Spirulina platensis and phycocyanobilin activate atheroprotective heme oxygenase-1: a possible implication for atherogenesis
Abstract
Spirulina platensis, a water blue-green alga, has been associated with potent biological effects, which might have important relevance in atheroprotection. We investigated whether S. platensis or phycocyanobilin (PCB), its tetrapyrrolic chromophore, can activate atheroprotective heme oxygenase-1 (Hmox1), a key enzyme in the heme catabolic pathway responsible for generation of a potent antioxidant bilirubin, in endothelial cells and in a mouse model of atherosclerosis. In vitro experiments were performed on EA.hy926 endothelial cells exposed to extracts of S. platensis or PCB. In vivo studies were performed on ApoE-deficient mice fed a cholesterol diet and S. platensis. The effect of these treatments on Hmox1, as well as other markers of oxidative stress and endothelial dysfunction, was then investigated. Both S. platensis and PCB markedly upregulated Hmox1 in vitro, and a substantial overexpression of Hmox1 was found in aortic atherosclerotic lesions of ApoE-deficient mice fed S. platensis. In addition, S. platensis treatment led to a significant increase in Hmox1 promoter activity in the spleens of Hmox-luc transgenic mice. Furthermore, both S. platensis and PCB were able to modulate important markers of oxidative stress and endothelial dysfunction, such as eNOS, p22 NADPH oxidase subunit, and/or VCAM-1. Both S. platensis and PCB activate atheroprotective HMOX1 in endothelial cells and S. platensis increased the expression of Hmox1 in aortic atherosclerotic lesions in ApoE-deficient mice, and also in Hmox-luc transgenic mice beyond the lipid lowering effect. Therefore, activation of HMOX1 and the heme catabolic pathway may represent an important mechanism of this food supplement for the reduction of atherosclerotic disease.
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By suppressing adipocyte oxidative stress, spirulina may lead to systemic anti-inflammatory and insulin-sensitising effects.
“Thus, by suppressing adipocyte oxidative stress, spirulina may lead to systemic anti-inflammatory and insulin-sensitising effects.12–20”
From Effects of spirulina on weight loss and blood lipids: A review (2020) · cites this paper as [14]
Phycocyanobilin is structurally similar to bilirubin and can inhibit NADPH oxidase.
“Phycocyanobilin is structurally similar to bilirubin and can inhibit NADPH oxidase.”
From Effects of spirulina on weight loss and blood lipids: A review (2020) · cites this paper as [14]
The antioxidant activity of spirulina is directly proportional to the quantity of phycocyanin.
“The antioxidant activity of spirulina has been proven to be directly proportional to the quantity of phycocyanin (which contains phycocyanobilin).12–14 45”
From Effects of spirulina on weight loss and blood lipids: A review (2020) · cites this paper as [14]
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- Authors
- Strasky, Z., Zemankova, L., Nemeckova, I., Rathouska, J., Wong, R. J., Muchova, L., Subhanova, I., Vanikova, J., Vanova, K., Vitek, L., & Nachtigal, P.
- Affiliations
- Charles University (CZ)
- Stanford Medicine (US)
- Corresponding author
- Nachtigal, Petr
- Venue
- Food & Function
- Publisher
- Royal Society of Chemistry (RSC)
- Published
- 2013
- Volume
- 4
- Issue
- 11
- Pages
- 1586
- ISSN
- 2042-6496 (ISSN-L)
- 2042-650X
- OpenAlex
- W2156023840
- Cited by
- 87
- References
- 44
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 11 · 2023: 6 · 2022: 15 · 2021: 11 · 2020: 4 · 2019: 5 · 2018: 4 · 2017: 3 · 2016: 6 · 2015: 4 · 2014: 3 · 2013: 1
- FWCI
- 2.09
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Food & Function (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- Spirulina platensis, phycocyanobilin, heme oxygenase-1, atherosclerosis, atheroprotection, oxidative stress, endothelial dysfunction, bilirubin, heme degradation, ApoE-deficient mice, endothelial nitric oxide synthase, NADPH oxidase, VCAM-1, dietary supplementation, cyanobacteria
- MeSH terms
- Animals, Aorta, Female, Humans, Male, Mice, Inbred C57BL, Mice, Transgenic, Phycocyanin, Up-Regulation, Oxidative Stress, Vascular Cell Adhesion Molecule-1, NADPH Oxidases, Atherosclerosis, Mice, Heme Oxygenase-1, Phycobilins, Spirulina
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