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Cited by 109Seaweed-derived Bioactive CompoundsNatural Compounds in Disease TreatmentFatty Acid Research and Health

Edible blue-green algae reduce the production of pro-inflammatory cytokines by inhibiting NF-κB pathway in macrophages and splenocytes

Open access
Ku, Chai Siah, Pham, Tho X., Park, Youngki, Kim, Bohkyung, Shin, Min Sun, Kang, Insoo, Lee, Jiyoung·2013·Biochimica et Biophysica Acta (BBA) - General Subjects
DOI 10.1016/j.bbagen.2013.01.018PMC PMC3594481
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Abstract

Background Chronic inflammation contributes to the development of pathological disorders including insulin resistance and atherosclerosis. Identification of anti-inflammatory natural products can prevent the inflammatory diseases. Methods Anti-inflammatory effects of blue-green algae (BGA), i.e., Nostoc commune var. Sphaeroides Kützing (NO) and Spirulina Platensis (SP), were compared in RAW 264.7 and mouse bone marrow-derived macrophages (BMM) as well as splenocytes from apolipoprotein E knockout (apoE−/−) mice fed BGA. Results When macrophages pretreated with 100 μg/ml NO lipid extract (NOE) or SP lipid extract (SPE) were activated by lipopolysaccharide (LPS), expression and secretion of pro-inflammatory cytokines, such as tumor necrosis factor α (TNFα), interleukin 1β (IL-1β), and IL-6, were significantly repressed. NOE and SPE also significantly repressed the expression of TNFα and IL-1β in BMM. LPS-induced secretion of IL-6 was lower in splenocytes from apoE−/− fed an atherogenic diet containing 5% NO or SP for 12 weeks. In RAW 264.7 macrophages, NOE and SPE markedly decreased nuclear translocation of NF-κB. The degree of repression of pro-inflammatory gene expression by algal extracts was much stronger than that of SN50, an inhibitor of NF-κB nuclear translocation. Trichostatin A, a pan histone deacetylase inhibitor, increased basal expression of IL-1β and attenuated the repression of the gene expression by SPE. SPE significantly down-regulated mRNA abundance of 11 HDAC isoforms, consequently increasing acetylated histone 3 levels. Conclusion NOE and SPE repress pro-inflammatory cytokine expression and secretion in macrophages and splenocytes via inhibition of NF-κB pathway. Histone acetylation state is likely involved in the inhibition. General significance This study underscores natural products can exert anti-inflammatory effects by epigenetic modifications such as histone acetylation.

AI snapshot

Written from the paper’s full text.

TL;DR

Lipid extracts of edible blue-green algae *Nostoc commune* (NOE) and *Spirulina platensis* (SPE) reduce pro-inflammatory cytokine expression and secretion in macrophages and splenocytes, at least partly by inhibiting NF-κB nuclear translocation. The data also implicate histone deacetylase downregulation and increased histone H3 acetylation in the anti-inflammatory effect.

Key findings

  • In RAW 264.7 macrophages, 100 μg/ml NOE or SPE significantly repressed LPS-induced TNFα, IL-1β, and IL-6 mRNA expression and decreased secretion of TNFα, IL-6, G-CSF, GM-CSF, and MCP-1; significant reductions occurred dose-dependently as low as 25 μg/ml.
  • NOE and SPE also significantly lowered TNFα and IL-1β expression in mouse bone marrow-derived macrophages, and splenocytes from apoE−/− mice fed an atherogenic diet containing 5% NO or SP for 12 weeks secreted significantly less IL-6 after LPS challenge.
  • Both extracts decreased LPS-induced nuclear translocation of NF-κB p65 in RAW 264.7 macrophages, but the repression of TNFα and IL-1β expression was stronger with NOE/SPE than with SN50, an NF-κB nuclear translocation inhibitor.
  • SPE significantly downregulated mRNA abundance of 11 HDAC isoforms and increased acetylated histone 3 by ~2-fold; TSA, a pan HDAC inhibitor, increased basal IL-1β and attenuated SPE-mediated repression.

