A novel protein C-phycocyanin plays a crucial role in the hypocholesterolemic action of Spirulina platensis concentrate in rats
Open accessAbstract
This study was designed to clarify the mechanisms of the hypocholesterolemic action of Spirulina platensis concentrate (SPC) and identify the novel hypocholesterolemic protein derived from SPC. We investigated the effects of casein or SPC on the solubility of cholesterol, taurocholate binding capacity in vitro, cholesterol absorption in Caco-2 cells, and cholesterol metabolism in rats for 10 d. We also evaluated the effects of SPC, C-phycocyanin (PHY), and PHY residue on cholesterol metabolism in rats fed a high-cholesterol diet for 5 d, and SPC or SPC-acetone extract for 10 d. SPC had a significantly greater bile acid-binding capacity than casein in vitro. Micellar cholesterol solubility and cholesterol uptake by Caco-2 cells was significantly lower in the presence of SPC compared with casein. Fecal excretion of cholesterol and bile acids was significantly greater in rats fed the SPC-supplemented diet than in those fed the casein control diet. Serum and liver cholesterol concentrations were significantly lower in rats fed SPC than in those fed casein. Thus, the hypocholesterolemic action of SPC may involve the inhibition of both jejunal cholesterol absorption and ileal bile acid reabsorption. Although no studies to date have found a hypocholesterolemic protein among the algal proteins, we report here the discovery of a hypocholesterolemic effect in the novel protein C-phycocyanin. This study provides the first direct evidence that PHY, a novel hypocholesterolemic protein derived from Spirulina platensis, can powerfully influence serum cholesterol concentrations and impart a stronger hypocholesterolemic activity than SPC in animals.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Nagoaka et al demonstrated that spirulina concentrates lower micellar solubility of cholesterol with bile acids, reduce absorption of fats in the small intestine, and increase faecal excretion of cholesterol and bile acid.
“In 2005, Nagoaka et al demonstrated lower micellar solubility of cholesterol with bile acids and as a result reduced absorption of fats in the small intestine with higher faecal excretion of cholesterol and bile acid when fed with spirulina concentrates.”
From Effects of spirulina on weight loss and blood lipids: A review (2020) · cites this paper as [44]
Phycocyanin residue diet increased the proportion of cholesterol excretion, indicating hypolipaemic effects of spirulina, particularly from phycocyanin.
“Additionally, phycocyanin residue diet increased the proportion of cholesterol excretion, thus indicating the hypolipaemic effects of spirulina, particularly from phycocyanin.44”
From Effects of spirulina on weight loss and blood lipids: A review (2020) · cites this paper as [44]
Cites
Official Methods of Analysis of
Helrick, K. (1980) · Analytical Chemistry · doi:10.1021/ac50052a726 · Cited by 59,351 · see citing works
Colorimetric Method for Determination of Sugars and Related Substances
DuBois, M., Gilles, K. A., Hamilton, J. K., Rebers, P. A., & Smith, F. (1956) · Analytical Chemistry · doi:10.1021/ac60111a017 · Cited by 52,269 · see citing works
Snedecor, G. W., & Cochran, W. G. (1967) · Cited by 6,573 · see citing works
Report of the American Institute of Nutrition Ad Hoc Committee on Standards for Nutritional Studies
(1977) · Journal of Nutrition · doi:10.1093/jn/107.7.1340 · Cited by 2,867 · see citing works
Multiple Range Tests for Correlated and Heteroscedastic Means
Duncan, D. B. (1957) · Biometrics · doi:10.2307/2527799 · Cited by 962 · see citing works
Antioxidant and anti-inflammatory properties of C-phycocyanin from blue-green algae
Romay, C., Armesto, J., Remirez, D., González, R., Ledon, N., & García, I. (1998) · Inflammation Research · doi:10.1007/s000110050256 · Cited by 511 · see citing works
C-Phycocyanin: A potent peroxyl radical scavenger in Vivo and in Vitro
Bhat, V. B., & Madyastha, K. M. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.3270 · Cited by 477 · see citing works
Overview of proposed mechanisms for the hypocholesterolemic effect of soy.
