Table 2.
Biological roles of phycocyanin recovered from Spirulina and description of its main functions, dose, or concentration, and methods used to analyze this effect.
| Role | Effect | Dose or Concentration (Route of Administration) |
Analysis Methodology | Ref. |
|---|---|---|---|---|
| Anti-oxidative | Scavenging of free radicals, lipid peroxidation inhibitor and metal chelator | 1–3 mg/mL | Luminol-enhanced chemiluminescence | [54] |
| 0–0.16 mM | Deoxyribose assay | |||
| 8–20 mg/mL | Inhibition of liver microsomal lipid peroxidation induced by Fe-ascorbic acid | |||
| 50–200 mg/kg (oral) |
Glucose oxidase-induced inflammation in vivo | |||
| 62.34 mg/g | DPPH, FRAP and Fe2+—chelating activity | [55] | ||
| 0.125–2.00 mg/mL 0.3125–5.00 mg/mL |
ABTS and DPPH | [56] | ||
| 10–100 μg/mL | DPPH | [57] | ||
| Serum antioxidant | 200–1000 mg/kg (oral) |
SOD and catalase activity in vivo | [58] | |
| Attenuation of MMPs and ROS | 20–80 μg/mL | MMP-1 and MMP-9 and DCFDA staining | [59] | |
| Attenuation of platelet aggregation by decreasing hydroxyl radicals | 0.5–10 nM | Electron Spin Resonance Spectrometry | [60] | |
| Increase of antioxidant enzymes | 5 μM + 2 Gy radiation | RANDOX kit | [61] | |
| Attenuation of ROS | 10 μM (rat heart perfusion) |
Electron paramagnetic resonance spectroscopy | [62] | |
| Attenuation of ROS, MDA and GSH, and maintenance of SOD activity | 100–400 mg/kg (intraperitoneal injection) 31–250 μg/mL |
DCFDA staining and histopathologic analysis | [63] | |
| Free radical scavenger | 5–50 mM pre-treatment for 1 h and then co-treatment | DCFDA staining | [64] | |
| Anticancer | Cell cycle arrest in G0/G1, attenuation of proliferation and stimulation of apoptosis | 1–20 μM | Propidium iodide, annexin V-PE, 7-AAD, proliferative, and apoptotic markers | [65] |
| 10–100 μM | MTT assay, cytochrome c, ethidium bromide | [66] | ||
| Alteration of the mitochondrial membrane potential | 10–100 μM | Rhodamine 123 | [67] | |
| Attenuation of MMPs | 5–40 μg/mL | MMP-1, MMP-2, MMP-9, TIMP-1, TIMP-2 | [68] | |
| Attenuation of metastasis | 200 mg/kg (oral) |
MMPs, VEGF-A and HIF-1α, activity of MMPs and HIF-1α | [69] | |
| Stimulation of mitochondria-mediated apoptosis | 5–40 μg | Depolarized mitochondria, apoptotic, and proliferative markers | [70] | |
| Drug resistance by preventing the induction of multidrug resistance protein | 1–100 μM | ROS production and COX-2 expression | [71] | |
| Anti-inflammatory | Attenuation of pro-inflammatory mediators and neutrophil infiltration | 30–50 mg/kg | TNF-α, IL-1β, IL-10, nitrite, nitrate, PGE2, COX-2, iNOS, MPO, and NF-kB activity | [72] |
| 0–250 μg/mL | [73] | |||
| Attenuation of lung injury | 50 mg/kg 100–400 mg/kg (intraperitoneal injection) |
Lung injury, nitrate/nitrite, pro-inflammatory cytokines in BALF, MPO and NF-kB activity, iNOS, COX-2, lung edema, proapoptotic proteins | [74,75] | |
| Prevention of fibrosis | 10–50 μg/mL 0–200 μg/mL |
Nrf2, NQO-1, EMT evaluated through the expression of vimentin, type-1-collagen, fibronectin, α-SMA, N-cadherin, and E-cadherin | [76,77] | |
| Antimicrobial | Decrease the growth of Escherichia coli, Bacillus sp., Staphylococcus aureus, and Salmonella Typhi | 35 μg/mL | Disc diffusion assay and determination of MIC. Comparation with Antibiotic Assay Medium (Himedia). | [78] |
| Attenuate the growth of Listeria monocytogenes, S. aureus, Yersinia ruckeri, E. coli, and Streptococcus iniae | 25 μg/mL | Agar well diffusion assay, MIC and MBC. Comparation with Tetracycline, Amikacin, and Doxycycline | [55] | |