Methods

  • RAW 264.7 macrophages and mouse bone marrow-derived macrophages were pretreated with 0–100 μg/ml NOE or SPE for 12 h, then activated with LPS (100 ng/ml) for 18 h; splenocytes were isolated from male apoE−/− mice fed a high-fat/high-cholesterol diet with 5% NO or SP for 12 weeks and stimulated with LPS (500 ng/ml) for 20 h.
  • Pro-inflammatory cytokine mRNA was measured by qRT-PCR, secreted cytokines by cytokine array or ELISA, NF-κB p65 nuclear/cytoplasmic localization by Western blot, and acetylated histone H3 by Western blot.
  • Statistical analysis used one-way ANOVA with Newman-Keuls pairwise comparisons; p < 0.05 was considered significant, and values were expressed as mean ± SEM.

Limitations

  • The paper states that future study is warranted to identify specific HDAC isoforms involved in inflammatory gene regulation and to determine how their activity is regulated, including cellular localization, posttranslational modification, and association with regulatory proteins.
  • The paper states it cannot rule out possible alterations in histone acetyltransferase (HAT) activity by SPE, and notes that LPS and SPE may differentially regulate HDAC expression posttranscriptionally.
  • Evident from the text: the main mechanistic findings are in cell culture and ex vivo splenocytes, with in vivo anti-inflammatory support limited to lower IL-6 secretion from splenocytes of BGA-fed mice; no human clinical outcomes are reported.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1016/j.bbagen.2013.01.018

Cites

58 of 58 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 43 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    In this study, NO and SP, whether given as lipid extract or whole algae, repressed pro-inflammatory gene expression and production across RAW 264.7 macrophages, BMM, and mouse splenocytes.

    “We found that in all of three systems, NO and SP either as lipid extract or as whole algae repressed pro-inflammatory gene expression and production.”
    • Also stated in: § 4. DISCUSSION · plain
      “In conclusion, we found that NO and SP either as a whole or a lipid extract have an anti-inflammatory effect using several model systems, i.e., RAW 264.7 macrophages, BMM and mouse splenocytes.”
    Quote in the paperSubstantial claim
  • Findingown data

    BMM exposed to NOE and SPE had significantly lower TNFα and IL-1β expression than control BMM.

    “Consistent with our observations in RAW 264.7 macrophages, BMM treated with NOE and SPE showed significantly lower expression of TNFα and IL-1β compared with control BMM (Figure 3).”
    Quote in the paperSubstantial claim
  • Findingown data

    In LPS-stimulated RAW 264.7 macrophages, NOE and SPE lowered movement of NF-κB p65 into the nucleus.

    “In contrast, macrophages pretreated with NOE and SPE had less p65 translocation to the nucleus and detectible amount of p65 was present in the cytoplasm.”
    Quote in the paperSubstantial claim
  • Findingown data

    SPE raised acetylated histone H3 levels about 2-fold in RAW 264.7 macrophages.

    “SPE increased the level of acetylated H3 by ~2-fold (Figure 7B).”
    Quote in the paperSubstantial claim
  • Findingown data

    HDAC 1, 2, 3, 4, 5, and 9 are the main HDAC isoforms in RAW 264.7 macrophages.

    “Among 11 HDAC isoforms, HDAC 1, 2, 3, 4, 5 and 9 are major isoforms in RAW 264.7 macrophages (data not shown).”
    Quote in the paperNot a substantial claim
  • May combine two claims. 18
  • Classified as probably not a substantial claim. 9

  • May combine two claims.

    Findingown data

    NOE and SPE reduced pro-inflammatory gene expression dose-dependently, with significant effects at concentrations as low as 25 μg/mL.

    “Significant reductions in the gene expression were observed in a dose-dependent manner as low as 25 μg/mL (data not shown).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In RAW 264.7 macrophages, NOE and SPE significantly lowered LPS-stimulated mRNA levels of TNFα, IL-1β, and IL-6 relative to control, with similar potency.

