The DOI matches its Crossref record; 58 of the 58 references it cites were found in a registry or an index; none of the 43 sources its claims cite is checked for support yet.
Edible blue-green algae reduce the production of pro-inflammatory cytokines by inhibiting NF-κB pathway in macrophages and splenocytes
Open accessAbstract
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.
Overview
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
Cites
Statistics
Verification
Claims the paper makes
0 of 43 cited sources checked · 0 supported · 0 flagged
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Edible blue-green algae reduce the production of pro-inflammatory cytokines by inhibiting NF-κB pathway in macrophages and splenocytes > 1. INTRODUCTION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § 4. DISCUSSION · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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).”
§ Edible blue-green algae reduce the production of pro-inflammatory cytokines by inhibiting NF-κB pathway in macrophages and splenocytes > 3. RESULTS > 3.1. Pro-inflammatory cytokine expression and secretion were repressed by NOE and SPE in macrophages
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Edible blue-green algae reduce the production of pro-inflammatory cytokines by inhibiting NF-κB pathway in macrophages and splenocytes > 3. RESULTS > 3.3. Algal lipid extracts inhibited NF-κB nuclear translocation in macrophages
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“SPE increased the level of acetylated H3 by ~2-fold (Figure 7B).”
§ Edible blue-green algae reduce the production of pro-inflammatory cytokines by inhibiting NF-κB pathway in macrophages and splenocytes > 3. RESULTS > 3.5. Down regulation of HDAC expression and subsequent increases in acetylated histone 3 by SPE in macrophages
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Among 11 HDAC isoforms, HDAC 1, 2, 3, 4, 5 and 9 are major isoforms in RAW 264.7 macrophages (data not shown).”
§ Edible blue-green algae reduce the production of pro-inflammatory cytokines by inhibiting NF-κB pathway in macrophages and splenocytes > 4. DISCUSSION
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“When the splenocytes were challenged by LPS for 20 h, cells from NO or SP-fed mice showed significantly lower IL-6 levels in cell medium than control mice (Figure 4).”
§ Edible blue-green algae reduce the production of pro-inflammatory cytokines by inhibiting NF-κB pathway in macrophages and splenocytes > 3. RESULTS > 3.2. IL-6 secretion was decreased from splenocytes of mice fed NO and SP supplements
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Furthermore, NOE and SPE markedly decreased the secretion of TNFα, IL-6, granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating factor, and monocyte chemoattractant protein 1 (Figure 2).”
§ Edible blue-green algae reduce the production of pro-inflammatory cytokines by inhibiting NF-κB pathway in macrophages and splenocytes > 3. RESULTS > 3.1. Pro-inflammatory cytokine expression and secretion were repressed by NOE and SPE in macrophages
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“mRNA abundance of all HDAC isoforms was significantly decreased by SPE in both unstimulated and LPS-stimulated macrophages (Figure 7A).”
§ Edible blue-green algae reduce the production of pro-inflammatory cytokines by inhibiting NF-κB pathway in macrophages and splenocytes > 3. RESULTS > 3.5. Down regulation of HDAC expression and subsequent increases in acetylated histone 3 by SPE in macrophages
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“HDAC expression was also significantly lowered by LPS.”
§ Edible blue-green algae reduce the production of pro-inflammatory cytokines by inhibiting NF-κB pathway in macrophages and splenocytes > 3. RESULTS > 3.5. Down regulation of HDAC expression and subsequent increases in acetylated histone 3 by SPE in macrophages
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Nuclear factor κ B (NF-κB) is a major transcriptional factors responsible for pro-inflammatory cytokine production, such as tumor necrosis factor α (TNFα), interleukins (ILs), inducible nitric oxide synthase and cyclooxygenase-2, under inflammatory conditions [9, 10].”
