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Cited by 98Seaweed-derived Bioactive CompoundsMedicinal Plants and NeuroprotectionAlzheimer's disease research and treatments

Beneficial Effects of Spirulina Consumption on Brain Health

Open access
Trotta, Teresa, Porro, Chiara, Cianciulli, Antonia, Panaro, Maria Antonietta·2022·Nutrients
DOI 10.3390/nu14030676PMC PMC8839264
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Abstract

Spirulina is a microscopic, filamentous cyanobacterium that grows in alkaline water bodies. It is extensively utilized as a nutraceutical food supplement all over the world due to its high levels of functional compounds, such as phycocyanins, phenols and polysaccharides, with anti-inflammatory, antioxidant, immunomodulating properties both in vivo and in vitro. Several scientific publications have suggested its positive effects in various pathologies such as cardiovascular diseases, hypercholesterolemia, hyperglycemia, obesity, hypertension, tumors and inflammatory diseases. Lately, different studies have demonstrated the neuroprotective role of Spirulina on the development of the neural system, senility and a number of pathological conditions, including neurological and neurodegenerative diseases. This review focuses on the role of Spirulina in the brain, highlighting how it exerts its beneficial anti-inflammatory and antioxidant effects, acting on glial cell activation, and in the prevention and/or progression of neurodegenerative diseases, in particular Parkinson’s disease, Alzheimer’s disease and Multiple Sclerosis; due to these properties, Spirulina could be considered a potential natural drug.

AI snapshot

Written from the paper’s full text.

TL;DR

This review synthesizes in vitro and in vivo evidence that Spirulina and its bioactive components (notably C-phycocyanin and phycocyanobilin) exert antioxidant and anti-inflammatory effects in the brain, largely by suppressing glial cell activation. The authors argue Spirulina could be considered a potential natural drug for the prevention and/or treatment of Parkinson's disease, Alzheimer's disease and Multiple Sclerosis.

Key findings

  • Spirulina-enriched diets increased cerebellar glutathione (GSH), reduced malondialdehyde (MDA) and pro-inflammatory cytokines, and improved spatial and motor learning in aged rats; in cerebral ischemia, treatment produced a progressive decline in TUNEL-positive cells and caspase-3 activity in the ischemic hemisphere.
  • In a neuroblastoma cell line (SH-SY5Y), S. platensis protein extract protected total GPx, GPx-Se and GR activity and increased reduced GSH via free-radical scavenging and iron-chelating ability, increasing cell viability against iron-induced oxidative stress.
  • C-Phycocyanin (C-PC) reduced ROS generation, decreased astroglia activation and restored microglial markers (CD11b, LC3-II, beclin) in tributyltin chloride-treated male Wistar rats; it failed to fully restore BBB disruption but restored p-glycoprotein and claudin-5 levels and partially restored calpain and matrix metalloproteinase activity.
  • In PD models, Spirulina was neuroprotective in an α-Syn rat model (more TH+ and NeuN+ cells, fewer MHC II-expressing activated microglia); in DJ-1βΔ93 Drosophila, dietary Spirulina decreased SOD and CAT activities and improved lifespan and locomotor activity. In AD models, SM70EE reduced Aβ1-42 levels in hippocampus, suppressed acetylcholinesterase, increased GPx/GR and glutathione, and increased BDNF via the BDNF/PI3K/Akt pathway. In MS (EAE) models, C-PC induced Treg, reduced inflammatory infiltrates and Mac-3/CD3-positive cells, and up-regulated remyelination-related genes (Mal, Mog, Mobp, Nkx6-2, Nkx2-2, Bmpa, Olig1).

Methods

Narrative review; no primary data. The authors synthesize published in vitro (SH-SY5Y, PC12, HT-22, primary hippocampal neurons, astrocyte models) and in vivo studies (aged rats, Sprague Dawley spinal cord injury, Wistar rats, 6-OHDA/MPTP/α-Syn PD models, Aβ1-42 and APP/PS1 AD models, EAE rodent models, Drosophila) on Spirulina, C-PC, PCB and related extracts. Only Mitra et al. measured C-PC bioavailability in cerebral cortical homogenates (absorbance at 620 nm) in Wistar rats given intraperitoneal injections.

Limitations

The paper states that although different studies have tried to elucidate the signaling pathways involved in Spirulina's antioxidant and anti-inflammatory effects, the molecular mechanism(s) remain unknown, and that additional studies are needed to clarify the mechanisms of action. Evident from the text: the review is narrative rather than systematic, most evidence is preclinical (cell lines and rodent models), and the authors note that only one cited study assessed C-PC bioavailability in brain tissue, leaving the question of whether active components cross the BBB largely inferential.

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

Integrity signals

Registry

Crossref · 10.3390/nu14030676

Cites

162 of 162 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 179 cited sources checked · 0 supported · 0 flagged

  • Premisecitation

    The anti-inflammatory properties of Spirulina may be due to inhibition of COX-2 activity.

    “The anti-inflammatory properties of Spirulina may be due to the inhibition of cyclooxygenase-2 (COX-2) activity [22]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [22] Reddy, 2000, Selective inhibition of cyclooxygenase-2 by C-phycocyanin, a biliprotein from Spirulina platensis, Biochem. Biophys. Res. Commun. source

      Not checked in the free run.

  • Premisecitation

    Spirulina regulates key cytokines, including IL-1β, IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ.

    “Spirulina regulates key cytokines, including IL-1β, IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ [9].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [9] Wu, 2016, The antioxidant, immunomodulatory, and anti-inflammatory activities of Spirulina: An overview, Arch. Toxicol. source

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  • Premisecitation

    When administered in vivo by oral or parenteral routes, C-PC is degraded by proteolysis into PCB or PCB-linked peptides that probably are responsible for the pharmacological actions reported for this biliprotein.

    “When administrated in vivo by oral or parenteral routes, C-PC is degraded by proteolysis in PCB or PCB-linked peptides that probably are responsible for the pharmacological actions reported for this biliprotein [28,29].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [28] Minic, 2016, Digestion by pepsin releases biologically active chromopeptides from C-phycocyanin, a blue-colored biliprotein of microalga Spirulina, J. Proteom. source

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    • cites [29] Minic, 2018, Characterization and effects of binding of food-derived bioactive phycocyanobilin to bovine serum albumin, Food Chem. source

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  • Premisecitation

    The protein extract of Spirulina scavenges free radicals.

    “but the protein extract of Spirulina also shows chelating ability, reduces lipid peroxidation and DNA damage, and scavenges free radicals [23,24].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [23] Abdelkhalek, 2015, Pharmacodynamic interaction of Spirulina platensis and deltamethrin in freshwater fish Nile tilapia, Oreochromis niloticus: Impact on lipid peroxidation and oxidative stress, Environ. Sci. Pollut. Res. source

      Not checked in the free run.