    “In RAW 264.7 macrophages, both algal lipid extracts significantly repressed LPS-induced TNFα, IL-1β and IL-6 mRNA expression compared with control and their repressive effects showed a similar potency (Figure 1).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    TSA, a pan HDAC inhibitor, significantly raised basal IL-1β and TNFα expression and weakened SPE's repression of these genes in LPS-stimulated RAW 264.7 macrophages.

    “Interestingly, TSA significantly increased basal expression of IL-1β and TNFα and furthermore the repressive effect of SPE on the gene expression was attenuated by TSA (Figure 6B).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    LPS-stimulated cells had only about a 40% rise in acetylated H3 versus controls, despite LPS lowering HDAC mRNA similarly to SPE.

    “Interestingly, although LPS repressed HDAC mRNA levels to a similar extent to SPE, there was only ~40% increase in acetylated H3 in LPS-stimulated cells compared with controls.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    SN50, which blocks NF-κB nuclear translocation, significantly reduced LPS-induced TNFα and IL-1β mRNA relative to control, but NOE or SPE repressed these genes much more strongly than SN50 in RAW 264.7 macrophages.

    “Although SN50 significantly lowered mRNA levels of TNFα and IL-1β compared with control, repression of the gene expression was markedly stronger in NOE or SPE-treated RAW 264.7 macrophages than SN50-treated cells (Figure 6A).”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Persistent inflammation contributes to the development of several diseases, such as insulin resistance, dementia, rheumatoid arthritis, atherosclerosis, and cancer.

    “Chronic inflammation is an underlying cause of several pathological disorders including insulin resistance, dementia, rheumatoid arthritis, atherosclerosis, and cancer [1, 2].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [1] Chung HY Cesari M Anton S Marzetti E Giovannini S Seo AY Carter C Yu BP Leeuwenburgh C Molecular inflammation: underpinnings of aging and age-related diseases Ageing Res Rev 8 2009 18 30 18692159 PMC3782993 source

      Not checked in the free run.

    • cites [2] Del Prete A Allavena P Santoro G Fumarulo R Corsi MM Mantovani A Molecular pathways in cancer-related inflammation Biochem Med (Zagreb) 21 2011 264 275 22420240 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In resting cells, NF-κB resides in the cytoplasm bound to IκBα, which blocks the nuclear localization signal of p65.

    “In an unstimulated state, NF-κB is present in the cytoplasm bound with inhibitor of κB α (IκBα), which masks the nuclear localization sequence of p65 [12]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [12] Hayden MS Ghosh S Signaling to NF-kappaB Genes Dev 18 2004 2195 2224 15371334 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Long-term use of several NSAIDs is linked to adverse side-effects and a higher risk of cardiovascular disease.

    “However, due to their adverse side-effects and increased cardiovascular disease (CVD) risk associated with chronic use of several NSAID [3], there is a critical need to identify natural products with anti-inflammatory properties.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [3] Jugdutt BI Cyclooxygenase inhibition and adverse remodeling during healing after myocardial infarction Circulation 115 2007 288 291 17242292 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The authors previously reported that NOE inhibited NF-κB DNA binding activity and repressed pro-inflammatory gene expression in RAW 264.7 macrophages.

    “We have previously reported that lipid extract of Nostoc commune var. sphaeroides Kützing (NO), another BGA species, inhibited NF-κB DNA binding activity and consequently repressed the pro-inflammatory gene expression in RAW 264.7 macrophages [30].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [30] Park YK Rasmussen HE Ehler SJ Blobaum KR Lu F Schlegel VL Carr TP Lee JY Repression of proinflammatory gene expression by lipid extract of Nostoc commune var sphaeroides Kutzing, a blue-green alga, via inhibition of nuclear factor-kappa B in RAW 264.7 macrophages Nutr Res 28 2008 83 92 19083393 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Blue-green algae are recognized for protective effects against viral and bacterial infections, cancer, allergy, diabetes, inflammation, and hyperlipidemia.

