Bioactive C-phycocyanin exerts immunomodulatory and antitumor activity in mice with induced melanoma.

Melanoma is the most aggressive and deadly skin cancer. The difficulty in its treatment arises from its ability to suppress the immune system, making it crucial to find a substance that increases anti-tumor immunity. C-phycocyanin (C-PC) appears as a promising bioactive, with multifaceted effects against several cancers, but its efficacy against melanoma has only been tested in vitro. Therefore, we investigated C-PC's the anti-tumor and immunomodulatory action in a murine melanoma model. The tumor was subcutaneously induced in C57BL/6 mice by injecting B16F10 cells. The animals were injected subcutaneously with C-PC for three consecutive days. After euthanasia, the tumor was weighed and measured. The inguinal lymph node was removed, and the cells were stained with antibodies and analyzed by flow cytometry. The heart, brain and lung were analyzed by histopathology. C-PC increased the B cell population of the inguinal lymph node in percentage and absolute number. The absolute number of T lymphocytes and myeloid cells were also increased in the groups treated with C-PC. Thus, C-PC showed a positive immunomodulatory effect both animals with and without tumor. However, this effect was more pronounced in the presence of the tumor. Positive immune system modulation may be associated with a reduction in tumor growth in animals treated with C-PC. Administration of C-PC subcutaneously did not cause organ damage. Our findings demonstrate C-PC's immunomodulatory and anti-melanoma action, paving the way for clinical research with this bioactive.

The antihypertensive action of C-phycocyanin is related to the prevention of angiotensin II-caused vascular dysfunction in chronic kidney disease.

C-phycocyanin (CPC) is a photosynthetic protein found in Arthrospira maxima with a nephroprotective and antihypertensive activity that can prevent the development of hemodynamic alterations caused by chronic kidney disease (CKD). However, the complete nutraceutical activities are still unknown. This study aims to determine if the antihypertensive effect of CPC is associated with preventing the impairment of hemodynamic variables through delaying vascular dysfunction. Twenty-four normotensive male Wistar rats were divided into four groups: (1) sham + 4 mL/kg/d vehicle (100 mM of phosphate buffer, PBS) administered by oral gavage (og), (2) sham + 100 mg/kg/d og of CPC, (3) CKD induced by 5/6 nephrectomy (CKD) + vehicle, (4) CKD + CPC. One week after surgery, the CPC treatment began and was administrated daily for four weeks. At the end treatment, animals were euthanized, and their thoracic aorta was used to determine the vascular function and expression of AT1, AT2, and Mas receptors. CKD-induced systemic arterial hypertension (SAH) and vascular dysfunction by reducing the vasorelaxant response of angiotensin 1-7 and increasing the contractile response to angiotensin II. Also, CKD increased the expression of the AT1 and AT2 receptors and reduced the Mas receptor expression. Remarkably, the treatment with CPC prevented SAH, renal function impairment, and vascular dysfunction in the angiotensin system. In conclusion, the antihypertensive activity of CPC is associated with avoiding changes in the expression of AT1, AT2, and Mas receptors, preventing vascular dysfunction development and SAH in rats with CKD.

A tumor microenvironment-activatable nanoplatform with phycocyanin-assisted in-situ nanoagent generation for synergistic treatment of colorectal cancer.

