Other Names
BiliproteinC-PCCPCCyano-phycocyaninPhycobiliproteinPhycocyanPhycocyaninPhycocyanin CPhycocyanins, C-
C-Phycocyanin (C-PC) is a pigment-protein complex found in cyanobacteria that biologically cooperates with chlorophyll in photosynthesis. Structurally, it belongs to the phycobiliproteins (PBPs), which are classified according to their colours as blue phycocyanin (C-PC), allophycocyanin (APC), and red phycoerythrin (PE). The "C" prefix stands for "cyanobacterial," distinguishing it from other spectral forms of phycocyanin. It is also referred to as phycocyanin C, or abbreviated as C-PC or Pc in the scientific literature. Its chromophore component is independently identified as phycocyanobilin (PCB), sometimes written PCB-B when designating the specific B-variant found in Arthrospira platensis.
Arthrospira platensis, commonly known as Spirulina, is a photosynthetic filamentous cyanobacterium (blue-green microalga) that has been utilized as a food source since ancient times. More recently, it has gained significant popularity as a dietary supplement due to its rich content of micro- and macro-nutrients. Of particular interest is a water-soluble phycobiliprotein derived from Spirulina known as phycocyanin C (C-PC), which stands out as the most abundant protein in this cyanobacterium.
Spirulina possesses 25% w/w of phycocyanin in its total biomass. While Arthrospira platensis is the dominant commercial source, C-phycocyanin is also found in other cyanobacterial species. In addition to the most widely used Spirulina, some red algae and Thermosynechococcus can serve as good sources of PC. Arthrospira is a well-known type of blue-green algae frequently used as a food supplement. It is a multicellular, filamentous, and photosynthetic cyanobacteria whose life cycle comprises several stages, such as trichome fragmentation, hormogonia cell enlargement and maturation, and trichome elongation. The mature trichomes divide into filaments (2–16 μm) or hormogonia cells of different sizes, which reproduce by binary fission and take a helical or spiral shape.
Phycocyanin is a blue-red fluorescent, water-soluble, and non-toxic biliprotein pigment. C-PC is a fluorescent protein, with its chromophore represented by the tetrapyrrole molecule phycocyanobilin B (PCB-B). Both C-phycocyanins contain α-subunits of 15.0 kDa and β-subunits of 16.4 kDa. The protein assembles into trimeric (αβ)₃ and hexameric (αβ)₆ forms. In crystals, the C-phycocyanin hexamers formed by face-to-face association of two trimers are arranged in layers rather than in columns. C-PC has a medium molecular weight of approximately 82.992 kDa.
The amino acid content of C-PC reveals the presence of eight of nine essential amino acids and eight of eleven non-essential amino acids. The open-chain tetrapyrrole chromophore (phycocyanobilin) is responsible for the molecule's intense blue color and is covalently linked to the apoprotein via a thioether bond.
Phycocyanin is used in several industries such as food, cosmetics, and pharmaceuticals, which increases its market value. In commerce, C-PC is available in several purity grades, typically characterized by the ratio of absorbance at 620 nm to absorbance at 280 nm (the "purity ratio" or A620/A280). A ratio above 0.7 is considered food-grade; ratios above 3.9 or 4.0 are considered reagent or analytical grade. A final product with an analytical purity greater than 4 is suitable for use in food, biomedicine, and as a therapeutic agent.
Common commercial forms include aqueous liquid extracts, spray-dried or freeze-dried powders, and microencapsulated preparations intended to improve stability. Phycocyanin is used as a colorant in food (chewing gums, dairy products, jellies, etc.) and cosmetics such as lipstick and eye liners in Japan, Thailand, and China. Encapsulated variants have been developed specifically to overcome the stability limitations of the native protein.