    “They are recognized for their protective effects against viral and bacterial infections, cancer, allergy, diabetes, inflammation and hyperlipidemia [26–29].”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [26] Samuels R Mani UV Iyer UM Nayak US Hypocholesterolemic effect of spirulina in patients with hyperlipidemic nephrotic syndrome J Med Food 5 2002 91 96 12487756 source

      Not checked in the free run.

    • cites [27] Rodriguez-Hernandez A Ble-Castillo JL Juarez-Oropeza MA Diaz-Zagoya JC Spirulina maxima prevents fatty liver formation in CD-1 male and female mice with experimental diabetes Life Sci 69 2001 1029 1037 11508645 source

      Not checked in the free run.

    • cites [28] Kushak RI Drapeau C Van Cott EM Favorable effects of blue-green algae Aphanizomenon flos-aquae on rat plasma lipids Journal of the American Nutraceutical Association 2 2000 59 65

      Not checked in the free run.

    • cites [29] Hori K Ishibashi G Okita T Hypocholesterolemic effect of blue-green alga, ishikurage (Nostoc commune) in rats fed atherogenic diet Plant Foods Hum Nutr 45 1994 63 70 8146104 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Inflammatory signals such as LPS, pro-inflammatory cytokines, reactive oxygen species, advanced glycation end products, and oxidized LDL cause IKKβ phosphorylation; this phosphorylates IκBα, leading to its ubiquitination and degradation, which releases NF-κB to enter the nucleus and induce pro-inflammatory genes.

    “Extracellular inflammatory signals including lipopolysaccharide (LPS), pro-inflammatory cytokines, reactive oxygen species, advanced glycation end products, and oxidized low-density lipoprotein trigger the phosphorylation of IKKβ, which in turn phosphorylates IκBα for ubiquitination and degradation by proteasome [13–18].”
    • Also stated in: § 1. INTRODUCTION · plain
      “This event liberates NF-κB to enter the nucleus for the induction of pro-inflammatory gene expression [19–24].”
    Quote in the paperSubstantial claim0 of 10 sources checked
    • cites [13] Chen LF Williams SA Mu Y Nakano H Duerr JM Buckbinder L Greene WC NF-kappaB RelA phosphorylation regulates RelA acetylation Mol Cell Biol 25 2005 7966 7975 16135789 PMC1234328 source

      Not checked in the free run.

    • cites [14] Chen ZJ Bhoj V Seth RB Ubiquitin TAK1 and IKK: is there a connection? Cell Death Differ 13 2006 687 692 16485032 source

      Not checked in the free run.

    • cites [15] Krappmann D Scheidereit C A pervasive role of ubiquitin conjugation in activation and termination of IkappaB kinase pathways EMBO Rep 6 2005 321 326 15809659 PMC1299290 source

      Not checked in the free run.

    • cites [16] Pamukcu B Lip GY Shantsila E The nuclear factor--kappa B pathway in atherosclerosis: a potential therapeutic target for atherothrombotic vascular disease Thromb Res 128 2011 117 123 21636112 source

      Not checked in the free run.

    • cites [17] Yan SF Ramasamy R Naka Y Schmidt AM Glycation, inflammation, and RAGE: a scaffold for the macrovascular complications of diabetes and beyond Circ Res 93 2003 1159 1169 14670831 source

      Not checked in the free run.

    • cites [18] Foncea R Carvajal C Almarza C Leighton F Endothelial cell oxidative stress and signal transduction Biol Res 33 2000 89 96 15693275 source

      Not checked in the free run.

    • cites [19] DiDonato J Mercurio F Rosette C Wu-Li J Suyang H Ghosh S Karin M Mapping of the inducible IkappaB phosphorylation sites that signal its ubiquitination and degradation Mol Cell Biol 16 1996 1295 1304 8657102 PMC231113 source

      Not checked in the free run.