    • cites [24] Gemma, 2002, Diets enriched in foods with high antioxidant activity reverse age-induced decreases in cerebellar β-adrenergic function and increases in proinflammatory cytokines, J. Neurosci. source

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  • Premisecitation

    Both P1 and P2 exhibited a suppressive effect on IL-8 expression in histamine-stimulated EA.hy926 endothelial cells.

    “Both P1 and P2 exhibited a suppressive effect on IL-8 expression in histamine-stimulated EA.hy926 endothelial cells, and on the production of intracellular reactive oxygen species (ROS) in the mast and endothelial cells [33].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [33] Vo, 2013, Purification of novel anti-inflammatory peptides from enzymatic hydrolysate of the edible microalgal Spirulina maxima, J. Funct. Foods source

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  • The quote only partly states this claim. 3
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    Premisecitation

    Spirulina has neuroprotective effects on the development of the neural system and in senility and neurological/neurodegenerative diseases.

    “In the last few years, a large number of studies have demonstrated that Spirulina not only has beneficial effects on the development of the neural system but also neuroprotective effects through attenuating oxidative stress and antioxidant properties [40,41,42,43].”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [40] Patil, 2018, Spirulina diet to lactating mothers protects the antioxidant system and reduces inflammation in post-natal brain after systemic inflammation, Nutr. Neurosci. source

      Not checked in the free run.

    • cites [41] Patro, 2011, Spirulina platensis protects neurons via suppression of glial activation and peripheral sensitization leading to restoration of motor function in collagen-induced arthritic rats, Indian J. Exp. Biol.

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    • cites [42] Tocher, D.R., Betancor, M.B., Sprague, M., Olsen, R.E., and Napier, J.A. (2019). Omega-3 Long-Chain Polyunsaturated Fatty Acids, EPA and DHA: Bridging the Gap between Supply and Demand. Nutrients, 11. source

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    • cites [43] Capelli, 2010, Potential health benefits of spirulina microalgae, Nutrafoods source

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

    Premisecitation

    Spirulina is considered safe for human consumption, having very low toxicity.

    “nowadays it is considered safe for human consumption, having very low toxicity [4]”
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    • cites [4] 2015, Nutritional and toxicological aspects of Spirulina (Arthrospira), Nutr. Hosp.

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    Premisecitation

    Allophycocyanin has strong antioxidant activity, proving higher than phycocyanin at scavenging peroxyl radicals, whereas phycocyanin is better at scavenging hydroxyl radicals.

    “In addition to phycocyanin, allophycocyanin has strong antioxidant activity, proving to be higher than phycocyanin as scavenging peroxyl radicals whereas phycocyanin is better at scavenging hydroxyl radicals [32].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [32] Cherdkiatikul, 2014, Production of the α and β Subunits of Spirulina Allophycocyanin and C-Phycocyanin in Escherichia coli: A Comparative Study of Their Antioxidant Activities, J. Biomol. Screen source

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    Premisecitation

    The protein extract of Spirulina reduces lipid peroxidation and DNA damage.

    “but the protein extract of Spirulina also shows chelating ability, reduces lipid peroxidation and DNA damage, and scavenges free radicals [23,24].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [23] Abdelkhalek, 2015, Pharmacodynamic interaction of Spirulina platensis and deltamethrin in freshwater fish Nile tilapia, Oreochromis niloticus: Impact on lipid peroxidation and oxidative stress, Environ. Sci. Pollut. Res. source

      Not checked in the free run.

    • cites [24] Gemma, 2002, Diets enriched in foods with high antioxidant activity reverse age-induced decreases in cerebellar β-adrenergic function and increases in proinflammatory cytokines, J. Neurosci. source

      Not checked in the free run.

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

    Premisecitation

    PCB would inhibit NADPH oxidase because its chemical structure is similar to that of bilirubin, a highly specific inhibitor of NADPH oxidase.

    “It was postulated that PCB would inhibit NADPH oxidase since the chemical structure of PCB is similar to that of bilirubin, which is a highly specific inhibitor of NADPH oxidase [30,31].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [30] McCarty, 2007, Clinical potential of Spirulina as a source of phycocyanobilin, J. Med. Food source

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    • cites [31] Riss, 2007, Phycobiliprotein C-phycocyanin from Spirulina platensis is powerfully responsible for reducing oxidative stress and NADPH oxidase expression induced by an atherogenic diet in hamsters, J. Agric. Food Chem. source

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    Premisecitation

    The DSI-EC granted 'Class A' to Spirulina after rigorous analysis of clinical case reports, animal toxicological data and adverse event reports, making it safe for human consumption when grown under controlled conditions.

    “Moreover, the Dietary Supplements Information Expert Committee (DSI-EC) of the United States Pharmacopeial Convention (USP) granted ‘Class A’ to Spirulina after rigorous analysis of clinical case reports, animal toxicological data and adverse event reports, thus making it safe for human consumption [6] when grown under controlled conditions [4,7].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [6] Marles, 2011, United States pharmacopeia safety evaluation of spirulina, Crit. Rev. Food Sci. Nutr. source

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    • cites [4] 2015, Nutritional and toxicological aspects of Spirulina (Arthrospira), Nutr. Hosp.

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    • cites [7] Reanmongkol, 2010, Evaluation of the toxicity of Arthrospira (Spirulina) platensis extract, J. Appl. Phycol. source

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    Premisecitation

    Spirulina is a rich source of PCB, an inhibitor of NADPH oxidase, which is implied to be a contributor to oxidative stress in a variety of neurological/neurodegenerative diseases.

    “It is a rich source of PCB, an inhibitor of NADPH oxidase, which is implied to be a contributor to oxidative stress in a variety of neurological/neurodegenerative diseases [38].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [38] Kim, K.M., Lee, J.Y., Im, A.-R., and Chae, S. (2018). Phycocyanin Protects Against UVB-induced Apoptosis Through the PKC α/βII-Nrf-2/HO-1 Dependent Pathway in Human Primary Skin Cells. Molecules, 23. source

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    Interpretationcitation

    Spirulina has neuroprotective potential in mitigating the effects of spinal cord injury and causing functional recovery.

    “thereby indicating the neuroprotective potential of Spirulina in mitigating the effects of spinal cord injury and causing functional recovery [49].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [49] Abdullahi, 2020, Improved spinal cord gray matter morphology induced by Spirulina platensis following spinal cord injury in rat models, Ultrastruct. Pathol. source

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    Premisecitation

    β-carotene is an efficient membrane antioxidant showing antioxidant properties and providing protection against singlet oxygen-mediated lipid peroxidation damage.

