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Cited by 73Heme Oxygenase-1 and Carbon MonoxideNeonatal Health and BiochemistryMicrobial Metabolism and Applications

The DOI matches its Crossref record; 266 of the 266 references it cites were found in a registry or an index.

C-Phycocyanin-derived Phycocyanobilin as a Potential Nutraceutical Approach for Major Neurodegenerative Disorders and COVID-19-induced Damage to the Nervous System

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Pentón-Rol, Giselle, Marín-Prida, Javier, McCarty, Mark F.·2021·Current Neuropharmacology
DOI 10.2174/1570159x19666210408123807PMC PMC9185767
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Abstract

The edible cyanobacterium Spirulina platensis and its chief biliprotein C-Phycocyanin have shown protective activity in animal models of diverse human health diseases, often reflecting antioxidant and anti-inflammatory effects. The beneficial effects of C-Phycocyanin seem likely to be primarily attributable to its covalently attached chromophore Phycocyanobilin (PCB). Within cells, biliverdin is generated from free heme and it is subsequently reduced to bilirubin. Although bilirubin can function as an oxidant scavenger, its potent antioxidant activity reflects its ability to inactivate some isoforms of NADPH oxidase. Free bilirubin can also function as an agonist for the aryl hydrocarbon receptor (AhR); this may explain its ability to promote protective Treg activity in cellular and rodent models of inflammatory disease. AhR agonists also promote transcription of the gene coding for Nrf-2, and hence can up-regulate phase 2 induction of antioxidant enzymes, such as HO-1. Hence, it is proposed that C-Phycocyanin/PCB chiefly exert their protective effects via inhibition of NADPH oxidase activity, as well as by AhR agonism that both induces Treg activity and up-regulates phase 2 induction. This simple model may explain their potent antioxidant/antiinflammatory effects. Additionally, PCB might mimic biliverdin in activating anti-inflammatory signaling mediated by biliverdin reductase. This essay reviews recent research in which CPhycocyanin and/or PCB, administered orally, parenterally, or intranasally, have achieved marked protective effects in rodent and cell culture models of Ischemic Stroke and Multiple Sclerosis, and suggests that these agents may likewise be protective for Alzheimer's disease, Parkinson's disease, and in COVID-19 and its neurological complications.

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Figures

Fig. (1) Chemical structures of heme (A), Phycocyanobilin (B), Biliverdin (C) and Bilirubin (D). Biliverdin isomers are produced depending on whether the α, β, γ or δ methene bridge of heme is cleaved by HO-1, being the most common cleavage at the α position.
Fig. (1) Chemical structures of heme (A), Phycocyanobilin (B), Biliverdin (C) and Bilirubin (D). Biliverdin isomers are produced depending on whether the α, β, γ or δ methene bridge of heme is cleaved by HO-1, being the most common cleavage at the α position.CC BY-NC · PubMed Central
Fig. (2) Heme catabolism pathway in mammals. Labile (protein free) heme group is catabolized by the inducible enzyme heme oxygenase-1 (HO-1) into Biliverdin, carbon monoxide (CO) and Fe2+. Biliverdin can be converted into Bilirubin by the enzymatic activity of Biliverdin Reductase (BVR, type A in adults, type B in fetus). In the opposite direction, Bilirubin can produce Biliverdin through the reduction of Reactive Oxygen Species (ROS). Bilirubin acts as an endogenous ROS scavenger, mediates signaling pathways, is involved in metabolism modulation and exerts anti-inflammatory actions. In the liver, uridine 5’-diphosphate glucuronosyl transferase (UGT1A1) catalyzes the conjugation of Bilirubin with glucuronic acid producing a hydrophilic derivative for bile and urine excretion. The gut microbiota can transform these Bilirubin mono- and di-glucuronides into urobilinogen, which is excreted in the feces. (A higher resolution / colour version of this figure is available in the electronic copy of the article).
Fig. (2) Heme catabolism pathway in mammals. Labile (protein free) heme group is catabolized by the inducible enzyme heme oxygenase-1 (HO-1) into Biliverdin, carbon monoxide (CO) and Fe2+. Biliverdin can be converted into Bilirubin by the enzymatic activity of Biliverdin Reductase (BVR, type A in adults, type B in fetus). In the opposite direction, Bilirubin can produce Biliverdin through the reduction of Reactive Oxygen Species (ROS). Bilirubin acts as an endogenous ROS scavenger, mediates signaling pathways, is involved in metabolism modulation and exerts anti-inflammatory actions. In the liver, uridine 5’-diphosphate glucuronosyl transferase (UGT1A1) catalyzes the conjugation of Bilirubin with glucuronic acid producing a hydrophilic derivative for bile and urine excretion. The gut microbiota can transform these Bilirubin mono- and di-glucuronides into urobilinogen, which is excreted in the feces. (A higher resolution / colour version of this figure is available in the electronic copy of the article).CC BY-NC · PubMed Central

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Research works printed but not linked: 3

  1. [11]Mathur M. Bioactive Molecules of Spirulina: A Food Supplement. Bioactive Molecules in Food. Mérillon J-M. Ramawat K.G. Cham Springer International Publishing 2018 1 22
  2. [229]Mesci P. Macia A. Saleh A. Martin-Sancho L. Yin X. Snethlage C. Avansini S. Chanda S.K. Muotri A. Sofosbuvir protects human brain organoids against SARS-CoV-2. bioRxiv 2020 2020 05.30.125856
  3. [233]Brahmaiah P. Ankit P. In silico screening of food bioactive compounds to predict potential inhibitors of COVID-19 main protease (Mpro) and RNA-dependent RNA polymerase (RdRp). ChemRxiv 2020

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Metadata

Authors
Pentón-Rol, G., Marín-Prida, J., & McCarty, M. F.
Affiliations
  • Centre for Genetic Engineering and Biotechnology, Ave. 31 e/158 y 190, Playa. PO Box: 6162, Havana,Cuba
  • Centre for Research and Biological Evaluations, Institute of Pharmacy and Food, University of Havana, Ave. 23 e/ 214 y 222, La Lisa. PO Box: 430, Havana,Cuba
  • Catalytic Longevity (US)
ORCID
McCarty, Mark F.
Venue
Current Neuropharmacology
Publisher
Bentham Science Publishers Ltd.
Published
2021-12
Volume
19
Issue
12
Pages
2250-2275
ISSN
1570-159X (ISSN-L)
DOI
10.2174/1570159x19666210408123807
PMC
PMC9185767
OpenAlex
W3140179711
Cited by
73
References
266
Citations by year
2026: 16 · 2025: 13 · 2024: 21 · 2023: 11 · 2022: 10 · 2021: 2
FWCI
3.45
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Current Neuropharmacology (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Neonatal Health and Biochemistry
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Microbial Metabolism and Applications
Keywords
C-phycocyanin, phycocyanobilin, Spirulina platensis, cyanobacteria, neuroprotection, neurodegenerative diseases, Alzheimer's disease, Parkinson's disease, multiple sclerosis, ischemic stroke, neurological complications of COVID-19, bilirubin, NADPH oxidase inhibition, aryl hydrocarbon receptor, Nrf2, heme oxygenase-1, biliverdin reductase, regulatory T cells, antioxidant activity, anti-inflammatory activity, nutraceuticals
MeSH terms
COVID-19, SARS-CoV-2, Animals, Humans, Phycocyanin, Dietary Supplements, Neurodegenerative Diseases, Phycobilins

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