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Depression: 21st Century Solutions + The Dark Side of Wheat

Abstract Title:

Apigenin and luteolin modulate microglial activation via inhibition of STAT1-induced CD40 expression.

Abstract Source:

J Neuroinflammation. 2008;5:41. Epub 2008 Sep 25. PMID: 18817573

Abstract Author(s):

Kavon Rezai-Zadeh, Jared Ehrhart, Yun Bai, Paul R Sanberg, Paula Bickford, Jun Tan, R Douglas Shytle

Abstract:

BACKGROUND: It is well known that most neurodegenerative diseases are associated with microglia-mediated inflammation. Our previous research demonstrates that the CD40 signaling is critically involved in microglia-related immune responses in the brain. For example, it is well known that the activation of the signal transducer and activator of transcription (STAT) signaling pathway plays a central role in interferon-gamma (IFN-gamma)-induced microglial CD40 expression. We and others have previously reported that microglial CD40 expression is significantly induced by IFN-gamma and amyloid-beta (A beta) peptide. Recent studies have shown that certain flavonoids possess anti-inflammatory and neuroprotective properties distinct from their well-known anti-oxidant effects. In particular, flavonoids, apigenin and luteolin have been found to be effective CD40 immunomodulators. METHODS: Cultured microglia, both N9 and primary derived lines, were treated with flavonoids in the presence of IFN-gamma and/or CD40 ligation to assess any anti-inflammatory effects and/or mechanisms. CD40 expression on microglia was analyzed by fluorescence activated cell sorting (FACS). Anti-inflammatory effects and mechanisms were confirmed by ELISA for interleukin-6 (IL-6) and TNF-alpha, lactate dehydrogenase (LDH) assay, and STAT1 Western blotting. RESULTS: Apigenin and luteolin concentration-dependently suppressed IFN-gamma-induced CD40 expression. Apigenin and luteolin also suppressed microglial TNF-alpha and IL-6 production stimulated by IFN-gamma challenge in the presence of CD40 ligation. In addition, apigenin and luteolin markedly inhibited IFN-gamma-induced phosphorylation of STAT1 with little impact on cell survival. CONCLUSION: Our findings provide further support for apigenin and luteolin's anti-inflammatory effects and suggest that these flavonoids may have neuroprotective/disease-modifying properties in various neurodegenerative disorders, including Alzheimer's disease (AD).

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Sayer Ji
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Depression: 21st Century Solutions + The Dark Side of Wheat

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