§ Edible blue-green algae reduce the production of pro-inflammatory cytokines by inhibiting NF-κB pathway in macrophages and splenocytes > 1. INTRODUCTION
What the sources say
- Not checked yetcites [9] Zou Y Jung KJ Kim JW Yu BP Chung HY Alteration of soluble adhesion molecules during aging and their modulation by calorie restriction FASEB J 18 2004 320 322 14688195 source
- Not checked yetcites [10] Chung HY Sung B Jung KJ Zou Y Yu BP The molecular inflammatory process in aging Antioxid Redox Signal 8 2006 572 581 16677101 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- It may state two separate claims as one. 18
- Probably not a substantial claim. 9
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Significant reductions in the gene expression were observed in a dose-dependent manner as low as 25 μg/mL (data not shown).”
§ Edible blue-green algae reduce the production of pro-inflammatory cytokines by inhibiting NF-κB pathway in macrophages and splenocytes > 3. RESULTS > 3.1. Pro-inflammatory cytokine expression and secretion were repressed by NOE and SPE in macrophages
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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).”
§ Edible blue-green algae reduce the production of pro-inflammatory cytokines by inhibiting NF-κB pathway in macrophages and splenocytes > 3. RESULTS > 3.1. Pro-inflammatory cytokine expression and secretion were repressed by NOE and SPE in macrophages
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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).”
§ Edible blue-green algae reduce the production of pro-inflammatory cytokines by inhibiting NF-κB pathway in macrophages and splenocytes > 3. RESULTS > 3.4. Inhibition of NF-κB nuclear translocation could not solely account for the repression of pro-inflammatory cytokine expression by NOE and SPE in macrophages
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Edible blue-green algae reduce the production of pro-inflammatory cytokines by inhibiting NF-κB pathway in macrophages and splenocytes > 3. RESULTS > 3.5. Down regulation of HDAC expression and subsequent increases in acetylated histone 3 by SPE in macrophages
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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).”
§ Edible blue-green algae reduce the production of pro-inflammatory cytokines by inhibiting NF-κB pathway in macrophages and splenocytes > 3. RESULTS > 3.4. Inhibition of NF-κB nuclear translocation could not solely account for the repression of pro-inflammatory cytokine expression by NOE and SPE in macrophages
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Chronic inflammation is an underlying cause of several pathological disorders including insulin resistance, dementia, rheumatoid arthritis, atherosclerosis, and cancer [1, 2].”
§ Edible blue-green algae reduce the production of pro-inflammatory cytokines by inhibiting NF-κB pathway in macrophages and splenocytes > 1. INTRODUCTION
What the sources say
- Not checked yetcites [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 yetcites [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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
In the paper
“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]”
§ Edible blue-green algae reduce the production of pro-inflammatory cytokines by inhibiting NF-κB pathway in macrophages and splenocytes > 1. INTRODUCTION
What the sources say
- Not checked yetcites [12] Hayden MS Ghosh S Signaling to NF-kappaB Genes Dev 18 2004 2195 2224 15371334 source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“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.”
§ Edible blue-green algae reduce the production of pro-inflammatory cytokines by inhibiting NF-κB pathway in macrophages and splenocytes > 1. INTRODUCTION
What the sources say
- Not checked yetcites [3] Jugdutt BI Cyclooxygenase inhibition and adverse remodeling during healing after myocardial infarction Circulation 115 2007 288 291 17242292 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“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].”
§ Edible blue-green algae reduce the production of pro-inflammatory cytokines by inhibiting NF-κB pathway in macrophages and splenocytes > 1. INTRODUCTION
What the sources say
- Not checked yetcites [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
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“They are recognized for their protective effects against viral and bacterial infections, cancer, allergy, diabetes, inflammation and hyperlipidemia [26–29].”
§ Edible blue-green algae reduce the production of pro-inflammatory cytokines by inhibiting NF-κB pathway in macrophages and splenocytes > 1. INTRODUCTION
What the sources say
- Not checked yetcites [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 yetcites [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 yetcites [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 yetcites [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
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“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].”