Potter, S. M. (1995) · PubMed · doi:10.1093/jn/125.3_suppl.606s · Cited by 384 · see citing works
Identification of novel hypocholesterolemic peptides derived from bovine milk β-lactoglobulin.
Nagaoka, S., Futamura, Y., Miwa, K., Awano, T., Yamauchi, K., Kanamaru, Y., Tadashi, K., & Kuwata, T. (2001) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2001.4298 · Cited by 378 · see citing works
Self-citationTea catechins decrease micellar solubility and intestinal absorption of cholesterol in rats
Ikeda, I., Imasato, Y., Sasaki, E., Nakayama, M., Nagao, H., TAKEO, T., Yayabe, F., & Sugano, M. (1992) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/0005-2760(92)90269-2 · Cited by 337 · see citing works
Isolation and characterization of phycocyanins from the blue-green alga Spirulina platensis
Boussiba, S., & RICHMOND, A. E. (1979) · Archives of Microbiology · doi:10.1007/bf00409102 · Cited by 321 · see citing works
Carroll, K. K., & Hamilton, R. M. G. (1975) · Journal of Food Science · doi:10.1111/j.1365-2621.1975.tb03726.x · Cited by 306 · see citing works
Inhibition of cholesterol absorption in rats by plant sterols.
Ikeda, I., Tanaka, K., SUGANO, M., Vahouny, G. V., & Gallo, L. L. (1988) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)38403-0 · Cited by 304 · see citing works
Inhibition of cholesterol absorption and synthesis in rats by sesamin
Hirose, N., Inoue, T., Nishihara, K., SUGANO, M., Akimoto, K., Shimizu, S., & Yamada, H. (1991) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)42050-4 · Cited by 298 · see citing works
Review of cholesterol absorption with emphasis on dietary and biliary cholesterol.
Wilson, M. D., & Rudel, L. L. (1994) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)40109-9 · Cited by 263 · see citing works
Nagata, Y., Ishiwaki, N., & Sugano, M. (1982) · Journal of Nutrition · doi:10.1093/jn/112.8.1614 · Cited by 231 · see citing works
Bhat, V. B., Gaikwad, N. W., & Madyastha, K. M. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.9149 · Cited by 215 · see citing works
IWATA, K., INAYAMA, T., & KATO, T. (1990) · Journal of Nutritional Science and Vitaminology · doi:10.3177/jnsv.36.165 · Cited by 153 · see citing works
Self-citationNagaoka, S., Miwa, K., Eto, M., KUZUYA, Y., Hori, G., & Yamamoto, K. (1999) · Journal of Nutrition · doi:10.1093/jn/129.9.1725 · Cited by 153 · see citing works
Self-citationOverview of Proposed Mechanisms for the Hypocholesterolemic Effect of Soy
Potter, S. M. (1995) · Journal of Nutrition · doi:10.1093/jn/125.suppl_3.606s · Cited by 138 · see citing works
A novel cell line (Caco-2) for the study of intestinal lipoprotein synthesis.
Hughes, T. E., Sasak, W., Ordovás, J. M., Forte, T. M., Lamon‐Fava, S., & Schaefer, E. J. (1987) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)61420-6 · Cited by 129 · see citing works
Effects of Dietary Proteins and Amino Acid Mixtures on Plasma Cholesterol Levels in Rabbits
Huff, M. W., & Carroll, K. K. (1980) · Journal of Nutrition · doi:10.1093/jn/110.8.1676 · Cited by 119 · see citing works
Dvir, I., Chayoth, R., Sod-Moriah, U. A., et al. (2000) · British Journal Of Nutrition · doi:10.1017/s000711450000177x · Cited by 114 · see citing works
Cholesterol lowering effect of spirulina.