    “The carotenoids in Spirulina are as high as 4000 mg/kg, among which β-carotene predominates [34], and is considered an efficient membrane antioxidant showing antioxidant properties and providing protection against singlet oxygen-mediated lipid peroxidation damage [15].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [15] Deng, 2010, Hypolipidemic, antioxidant, and antiinflammatory activities of microalgae Spirulina, Cardiovasc. Ther. source

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    Premisecitation

    Spirulina treatment enhanced behavioral and cognitive functions in PMN rats.

    “thus enhancing behavioral and cognitive functions [64].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [64] Sinha, 2020, Maternal Spirulina supplementation during pregnancy and lactation partially prevents oxidative stress, glial activation and neuronal damage in protein malnourished F1 progeny, Neurochem. Int. source

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    Premisecitation

    Maternal malnutrition affects brain development and probably represents a leading factor in the pathogenesis of neurological and psychiatric disorders in offspring.

    “several studies showed that maternal malnutrition affects brain development and probably represents a leading factor in the pathogenesis of neurological and psychiatric disorders in an offspring [60,61,62].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [60] Tiemeier, 2014, Maternal dietary patterns during pregnancy and child internalising and externalising problems. The Generation R Study, Clin. Nutr. source

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    • cites [61] Takeda, 2015, Influx of extracellular Zn(2+) into the hippocampal CA1 neurons is required for cognitive performance via long-term potentiation, Neuroscience source

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    • cites [62] Quirarte, 2018, Hippocampal mechanisms in impaired spatial learning and memory in male offspring of rats fed a low-protein isocaloric diet in pregnancy and/or lactation, Hippocampus source

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    Premisecitation

    During aging and neurodegeneration, there is a decrease in normal antioxidant and anti-inflammatory defense mechanisms, making the brain more susceptible to detrimental effects of oxidative stress.

    “During aging and neurodegeneration, there is a decrease in normal antioxidant and anti-inflammatory defense mechanisms, making the brain more susceptible to the detrimental effects of oxidative stress [44,45,46].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [44] Cianciulli, 2017, Understanding the role of SOCS signaling in neurodegenerative diseases: Current and emerging concepts, Cytokine Growth Factor Rev. source

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    • cites [45] Finkel, 2000, Oxidants, oxidative stress and the biology of ageing, Nature source

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    • cites [46] Bickford, 2000, Antioxidant-rich diets improve cerebellar physiology and motor learning in aged rats, Brain Res. source

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    Premisecitation

    Nutrition is one of the most important environmental factors that influence brain development.

    “Nutrition is one of the most important environmental factors that influence brain development [58,59];”
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    • cites [58] Healy, 2007, A critique of comparative studies of brain size, Proc. Biol. Sci.

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    • cites [59] Coviello, 2018, Effects of early nutrition and growth on brain volumes, white matter microstructure, and neurodevelopmental outcome in preterm newborns, Pediatr. Res. source

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    Premisecitation

    PCB treatment significantly reduced brain infarct volume, limited exploratory behavior impairment, and preserved viable cortical neurons in ischemic rats in a dose-dependent manner with respect to the vehicle group.

    “PCB treatment significantly reduced brain infarct volume, limited exploratory behavior impairment, and preserved viable cortical neurons in ischemic rats in a dose-dependent manner with respect to the vehicle group.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [65] 2020, Phycocyanobilin reduces brain injury after endothelin-1- induced focal cerebral ischaemia, Clin. Exp. Pharmacol. Physiol. source

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    Premisecitation

    Spirulina supplementation to protein-deprived mothers intensifies reflex maturation, reduces mortality, and ameliorates behavioral and cognitive problems in the offspring.

    “A more recent article demonstrated that Spirulina supplementation to protein-deprived mothers intensifies reflex maturation, reduces mortality, and ameliorates behavioral and cognitive problems in the offspring;”
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    • cites [63] Sinha, 2020, Amelioration of neurobehavioral and cognitive abilities of F1 progeny following dietary supplementation with Spirulina to protein malnourished mothers, Brain Behav. Immun. source

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    Premisecitation

    S. platensis protein extract protects the activity of total GPx, GPx-Se and GR, and increases reduced GSH in SH-SY5Y cells.

    “This study showed that S. platensis protein extract protects the activity of total GPx, GPx-Se and GR, and increases reduced GSH thanks to the scavenger activity of free radicals and iron chelator ability, thus increasing cell viability [57].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [57] 2008, Neuroprotection by Spirulina platensis protean extract and phycocyanin against iron-induced toxicity in SH-SY5Y neuroblastoma cells, Toxicol. In Vitro source

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    Premisecitation

    C-PC failed to fully restore BBB disruption induced by TBTC, although it restored p-glycoprotein and claudin-5 levels and partially enzyme activity of calpain and matrix metalloproteinase.

    “C-PC failed to fully restore BBB disruption, although it was able to restore p-glycoprotein (PGP) and claudin-5 levels and, partially, enzyme activity of tissue remodeling such as calpain and matrix metalloproteinase [83].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [83] Mitra, 2015, C-Phycocyanin protects against acute tributyltin chloride neurotoxicity by modulating glial cell activity along with its anti-oxidant and anti-inflammatory property: A comparative efficacy evaluation with N-acetyl cysteine in adult rat brain, Chem. Biol. Interact. source

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    Premisecitation

    SM70EE inhibits AChE activity and PARP cleavage, and increases expression of p-CREB, p-TrkB and BDNF, promoting activation of BDNF/CREB neuroprotective signaling pathways in HT-22 neuronal cells.

    “SM70EE is able to inhibit AChE activity and PARP cleavage, and increase the expression of p-CREB, p-TrkB and BDNF, promoting the activation of BDNF/CREB neuroprotective signaling pathways in HT-22 neuronal cells [67].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [67] Koh, E.-J., Seo, Y.-J., Choi, J., Lee, H.Y., Kang, D.-H., Kim, K.-J., and Lee, B.-Y. (2017). Spirulina maxima Extract Prevents Neurotoxicity via Promoting Activation of BDNF/CREB Signaling Pathways in Neuronal Cells and Mice. Molecules, 22. source

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    Premisecitation

    Astrocyte-derived BDNF supports OPC maturation under hypoxic conditions in vitro and oligodendrogenesis after white matter damage in vivo.

    “It was seen that astrocyte-derived BDNF supports OPC maturation under hypoxic conditions in vitro and oligodendrogenesis after white matter damage in vivo, also indicating a positive role of C-PC in myelin regeneration [101].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [101] Pentón-Rol, G., Marín-Prida, J., and Falcón-Cama, V. (2018). C-Phycocyanin and Phycocyanobilin as Remyelination Therapies for Enhancing Recovery in Multiple Sclerosis and Ischemic Stroke: A Preclinical Perspective. Behav. Sci., 8. source

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    Premisecitation

    Post-mortem clinical studies demonstrated high levels of pro-inflammatory molecules in the brains of individuals with PD, as well as in the cerebrospinal fluid.