The in-situ generation of therapeutic agents in targeted lesions is promising for revolutionizing oncotherapy but is limited by the low production efficiency. Given the specific tumor microenvironment (TME) of colorectal cancer (CRC), i.e., mild acidity, overexpressed H2O2, glutathione (GSH) and H2S, we develop phycocyanin (PC) encapsulated PZTC/SS/HA nanocapsules (NCs) for TME-responsive, protein-assisted "turn-on'' therapy of CRC. The NCs are prepared by sequentially assembling Cu2+-tannic acid (TA) coordination shell, disulfide bond-bearing cross-linker, and hyaluronic acid (HA) on the sacrificial template ZIF-8, thus achieving pH-, GSH-responsiveness, and tumor targeting capability, respectively. Once reaching the CRC sites, the NCs can quickly disintegrate and release Cu2+ and PC, accompanied by subsequent endogenous H2S-triggered generation of copper sulfide (CuS). Significantly, the intracellular sulfidation process can be accelerated by PC, thereby enabling efficient photothermal therapy (PTT) under NIR-Ⅱ laser. Besides, Cu2+-associated chemodynamic therapy (CDT) can be simultaneously activated and enhanced by PTT-induced local hyperthermia and disulfide bond-induced GSH consumption. This CRC-targeted and TME-activated synergistic PTT/CDT strategy displays high therapeutic efficacy both in vitro and in vivo, which can open up a new avenue for biomolecule-assisted in-situ nanoagent generation and effective TME-responsive synergistic treatment of CRC.

Caries affected disinfection using Phycocyanin activated by PDT, Holy Basil, and Ti-sapphire laser on adhesive bond strength, microleakage, and bond failure.

AIM: To investigate the effect of different cavity disinfectants, Phycocyanin (PC), Ocimum Sanctum (OS), and Ti Sapphire Laser, on the bond integrity and microleakage of resin restorations. MATERIAL AND METHOD: 60 human mandibular molars were extracted and prepared based on ICDAS scores of 4 and 5. To obtain the CAD surface, a visual examination was supported by tactile sensation and a dye for caries detection. Samples were randomly allocated into 4 groups based on cavity disinfectants applied (n = 15). Group 1: Specimens disinfected with CHX, Group 2: Specimens disinfected with Ti sapphire laser, Group 3: Specimens disinfected with Phycocyanin activated by Photodynamic therapy, and Group 4: Specimens disinfected with OS. Following the disinfection of the CAD surfaces, composite bulk-fill restorative material was bonded to each specimen and all samples were subjected to thermocycling. Ten samples from each group underwent SBS testing performed on a universal testing machine. Five samples were subjected to a microleakage analysis. RESULT: The maximum microleakage scores were displayed by Group 3: PC (0.521 nm) treated specimens. Whereas, and minimum microleakage was exhibited by Group 4: OS (0.471 nm). Group 4: OS (23.06±0.21 MPa) treated group displayed the maximum bond scores of resin adhesive to the CAD surface. However, Group 3: PC (21.67±0.24 MPa) treated specimens exhibited the lowest bond scores. Failure mode analysis revealed that among all the investigated groups the predominant type of failure was cohesive failure i.e., Group 1 (80%), Group 2 (80%), Group 3 (70%), and Group 4 (90%). CONCLUSION: Ocimum Sanctum, Phycocyanin activated by Photodynamic therapy, and Ti-sapphire laser for disinfection of caries-affected dentin have shown promise in terms of improved bond strength and reduced microleakage.

The molecular mechanism of three novel peptides from C-phycocyanin alleviates MPTP-induced Parkinson's disease-like pathology in zebrafish.

Previous studies have shown that peptides isolated from C-phycocyanin (C-PC) possess various functions including antioxidant and anticancer activities. However, there is little research on C-PC peptides applied for the neuroprotective effect against a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) model. In this study, twelve novel peptides from C-PC were isolated, purified and identified, and the anti-PD effect of the synthesized peptides was evaluated in a zebrafish PD model. As a result, three of these peptides (MAAAHR, MPQPPAK, and MTAAAR) significantly reversed the loss of dopamine neurons and cerebral vessels, and reduced the locomotor impairment in PD zebrafish. In addition, three novel peptides could inhibit the MPTP-induced decrease of antioxidant enzymes (SOD, CAT, and GSH-Px) and increase the ROS and protein carbonylation content. In addition, they can also alleviate apoptosis of brain regions and acetylcholinesterase (AChE) activity in zebrafish. Further studies elucidated the potential molecular mechanism of peptides' anti-PD effects in the larvae. The results showed that C-PC peptides could modulate multiple genes associated with oxidative stress, autophagy and apoptosis signaling pathways, and thereby alleviate the occurrence of PD symptoms. Overall, our results highlight the neuroprotective effects of three novel peptides and provide valuable mechanistic insights and a promising drug target for the treatment of PD.