    • cites [20] Chang CC Chen J Thomas MA Cheng D Del Priore VA Newton RS Pape ME Chang TY Regulation and immunolocalization of acyl-coenzyme A: cholesterol acyltransferase in mammalian cells as studied with specific antibodies J Biol Chem 270 1995 29532 29540 7493995 source

      Not checked in the free run.

    • cites [21] Brown K Gerstberger S Carlson L Franzoso G Siebenlist U Control of I kappa B-alpha proteolysis by site-specific, signal-induced phosphorylation Science 267 1995 1485 1488 7878466 source

      Not checked in the free run.

    • cites [22] DiDonato JA Mercurio F Karin M Phosphorylation of I kappa B alpha precedes but is not sufficient for its dissociation from NF-kappa B Mol Cell Biol 15 1995 1302 1311 7862124 PMC230353 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    p300 and CREB binding protein acetylate p65 at Lys218, 221, and 310, which boosts p65 DNA binding and blocks its binding to nuclear IκBα, thereby regulating transcription.

    “It is our particular interest that acetylation of p65 at Lys218, 221 and 310 by p300 and cAMP response element binding (CREB) binding protein (CBP) regulates its transcriptional activity by increasing p65 DNA binding and by inhibiting its association with nuclear IκBα for the prevention of NF-κB relocation to the cytoplasm [55].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [55] Chen LF Mu Y Greene WC Acetylation of RelA at discrete sites regulates distinct nuclear functions of NF-kappaB EMBO J 21 2002 6539 6548 12456660 PMC136963 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In 2011, the Dietary Supplements Information Expert Committee gave SP a Class A safety rating and allowed quality monographs for SP in the USP and National Formulary.

    “Furthermore, in 2011, The Dietary Supplements Information Expert Committee assigned a Class A safety rating for SP and permitted the admission of quality monographs for SP in the United States Pharmacopeia and National Formulary [38].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [38] Klivenyi P Andreassen OA Ferrante RJ Dedeoglu A Mueller G Lancelot E Bogdanov M Andersen JK Jiang D Beal MF Mice deficient in cellular glutathione peroxidase show increased vulnerability to malonate, 3-nitropropionic acid, and 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine J Neurosci 20 2000 1 7 10627575 PMC6774090 source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Bailey and Ghosh proposed that in unstimulated macrophages, NF-κB together with a corepressor complex actively suppresses pro-inflammatory genes, and this complex contains nuclear receptor corepressor, HDAC3, and other proteins.

    “Bailey and Ghosh [58] suggested that NF-κB in association with a corepressor complex actively represses pro-inflammatory gene expression in unstimulated macrophages and the corepressor complex is composed of nuclear receptor corepressor, HDAC3 and others.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [58] Bailey ST Ghosh S ‘PPAR’ting ways with inflammation Nat Immunol 6 2005 966 967 16177802 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In NOE, unsaturated fatty acids make up about 15% of the extract and partly explain the reduced pro-inflammatory cytokine production, but other compounds are needed for the full effect in RAW 264.7 macrophages.

    “We found that in NOE, unsaturated fatty acids, which account for ~15% of the extract mass, are partly responsible for the repression of pro-inflammatory cytokine production but other compounds are required to achieve full degree of repression in RAW 264.7 macrophages [30].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [30] Park YK Rasmussen HE Ehler SJ Blobaum KR Lu F Schlegel VL Carr TP Lee JY Repression of proinflammatory gene expression by lipid extract of Nostoc commune var sphaeroides Kutzing, a blue-green alga, via inhibition of nuclear factor-kappa B in RAW 264.7 macrophages Nutr Res 28 2008 83 92 19083393 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Human studies indicate that polyphenol-rich foods like green tea and extra virgin olive oil suppress NF-κB activation.

    “Epidemiological and clinical studies have demonstrated the effect of polyphenol-rich foods, such as green tea and extra virgin olive oils, on the inhibition of NF-κB activation [54].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [54] Santangelo C Vari R Scazzocchio B Di Benedetto R Filesi C Masella R Polyphenols, intracellular signalling and inflammation Ann Ist Super Sanita 43 2007 394 405 18209273

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The high acetylated H3 levels in SPE-treated cells probably result from HDAC down-regulation, although SPE might also alter HAT activity.