C-phycocyanin stability is dependent principally on pH and temperature, and is higher between pH 5 and pH 7 and at temperatures below 40°C, but the use of various preservatives or conditioning can increase its lifetime. The optimal working pH range for phycocyanin is between 5.5 and 6.0 and it remains stable up to 45°C; however, exposure to relatively high temperatures or acidic pH decreases its half-life and increases the degradation kinetic constant. Phycobiliproteins are sensitive to light; preservatives such as mono- and di-saccharides, citric acid, or sodium chloride appear to be effective stabilizing agents.
Some mechanical, physical, or thermal treatments can improve the extraction yield and accelerate the release of C-phycocyanin. Ultrasound-assisted extraction has been widely studied and probes generally give higher extraction yields than baths (>100 mg/g) in less than 30 min. This technique can be coupled with others, such as freeze–thaw methods, to improve protein release. For purification of the extracted pigments, salting out or aqueous two-phase extraction can be used to increase phycocyanin grade. More advanced purification methods, mostly based on chromatography, can provide additional improvement.
Spirulina, also known as Arthrospira, is a type of blue-green algae that has been consumed by humans for centuries. Historical records reveal its use as a food source by the Aztecs and other Mesoamerican cultures dating back to the 16th century. Traditionally, it was harvested from the alkaline waters of Lake Texcoco in Mexico and transformed into dried cakes for consumption.
As described by one of Hernán Cortés' soldiers, algae were harvested at Lake Texcoco and turned into cakes called "tecuitlatl." Historically, it has been used as food by the Kanembu ethnic group in the Lake Chad region of the Republic of Chad to make and sell dried bread called "dihe." After being rediscovered by a European scientific mission in Chad, this traditional food has gained popularity in the human health food industry around the world.
It is important to note the evidential limits of these historical accounts. Whether Spirulina was used as medicine, per se, is hard to pin down. Historical documentation is patchy. Most of what we know about traditional use is anthropological rather than clinical. That means there is no solid evidence for specific therapeutic use in ancient cultures—more that this substance was nutritious and made people feel better, which could mean anything from protein supplementation to placebo effect. In other words, historical uses centered on Spirulina as a nutrient-dense foodstuff rather than a targeted medicinal preparation. The concept of C-phycocyanin as a distinct, isolated bioactive compound is entirely modern; ancient populations consumed the whole algal biomass without knowledge of its constituent proteins.
The primary bioactive chromophore within C-PC is phycocyanobilin (PCB), a linear tetrapyrrole structurally related to biliverdin and bilirubin. When C-PC is orally administered, the protein moiety is digested in the gastrointestinal tract, releasing PCB. PCB might be better absorbed when it is orally administered since it has good stability in acidic environments, in contrast to C-PC itself, which becomes unstable and unfolds at acidic pH. Previous observations have shown that eight PCB oligopeptides bearing 2–13 amino acids are obtained from the pepsin degradation of C-PC in artificial gastric solution (pH 1.2). These chromopeptides evidenced antioxidant, anti-hemolytic, and anticancer activities.
The protein scaffold of C-PC consists of α- and β-subunits that assemble into trimers and hexamers in solution. These subunits are not merely structural scaffolding; evidence suggests that the intact holoprotein, its peptic fragments, and the free PCB chromophore each contribute independently to the pharmacological activities of the molecule. While C-PC is commonly employed in food for its coloring properties, it also serves as the molecular basis for numerous nutraceutical features associated with Spirulina.
Antioxidant, anti-inflammatory, neuroprotective, and hepatoprotective effects have been experimentally attributed to Pc. When it was evaluated as an antioxidant in vitro, it was able to scavenge alkoxyl, hydroxyl, and peroxyl radicals and to react with peroxynitrite (ONOO⁻) and hypochlorous acid (HOCl). Pc also inhibits microsomal lipid peroxidation induced by Fe²⁺-ascorbic acid or the free radical initiator AAPH. Furthermore, it reduces carbon tetrachloride (CCl₄)-induced lipid peroxidation in vivo.