    “Post-mortem clinical studies demonstrated high levels of pro-inflammatory molecules in the brains of individuals with PD, as well as in the cerebrospinal fluid [114,115].”
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    • cites [114] Reale, 2009, Peripheral chemo-cytokine profiles in Alzheimer’s and Parkinson’s diseases, Mini Rev. Med. Chem. source

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    • cites [115] Reale, 2009, Peripheral cytokines profile in Parkinson’s disease, Brain Behav. Immun. source

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    Premisecitation

    Oxidative stress generated by NADPH oxidase may contribute to BBB damage, and PCB from Spirulina may improve the course of SVD by suppressing the activity of NADPH oxidase.

    “McCarty reported that oxidative stress generated by NADPH oxidase may contribute to BBB damage, and PCB from Spirulina may improve the course of SVD by suppressing the activity of NADPH oxidase [84].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [84] McCarty, 2015, NADPH Oxidase Activity in Cerebral Arterioles Is a Key Mediator of Cerebral Small Vessel Disease-Implications for Prevention, Healthcare source

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    Premisecitation

    C-PC significantly restored microglial activity, adjusting expression of cellular marker CD11b and formation of LC3-II and beclin, reduced by TBTC.

    “In addition, it significantly restored microglial activity, adjusting the expression of cellular marker CD11b and the formation of LC3-II and beclin (markers of autophagy), reduced by treatment with TBTC, apart from its considerable protective effect on redox signaling, stress proteins and inflammatory molecules [83].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [83] Mitra, 2015, C-Phycocyanin protects against acute tributyltin chloride neurotoxicity by modulating glial cell activity along with its anti-oxidant and anti-inflammatory property: A comparative efficacy evaluation with N-acetyl cysteine in adult rat brain, Chem. Biol. Interact. source

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    Premisecitation

    Astrocytes and microglia play a double role, both pro- and anti-inflammatory, and are involved in different functions under physiological and pathological conditions.

    “An important role for chronic neuroinflammation is fulfilled by neuroimmune cells, astrocytes and microglia, which play a double role, both pro- and anti-inflammatory, and are involved in different functions under physiological and pathological conditions [71].”
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    • cites [71] Schain, 2017, Neuroinflammation in Neurodegenerative Disorders-a Review, Curr. Neurol. Neurosci. Rep. source

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    Premisecitation

    Se-SP suppressed OGD-induced DNA damage by arresting ROS accumulation in neurons and improving mitochondrial dysfunction via balancing Bcl-2 family expression.

    “Se-SP was showed to suppress OGD-induced DNA damage by arresting ROS accumulation in neurons and improving mitochondrial dysfunction via balancing Bcl-2 family expression.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [66] Song, 2021, Selenium-containing protein from selenium-enriched Spirulina platensis antagonizes oxygen glucose deprivation-induced neurotoxicity by inhibiting ROS-mediated oxidative damage through regulating mPTP opening, Pharm. Biol. source

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    Neurodegenerative diseases are characterized by a series of aberrant protein folding events, which cause the formation of amorphous aggregates or amyloid fibrils.

    “Neurodegenerative diseases are characterized by a series of aberrant protein folding events, which cause the formation of amorphous aggregates or amyloid fibrils [103].”
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    • cites [103] Sweeney, 2017, Protein misfolding in neurodegenerative diseases: Implications and strategies, Transl. Neurodegener. source

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    Premisecitation

    Persistent activation of microglia and astrocytes elevates inflammatory mediators like chemokines and cytokines, and ROS and RNS release, with neurotoxic effects and responsible for chronic neurological/neurodegenerative disorders.

    “Persistent activation of microglia and astrocytes elevates inflammatory mediators like chemokines and cytokines [79], the ROS and RNS release, with neurotoxic effects and responsible for chronic neurological/neurodegenerative disorders [80,81,82].”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [79] Perea, 2017, Alzheimer’s disease as an inflammatory disease, Biomol. Concepts source

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    • cites [82] Piovan, 2021, Pre- and Early Post-treatment With Arthrospira platensis (Spirulina) Extract Impedes Lipopolysaccharide-triggered Neuroinflammation in Microglia, Front. Pharmacol. source

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    Premisecitation

    In the 3D oxidized astrocyte model, C-PC upregulated antioxidant enzymes such as SOD and CAT, and downregulated inflammatory factors IL-6 and IL-1β and glial scar.

    “In the 3D oxidized astrocyte model, C-PC upregulated antioxidant enzymes such as SOD and CAT, and downregulated inflammatory factors IL-6 and IL-1β and glial scar.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [98] Min, 2015, Assessment of C-phycocyanin effect on astrocytes-mediated neuroprotection against oxidative brain injury using 2D and 3D astrocyte tissue model, Sci. Rep. source

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    Neuroinflammation is an effective endogenous defense that protects the central nervous system and aims to eliminate threats and restore homeostasis.

    “Neuroinflammation is an effective endogenous defense that protects the central nervous system (CNS) and aims not only to eliminate threats but also restore homeostasis [69],”
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    • cites [69] Glass, 2010, Mechanisms underlying inflammation in neurodegeneration, Cell source

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    Premisecitation

    C-PC intranasal administration to rats with ischemic brain reduced infarct size and improved behavioral deficits.

    “Min et al. observed that C-PC intranasal administration to rats with ischemic brain reduced infarct size and improved behavioral deficits.”
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    • cites [98] Min, 2015, Assessment of C-phycocyanin effect on astrocytes-mediated neuroprotection against oxidative brain injury using 2D and 3D astrocyte tissue model, Sci. Rep. source

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    Premisecitation

    LPS insult causes increased astrogliosis with prominent activation of GFAP in existing cells and decreased proliferation of NPCs.

    “LPS insult causes increased astrogliosis with prominent activation of GFAP in existing cells and decreased proliferation of NPCs.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [102] Bachstetter, A.D., Jernberg, J., Schlunk, A., Vila, J.L., Hudson, C., Cole, M.J., Shytle, R.D., Tan, J., Sanberg, P.R., and Sanberg, C.D. (2010). Spirulina promotes stem cell genesis and protects against LPS induced declines in neural stem cell proliferation. PLoS ONE, 5. source

      Not checked in the free run.

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

    Premisecitation

    Activated microglia cause activation of astrocytes, which in turn can liberate signaling molecules that act on microglia.