    “High levels of acetyl H3 observed in the SPE-treated cells are likely due to the down-regulation of HDAC expression although we cannot rule out possible alterations in HAT by SPE.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Eating BGA boosts immunity and guards against inflammatory conditions including colitis, arthritis, and allergic rhinitis in animals and people.

    “Studies have demonstrated that BGA consumption promotes immunity and protects against inflammatory diseases such as colitis, arthritis, and allergic rhinitis in animals and humans [39–42].”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [39] Selmi C Leung PS Fischer L German B Yang CY Kenny TP Cysewski GR Gershwin ME The effects of Spirulina on anemia and immune function in senior citizens Cell Mol Immunol 8 2011 248 254 21278762 PMC4012879 source

      Not checked in the free run.

    • cites [40] Mao TK Van de Water J Gershwin ME Effects of a Spirulina-based dietary supplement on cytokine production from allergic rhinitis patients J Med Food 8 2005 27 30 15857205 source

      Not checked in the free run.

    • cites [41] Coskun ZK Kerem M Gurbuz N Omeroglu S Pasaoglu H Demirtas C Lortlar N Salman B Pasaoglu OT Turgut HB The study of biochemical and histopathological effects of spirulina in rats with TNBS-induced colitis Bratisl Lek Listy 112 2011 235 243 21682075

      Not checked in the free run.

    • cites [42] Rasool M Sabina EP Lavanya B Anti-inflammatory effect of Spirulina fusiformis on adjuvant-induced arthritis in mice Biol Pharm Bull 29 2006 2483 2487 17142986 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    SP and NO contain no microcystins, and giving these BGA long-term to mice produced no adverse side-effects.

    “We previously demonstrated that SP and NO are free of microcystins, the major algal toxin, and long-term supplementation of the two BGA did not show any adverse side-effects in mice [37].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [37] Yang Y Park Y Cassada DA Snow DD Rogers DG Lee J In vitro and in vivo safety assessment of edible blue-green algae, Nostoc commune var. sphaeroides Kutzing and Spirulina plantensis Food Chem Toxicol 49 2011 1560 1564 21473896 PMC3107672 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Corepressor complexes that remove acetyl groups from Lys310 reduce p65 activity.

    “In contrast, deacetylation at Lys310 by corepressor complexes inhibits p65 activity [56, 57].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [56] Hoberg JE Yeung F Mayo MW SMRT derepression by the IkappaB kinase alpha: a prerequisite to NF-kappaB transcription and survival Mol Cell 16 2004 245 255 15494311 source

      Not checked in the free run.

    • cites [57] Yeung F Hoberg JE Ramsey CS Keller MD Jones DR Frye RA Mayo MW Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase EMBO J 23 2004 2369 2380 15152190 PMC423286 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Modifications of p65 after translation, including phosphorylation and acetylation, change its activity by affecting DNA binding, its interaction with nuclear IκBα, and its association with chromatin modifiers like HAT and HDAC.

    “Although NF-κB nuclear translocation is the best-known mechanism for its activation [12], several lines of evidence indicate that posttranslational modifications in p65 subunit, such as phosphorylation and acetylation, impact its activity by altering DNA binding, interaction with inhibitor of κB α (IκBα) in the nucleus, and association with chromatin structure modifiers such as histone acetyltrans”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [32] Perkins ND Post-translational modifications regulating the activity and function of the nuclear factor kappa B pathway Oncogene 25 2006 6717 6730 17072324 source

      Not checked in the free run.

    • cites [33] Neumann M Naumann M Beyond IkappaBs: alternative regulation of NF-kappaB activity FASEB J 21 2007 2642 2654 17431096 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    HDAC may drive basal suppression of IL-1β and TNFα in unstimulated macrophages and also mediate the algal extracts' repression of pro-inflammatory genes in activated macrophages.

