Luteolin
Information on nutritional supplements people with ALS have been taking
Effects on ALS
Apigenin and luteolin concentration-dependently suppressed IFN-γ-induced CD40 expression. Apigenin and luteolin also suppressed microglial TNF-α and IL-6 production stimulated by IFN-gamma challenge in the presence of CD40 ligation. In addition, apigenin and luteolin markedly inhibited IFN-γ-induced phosphorylation of STAT1 with little impact on cell survival. [1]
Luteolin concentration-dependently abolished LPS/IFN-γ-induced NO, tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) production as well as inducible nitric oxide synthase (iNOS) protein and mRNA expression. Luteolin exerted an inhibitory effect on transcription factor activity including nuclear factor κB (NF-κB), signal transducer and activator of transcription 1 (STAT1) and interferon regulatory factor 1 (IRF-1) in LPS/IFN-γ-activated BV-2 microglial cells. Biochemical and pharmacological studies revealed that the anti-inflammatory effect of luteolin was accompanied by down-regulation of extracellular signal-regulated kinase (ERK), p38, c-Jun N-terminal kinase (JNK), Akt and Src. [2]
References
[1] <bibtex> @article{Rezai-Zadeh2008, 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).}, author = {Rezai-Zadeh, Kavon and Ehrhart, Jared and Bai, Yun and Sanberg, Paul R and Bickford, Paula and Tan, Jun and Shytle, R Douglas}, doi = {10.1186/1742-2094-5-41}, file = {:C$\backslash$:/Users/riku/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Rezai-Zadeh et al. - 2008 - Apigenin and luteolin modulate microglial activation via inhibition of STAT1-induced CD40 expression.pdf:pdf}, issn = {1742-2094}, journal = {Journal of neuroinflammation}, keywords = {Animals,Anti-Inflammatory Agents,Anti-Inflammatory Agents: pharmacology,Antigens, CD40,Antigens, CD40: metabolism,Apigenin,Apigenin: pharmacology,Brain,Brain: drug effects,Brain: immunology,Brain: physiopathology,Cells, Cultured,Dose-Response Relationship, Drug,Encephalitis,Encephalitis: drug therapy,Encephalitis: immunology,Encephalitis: physiopathology,Female,Immunologic Factors,Immunologic Factors: pharmacology,Interferon-gamma,Interferon-gamma: drug effects,Interferon-gamma: immunology,Interleukin-6,Interleukin-6: immunology,L-Lactate Dehydrogenase,L-Lactate Dehydrogenase: metabolism,Luteolin,Luteolin: pharmacology,Male,Mice,Mice, Inbred BALB C,Microglia,Microglia: drug effects,Microglia: immunology,Neuroimmunomodulation,Neuroimmunomodulation: drug effects,Neuroimmunomodulation: immunology,Recombinant Proteins,STAT1 Transcription Factor,STAT1 Transcription Factor: antagonists \& inhibito,Signal Transduction,Signal Transduction: drug effects,Signal Transduction: immunology,Tumor Necrosis Factor-alpha,Tumor Necrosis Factor-alpha: immunology}, mendeley-groups = {luteolin}, month = jan, pages = {41}, pmid = {18817573}, title = Template:Apigenin and luteolin modulate microglial activation via inhibition of STAT1-induced CD40 expression., url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2569027\&tool=pmcentrez\&rendertype=abstract}, volume = {5}, year = {2008} } </bibtex>
[2] <bibtex> @article{Kao2011, abstract = {Microglial activation plays a pivotal role in the pathogenesis of neurodegenerative disease by producing excessive proinflammatory cytokines and nitric oxide (NO). Luteolin, a naturally occurring polyphenolic flavonoid antioxidant, has potent anti-inflammatory and neuroprotective properties both in vitro and in vivo. However, the molecular mechanism of luteolin-mediated immune modulation in microglia is not fully understood. In the present study, we report the inhibitory effect of luteolin on lipopolysaccharide (LPS)/interferon $\gamma$ (IFN-$\gamma$)-induced NO and proinflammatory cytokine production in rat primary microglia and BV-2 microglial cells. Luteolin concentration-dependently abolished LPS/IFN-$\gamma$-induced NO, tumor necrosis factor $\alpha$ (TNF-$\alpha$) and interleukin 1$\beta$ (IL-1$\beta$) production as well as inducible nitric oxide synthase (iNOS) protein and mRNA expression. Luteolin exerted an inhibitory effect on transcription factor activity including nuclear factor $\kappa$B (NF-$\kappa$B), signal transducer and activator of transcription 1 (STAT1) and interferon regulatory factor 1 (IRF-1) in LPS/IFN-$\gamma$-activated BV-2 microglial cells. Biochemical and pharmacological studies revealed that the anti-inflammatory effect of luteolin was accompanied by down-regulation of extracellular signal-regulated kinase (ERK), p38, c-Jun N-terminal kinase (JNK), Akt and Src. Further studies have demonstrated that the inhibitory effect of luteolin on intracellular signaling execution and proinflammatory cytokine expression is associated with resolution of oxidative stress and promotion of protein phosphatase activity. Together, these results suggest that luteolin suppresses NF-$\kappa$B, STAT1 and IRF-1 signaling, thus attenuating inflammatory response of brain microglial cells.}, author = {Kao, Tsung-Kuei and Ou, Yen-Chuan and Lin, Shih-Yi and Pan, Hung-Chuan and Song, Pei-Jyuan and Raung, Shue-Ling and Lai, Ching-Yi and Liao, Su-Lan and Lu, Hsi-Chi and Chen, Chun-Jung}, doi = {10.1016/j.jnutbio.2010.01.011}, issn = {1873-4847}, journal = {The Journal of nutritional biochemistry}, keywords = {Animals,Anti-Inflammatory Agents,Anti-Inflammatory Agents: pharmacology,Down-Regulation,Interferon Regulatory Factor-1,Interleukin-1beta,Interleukin-1beta: drug effects,Lipopolysaccharides,Lipopolysaccharides: pharmacology,Luteolin,Luteolin: pharmacology,Mice,Microglia,Microglia: drug effects,NF-kappa B,NF-kappa B: metabolism,Nitric Oxide,Nitric Oxide: physiology,Phosphoprotein Phosphatases,Phosphoprotein Phosphatases: drug effects,Rats,Reactive Oxygen Species,Reactive Oxygen Species: metabolism,STAT1 Transcription Factor,STAT1 Transcription Factor: drug effects,STAT1 Transcription Factor: physiology,Signal Transduction,Signal Transduction: drug effects,Tumor Necrosis Factor-alpha,Tumor Necrosis Factor-alpha: drug effects,Tumor Necrosis Factor-alpha: metabolism}, mendeley-groups = {luteolin}, month = jul, number = {7}, pages = {612--24}, pmid = {21036586}, title = Template:Luteolin inhibits cytokine expression in endotoxin/cytokine-stimulated microglia., url = {http://www.ncbi.nlm.nih.gov/pubmed/21036586}, volume = {22}, year = {2011} } </bibtex>