The PCB chromophore is considered the principal free radical-scavenging moiety within the C-PC molecule. Its open-chain tetrapyrrole structure provides multiple conjugated double bonds that can donate electrons to neutralize radical species. C-phycocyanin also activates endogenous antioxidant defenses: HO-1 is an important molecule with inflammatory properties which is the host defense against oxidative stress. This activity of C-PC is mediated by the activation of nuclear factor erythroid-derived 2 (NF-E2) like 2 (Nrf-2) via phosphorylation of protein kinase C (PKC) α/β II.
Oxidative stress and inflammation were curtailed by affecting three main pathways: (1) inhibition of cyclooxygenase-2 enzyme and consequent decrease of signaling generating ROS; (2) increased synthesis of glutathione and therefore strengthening of the natural antioxidant defenses of the cells; (3) decreased infection-driven mitochondrial respiratory burst which generates oxidative stress.
Phycocyanin can inhibit the expression of COX-2 and prostaglandin E₂ (PGE₂), and down-regulate the MMP-9 expression by the mitogen-activated protein kinase (MAPK) signaling pathway.
C-phycocyanin can down-regulate the expression of pro-inflammatory cytokines (IL-1β, IL-2, interferon-γ, and tumor necrosis factor-α), transcription factors (Janus kinase 3 [Jak3], signal transducers and activators of transcription 3 [STAT3]), and enhance the expression of anti-inflammatory cytokines IL-4.
These anti-inflammatory effects of Pc can be due to its scavenging properties toward reactive oxygen species (ROS) and its inhibitory effects on cyclooxygenase-2 (COX-2) activity and on histamine release from mast cells. Pc also reduced the levels of tumor necrosis factor (TNF-α) in the blood serum of mice treated with endotoxin and showed neuroprotective effects in rat cerebellar granule cell cultures and in kainate-induced brain injury in rats.
C-phycocyanin is often used as a dietary nutritional supplement due to its various therapeutic values. The anti-inflammatory activity of C-PC, partly through inhibition of proinflammatory cytokine formation, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) expression, has been demonstrated in many in vitro and in vivo studies.
Mechanistically, PC exerts its anti-cancer activity by reducing cell proliferation and migration and inducing apoptosis. Although concentrations and exposure times—and possibly also PC purity—differed greatly between studies, the results clearly showed cell cycle arrest and, often, apoptosis/necrosis of the various tumor cells was induced. In contrast, PC had almost no or even slight proliferative effects on cells originating from normal tissue.
Cell death induced by phycocyanin is the result of cross-talk among the MAPK, Akt/mTOR/p70S6K, and NF-κB pathways. Phycocyanin is able to induce apoptosis of PANC-1 cells by activating p38 and JNK signaling pathways while inhibiting the Erk pathway.
In addition, C-phycocyanin could bind to VEGFR1 alone, and down-regulated levels of VEGF-A, MMP-2, and MMP-9. The anti-proliferation effect of phycocyanin is mediated by BCR-ABL signaling and inactivation of the downstream PI3K/Akt pathway.
Evidence level: Substantial in vitro and animal data; human clinical data remain limited.
Pc has been evaluated in twelve experimental models of inflammation and exerted anti-inflammatory effects in a dose-dependent fashion in all of these. Thus, Pc reduced edema, histamine release, myeloperoxidase (MPO) activity, and the levels of prostaglandin (PGE₂) and leukotriene (LTB₄) in inflamed tissue. These results were obtained in preclinical (rodent) models.
In vitro antioxidant assays (DPPH, FRAP, ORAC, hydroxyl radical scavenging, etc.) consistently demonstrate robust free radical scavenging capacity. Food-grade phycocyanin, a nutraceutical isolated from Spirulina platensis, has been evaluated for its in vitro and in vivo antioxidant potential using a battery of antioxidant assays including DPPH, TAC, FRAP, hydroxyl radical, hydrogen peroxide scavenging, SOD, GSH, and LPO assays.