| Impair the growth of S. aureus, Aeromonas hydrofila, and Salmonella Enteritidis. No effect in Enterococcus faecalis | 320 μg/mL | Agar well diffusion method and turbidity liquid media assay. MIC and turbidity at 600 nm | [79] | |
| Antibacterial activity against Pseudomonas aeruginosa MTCC 1034, Klebsiella pneumoniae (ESBL-KP) ATCC 700603, E. coli (ATCC 25922), and S. aureus ATCC 25,923 (MRSA). No effect on Acinetobacter baumanii, Enterococcus durans (P502). | 1000 μg/mL | Mueller–Hinton Agar plates and MIC using broth microdilution method | [80] | |
| Attenuation of acne symptoms and reduction of Propionibacterium acnes and Staphylococcus epidermidis | 10% extract | Disc diffusion method and MIC | [81] | |
| Inhibition of the growth of Candida albicans, Aspergillus niger, Aspergillus flavus, Penicillium sp., and Rhizopus sp. | 40–80 μg/mL | Agar block method and MIC | [82] | |
| Anti-neurodegenerative | Promotor of remyelination | 25 mg/kg (intraperitoneal injection) |
Brain biopsies, pro-inflammatory mediators and populations, lipid peroxidation | [83] |
| Attenuation of Alzheimer’s disease markers | 0–20 μg/mL | Intracellular GSH, APP, BACE2, GSH-Px, SOD2, GR, BDNF, α-tubulin | [84] | |
| 50 or 100 mg/kg (intraperitoneal injection) |
Morris water maze, novel object recognition and open field test, ChAT, inflammatory and apoptotic mediators, IRS-1, INS, PI3K/AKT, and PTEN gene expression | [85] | ||
| 200 mg/kg (intraperitoneal injection) |
Eight-arm radial maze, HAC3, pro-inflammatory, and proapoptic mediators | [86] | ||
| Attenuation of Parkinson’s disease markers | 2.5–7.5 μM | Fibril formation of αS or Aβ40/42, ADH, catalase | [87] | |
| Antidiabetic | Antidiabetic and antiglycation | 100–500 μg/mL | Inhibitory effect of PPA and β-glucosidase | [88] |
| 100 and 200 mg/kg 100 mg/kg 200 mg/kg 50 mg/kg (oral) |
Blood glucose, glycosylated hemoglobin HbA1c, BUN, urea, serum creatinine, SGOT/AST, SGPT/ALT, alkaline phosphatase, total bilirubin, TGs, LDL-C, TC, and HDL-C NBT assay, carbonyl content, reduced GSH | [89,90,91,92] | ||
| Hepatoprotection | Attenuation of nephrotoxicity | Not described | Plasma urea, creatinine, urinary N-acetyl-β-D-glucosaminidase, creatinine and lithium, histomorphology evaluation | [93] |
| Reduction of hepatocyte damage | 50–200 mg/kg (intraperitoneal injection) |
Hepatic lipid peroxidation assayed by measuring malondialdehyde | [94] | |
| 1–100 μgM | ROS, MDA, GSH, GSH-Px, ALT, AST, SOD, TGF-β1, HGF | [71] | ||
| Nephroprotection | Prevention of cisplatin induced nephrotoxicity by reducing oxidative stress | 5–30 mg/kg (intraperitoneal injection) |
Blood urea nitrogen, plasma glutathione peroxidase, plasma creatinine quantification, N-acetyl-β-D-glucosaminidase, apoptosis and histopathological changes; glutathione, malondialdehyde, 4-hydroxynonenal, and oxidized proteins quantification | [95] |
| Protection of Type 2 diabetes mice against oxidative stress and renal dysfunction | 300 mg/kg (oral) |
Urinary 8-hydroxy-2-deoxyguanosine, 8-iso-prostaglandin F2α and albumin quantification; immunohistochemistry | [96] | |
| Recovery of cisplatin-induced renal injury in renal tissue and HK-2 cell and reduction of p-ERK, p-JNK, p-p38, Bax, caspase-9, and caspase-3 | 50 mg/kg (intraperitoneal injection) |
Light microscopy examination, cell viability Assay, western blot, caspase-3 activity assay, and apoptosis detection by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling method | [97] | |