    “Notably, activated microglia is recognized to cause the activation of astrocytes, which in turn can also liberate signaling molecules that act on microglia [77].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [77] Liddelow, 2017, Neurotoxic reactive astrocytes are induced by activated microglia, Nature source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In male Wistar rats treated with TBTC, C-PC effectively reduced ROS generation, decreased astroglia activation, counteracting morphological alteration and upregulation of GFAP.

    “In male Wistar rats treated with tributyltin chloride (TBTC), an environmental pollutant and potent biocide, C-PC effectively reduced ROS generation, decreased astroglia activation, counteracting the morphological alteration, and upregulation of GFAP, indices of astroglia activation.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [83] Mitra, 2015, C-Phycocyanin protects against acute tributyltin chloride neurotoxicity by modulating glial cell activity along with its anti-oxidant and anti-inflammatory property: A comparative efficacy evaluation with N-acetyl cysteine in adult rat brain, Chem. Biol. Interact. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In the hippocampus of mice treated with oligomeric Aβ peptides, administration of C-PC increased miRNA-335 levels with reduced apoptosis and attenuated HDAC3 expression.

    “In another article, it was demonstrated that in the hippocampus of mice treated with oligomeric Aβ peptides, the administration of C-PC increased miRNA-335 levels with reduced apoptosis and attenuated the expression of HDAC3 [141]”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [141] Li, 2020, Effect of C-phycocyanin on HDAC3 and miRNA-335 in Alzheimer’s disease, Transl. Neurosci. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    α-Syn has been shown to increase the expression of COX-2 and the activity of microglial NADPH oxidase via CD11b.

    “Moreover, α-Syn has been shown to increase the expression of COX-2 [116] and the activity of microglial NADPH oxidase via CD11b [117].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [116] Rojanathammanee, 2011, Expression of mutant α-synuclein modulates microglial phenotype in vitro, J. Neuroinflamm. source

      Not checked in the free run.

    • cites [117] Hou, 2018, Integrin CD11b mediates α-synuclein-induced activation of NADPH oxidase through a Rho-dependent pathway, Redox Biol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    C-PC and α-Syn interact through unstable interactions, indicating that transient interactions can hinder fibril formation.

    “C-PC and α-Syn interact through unstable interactions, indicating that perhaps transient interactions can hinder fibril formation [118].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [118] Liu, 2019, C-Phycocyanin from Spirulina Inhibits α-Synuclein and Amyloid-β Fibril Formation but Not Amorphous Aggregation, J. Nat. Prod. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Pretreatment with Spirulina did not completely prevent the dopamine-consumption effect of MPTP and did not arrest oxidative stress.

    “pretreatment with Spirulina did not completely prevent the DA-consumption effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and arrest oxidative stress [90].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [90] Chamorro, 2006, Spirulina maxima pretreatment partially protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity, Nutr. Neurosci. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    SM770EE increased BDNF and potentiated BDNF/PI3K/Akt signaling, inducing suppression of GSK-3β phosphorylation, downregulating BACE1, and inhibiting APP processing.

    “SM770EE increased BDNF and potentiated the BDNF/PI3K/Akt signaling pathway, which induced the suppression of GSK-3β phosphorylation, consequently downregulating β-site APP-cleaving enzyme 1 (BACE1), which in turn inhibited the processing of APP [92].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [92] Koh, E.-J., Kim, K.-J., Song, J.-H., Choi, J., Lee, H.Y., Kang, D.-H., Heo, H.J., and Lee, B.-Y. (2017). Spirulina maxima Extract Ameliorates Learning and Memory Impairments via Inhibiting GSK-3β Phosphorylation Induced by Intracerebroventricular Injection of Amyloid-β 1-42 in Mice. Int. J. Mol. Sci., 18. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Spirulina was neuroprotective in an α-Syn rat model of Parkinson's disease, increasing TH+ and NeuN+ cells and decreasing activated microglial cells as evaluated by MHC II expression.

    “The authors showed that Spirulina was neuroprotective in this α-Syn model of PD, observing a major number of TH+ and NeuN+ cells and a decrease in the number of activated microglial cells as evaluated by MHC II expression.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [126] Pabon, 2011, CX3CL1 reduces neurotoxicity and microglial activation in a rat model of Parkinson’s disease, J. Neuroinflamm. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Inhibition of HDAC3 in hippocampal tissue reduced amyloid plaque load and Aβ levels and attenuated microglia activation in the brains of APP/PS1 mice.

    “inhibition of HDAC3 in the hippocampal tissue reduced amyloid plaque load and Aβ levels and attenuated microglia activation in the brains of APP/PS1 mice [143].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [143] Zhu, 2017, HDAC3 negatively regulates spatial memory in a mouse model of Alzheimer’s disease, Aging Cell. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In DJ-1βΔ93 Drosophila melanogaster flies, a Parkinson's disease model, dietary supplementation of Spirulina significantly decreased SOD and CAT activities and improved lifespan and locomotor activity.

    “Kumar et al. found that in DJ-1βΔ93 flies, a model of PD in Drosophila melanogaster, dietary supplementation of Spirulina leads to a significant decrease in SOD and CAT activities, improving lifespan and locomotor activity.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [127] Kumar, 2017, Supplementation of Spirulina (Arthrospira platensis) Improves Lifespan and Locomotor Activity in Paraquat-Sensitive DJ-1β Δ93 Flies, a Parkinson’s Disease Model in Drosophila melanogaster, J. Diet. Suppl. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Neuronal cells constitutively express CX3CL1, which binds to a G protein-coupled receptor CX3CR1 present in microglia, controlling microglia activation and lowering levels of IL-1β, TNF-α and IL-6.

    “Recent evidence has shown that neuronal cells constitutively express CX3CL1, which binds to a G protein-coupled receptor CX3CR1 present in microglia, controlling microglia activation and lowering levels of IL-1β, TNF-α and IL-6 [123,124].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [123] Zujovic, 2000, Fractalkine modulates TNF-αsecretion and neurotoxicity induced by microglial activation, Glia source

      Not checked in the free run.

    • cites [124] Zujovic, 2001, In vivo neutralization of endogenous brain fractalkine increases hippocampal TNF-α and 8-isoprostane production induced by intracerebroventricular injection of LPS, J. Neuroimmunol. source

      Not checked in the free run.

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

    Premisecitation

    Alzheimer's disease exhibits several possible causal mechanisms, including oxidative stress, chronic inflammation, impaired insulin metabolism and cholinergic deficiency.

    “AD is a disease that exhibits several possible causal mechanisms, including oxidative stress, chronic inflammation, impaired insulin metabolism and cholinergic deficiency [129].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [129] 2012, Contributions of brain insulin resistance and deficiency in amyloid-related neurodegeneration in Alzheimer’s disease, Drugs source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Dose- and time-dependent S. platensis extract inhibits histone deacetylase protein levels and shows anti-inflammatory activity.