A human safety trial indirectly captured antioxidant-relevant hepatic endpoints: Serum levels of aspartate transaminase (AST) showed a significant reduction after 2 weeks of ACE consumption (P < .001), in contrast to placebo where no changes were seen. However, no dedicated clinical trial in healthy or diseased humans has measured antioxidant biomarkers as the primary endpoint using isolated C-PC.
Evidence level: Robust in preclinical models; limited direct human clinical evidence.
Pc has been evaluated in twelve experimental models of inflammation and exerted anti-inflammatory effects in a dose-dependent fashion in all of these. Pc reduced edema, histamine release, myeloperoxidase (MPO) activity, and the levels of prostaglandin (PGE₂) and leukotriene (LTB₄).
Animal and in vitro studies dominate this area. Studies used male Sprague-Dawley rats and OF1 mice; oedema was induced by arachidonic acid (0.5 mg/ear) or TPA (4 μg/ear) in the mouse ear, by carrageenan injection (0.1 mL of 1% suspension) in the rat paw, and by cotton pellet implantation in the rat axilla. Phycocyanin (50–300 mg/kg, oral) or indomethacin (1 mg/ear or 3–10 mg/kg, oral) were tested as comparators in four animal models. Phycocyanin shows anti-inflammatory activity in four experimental models of inflammation. Its antioxidative and oxygen free radical scavenging properties may contribute, at least in part, to its anti-inflammatory activity.
At the cellular level, a 2025 study examined C-PC in human chondrocyte cells. The study investigates the efficacy of C-phycocyanin (C-PC), a pigment derived from Spirulina platensis cultivated under optimal light conditions, as an anti-inflammatory agent. This research focused on its effects on nitric oxide secretion and interleukin-1 beta (IL-1β) gene expression as inflammatory indicators, in phorbol 12-myristate 13-acetate (PMA)-stimulated human chondrocyte cells (C28/I2). C-PC was found to be not only non-toxic but also enhanced cell viability. Furthermore, it significantly reduced the expression of IL-1β and the secretion of nitric oxide, markers often associated with inflammatory responses. These results suggest that C-PC has considerable potential as a therapeutic agent in the management of inflammatory conditions. This was an in vitro study, not a clinical trial.
Previous pilot studies on the phycocyanin-rich aqueous cyanophyta extract (ACE) showed that the consumption of ACE at a dose of 0.25–1.0 g/day was associated with relief of chronic pain. These pilot findings require confirmation in larger, adequately powered randomized controlled trials.
Evidence level: Extensive in vitro data and some animal data; no human clinical trials to date.
Phycocyanin, a natural product purified from Spirulina, effectively inhibits pancreatic cancer cell proliferation in vitro and xenograft tumor growth in vivo. Phycocyanin induces G2/M cell cycle arrest, apoptotic and autophagic cell death in PANC-1 cells.
The antitumor function and regulatory mechanism of phycocyanin were investigated in three NSCLC cell lines for the first time: H358, H1650, and LTEP-a2. Cell phenotype experiments suggested that phycocyanin could suppress the survival rate, proliferation, colony formation, and migration abilities, as well as induce apoptosis of NSCLC cells. Transcriptome analysis revealed that receptor-interacting serine/threonine-protein kinase 1 (RIPK1) was significantly down-regulated by phycocyanin in LTEP-a2 cells.
In a dose-dependent way, C-phycocyanin inhibited all the tested cancer cells; the results showed that C-phycocyanin had potent anti-proliferative activity against liver and colon cancer, exceeding doxorubicin, and good anti-breast cancer activity comparable to doxorubicin. These comparisons were made in cell culture experiments and cannot be directly extrapolated to human patients.