Combination of Phycocyanin, Zinc, and Selenium Improves Survival Rate and Inflammation in the Lipopolysaccharide-Galactosamine Mouse Model.

Sepsis is related to systemic inflammation and oxidative stress, the primary causes of death in intensive care units. Severe functional abnormalities in numerous organs can arise due to sepsis, with acute lung damage being the most common and significant morbidity. Spirulina, blue-green algae with high protein, vitamins, phycocyanin, and antioxidant content, shows anti-inflammatory properties by decreasing the release of cytokines. In addition, zinc (Zn) and selenium (Se) act as an antioxidant by inhibiting the oxidation of macromolecules, as well as the inhibition of the inflammatory response. The current study aimed to examine the combined properties of Zn, Se, and phycocyanin oligopeptides (ZnSePO) against lipopolysaccharide-D-galactosamine (LPS-GalN)-induced septic lung injury through survival rate, inflammatory, and histopathological changes in Balb/c mice. A total of 30 mice were allocated into three groups: normal control, LPS-GalN (100 ng of LPS plus 8 mg of D-galactosamine), LPS-GalN + ZnSePO (ZnPic, 52.5 µg/mL; SeMet, 0.02 µg/mL; and phycocyanin oligopeptide (PO), 2.00 mg/mL; at 1 h before the injection of LPS-GalN). Lung tissue from mice revealed noticeable inflammatory reactions and typical interstitial fibrosis after the LPS-GalN challenge. LPS-GalN-induced increased mortality rate and levels of IL-1, IL-6, IL-10, TGF-ß, TNF-α, and NF-κB in lung tissue. Moreover, treatment of septic mice LPS-GalN + ZnSePO reduced mortality rates and inflammatory responses. ZnSePO considerably influenced tissue cytokine levels, contributing to its capacity to minimize acute lung injury (ALI) and pulmonary inflammation and prevent pulmonary edema formation in LPS-GalN-injected mice. In conclusion, ZnSePO treatment enhanced the survival rate of endotoxemia mice via improving inflammation and oxidative stress, indicating a possible therapeutic effect for patients with septic infections.

Therapeutic Efficacy of Natural Product 'C-Phycocyanin' in Alleviating Streptozotocin-Induced Diabetes via the Inhibition of Glycation Reaction in Rats.

Diabetes is a long-term metabolic disorder characterized by persistently elevated blood sugar levels. Chronic hyperglycemia enhances glucose-protein interactions, leading to the formation of advanced glycation end products (AGEs), which form irreversible cross-links with a wide variety of macromolecules, and accumulate rapidly in the body tissues. Thus, the objective of this study was to assess the therapeutic properties of C-phycocyanin (C-PC) obtained from Plectonema species against oxidative stress, glycation, and type 2 diabetes mellitus (T2DM) in a streptozotocin (STZ)-induced diabetic Wistar rat. Forty-five days of C-PC administration decreased levels of triglycerides (TGs), blood glucose, glycosylated hemoglobin, (HbA1c), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), liver and kidney function indices, and raised body weight in diabetic rats. C-PC suppressed biochemical glycation markers, as well as serum carboxymethyllysine (CML) and fluorescent AGEs. Additionally, C-PC maintained the redox state by lowering lipid peroxidation and protein-bound carbonyl content (CC), enhancing the activity of high-density lipoprotein cholesterol (HDL-C) and renal antioxidant enzymes, and preserving retinal and renal histopathological characteristics. Thus, we infer that C-PC possesses antidiabetic and antiglycation effects in diabetic rats. C-PC may also act as an antidiabetic and antiglycation agent in vivo that may reduce the risk of secondary diabetic complications.

The Inhibitory Effect of Phycocyanin Peptide on Pulmonary Fibrosis In Vitro.