    “Pham et al. demonstrated that dose- and time-dependent S. platensis extract inhibits histone deacetylase (HDAC) protein levels and shows anti-inflammatory activity [142].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [142] Pham, T.X., Park, Y.-K., and Lee, J.-Y. (2016). Anti-Inflammatory Effects of Spirulina platensis Extract via the Modulation of Histone Deacetylases. Nutrients, 8. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    S. maxima showed a protective effect against 6-OHDA-induced toxicity in the rat striatum, reducing NO, ROS and lipoperoxidation levels in the striatum.

    “S. maxima showed a protective effect in response to 6-OHDA-induced toxicity in the rat striatum, inducing a reduction in NO, ROS and lipoperoxidation levels in the striatum [89]”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [89] Mendieta, 2013, Anti-oxidant effect of Spirulina (Arthrospira) maxima in a neurotoxic model caused by 6-OHDA in the rat striatum, J. Neural. Transm. source

      Not checked in the free run.

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

    Premisecitation

    Pathognomonic signs of Alzheimer's disease include senile plaques with Aβ peptides in the extracellular environment, chronic neuroinflammation and neurofibrillary tangles comprising tau proteins.

    “Pathognomonic signs of AD include the presence of senile plaques with Aβ peptides in the extracellular environment, chronic neuroinflammation and neurofibrillary tangles comprising tau proteins [130].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [130] Magalingam, 2018, Current Concepts of Neurodegenerative Mechanisms in Alzheimer’s Disease, Biomed. Res. Int. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Oral treatment with C-PC shows its effect in the hippocampus, crossing the BBB.

    “An interesting aspect is that oral treatment with C-PC shows its effect in the hippocampus, crossing BBB [85].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [85] Rimbau, 1999, Protective effects of C-phycocyanin against kainic acid-induced neuronal damage in rat hippocampus, Neurosci. Lett. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    SM70EE suppressed acetylcholinesterase activity, increased expression levels of GPx and GR, and consequently increased glutathione level.

    “Additionally, SM70EE suppressed acetylcholinesterase activity, increased the expression levels of GPx and GR, and consequently, the glutathione level.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [92] Koh, E.-J., Kim, K.-J., Song, J.-H., Choi, J., Lee, H.Y., Kang, D.-H., Heo, H.J., and Lee, B.-Y. (2017). Spirulina maxima Extract Ameliorates Learning and Memory Impairments via Inhibiting GSK-3β Phosphorylation Induced by Intracerebroventricular Injection of Amyloid-β 1-42 in Mice. Int. J. Mol. Sci., 18. source

      Not checked in the free run.

  • May combine two claims. The quote only partly states this claim.

    Premisecitation

    SM70EE reduced Aβ1-42 levels in the hippocampus and inhibited factors associated with APP processing in mice with cognitive impairment induced by intracerebroventricular Aβ1-42.

    “Researchers found that SM70EE reduced Aβ1-42 levels in the hippocampus and inhibited factors associated with APP processing.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [92] Koh, E.-J., Kim, K.-J., Song, J.-H., Choi, J., Lee, H.Y., Kang, D.-H., Heo, H.J., and Lee, B.-Y. (2017). Spirulina maxima Extract Ameliorates Learning and Memory Impairments via Inhibiting GSK-3β Phosphorylation Induced by Intracerebroventricular Injection of Amyloid-β 1-42 in Mice. Int. J. Mol. Sci., 18. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    C-PC hinders the amyloid formation process of bovine serum albumin, inhibiting conformational conversion of α-helices and β-sheets of bovine serum albumin.

    “Luo and Jing demonstrated that C-PC is able to hinder the amyloid formation process of bovine serum albumin (BSA), inhibiting conformational conversion (α-helices and β-sheets) of BSA [136].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [136] Luo, Y.-C., and Jing, P. (2020). Molecular Interaction of Protein-Pigment C-Phycocyanin with Bovine Serum Albumin in a Gomphosis Structure Inhibiting Amyloid Formation. Int. J. Mol. Sci., 21. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In rats and mice with EAE, oral C-PC administration improved EAE clinical progression and re-established motor function and motor coordination.

    “More recently, in rat and mice with EAE, oral C-PC administration not only improved EAE clinical progression but also re-established motor function and motor coordination.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [95] 2018, Beneficial effects of oral ad-ministration of C-Phycocyanin and Phycocyanobilin in rodent models of experimental autoimmune encephalomyelitis, Life Sci. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Phycocyanin increases INS-IR binding affinity, IRS-1 activation of PI3K and AKT, resulting in initiation of the IRS/PI3K/AKT pathway, and slightly reduces expression of the PTEN gene.

    “Phycocyanin has been shown to increase INS-IR binding affinity, IRS-1 activation of PI3K and AKT, resulting in initiation of the IRS/PI3K/AKT pathway, and slightly reduced expression of the phosphatase and tensin homolog (PTEN) gene, an inhibitor of the PI3K/AKT pathway [94].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [94] Agrawal, 2020, Phycocyanin alleviates ICV-STZ induced cognitive and molecular deficits via PI3-Kinase dependent pathway, Food Chem. Toxicol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In EAE mice, C-PC ameliorated clinical deterioration due to a significant decrease in inflammatory infiltrates in spinal cord tissue, with reduction in Mac-3 positive activated macrophages/microglia and CD3-positive T cells in the lesions.

    “In EAE mice, C-PC was able to ameliorate the clinical deterioration of animals due to the significant decrease in inflammatory infiltrates in spinal cord tissue, with a reduction in Mac-3 positive activated macrophages/microglia and CD3-positive T cells in the lesions.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [158] Muzio, 2016, Comparative Neuroregenerative Effects of C-Phycocyanin and IFN-β in a Model of Multiple Sclerosis in Mice, J. Neuroimmune Pharmacol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Chemokines like CXCL2 work via the chemokine receptor CXCR2 in neuronal cells, where they are involved in the pathophysiology of Alzheimer's disease.

    “Moreover, chemokines like CXCL2 work via the chemokine receptor (CXCR2) in neuronal cells, where they are involved in the pathophysiology of AD [148].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [148] Buanne, 2007, Chemokine MIP-2/CXCL2, acting on CXCR2, induces motor neuron death in primary cultures, Neuroimmunomodulation source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationnone given

    The decrement in normal antioxidant and anti-inflammatory defense systems in various conditions makes the brain more vulnerable to damaging effects of ROS or RNS and plays an important role in most neurological disorders, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, inflammatory lesions and senility.