Accumulating evidence shows that phycocyanin has a potent anticancer effect both in vitro and in vivo on a variety of cancer cell types, such as lung cancer, colon cancer, breast cancer, and bone marrow cancer. Administration of phycocyanin at high doses from 0.25 to 5.0 g/kg body weight does not induce noticeable symptoms of toxicity nor mortality in animals. These studies suggest a therapeutic potential of phycocyanin in cancer treatment. Mechanistically, phycocyanin exerts its anti-cancer effect by modulating apoptosis and cell proliferation.
Importantly, no human clinical trials have been conducted to evaluate C-PC as an anticancer agent. All positive data derive from cell lines and rodent xenograft models, which have well-known translational limitations.
Evidence level: Preliminary; primarily preclinical (animal and in vitro) evidence.
One study demonstrated that a protein-enriched fraction (SPF) of Spirulina, at 5 and 10 mg/kg administered for 15 days per os, reduced brain oxidative stress, increasing the striatal expression of tyrosine hydroxylase and the dopamine transporter, while reducing hippocampal inducible NOS, COX-2, and glial fibrillary acidic protein expressions. These data suggest that C-PC, through its brain anti-inflammatory and antioxidant actions, exerts neuroprotective effects.
C-PC has potential use in the treatment of Alzheimer's and Parkinson's diseases. This claim is based on preclinical data, including animal models of kainate-induced neuronal damage, and not on human clinical trials. Pc showed neuroprotective effects in rat cerebellar granule cell cultures and in kainate-induced brain injury in rats.
Evidence level: Preclinical (animal) data; limited direct human evidence.
Phycocyanin plays an antioxidant role in inhibiting hepatic lipid peroxidation and is helpful to liver protection. Animal studies employing carbon tetrachloride-induced hepatotoxicity models consistently show protective effects attributed to the attenuation of lipid peroxidation and upregulation of endogenous antioxidant enzymes. High concentrations of glycated hemoglobin (HbA1c) in STZ-induced diabetic rats decreased after a daily treatment of 100–200 mg/kg of C-PC. The total cholesterol, triglycerides, LDL-C, SGOT, ALP, SGPT, and total bilirubin levels were also reduced, suggesting a hepatoprotective function by C-PC as the possible preventive basis against diabetes complications. These are animal model results.
The only human clinical data that touch on hepatic function is the Jensen et al. (2016) RCT, in which serum levels of aspartate transaminase (AST) showed a significant reduction after 2 weeks of ACE consumption (P < .001), in contrast to placebo where no changes were seen. This finding was a secondary endpoint in a safety study rather than a dedicated hepatoprotection trial and should be interpreted cautiously.
Evidence level: In vitro and animal data; no dedicated human RCTs.
Results of in vivo toxicity, immunomodulatory, and antioxidant effects of C-phycocyanin suggest that C-phycocyanin is very safe for consumption and has substantial antioxidant potential and also possesses immunomodulatory activities in Balb/c mice in a dosage-dependent manner. Specific immunostimulatory effects documented in animal models include augmentation of natural killer cell activity, enhanced lymphocyte proliferation, and modulation of cytokine profiles. Phycocyanin shows a wide range of pharmacological effects, with anti-oxidation, anti-cancer, anti-inflammatory activity, photo-induced cytotoxicity, and stimulation of the immune system.
Evidence level: Animal and in vitro data; no dedicated human clinical trials for isolated C-PC.
Animal studies show C-PC can lower blood glucose and improve insulin sensitivity in streptozotocin (STZ)-induced diabetic rodent models. High concentrations of glycated hemoglobin (HbA1c) in STZ-induced diabetic rats decreased after a daily treatment of 100–200 mg/kg of C-PC. The total cholesterol, triglycerides, LDL-C, SGOT, ALP, SGPT, and total bilirubin levels were also reduced. Human clinical evidence in this domain comes from trials using whole Spirulina biomass rather than isolated C-PC, making it difficult to attribute effects specifically to C-phycocyanin.
Evidence level: In vitro only.