Phycocyanin is an excellent antioxidant with anti-inflammatory effects on which recent studies are growing; however, its specific target remains unclear. Linear tetrapyrrole compounds such as bilirubin have been shown to lead to the induction of heme oxygenase 1 expression in vivo, thus achieving antioxidant and anti-inflammatory effects. Phycocyanin is bound internally with linear tetrapyrrole phycocyanobilin in a similar structure to bilirubin. We speculate that there is probably a way of inducing the expression of heme oxygenase 1, with which tissue oxidative stress and inflammation can be inhibited, thus inhibiting pulmonary fibrosis caused by oxidative damage and inflammation of lung. By optimizing the enzymatic hydrolysis process, phycocyanobilin-bound phycocyanin peptide were obtained, and its in vitro antioxidant, anti-inflammatory, and anti-pulmonary fibrosis activities were investigated. The results show that the phycocyanobilin peptide was able to alleviate oxidative and inflammatory damage in cells through the Keap1-Nrf2-HO-1 pathway, which in turn relieved pulmonary fibrosis symptoms.

C-Phycocyanin Suppresses Cell Proliferation and Promotes Apoptosis by Regulating the AMPK Pathway in NCL-H292 Non-Small Cell Lung Cancer Cells.

Non-small cell lung cancer (NSCLC) results in high mortality and has gained increasing attention. C-Phycocyanin (C-PC) has been identified as a potential therapeutic inhibitor for NSCLC, but its underlying mechanism remains obscure. The gene expression of the long noncoding RNA neighbour of BRCAI RNA 2 (NBR2) in NSCLC cells was evaluated by quantitative reverse transcription-PCR. The cell capacity for proliferation and migration was examined by EdU and wound-healing assays. Furthermore, the viability and apoptosis of cells was measured with CCK-8 and annexin V/PI, respectively. Next, the protein level of activation of adenosine monophosphate- activated protein kinase and the rapamycin kinase (mTOR) signalling pathway-associated molecules was evaluated by western blotting. H292 cells were pre-treated with C-PC or transfected with plasmids encoding NBR2 or the shNBR2 plasmid, to over-express or knock down NBR2 expression, respectively. NBR2 expression was robustly down-regulated in NSCLC cell lines compared with a normal cell line (BEAS-2B). NBR2 over-expression inhibited migration and promoted apoptosis of H292 cells. Treatment of H292 cells with C-PC enhanced NBR2 levels in a dose- and time-dependent manner. Downregulation of NBR2 in H292 cells inhibited the activity of C-PC on cell proliferation, viability and clone formation. Further mechanistic investigation showed that the down-regulation of NBR2 abolished the modulatory effects of C-PC on the AMPK/mTOR signalling pathway. In conclusion, C-PC inhibits H292 cell growth by enhancing the NBR2/AMPK signalling pathway.

Phycocyanin: Anti-inflammatory effect and mechanism.

As the host defense response to various injuries and pathogens in the body, inflammation can remove damaged cells and pathogens in the host organism and protect the body. However, excessive inflammation may cause damage to normal tissue cells while removing pathogens, which in turn cause numerous inflammatory diseases and adversely affect the human health. Phycocyanin is an active substance extracted from algae; it has outstanding antioxidant and anti-inflammatory activities, and can effectively inhibit various diseases caused by inflammation. This review systematically summarizes recent applications of phycocyanin against various inflammatory diseases in lung, liver, cardiovascular, and cerebrovascular systems. In addition, possible anti-inflammatory action pathways of phycocyanin are reviewed to canvass the anti-inflammatory mechanism. At last, based on the existing research, phycocyanobilin in phycocyanin is proposed as a bilirubin analog by inducing heme oxygenase 1 in vivo to suppress inflammation.

Phycocyanin stimulates ulcerative colitis healing via selective activation of cannabinoid receptor-2, intestinal mucosal healing, Treg accumulation, and p38MAPK/MK2 signaling inhibition.