    “The decrement in normal antioxidant and anti-inflammatory defense systems, which occurs in various conditions, makes the brain more vulnerable to the damaging effects of ROS or RNS and plays an important role in most neurological disorders (AD, PD, MS, lesions inflammatory and senility).”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Multiple sclerosis relapses are thought to be due to activated self-reactive myelin-specific T lymphocytes present in the central nervous system and recruitment of peripheral mononuclear phagocytes, producing inflammation, brain and spinal cord edema, and demyelination.

    “Interesting, MS relapses are thought to be due to activated self-reactive myelin-specific T lymphocytes present in the CNS and recruitment of peripheral mononuclear phagocytes, producing inflammation, brain and spinal cord edema, and demyelination [154].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [154] Martin, 1995, Immunological aspects of experimental allergic encephalomyelitis and multiple sclerosis, Crit. Rev. Clin. Lab. Sci. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Several lines of evidence testify to neuroprotection mechanisms of Spirulina, including antioxidant and anti-inflammatory activities in the brain parenchyma, which make Spirulina a potential pharmacological agent in the prevention and treatment of Parkinson's disease, Alzheimer's disease and multiple sclerosis.

    “Several lines of evidence testify to peculiar neuroprotection mechanisms, including antioxidant and anti-inflammatory activities in the brain parenchyma, which make Spirulina a potential pharmacological agent in the prevention and treatment of these neurological disorders.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Findings from animal models of Parkinson's disease, Alzheimer's disease and multiple sclerosis are predictive of effects in humans.

  • May combine two claims.

    Premisecitation

    C-PC up-regulated expression of genes related to remyelination, gliogenesis and axon-glia processes, and significantly reduced expression of genes involved in demyelination, including CD44 and PPAR.

    “Moreover, C-PC up-regulated the expression of a set of genes (Mal, Mog and Mobp, Nkx6-2, Nkx2-2, Bmpa and the transcription factor, Olig1) related to remyelination, gliogenesis and axon-glia processes, and significantly reduced the expression of genes involved in the process of demyelination, including CD44 and PPAR.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [158] Muzio, 2016, Comparative Neuroregenerative Effects of C-Phycocyanin and IFN-β in a Model of Multiple Sclerosis in Mice, J. Neuroimmune Pharmacol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    C-PC reduced both the levels of MDA and PP and the CAT/SOD ratio.

    “C-PC was also able to reduce both the levels of MDA and PP and the CAT/SOD ratio [158].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [158] Muzio, 2016, Comparative Neuroregenerative Effects of C-Phycocyanin and IFN-β in a Model of Multiple Sclerosis in Mice, J. Neuroimmune Pharmacol. source

      Not checked in the free run.

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

    Premisecitation

    Experimental Autoimmune Encephalomyelitis is the most used experimental model for multiple sclerosis and is capable of reproducing the main neuroimmunological and histopathological aspects of multiple sclerosis.

    “The most used experimental model for the study of this disease is the Experimental Autoimmune Encephalomyelitis (EAE), capable of reproducing the main neuroimmunological and histopathological aspects of MS [155,156].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [155] Constantinescu, 2011, Experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS), Br. J. Pharmacol. source

      Not checked in the free run.

    • cites [156] Bittner, 2014, Myelin oligodendrocyte glycoprotein (MOG35-55) induced experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice, J. Vis. Exp.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    ICAM-1, a biomarker of endothelial dysfunction, is increased in Alzheimer's disease, and endothelial cells, astrocytes and microglia show enhanced levels of ICAM-1 in pathological states.

    “Experimental evidence confirmed that biomarkers of endothelial dysfunction, such as intercellular adhesion molecule 1 (ICAM-1), are increased in AD; endothelial cells, astrocytes and microglia show enhanced levels of ICAM-1 in pathological states”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [145] Walker, 2017, Changes in CD200 and intercellular adhesion molecule-1 (ICAM-1) levels in brains of Lewy body disorder cases are associated with amounts of Alzheimer’s pathology not α-synuclein pathology, Neurobiol. Aging source

      Not checked in the free run.

    • cites [146] Frohman, 1991, Expression of intercellular adhesion molecule 1 (ICAM-1) in Alzheimer’s disease, J. Neurol. Sci. source

      Not checked in the free run.

    • cites [147] Guha, 2021, ICAM-1 protects neurons against Amyloid-β and improves cognitive behaviors in 5xFAD mice by inhibiting NF-Κb, Brain Behav. Immun. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    PCB administration significantly reduced expression levels of pro-inflammatory cytokines IL-6 and IFN-γ in the brain, positively modulated oxidative stress markers, and preserved the integrity of myelin sheaths in the brain.

    “PCB administration resulted in a significant reduction in the expression levels of pro-inflammatory cytokines like IL-6 and IFN-γ in the brain, positively modulated oxidative stress markers, and preserved the integrity of myelin sheaths in the brain [95].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [95] 2018, Beneficial effects of oral ad-ministration of C-Phycocyanin and Phycocyanobilin in rodent models of experimental autoimmune encephalomyelitis, Life Sci. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In rats with intracerebroventricular streptozotocin-induced Alzheimer's disease model, phycocyanin treatment significantly attenuated neuroinflammation and enhanced BDNF and IGF-1 levels that increased regulation of IRS-1.

    “In this experimental model of AD, phycocyanin treatment significantly attenuated neuroinflammation and enhanced BDNF as well as insulin-like growth factor-1 (IGF-1) levels that increased regulation of insulin receptor substrate-1 (IRS-1).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [94] Agrawal, 2020, Phycocyanin alleviates ICV-STZ induced cognitive and molecular deficits via PI3-Kinase dependent pathway, Food Chem. Toxicol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Rats treated with C-PC showed compressed, solid and squashed myelin and no signs of axonal breakdown, comparable to control animals.

    “Rats treated with C-PC showed compressed, solid and squashed myelin and no signs of axonal breakdown, characteristics comparable to control animals [153].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [153] 2011, C-Phycocyanin ameliorates experimental autoimmune encephalomyelitis and induces regulatory T cells, Int. Immunopharmacol. source

      Not checked in the free run.

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

    Premisecitation

    Multiple sclerosis is a chronic inflammatory and neurodegenerative disease of the central nervous system with a possible autoimmune etiology.

    “MS is a chronic inflammatory and neurodegenerative disease of CNS with a possible autoimmune etiology [149].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [149] Nylander, 2012, Multiple sclerosis, J. Clin. Investig. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Spirulina microalgae represent a rich source of antioxidant and anti-inflammatory substances able to support development of the nervous system and physiologic brain functions, compensate for nutritional deficiencies, and promote a beneficial immune response, reducing harmful consequences of an overactive immune system.