Some pharmacological effects like reducing inflammation (98.76% ± 0.065), fighting free radicals (99.12% ± 0.027), and being able to inhibit the human coronavirus 229E with a selective index of 27.9 were observed. These findings were obtained in cell culture models and have not been validated in human clinical studies.
The blue-green alga Spirulina platensis is rich in phycocyanins that exhibit a wide range of pharmacological actions. C-phycocyanin (C-PC), in particular, possesses hepatoprotective, nephroprotective, antioxidant, and anticancer effects. The following organ systems and health areas have been studied in connection with C-PC:
C-phycocyanin is encountered in dietary supplements in the following forms:
Reported dosages from the scientific literature:
No universally agreed-upon therapeutic dose for isolated C-PC in humans has been established from clinical trials. Human dosing data are limited to safety studies and small pilots.
In vivo toxicology studies of Arthrospira platensis have not revealed any toxic effects on kidney, liver, reproductive system, or body physiology during or after the administration of acute or chronic doses. A safety evaluation by the United States Pharmacopoeia—based on a 1966 to 2009 PubMed literature review—and adverse event reports of the United States Food and Drug Administration (FDA) concluded that Arthrospira platensis has a Class A safety rating. Several dried biomass products of Arthrospira have also been categorized as "generally recognized as safe" (GRAS) by the FDA.
Results of in vivo toxicity, immunomodulatory, and antioxidant effects suggest that C-phycocyanin is very safe for consumption and has substantial antioxidant potential and also possesses immunomodulatory activities in Balb/c mice in a dosage-dependent manner. C-phycocyanin does not cause acute and subacute toxicity in the animal model (male, Balb/c mice) studied.
It is important to note that the safety data cited above pertain to Spirulina biomass as a whole and to C-PC derived from confirmed-clean sources. Spirulina's safety as a food has been established through centuries of human use, as well as through numerous toxicology studies. However, such safety data do not automatically vouch for the safety of extracts and purified compounds from Spirulina, and hence further safety documentation is needed for such extracts.
A specific safety concern—the potential anticoagulant or antiplatelet action—was evaluated in a dedicated clinical study. Consuming ACE did not alter markers for platelet activation (P-selectin expression) or serum P-selectin levels. No changes were seen for activated partial thromboplastin time, thrombin clotting time, or fibrinogen activity. This was at a dose of 2.3 g ACE/day (~1 g phycocyanin/day) for two weeks in 24 subjects, a limited sample size and short duration. There is a potential for natural compounds to provide more multifaceted biological effects. As an example, phycocyanin's bioactivity extends beyond its COX-2 inhibiting properties. The possibility of interactions with anticoagulant or antiplatelet drugs has been raised based on laboratory data but was not confirmed at tested oral doses in this human study.
A documented safety concern with all Spirulina-derived products is contamination. Wild-harvested cyanobacterial biomass can contain toxic microcystins produced by other contaminating cyanobacterial species. Commercially cultivated Spirulina under controlled conditions is not expected to produce microcystins itself, but quality control of production environments is critical. This risk is distinct from the intrinsic toxicology of C-PC itself.
PCB might be better absorbed when orally administered since it has good stability in acidic environments, in contrast to C-PC that becomes unstable and unfolds at acidic pH. This instability in gastric acid means that the bioavailability of intact C-PC protein following oral ingestion may differ substantially from what is observed in in vitro or intravenous studies, a limitation that must be considered when interpreting any orally administered results.
Phycocyanin is a nontoxic photosensitizer that can be used as an adjuvant in the photodynamic therapy (PDT) of tumors. Its photo-induced cytotoxicity, which is an asset in cancer photodynamic therapy research contexts, is also a potential variable to consider in the context of light exposure in oral supplement use, although this concern is largely theoretical at current supplemental doses.
Health conditions that C-phycocyanin may help support.
Body systems that C-phycocyanin may help support.