Nakaya, N., Homma, Y., & Goto, Y. (1988) · Nutrition reports international · Cited by 108 · see citing works
Effect of Pectin Dose on Serum Cholesterol Levels
Palmer, G. H., & DIXON, D. G. (1966) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/18.6.437 · Cited by 97 · see citing works
Soybean Protein Diet and Plasma Cholesterol: From Therapy to Molecular Mechanisms
Sirtori, C. R., EVEN, R., & Lovati, M. R. (1993) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1993.tb38734.x · Cited by 91 · see citing works
Influence of dietary fish proteins on plasma and liver cholesterol concentrations in rats
Zhang, X., & Beynen, A. C. (1993) · British Journal Of Nutrition · doi:10.1079/bjn19930077 · Cited by 91 · see citing works
Regulation of cholesterol esterification by micellar cholesterol in CaCo-2 cells
Field, F. J., Albright, E., & Mathur, S. N. (1987) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)38620-x · Cited by 88 · see citing works
Nagaoka, S., Masaoka, M., Zhang, Q., HASEGAWA, M., & Watanabe, K. (2002) · Lipids · doi:10.1007/s11745-002-0890-6 · Cited by 73 · see citing works
Self-citationJacques, H., Deshaies, Y., & Savoie, L. (1986) · Atherosclerosis · doi:10.1016/0021-9150(86)90067-5 · Cited by 71 · see citing works
Torres-Durán, P. V., Miranda‐Zamora, R., Paredes-Carbajal, M. C., Mascher, D., Blé‐Castillo, J. L., Díaz-Zagoya, J. C., & Juárez-Oropeza, M. A. (1999) · Journal of Ethnopharmacology · doi:10.1016/s0378-8741(98)00120-2 · Cited by 69 · see citing works
SUGIYAMA, K., Ohkawa, S., & MURAMATSU, K. (1986) · Journal of Nutritional Science and Vitaminology · doi:10.3177/jnsv.32.413 · Cited by 61 · see citing works
Nagaoka, S., Awano, T., Nagata, N., et al. (1997) · Bioscience Biotechnology and Biochemistry · doi:10.1271/bbb.61.354 · Cited by 60 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Phycobiliproteins as a commodity: Trends in applied research, patents and commercialization
Sekar, S., & Chandramohan, M. (2008) · Journal of Applied Phycology · doi:10.1007/s10811-007-9188-1 · Cited by 589 · see citing works
Hypolipidemic, Antioxidant, and Antiinflammatory Activities of Microalgae <i>Spirulina</i>
Deng, R., & Chow, T. (2010) · Cardiovascular Therapeutics · doi:10.1111/j.1755-5922.2010.00200.x · Cited by 435 · see citing works
Cicero, A. F. G., Colletti, A., Bajraktari, G., Descamps, O., Djuric, D. M., Ezhov, M., Fras, Z., Katsiki, N., Langlois, M., Latkovskis, G., et al. (2017) · Archives of Medical Science · doi:10.5114/aoms.2017.69326 · Cited by 281 · see citing works
Antioxidant Activity and Hepatoprotective Effects of Whey Protein and Spirulina in Rats
Gad, A. S., Khadrawy, Y. A., El-Nekeety, A. A., Mohamed, S. R., Hassan, N. S., & Abdel-Wahhab, M. A. (2011) · Nutrition · doi:10.1016/j.nut.2010.04.002 · Cited by 218 · see citing works
Riss, J., Décordé, K., Sutra, T., Delage, M., Baccou, J.-C., Jouy, N., Brune, J.-P., Oréal, H., Cristol, J.-P., & Rouanet, J.-M. (2007) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf070529g · Cited by 208 · see citing works
Torres-Duran, P. V., Ferreira-Hermosillo, A., & Juarez-Oropeza, M. A. (2007) · Lipids in Health and Disease · doi:10.1186/1476-511x-6-33 · Cited by 181 · see citing works
Park, H. J., Lee, Y. J., Ryu, H. K., Kim, M. H., Chung, H. W., & Kim, W. Y. (2008) · Annals of Nutrition and Metabolism · doi:10.1159/000151486 · Cited by 154 · see citing works
Grover, P., Bhatnagar, A., Kumari, N., Narayan Bhatt, A., Kumar Nishad, D., & Purkayastha, J. (2021) · Saudi Journal of Biological Sciences · doi:10.1016/j.sjbs.2020.12.037 · Cited by 156 · see citing works
Potential health benefits of spirulina microalgae*: A review of the existing literature
Capelli, B., & Cysewski, G. R. (2010) · Nutrafoods · doi:10.1007/bf03223332 · Cited by 147 · see citing works