    “Spirulina microalgae represent a rich source of antioxidant and anti-inflammatory substances that is able not only to support the development of the nervous system and physiologic brain functions, compensating for nutritional deficiencies, but also promote a beneficial immune response, reducing the harmful consequences of an overactive immune system.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    RGFP-966, a selective HDAC3 silencing agent, reduces both Aβ protein load and hyperphosphorylated Tau.

    “RGFP-966, a selective HDAC3 silencing agent, reduces not only the Aβ protein load but also hyperphosphorylated Tau [144]”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [144] Janczura, 2018, Inhibition of HDAC3 reverses Alzheimer’s disease-related pathologies in vitro and in the 3xTg-AD mouse model, Proc. Natl. Acad. Sci. USA source

      Not checked in the free run.

66 of 66

  • The paper relies on this without support.

    Findings from animal and cell-culture studies of Spirulina or its components are relevant to human brain health and to the prevention/progression of human neurodegenerative diseases.

    “due to these properties, Spirulina could be considered a potential natural drug.”

  • The paper relies on this without support.

    Findings from animal models of Parkinson's disease, Alzheimer's disease and multiple sclerosis are predictive of effects in humans.

    “Several lines of evidence testify to peculiar neuroprotection mechanisms, including antioxidant and anti-inflammatory activities in the brain parenchyma, which make Spirulina a potential pharmacological agent in the prevention and treatment of these neurological disorders.”
2 of 2

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?

  • Spirulina is regarded as a natural medicine and is used in manufacturing functional foods and nutritional supplements worldwide.

    “Spirulina is regarded as a natural medicine and is utilized in the manufacturing of functional foods and nutritional supplements all over the world due to the qualities that have been described [5,6].”

    From Trends and Technological Advancements in the Possible Food Applications of Spirulina and Their Health Benefits: A Review. (2022) · cites this paper as [5]

    The Introduction says Spirulina is cultivated worldwide as an ingredient in nutraceutical formulations or as food, supporting the claim about its use in foods and supplements. The Conclusions discuss its potential health benefits and natural bioactive products as possible drugs, but do not establish that Spirulina is regarded as a natural medicine. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • Spirulina has been incorporated into medicinal foods, functional foods, and nutritional supplements.

    “As a result of this, spirulina has found its way into the formulation of a great number of medicinal foods, functional foods, and nutritional supplements.”

    From Trends and Technological Advancements in the Possible Food Applications of Spirulina and Their Health Benefits: A Review. (2022) · cites this paper as [5]

    The Introduction says Spirulina is used as an ingredient in many nutraceutical formulations or as food, and the Abstract describes its widespread use as a nutraceutical food supplement. These passages support food and supplement uses, but the paper does not specifically establish its incorporation into medicinal foods. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • Spirulina's bioactive compounds participate in antioxidant and anti-inflammatory activities.

    “In addition to this, spirulina has a high concentration of bioactive compounds, such as phenols, phycocyanin pigment, and polysaccharides, which all take part in a number of biological activities, such as antioxidant and anti-inflammatory activity.”

    From Trends and Technological Advancements in the Possible Food Applications of Spirulina and Their Health Benefits: A Review. (2022) · cites this paper as [5]

    The Introduction links Spirulina’s phycocyanin to antioxidant activity, and the Conclusions describe Spirulina as a rich source of antioxidant and anti-inflammatory substances. Outside the abstract, the cited passages do not establish that phenols and polysaccharides each contribute to both activities, as the citing sentence’s “all” implies. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • The majority of spirulina's bioactive compounds play a therapeutic role in treating cardiovascular diseases, high cholesterol, high blood sugar, obesity, high blood pressure, tumors, and inflammatory diseases.

    “The majority of these compounds play an important therapeutic role in the treatment of cardiovascular diseases (CVDs), high cholesterol, high blood sugar, obesity, high blood pressure, tumors, and inflammatory diseases.”

    From Trends and Technological Advancements in the Possible Food Applications of Spirulina and Their Health Benefits: A Review. (2022) · cites this paper as [5]

    The Abstract lists positive effects of Spirulina in all the named conditions, and the Introduction describes several relevant properties. But the Abstract says publications have suggested benefits from Spirulina; it does not establish that a majority of its compounds have an important therapeutic role in treating those diseases. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Spirulina has a high concentration of bioactive compounds such as phenols, phycocyanin pigment, and polysaccharides.

    “In addition to this, spirulina has a high concentration of bioactive compounds, such as phenols, phycocyanin pigment, and polysaccharides, which all take part in a number of biological activities, such as antioxidant and anti-inflammatory activity.”

    From Trends and Technological Advancements in the Possible Food Applications of Spirulina and Their Health Benefits: A Review. (2022) · cites this paper as [5]

    The Introduction (page unavailable) identifies phycocyanin as a major Spirulina phytochemical, lists polysaccharides among its constituents, and discusses antioxidant and anti-inflammatory effects. It does not identify phenols as a Spirulina constituent or establish that each of the three named compounds is present at a high concentration and contributes to both activities. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

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.

  • Extract identifier changes from SM70EE to SM770EE

    Minor

    The paragraph identifies the extract as SM70EE, then calls it SM770EE while describing the same study's results.

1 of 1

Cites

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1 of the 163 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

  1. Bittner, 2014, Myelin oligodendrocyte glycoprotein (MOG35-55) induced experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice, J. Vis. Exp., 15, 51275

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Authors
Trotta, T., Porro, C., Cianciulli, A., & Panaro, M. A.
Affiliations
  • University of Foggia (IT)
  • University of Bari Aldo Moro (IT)
Corresponding author
Panaro, Maria Antonietta
ORCID
Venue
Nutrients
Publisher
MDPI AG
Published
2022-02-05
Volume
14
Issue
3
Pages
676
ISSN
2072-6643 (ISSN-L)
DOI
10.3390/nu14030676
PMC
PMC8839264
OpenAlex
W4210246897
Semantic Scholar
d534a5444693ac4080619473f9c456e535cef0f5
Cited by
98
References
163
Citations by year
2026: 19 · 2025: 29 · 2024: 30 · 2023: 12 · 2022: 8
FWCI
1.67
Type
journal article
Language
en
Open access
Licence
Locations
  • Nutrients (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • CINECA IRIS Institutional Research Information System (University of Bari Aldo Moro) (submittedVersion, cc-by-nc-nd)
Topics
  • Life Sciences › Agricultural and Biological Sciences › Aquatic Science › Seaweed-derived Bioactive Compounds
  • Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
Spirulina, cyanobacteria, nutraceuticals, neuroprotection, neurodegenerative diseases, Parkinson's disease, Alzheimer's disease, multiple sclerosis, anti-inflammatory activity, antioxidant activity, glial activation, phycocyanin, brain health
MeSH terms
Anti-Inflammatory Agents, Antioxidants, Brain, Dietary Supplements, Spirulina

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.

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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