Ulcerative colitis (UC) is a chronic inflammatory condition that until this date, lacks curative treatments. Previously, synthetic selective CB2 receptor (CB2R) agonists demonstrated effective preclinical anti-inflammatory activities in UC. Phycocyanin (PC), photosynthetic assistant protein isolated from Microcystis aeruginosa Kützing blue green algae, has multiple pharmacological effects, however, it's effect against UC remains unexplored. Our study aimed at investigating the therapeutic effectiveness of PC against UC, and correlating its mechanisms with CB2R agonistic activities. In silico; PC showed structural similarity with endocannabinoid receptors' ligand "Δ9-tetrahydrocannabinol", target prediction studies suggested high affinity for G-coupled protein family-receptors, and molecular docking affirmed preferable affinity towards CB2R vs CB1R. In LPS-exposed-Caco-2 cell line; PC demonstrated comparable interaction with CB2R, and downregulation of CB2R, p38 and MK2 gene expressions with reference agonist "6d", and exhibited preferred selectivity towards CB2R over CB1R. In DSS-induced mice; PC-treatment ameliorated DSS-induced colon shortening, elevated disease activity index, and colonic pathological alterations. PC showed effective CB2R activation through potent anti-inflammatory activities, Treg-cell accumulation, suppression in p38MAPK/MK2 signaling, and tight junction barrier restoration as indicated by ultrastructural examinations, elevated ZO-1 and occludin protein expressions, and Ki67 immunohistochemical expression in colonic tissues. Additionally, PC alleviated intestinal dysbiosis via downregulating LPS/TLR4/NF-κB signaling and gut microbiota maintenance. Notably, PC-protective activities were abolished when co-administered with SR144528 (selective CB2 antagonist) except for gut microbiota maintenance, which was independent from CB2R activation. Our findings provide evidence of PC effectiveness against UC through acting as CB2R agonist, thus expanding its possible therapeutic application against other inflammatory diseases.

Spirulina phycocyanin extract and its active components suppress epithelial-mesenchymal transition process in endometrial cancer via targeting TGF-beta1/SMAD4 signaling pathway.

Metastasis is a major challenge in aggressive endometrial cancer treatment accounting for the high recurrence risk and poor prognosis of epithelial-mesenchymal transition (EMT), regulated by the transforming growth factor beta (TGFß) signaling pathway, facilitates tumor metastasis. Spirulina phycocyanin extract (SPE) and its purified products allophycocyanin (APC) and C-phycocyanin (C-PC), derived from Spirulina platensis, can be considered a nutraceutical compound with the ability to inhibit tumor growth and metastasis. Current study aims to investigate the anti-metastatic potential of SPE, and its purified products APC, and C-PC on endometrial cancer both in vitro and in vivo. Firstly, human endometrial cancer cell lines (HEC-1A and Ishikawa) as an in vitro model. Secondly, HEC-1A cells transfected with luminescence gene were implanted into female nude mice as a xenograft model. MTT assay, transwell migration assay, immunoblotting assay, quantitative real-time polymerase chain reaction assay, and IVIS XRMS analysis techniques were used. The in vitro results showed that SPE and its purified products APC and C-PC inhibited cell migration, and altered the expression of EMT-related phenotypes by reversing the TGFß/SMADs signaling pathway. The in vivo results indicated that SPE repressed the metastasis of HEC-1A-LUC cells through modulating EMT-related markers expression. Overall, SPE and its efficient components APC and C-PC reversed the EMT through targeting the TGFß/SMADs signaling pathway, suggesting an effective therapeutic strategy for metastatic endometrial cancer.

Novel Insights into the Molecular Mechanisms Involved in the Neuroprotective Effects of C-Phycocyanin against Brain Ischemia in Rats.

