage after transient middle cerebral artery occlusion in the rat.Neurology. 1994; 44: 1747-1751
- Sildenafil (Viagra) induces neurogenesis and promotes functional recovery after stroke in rats.Stroke. 2002; 33: 2675-2680
Article info
Publication history
Published online: November 25, 2008
Accepted:
October 13,
2008
Received in revised form:
October 7,
2008
Received:
May 10,
2008
Identification
Copyright
© 2008 Elsevier B.V. Published by Elsevier Inc. All rights reserved.