Zeinalian, R., Farhangi, M. A., Shariat, A., & Saghafi-Asl, M. (2017) · BMC Complementary and Alternative Medicine · doi:10.1186/s12906-017-1670-y · Cited by 127 · see citing works
Furmaniak, M. A., Misztak, A. E., Franczuk, M. D., Wilmotte, A., Waleron, M., & Waleron, K. F. (2017) · Frontiers in Microbiology · doi:10.3389/fmicb.2017.02541 · Cited by 121 · see citing works
Colla, L. M., Muccillo-Baisch, A. L., & Costa, J. A. V. (2008) · Brazilian Archives of Biology and Technology · doi:10.1590/s1516-89132008000200022 · Cited by 116 · see citing works
Cicero, A. F. G., Fogacci, F., Stoian, A. P., Vrablik, M., Al Rasadi, K., Banach, M., Toth, P. P., & Rizzo, M. (2021) · Current Atherosclerosis Reports · doi:10.1007/s11883-021-00955-y · Cited by 110 · see citing works
Effects of spirulina on weight loss and blood lipids: A review
DiNicolantonio, J. J., Bhat, A. G., & OKeefe, J. (2020) · Open Heart · doi:10.1136/openhrt-2018-001003 · Cited by 98 · see citing works
Moradi, S., Ziaei, R., Foshati, S., Mohammadi, H., Nachvak, S. M., & Rouhani, M. H. (2019) · Complementary Therapies in Medicine · doi:10.1016/j.ctim.2019.102211 · Cited by 88 · see citing works
Strasky, Z., Zemankova, L., Nemeckova, I., Rathouska, J., Wong, R. J., Muchova, L., Subhanova, I., Vanikova, J., Vanova, K., Vitek, L., et al. (2013) · Food & Function · doi:10.1039/c3fo60230c · Cited by 87 · see citing works
Food and drug industry applications of microalgae <i>Spirulina platensis</i>: A review
Maddiboyina, B., Vanamamalai, H. K., Roy, H., Ramaiah, Gandhi, S., Kavisri, M., & Moovendhan, M. (2023) · Journal of Basic Microbiology · doi:10.1002/jobm.202200704 · Cited by 80 · see citing works
A Prominent Superfood: Spirulina platensis
Seyidoglu, N., Inan, S., & Aydin, C. (2017) · Superfood and Functional Food - The Development of Superfoods and Their Roles as Medicine · doi:10.5772/66118 · Cited by 78 · see citing works
Alwaleed, E. A., El-Sheekh, M., Abdel-Daim, M. M., & Saber, H. (2021) · Environmental Science and Pollution Research · doi:10.1007/s11356-020-10597-3 · Cited by 75 · see citing works
Natural ACE inhibitory peptides discovery from Spirulina (Arthrospira platensis) strain C1
Anekthanakul, K., Senachak, J., Hongsthong, A., Charoonratana, T., & Ruengjitchatchawalya, M. (2019) · Peptides · doi:10.1016/j.peptides.2019.170107 · Cited by 63 · see citing works
Evaluation of protective efficacy of Spirulina platensis against collagen-induced arthritis in rats
Kumar, N., Singh, S., Patro, N., & Patro, I. (2009) · Inflammopharmacology · doi:10.1007/s10787-009-0004-1 · Cited by 59 · see citing works
Nutritional Quality and Safety of the Spirulina Dietary Supplements Sold on the Slovenian Market
Masten Rutar, J., Jagodic Hudobivnik, M., Nečemer, M., Vogel Mikuš, K., Arčon, I., & Ogrinc, N. (2022) · Foods · doi:10.3390/foods11060849 · Cited by 59 · see citing works
Chamorro, G., Pérez-Albiter, M., Serrano-García, N., Mares-Sámano, J. J., & Rojas, P. (2006) · Nutritional Neuroscience · doi:10.1080/10284150600929748 · Cited by 50 · see citing works
Huang, H., Liao, D., Pu, R., & Cui, Y. (2018) · Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy · doi:10.2147/dmso.s185672 · Cited by 44 · see citing works
SPIRULINA: A SPOTLIGHT ON ITS NUTRACEUTICAL PROPERTIES AND FOOD PROCESSING APPLICATIONS
Priyanka, S., Varsha, R., Verma, R., & Ayenampudi, S. B. (2023) · Journal of microbiology, biotechnology and food sciences · doi:10.55251/jmbfs.4785 · Cited by 42 · see citing works
El-Sayed, E.-S., Hikal, M., Abo El- Khair, B., El-Ghobashy, R., & El-Assar, A. (2018) · Arab Universities Journal of Agricultural Sciences · doi:10.21608/ajs.2018.28365 · Cited by 26 · see citing works
“These results are in agreement with Nagaoka et al (2005) who observed that both, S. platensis concentrates or phycocyanin and other pigment extracted from Spirulina were caused hypocholesterolemic activity in rats.”