BACKGROUND: Ischemic stroke produces a large health impact worldwide, with scarce therapeutic options. OBJECTIVE: This study aimed to reveal the role of NADPH oxidase and neuroinflammatory genes in the cerebral anti-ischemic effects of C-Phycocyanin (C-PC), the chief biliprotein of Spirulina platensis. METHODS: Rats with either focal cerebral ischemia/reperfusion (I/R) or acute brain hypoperfusion, received C-PC at different doses, or a vehicle, for up to 6 h post-stroke. Neurological, behavioral and histochemical parameters were assessed in I/R rats at 24 h. Cerebral gene expression and hippocampal neuron viability were evaluated in hypoperfused rats at acute (24 h) or chronic phases (30 days), respectively. A molecular docking analysis of NOX2 and C-PC-derived Phycocyanobilin (PCB) was also performed. RESULTS: C-PC, obtained with a purity of 4.342, significantly reduced the infarct volume and neurological deficit in a dose-dependent manner, and improved the exploratory activity of I/R rats. This biliprotein inhibited NOX2 expression, a crucial NADPH oxidase isoform in the brain, and the superoxide increase produced by the ischemic event. Moreover, C-PC-derived PCB showed a high binding affinity in silico with NOX2. C-PC downregulated the expression of pro-inflammatory genes (IFN-γ, IL-6, IL-17A, CD74, CCL12) and upregulated immune suppressive genes (Foxp3, IL-4, TGF-ß) in hypoperfused brain areas. This compound also decreased chronic neuronal death in the hippocampus of hypoperfused rats. CONCLUSION: These results suggest that the inhibition of cerebral NADPH oxidase and the improvement of neuroinflammation are key mechanisms mediating the neuroprotective actions of C-PC against brain ischemia.

Phycocyanin Ameliorates Colitis-Associated Colorectal Cancer by Regulating the Gut Microbiota and the IL-17 Signaling Pathway.

Phycocyanin (PC) is a pigment-protein complex. It has been reported that PC exerts anti-colorectal cancer activities, although the underlying mechanism has not been fully elucidated. In the present study, azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced mice were orally administrated with PC, followed by microbiota and transcriptomic analyses to investigate the effects of PC on colitis-associated cancer (CAC). Our results indicated that PC ameliorated AOM/DSS induced inflammation. PC treatment significantly reduced the number of colorectal tumors and inhibited proliferation of epithelial cell in CAC mice. Moreover, PC reduced the relative abundance of Firmicutes, Deferribacteres, Proteobacteria and Epsilonbacteraeota at phylum level. Transcriptomic analysis showed that the expression of genes involved in the intestinal barrier were altered upon PC administration, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed the IL-17 signaling pathway was affected by PC treatment. The study demonstrated the protective therapeutic action of PC on CAC.

Phycocyanin ameliorates mouse colitis via phycocyanobilin-dependent antioxidant and anti-inflammatory protection of the intestinal epithelial barrier.

Phycocyanin is a typical microalgal active compound with antioxidant and anti-inflammatory efficacy, and the pigment moiety phycocyanobilin has been recently proposed as its active structural component. Here, to explore the structural basis for phycocyanin's intestinal protective action, we evaluated the therapeutic effects and mechanism of action of phycocyanin and phycocyanobilin in dextran sodium sulphate (DSS)-induced colitis mice and in Caco-2 and RAW 264.7 cells. Phycocyanobilin was obtained by solvothermal alcoholysis of phycocyanin and characterized by spectroscopy and mass spectrometry methods. Phycocyanin, phycocyanobilin and a positive drug mesalazine were intragastrically administered to C57BL/6 mice daily for 7 days during and after 4-day DSS exposure. Clinical signs and colon histopathology revealed that phycocyanin and phycocyanobilin had an equivalent anti-colitis efficacy that was even superior to mesalazine. Based on biochemical analysis of colonic tight junction proteins, mucus compositions and goblet cells, and colonic and peripheral proinflammatory cytokines, phycocyanin and phycocyanobilin displayed equivalent intestinal epithelial barrier-protecting and anti-inflammatory potential that was evidently superior to that of mesalazine. Flow cytometry analysis of phycocyanobilin fluorescence in Caco-2 cells unveiled a similar uptake efficacy of phycocyanin and phycocyanobilin by intestinal epithelial cells. According to lactic dehydrogenase release, 2',7'-dichlorodihydrofluorescein fluorescence and methylthiazolyldiphenyl-tetrazolium bromide assay in Caco-2 cells, phycocyanin and phycocyanobilin could equally and effectively protect the intestinal epithelial barrier from oxidant-induced disruption. Phycocyanin and phycocyanobilin also showed equivalent anti-inflammatory effects in tumor necrosis factor-α-stimulated Caco-2 cells and in lipopolysaccharides- and tumor necrosis factor-α-activated RAW264.7 cells. Overall, our results demonstrate the phycocyanobilin-dependent anti-colitis role of phycocyanin via antioxidant and anti-inflammatory mechanisms.