    “The data suggest that HDAC may be involved in basal transrepression of IL-1β and TNFα when there are no extracellular inflammatory insults, while it mediates the repressive effect of the algal extracts on the expression of the pro-inflammatory genes in the activated macrophages.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    NF-κB pathway activation is a key event in inflammatory disease development, and blocking it can slow disease progression.

    “Mounting evidence suggests that activation of NF-κB pathway is a major underlying event for the development of inflammatory diseases and its inhibition can decrease the disease progression [51–53].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [51] Rial NS Choi K Nguyen T Snyder B Slepian MJ Nuclear factor kappa B (NF-kappaB): a novel cause for diabetes, coronary artery disease and cancer initiation and promotion? Med Hypotheses 78 2012 29 32 22014759 source

      Not checked in the free run.

    • cites [52] Madonna R De Caterina R Relevance of new drug discovery to reduce NF-κB activation in cardiovascular disease Vascular Pharmacology 57 2012 41 47 22366375 source

      Not checked in the free run.

    • cites [53] Karin M Yamamoto Y Wang QM The IKK NF-kappa B system: a treasure trove for drug development Nat Rev Drug Discov 3 2004 17 26 14708018 source

      Not checked in the free run.

23 of 23

  • The paper relies on this without support.

    Dysregulated production of pro-inflammatory mediators by macrophages is a major contributor to inflammation-related diseases such as insulin resistance and atherosclerosis.

    “Dysregulation of pro-inflammatory mediator production from macrophages is a major contributor to the development of pathological conditions related to inflammation such as insulin resistance and atherosclerosis.”

  • The paper relies on this without support.

    Findings in RAW 264.7 macrophages, mouse BMM, and mouse splenocytes are predictive of anti-inflammatory effects in humans.

    “Therefore, the two BGA species tested in the present study may be used as a natural product to prevent inflammatory diseases.”
2 of 2

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  • Spirulina safety-rating claim cites an unrelated study

    Minor

    The sentence attributes a Spirulina safety rating to reference 38, but reference 38 is a study of glutathione-peroxidase-deficient mice and does not describe that rating.

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Authors
Ku, C. S., Pham, T. X., Park, Y., Kim, B., Shin, M. S., Kang, I., & Lee, J.
Affiliations
  • University of Connecticut (US)
  • Yale University (US)
ORCID
Venue
Biochimica et Biophysica Acta (BBA) - General Subjects
Publisher
Elsevier BV
Published
2013-04
Volume
1830
Issue
4
Pages
2981-2988
ISSN
0304-4165 (ISSN-L)
DOI
10.1016/j.bbagen.2013.01.018
PMC
PMC3594481
OpenAlex
W2066758152
Semantic Scholar
85d7379d24831618cba9700001c882518fb76bf5
Cited by
109
References
58
Citations by year
2026: 4 · 2025: 6 · 2024: 9 · 2023: 7 · 2022: 6 · 2021: 10 · 2020: 17 · 2019: 6 · 2018: 6 · 2017: 9 · 2016: 10 · 2015: 8 · 2014: 8 · 2013: 3
FWCI
14.77
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Biochimica et Biophysica Acta (BBA) - General Subjects (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Center for Complementary and Integrative Health (R21AT005152)
Topics
  • Life Sciences › Agricultural and Biological Sciences › Aquatic Science › Seaweed-derived Bioactive Compounds
  • Health Sciences › Medicine › Complementary and alternative medicine › Natural Compounds in Disease Treatment
  • Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
Keywords
cyanobacteria, Spirulina platensis, anti-inflammatory activity, inflammatory cytokines, NF-κB signaling, macrophages, splenocytes, histone acetylation, histone deacetylase, lipid extracts, chronic inflammation, atherosclerosis, ApoE-deficient mice, epigenetic regulation
MeSH terms
Cyanobacteria, Animals, Cells, Cultured, Histone Deacetylases, Histones, Macrophages, Mice, Inbred C57BL, Spleen, Cytokines, NF-kappa B, Active Transport, Cell Nucleus, Mice

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Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-07.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-07.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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