§ Edible blue-green algae reduce the production of pro-inflammatory cytokines by inhibiting NF-κB pathway in macrophages and splenocytes > 1. INTRODUCTION
What the sources say
- Not checked yetcites [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 yetcites [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 yetcites [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 yetcites [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 yetcites [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 yetcites [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 yetcites [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 yetcites [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 yetcites [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 yetcites [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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Also stated in: § 1. INTRODUCTION · plain
In the paper
“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].”
§ Edible blue-green algae reduce the production of pro-inflammatory cytokines by inhibiting NF-κB pathway in macrophages and splenocytes > 4. DISCUSSION
What the sources say
- Not checked yetcites [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
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“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].”
§ Edible blue-green algae reduce the production of pro-inflammatory cytokines by inhibiting NF-κB pathway in macrophages and splenocytes > 4. DISCUSSION
What the sources say
- Not checked yetcites [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
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“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.”
§ Edible blue-green algae reduce the production of pro-inflammatory cytokines by inhibiting NF-κB pathway in macrophages and splenocytes > 4. DISCUSSION
What the sources say
- Not checked yetcites [58] Bailey ST Ghosh S ‘PPAR’ting ways with inflammation Nat Immunol 6 2005 966 967 16177802 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
In the paper
“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].”
§ Edible blue-green algae reduce the production of pro-inflammatory cytokines by inhibiting NF-κB pathway in macrophages and splenocytes > 4. DISCUSSION
What the sources say
- Not checked yetcites [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
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“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].”
§ Edible blue-green algae reduce the production of pro-inflammatory cytokines by inhibiting NF-κB pathway in macrophages and splenocytes > 4. DISCUSSION
What the sources say
- Not checked yetcites [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
Strength:boosted· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Edible blue-green algae reduce the production of pro-inflammatory cytokines by inhibiting NF-κB pathway in macrophages and splenocytes > 4. DISCUSSION
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“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].”
§ Edible blue-green algae reduce the production of pro-inflammatory cytokines by inhibiting NF-κB pathway in macrophages and splenocytes > 4. DISCUSSION
What the sources say
- Not checked yetcites [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 yetcites [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 yetcites [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 yetcites [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
Strength:boosted· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“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].”
§ Edible blue-green algae reduce the production of pro-inflammatory cytokines by inhibiting NF-κB pathway in macrophages and splenocytes > 4. DISCUSSION
What the sources say
- Not checked yetcites [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
Load-bearingStrength:boosted· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In contrast, deacetylation at Lys310 by corepressor complexes inhibits p65 activity [56, 57].”
§ Edible blue-green algae reduce the production of pro-inflammatory cytokines by inhibiting NF-κB pathway in macrophages and splenocytes > 4. DISCUSSION
What the sources say
- Not checked yetcites [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 yetcites [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
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“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”
§ Edible blue-green algae reduce the production of pro-inflammatory cytokines by inhibiting NF-κB pathway in macrophages and splenocytes > 4. DISCUSSION
What the sources say
- Not checked yetcites [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 yetcites [33] Neumann M Naumann M Beyond IkappaBs: alternative regulation of NF-kappaB activity FASEB J 21 2007 2642 2654 17431096 source
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Edible blue-green algae reduce the production of pro-inflammatory cytokines by inhibiting NF-κB pathway in macrophages and splenocytes > 4. DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“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].”
§ Edible blue-green algae reduce the production of pro-inflammatory cytokines by inhibiting NF-κB pathway in macrophages and splenocytes > 4. DISCUSSION
What the sources say
- Not checked yetcites [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 yetcites [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 yetcites [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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Also Spirulina lipid extract [67] has been shown to repress proinflammatory cytokine (TNF-α, IL-1β, and IL-6) expression and secretion via inhibition of NF-kB pathway.”
From Antioxidant, Immunomodulating, and Microbial‐Modulating Activities of the Sustainable and Ecofriendly Spirulina (2017) · cites this paper as [67]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Spirulina safety-rating claim cites an unrelated study
MinorThe 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.
“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].”