Bioactive Compounds of Arthrospira spp. (Spirulina) with Potential Anticancer Activities: A Systematic Review.

Arthrospira, a genus of blue-green cyanobacteria, is known for its great biological activity due to the presence of a large number of substances that are potentially active against tumor cells. This review aimed to evaluate the potential of Arthrospira spp. for the treatment or reduction of several types of cancer, in addition to elucidating the mechanism of action by which their compounds act on tumor cells. A systematic review was carried out in PubMed, Science Direct, LILACS, and SciELO databases, including original studies from 2009 to 2020. A total of 1306 articles were independently assessed according to the eligibility criteria, of which 20 articles were selected and assessed for the risk of bias using seven criteria developed by the authors. Arthrospira spp. of cyanobacteria have been evaluated against eight different types of cancer, mainly colon cancer. Among all the compounds, phycocyanin was the most used, followed by peptides and photosensitizers. In general, compounds from Arthrospira spp. act as anticancer agents by inhibiting the proliferation of tumor cells, triggering cell cycle arrest, and inducing apoptosis via different signaling pathways. In addition, these compounds also exhibited antioxidant, antiangiogenic, and antimetastatic activities. Phycocyanin demonstrated better efficacy against several types of cancer via different activities and therapeutic targets. Furthermore, it was the only molecule that functioned in synergy with other drugs that are already well established for the treatment of cancer.

Phycocyanobilin is the molecule responsible for the nephroprotective action of phycocyanin in acute kidney injury caused by mercury.

C-Phycocyanin (CPC) exerts therapeutic, antioxidant, anti-inflammatory and immunomodulatory actions. It prevents oxidative stress and acute kidney damage caused by HgCl2. However, the exact mechanism of the pharmacological action of C-phycocyanin is as yet unclear. Some proposals express that CPC metabolism releases the active compound phycocyanobilin (PCB) that is able to induce CPC's therapeutical effects as an antioxidant, anti-inflammatory and nephroprotective. This study is aimed to demonstrate that PCB is the molecule responsible for C-phycocyanin's nephroprotective action in the acute kidney injury model caused by HgCl2. PCB was purified from C-phycocyanin and characterized by spectroscopy and mass spectrometry methods. Thirty-six male mice were administrated with 0.75, 1.5, or 3 mg per kg per d of PCB 30 min before the 5 mg kg-1 HgCl2 administration. PCB was administered during the following five days, after which the mice were euthanized. Kidneys were dissected to determine oxidative stress and redox environment markers, first-line antioxidant enzymes, effector caspase activities, and kidney damage markers.The quality of purified PCB was evaluated by spectroscopy and mass spectrometry. All PCB doses prevented alterations in oxidative stress markers, antioxidant enzymes, and caspase 9 activities. However, only the dose of 3 mg per kg per d PCB avoided the redox environment disturbance produced by mercury. All doses of PCB partially prevented the down-expression of nephrin and podocin with a consequent reduction in the damage score in a dose-effect manner. In conclusion, it was proven that phycocyanobilin is the molecule responsible for C-phycocyanin's nephroprotective action on acute kidney injury caused by mercury.

Tumor Microenvironment-Responsive Nanococktails for Synergistic Enhancement of Cancer Treatment via Cascade Reactions.