ResultEvaluation of the toxicity of Arthrospira (Spirulina) platensis extract
Hutadilok-Towatana, N., Reanmongkol, W., & Panichayupakaranant, P. (2010) · Journal of Applied Phycology · doi:10.1007/s10811-009-9499-5 · Cited by 24 · see citing works
Hernández-Lepe, M. A., Olivas-Aguirre, F. J., Gómez-Miranda, L. M., Hernández-Torres, R. P., Manríquez-Torres, J. D. J., & Ramos-Jiménez, A. (2019) · Antioxidants · doi:10.3390/antiox8110507 · Cited by 24 · see citing works
Enhancing microalgal proteins for nutraceutical and functional food applications
Kaur, M., Bhatia, S., Bagchi, D., Tak, Y., Kaur, G., Kaur, C., Kaur, A., & Sharma, N. (2025) · Future Foods · doi:10.1016/j.fufo.2025.100564 · Cited by 19 · see citing works
Dhandayuthapani, K., Malathy, S., Mulla, S. I., & Gupta, S. K. (2021) · Algae · doi:10.1007/978-981-15-7518-1_7 · Cited by 19 · see citing works
Spirulina and Herbal Combination on Metabolic Alterations of Cardiovascular Diseases (CVDs)
Pandey, R., & Singh, S. (2022) · International Journal of Research and Review · doi:10.52403/ijrr.20220334 · Cited by 6 · see citing works
- Authors
- Nagaoka, S., Shimizu, K., Kaneko, H., Shibayama, F., Morikawa, K., Kanamaru, Y., Otsuka, A., Hirahashi, T., & Kato, T.
- Affiliations
- Gifu University (JP)
- Corresponding author
- Nagaoka, Satoshi
- Venue
- The Journal of Nutrition
- Publisher
- Elsevier BV
- Published
- 2005-10
- Volume
- 135
- Issue
- 10
- Pages
- 2425-2430
- ISSN
- 0022-3166 (ISSN-L)
- OpenAlex
- W1916852161
- Cited by
- 246
- References
- 33
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 20 · 2023: 10 · 2022: 18 · 2021: 11 · 2020: 24 · 2019: 15 · 2018: 16 · 2017: 14 · 2016: 11 · 2015: 12 · 2014: 12 · 2013: 10 · 2012: 7
- FWCI
- 9.04
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Aquatic Science › Seaweed-derived Bioactive Compounds
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Surgery › Natural Products and Biological Research
- Keywords
- C-phycocyanin, Spirulina platensis, cholesterol-lowering effect, cholesterol absorption, bile acid reabsorption, Caco-2 cells, serum cholesterol, high-cholesterol diet, algal proteins, bile acid excretion
- MeSH terms
- Acetone, Cyanobacteria, Animals, Anticholesteremic Agents, Bacterial Proteins, Caseins, Cholesterol, Cholesterol, Dietary, Humans, Hypercholesterolemia, Male, Micelles, Phycocyanin, Solubility, Solvents, Taurocholic Acid, Rats, Wistar, Caco-2 Cells, Rats, Spirulina, In Vitro Techniques
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.
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