“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”
Citations
Cites
Hayden, M. S., & Ghosh, S. (2004) · Genes & Development · doi:10.1101/gad.1228704 · Cited by 3,842
Baeuerle, P. A., & Baltimore, D. (1996) · Cell · doi:10.1016/s0092-8674(00)81318-5 · Cited by 3,002
Modulation of NF‐κB‐dependent transcription and cell survival by the SIRT1 deacetylase
Yeung, F., Hoberg, J. E., Ramsey, C. S., Keller, M. D., Jones, D. R., Frye, R. A., & Mayo, M. W. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600244 · Cited by 2,750
Control of IκB-α Proteolysis by Site-Specific, Signal-Induced Phosphorylation
Brown, K., Gerstberger, S., Carlson, L., Franzoso, G., & Siebenlist, U. (1995) · Science · doi:10.1126/science.7878466 · Cited by 1,434
The IKK NF-κB system: a treasure trove for drug development
Karin, M., Yamamoto, Y., & Wang, Q. M. (2004) · Nature Reviews Drug Discovery · doi:10.1038/nrd1279 · Cited by 1,364
Molecular inflammation: Underpinnings of aging and age-related diseases
Chung, H. Y., Cesari, M., Anton, S., Marzetti, E., Giovannini, S., Seo, A. Y., Carter, C., Yu, B. P., & Leeuwenburgh, C. (2009) · Ageing Research Reviews · doi:10.1016/j.arr.2008.07.002 · Cited by 1,203
Klivenyi, P., Andreassen, O. A., Ferrante, R. J., Dedeoglu, A., Mueller, G., Lancelot, E., Bogdanov, M., Andersen, J. K., Jiang, D., & Beal, M. F. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-01-00001.2000 · Cited by 1,111
Carmichael, W. W. (1994) · Scientific American · doi:10.1038/scientificamerican0194-78 · Cited by 1,100
Acetylation of RelA at discrete sites regulates distinct nuclear functions of NF‐κB
Chen, L., Mu, Y., & Greene, W. C. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf660 · Cited by 827
Spirulina, the edible microorganism.
Ciferri, O. (1983) · Microbiological Reviews · doi:10.1128/mmbr.47.4.551-578.1983 · Cited by 745 · cited 2×
“Currently, SP is the most commonly consumed and commercialized BGA species [25].”
Background
Flagged first, then by citations
Cited by
Sorted by citations
Items 101–109 of 109
Alagbe, E. O., Ajuwon, K. M., Schulze, H., & Adeola, O. (2025) · Journal of Animal Science · doi:10.1093/jas/skaf338 · Cited by 1
Goel, N., & Choudhary, P. (2025) · Wiley eBooks · doi:10.1002/9781394241538.ch19 · Cited by 1
(2013) · Revue du Rhumatisme · doi:10.1016/s1169-8330(13)70069-3
Marine Algal Polysaccharides in the Management of Liver Disease
Qeshmi, F. I., Ghattavi, S., & Homaei, A. A. (2026) · Springer eBooks · doi:10.1007/978-981-95-4126-3_8
Delfan, M., Zeidi, A. H. N., Kashani, F. R., Zeynali, F., Juybari, R. A., Rahimpour, M., Willems, M. E. T., Saeidi, A., & Zouhal, H. (2026) · Nutrition Research · doi:10.1016/j.nutres.2026.02.003 · Cited by 1
El‐Saadony, M. T., Saad, A. M., Sitohy, M. Z., Mohammed, D. M., Alkafaas, S. S., Salem, H. M., Ahmed, A. E., Fahmy, M. A., Mathew, B. T., AbuQamar, S. F., et al. (2026) · Springer eBooks · doi:10.1007/978-3-032-22521-4_21
Harness, E. (2015) · OpenCommons - UConn (University of Connecticut)
Metadata
- 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)
- 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)
- 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
- green
- europepmc.org
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-07, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-07 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
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 ›
Are you an author, or do you see a problem with this page? Request a review