A combination treatment strategy that relies on the synergetic effects of different therapeutic approaches has been considered to be an effective method for cancer therapy. Herein, a chemotherapeutic drug (doxorubicin, Dox) and a manganese ion (Mn2+) were co-loaded into regenerated silk fibroin-based nanoparticles (NPs), followed by the surface conjugation of phycocyanin (PC) to construct tumor microenvironment-activated nanococktails. The resultant PC-Mn@Dox-NPs showed increased drug release rates by responding to various stimulating factors (acidic pH, hydrogen peroxide (H2O2), and glutathione), revealing that they could efficiently release the payloads (Dox and Mn2+) in tumor cells. The released Dox could not only inhibit the growth of tumor cells but also generated a large amount of H2O2. The elevated H2O2 was decomposed into the highly harmful hydroxyl radicals and oxygen through an Mn2+-mediated Fenton-like reaction. Furthermore, the generated oxygen participated in photodynamic therapy (PDT) and produced abundant singlet oxygen. Our investigations demonstrate that these PC-Mn@Dox-NPs exhibit multiple bioresponsibilities and favorable biosafety. By integrating Dox-induced chemotherapy, Mn2+-mediated chemodynamic therapy, and PC-based PDT via cascade reactions, PC-Mn@Dox-NPs achieved enhanced in vitro and in vivo anticancer efficacies compared to all the mono- or dual-therapeutic approaches. These findings reveal that PC-Mn@Dox-NPs can be exploited as a promising nanococktail for cascade reaction-mediated synergistic cancer treatment.

C-phycocyanin Mitigates Cognitive Impairment in Doxorubicin-Induced Chemobrain: Impact on Neuroinflammation, Oxidative Stress, and Brain Mitochondrial and Synaptic Alterations.

Chemotherapy-induced cognitive impairment (CICI) is a common detrimental effect of cancer treatment, occurring in up to 75% of cancer patients. The widely utilized chemotherapeutic agent doxorubicin (DOX) has been implicated in cognitive decline, mostly via cytokine-induced neuroinflammatory and oxidative and mitochondrial damage to brain tissues. C-phycocyanin (CP) has previously been shown to have potent anti-inflammatory, antioxidant, and mitochondrial protective properties. Therefore, this present study was aimed to investigate the neuroprotective effects of CP against DOX-elicited cognitive impairment and explore the underlying mechanisms. CP treatment (50 mg/kg) significantly improved behavioral deficits in DOX-treated mice. Furthermore, CP suppressed DOX-induced neuroinflammation and oxidative stress, mitigated mitochondrial abnormalities, rescued dendritic spine loss, and increased synaptic density in the hippocampus of DOX-treated mice. Our results suggested that CP improves established DOX-induced cognitive deficits, which could be explained at least partly by inhibition of neuroinflammatory and oxidant stress and attenuation of mitochondrial and synaptic dysfunction.

Therapeutic effect of phycocyanin on acute liver oxidative damage caused by X-ray.

1) BACKGROUND: Phycocyanin (PC) is a type of natural protein in algae with antioxidant and anti-inflammatory properties. However, the protective effect of PC on hepatic damage induced by X-ray remains unknown. 2) METHODS: Male C57BL/6 mice were gavaged with 200mg/kg PC for consecutive 7 days before or after radiation. The blood samples and tissues were collected on days 1 and 7 after radiation exposure. 3) RESULTS: Pretreatment or treatment with PC decreased significantly the levels of alanine aminotransferase (ALT), aspartate aminotransferase(AST) in the plasma. Histological evaluation further confirmed the protection of PC against radiation-induced hepatotoxicity. PC-treatment also increased the relative mRNA expression of superoxide dismutase (SOD) and glutathione (GSH-PX), and descended the ROS in the liver. Moreover, the expression of H2AX, an indicator of DNA damage in mice, of the PC-intervention group was much smaller than that of the radiation group. In vivo, PC-treatment markedly up-regulated NF-E2-related factor 2(Nrf2) expression and downstream gene such as hemeoxygenase-1 (HO-1), NQO1. 4) Conclusion: PC could attenuate the radiation-induced oxidative stress damage by activating Nrf2/ HO-1 signaling pathway, and reduce the radiation-induced DNA damage. Therefore, PC is a protective agent against radiation-induced liver damage.