Phycocyanobilin promotes PC12 cell survival and modulates immune and inflammatory genes and oxidative stress markers in acute cerebral hypoperfusion in rats
Abstract
Since the inflammatory response and oxidative stress are involved in the stroke cascade, we evaluated here the effects of Phycocyanobilin (PCB, the C-Phycocyanin linked tetrapyrrole) on PC12 cell survival, the gene expression and the oxidative status of hypoperfused rat brain. After the permanent bilateral common carotid arteries occlusion (BCCAo), the animals were treated with saline or PCB, taking samples 24h post-surgery. Global gene expression was analyzed with GeneChip Rat Gene ST 1.1 from Affymetrix; the expression of particular genes was assessed by the Fast SYBR Green RT-PCR Master Mix and Bioplex methods; and redox markers (MDA, PP, CAT, SOD) were evaluated spectrophotometrically. The PCB treatment prevented the H2O2 and glutamate induced PC12 cell injury assessed by the MTT assay, and modulated 190 genes (93 up- and 97 down-regulated) associated to several immunological and inflammatory processes in BCCAo rats. Furthermore, PCB positively modulated 19 genes mostly related to a detrimental pro-inflammatory environment and counteracted the oxidative imbalance in the treated BCCAo animals. Our results support the view of an effective influence of PCB on major inflammatory mediators in acute cerebral hypoperfusion. These results suggest that PCB has a potential to be a treatment for ischemic stroke for which further studies are needed.
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In ischemic rats treated with PCB, mRNA expression levels of ICAM-1 and CXCL2 were strongly reduced.
“In ischemic rats treated with PCB, the mRNA expression levels of both markers were strongly reduced [93]”
From Beneficial Effects of Spirulina Consumption on Brain Health (2022) · cites this paper as [93]
A similar counteracting effect on Alzheimer's disease may improve ICAM-1- and CXCL2-mediated damage in this disease.
“suggesting that a similar counteracting effect on AD may improve ICAM-1 and CXCL2-mediated damage in this disease.”
From Beneficial Effects of Spirulina Consumption on Brain Health (2022) · cites this paper as [93]
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InfluentialSelf-citationPotential Therapeutic Applications of C-Phycocyanin
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“Furthermore, in a model of acute cerebral hypoperfusion conducted on male Wistar rats, PCB-B decreased the levels of pro-inflammatory genes when administered at 47 or 213 µ g kg − 1 i.p. for 30 min and 1, 3, and 6 h after the permanent occlusion of the bilateral common carotid arteries [41].”
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Self-citationNutraceutical and therapeutic potential of Phycocyanobilin for treating Alzheimer’s disease
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Self-citationPhycocyanobilin reduces brain injury after endothelin-1- induced focal cerebral ischaemia
Pavón‐Fuentes, N., Marín‐Prida, J., Llópiz‐Arzuaga, A., Falcón‐Cama, V., Campos‐Mojena, R., Cervantes‐Llanos, M., Piniella‐Matamoros, B., Pentón‐Arias, E., & Pentón‐Rol, G. (2020) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/1440-1681.13214 · Cited by 29 · see citing works
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“Marín-Prida et al. [144]. showed that PCB-mod-ulated genes related to cerebroprotection (Mal, NADH dehydrogenase, Bcl-2a1, Gadd45g, Baiap2 and VEGFA), remyelination/demyelination processes ( Foxp3, TGF-β, TNF-α, IL-17A , IL-1β ), and inflammatory processes in a rat cerebral hypoperfusion model.”
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“In addition to color, phycocyanin derives many of its therapeutic effects from phycocyanobilin (Chew et al., 2017; Eriksen, 2008; Marín-Prida et al., 2013).”
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“No obvious changes in CAT activity were noted in the brain tissue; this result was consistent with that reported previously for rats injected with PCB in the cerebral areas (Marin-Prida et al., 2013).”
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“Interestingly, a positive modulation of the MAL gene expression was also found in studies of our team using C-PC and PCB in animal models of MS (6) and cerebral ischemia (9), respectively.”
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An Overview of Pharmacological and Clinical Aspects of Spirulina
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The Cyanobacterial “Nutraceutical” Phycocyanobilin Inhibits Cysteine Protease Legumain
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“Also, another study by (21) biologically supports these readings.”
- Authors
- Marín-Prida, J., Pavón-Fuentes, N., Llópiz-Arzuaga, A., Fernández-Massó, J. R., Delgado-Roche, L., Mendoza-Marí, Y., Santana, S. P., Cruz-Ramírez, A., Valenzuela-Silva, C., Nazábal-Gálvez, M., Cintado-Benítez, A., Pardo-Andreu, G. L., Polentarutti, N., Riva, F., Pentón-Arias, E., & Pentón-Rol, G.
- Affiliations
- University of Havana (CU)
- Centro de Ingeniería Genética y Biotecnología (CU)
- IRCCS Humanitas Research Hospital (IT)
- University of Milan (IT)
- Venue
- Toxicology and Applied Pharmacology
- Publisher
- Elsevier BV
- Published
- 2013-10
- Volume
- 272
- Issue
- 1
- Pages
- 49-60
- ISSN
- 0041-008X (ISSN-L)
- OpenAlex
- W1969587909
- Cited by
- 61
- References
- 112
- Citations by year
- 2026: 6 · 2025: 1 · 2024: 8 · 2023: 6 · 2022: 9 · 2021: 8 · 2020: 3 · 2019: 4 · 2018: 2 · 2017: 2 · 2016: 6 · 2015: 3 · 2014: 2 · 2013: 1
- FWCI
- 2.23
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Toxicology and Applied Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
- Keywords
- phycocyanobilin, phycocyanin, ischemic stroke, cerebral hypoperfusion, neuroprotection, oxidative stress, inflammation, gene expression profiling, common carotid artery occlusion, glutamate-induced neuronal injury, hydrogen peroxide, antioxidant enzymes, lipid peroxidation
- MeSH terms
- Animals, Brain Chemistry, Cell Survival, Cerebrovascular Disorders, Coloring Agents, Genes, MHC Class II, Hydrogen Peroxide, Inflammation, Male, Oxidation-Reduction, Phycocyanin, Tetrazolium Salts, Thiazoles, Biomarkers, Cytokines, PC12 Cells, Rats, Wistar, Oxidative Stress, Glutamic Acid, Vascular Endothelial Growth Factor A, Microarray Analysis, Rats, Phycobilins, Spirulina, Real-Time Polymerase Chain Reaction
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