Anti-neuroinflammatory Activity of Kamebakaurin From Isodon japonicus via Inhibition of c-Jun NH(2)-Terminal Kinase and p38 Mitogen-Activated Protein Kinase Pathway in Activated Microglial Cells.
Summary of "Anti-neuroinflammatory Activity of Kamebakaurin From Isodon japonicus via Inhibition of c-Jun NH(2)-Terminal Kinase and p38 Mitogen-Activated Protein Kinase Pathway in Activated Microglial Cells."
Compelling evidence supports the notion that the majority of neurodegenerative diseases are associated with microglia-mediated neuroinflammation. Therefore, quelling of microglial activation may lead to neuronal cell survival. The present study investigated the effects of Kamebakaurin (KMBK), a kaurane diterpene isolated from Isodon japonicus HARA (Labiatae), on the production of pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated cytotoxicity in rat primary microglial cultures and the BV-2 cell line. KMBK significantly inhibited the LPS-induced production of nitric oxide (NO) in a concentration-dependent fashion in activated microglial cells. The mRNA and protein levels of inducible nitric oxide synthase (iNOS) and cyclooxycenase-2 (COX-2) were also decreased dose-dependently. Furthermore KMBK inhibited the JNK and p38 mitogen-activated protein kinases (MAPKs) in LPS-stimulated BV-2 microglial cells. Considering the results obtained, the present study authenticated the potential benefits of KMBK as a therapeutic target in ameliorating microglia-mediated neuroinflammatory diseases.
Affiliation
Department of Biotechnology, Konkuk University, Korea.
Journal Details
This article was published in the following journal.
Name: Journal of pharmacological sciences
ISSN: 1347-8648
Pages: 296-308
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21705843
- DOI: http://dx.doi.org/
Medical and Biotech [MESH] Definitions
Betamethasone 17-valerate
The 17-valerate derivative of BETAMETHASONE. It has substantial topical anti-inflammatory activity and relatively low systemic anti-inflammatory activity.
Anti-inflammatory Agents, Non-steroidal
Anti-inflammatory agents that are not steroids. In addition to anti-inflammatory actions, they have analgesic, antipyretic, and platelet-inhibitory actions. They are used primarily in the treatment of chronic arthritic conditions and certain soft tissue disorders associated with pain and inflammation. They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. Inhibition of prostaglandin synthesis accounts for their analgesic, antipyretic, and platelet-inhibitory actions; other mechanisms may contribute to their anti-inflammatory effects. Certain NSAIDs also may inhibit lipoxygenase enzymes or TYPE C PHOSPHOLIPASES or may modulate T-cell function. (AMA Drug Evaluations Annual, 1994, p 1814-5)
Isodon
A plant genus of the family LAMIACEAE. Members contain ent-kaurene type DITERPENES.
Drug Design
The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis.
Bepridil
A long-acting calcium-blocking agent with significant anti-anginal activity. The drug produces significant coronary vasodilation and modest peripheral effects. It has antihypertensive and selective anti-arrhythmia activities and acts as a calmodulin antagonist.
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