| Cardiovascular protection | Reduction of atherosclerotic disease | 200 μM | HMOX-1, eNOS, P22, VCAM-1 | [98] |
| Prevention of AMI-induced oxidative stress, inflammation and heart damage | 50 mg/kg (subcutaneous injection) |
CK, AST, ALT, ROS, nitrites, oxidized glutathione, pro-inflammatory and proapoptotic cytokines, lipid peroxidation | [99] | |
| Prevention of cardiovascular diseases and atherosclerotic formation | 0.25% and 1.25% (oral) |
Cholesterol, MDA, GOT, GPT, catalase, SOD, GSH-Px, HMG CoA | [100] | |
| Anti-obesity | Prevention of endothelial dysfunction and attenuation of obesity | 2500, 5000, or 10,000 mg/kg (oral) |
Serum triglyceride, total cholesterol, HDL-C, and glucose, insulin and leptin, immunohistochemistry analysis | [101] |
| Reduction of adipogenesis and lipogenesis | 0, 0.625, 1.25, 2.5, 5, 10, or 20 μg/mL (oral) |
Western blots of adipogenic proteins (C/EBPα, PPARγ, and aP2) and lipogenic proteins (SREBP1, ACC, FAS, LPAATβ, Lipin1, and DGAT1) | [102] | |
| Wound healing |
Proliferation of fibroblasts, synthesis of ECM components and regeneration | 10–200 μg/mL (superficial collagen films) 50 μg/mL |
Cytotoxicity and proliferation/viability of fibroblasts, cdK1, cdK2, uPA, PI3K, and in vivo wound healing analysis | [103,104] |
| Antimelanogenic | Attenuation of melanin production | Not described | Cellular tyrosinase, production of melanin, DPPH | [105] |
| 0.05–2.00 mg/mL | Tyrosinase activity, melanin, intracellular cAMP, MITF, tyrosinase, ERK, pERK1/2, MEK1/2, p38, CREB | [106] |
ABTS: 2,2′-azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid), ACC: acetyl-CoA carboxylase, ALT: alanine transaminase, APP: amyloid precursor protein, aP2: adipocyte protein 2, ALT: alanine transaminase, AST: aspartate transaminase, BACE: β-site APP-cleaving enzyme, BALF: bronchoalveolar lavage fluid, BDNF: brain-derived neurotrophic factor, BUN: blood urea nitrogen, cAMP: Cyclic adenosine monophosphate, cdK: cyclin-dependent kinases, C/EBPα: CCAAT/enhancer-binding protein alpha, ChAT: choline acetyltransferase, CK: creatine kinase, COX: cyclooxygenase, CREB: cAMP-response element binding protein, DCF: 2,7-dichlorofluorescein, DCFDA: 2′,7′-dichlorodihydrofluorescein diacetate, DGAT: diacylglycerol acyltransferases, DPPH: α, α, diphenyl-β-picrylhydrazyl, ECM: extracellular matrix, EIA: enzyme immunoassay, ELISA: enzyme-linked immunosorbent assay, EMT: epithelial-mesenchymal transition, eNOS: endothelial nitric oxide synthase, ERK: extracellular signal-regulated protein kinases, FAS: fatty acid synthase, FRAP: ferric reducing antioxidant power, GOT: glutamate-oxaloacetate transaminase, GPT: glutamate-pyruvate transaminase, GR: glutathione reductase, GSH: glutathione, GSH-Px: glutathione peroxidase, HDAC: histone deacetylase, HDL-C: high-density lipoprotein cholesterol, HGF: hepatocyte growth factor, HIF-1α: hypoxia-inducible factor 1-alpha, HMG CoA: 3-hydroxy-3-methylglutaryl-coenzyme A, HMOX: heme oxygenase, IL: interleukin, iNOS: inducible nitric oxide synthase, INS: insulin, IRS: insulin receptor substrate, LDH: lactate dehydrogenase, LDL-C: low-density lipoprotein cholesterol, LPAAT: lysophosphatidic acid acyltransferase, MBC: minimum bactericidal concentration, MDA: malondialdehyde, MIC: minimal inhibitory concentration, MITF: microphthalmia-associated transcription factor, MMP: matrix metalloproteinase, MPO: myeloperoxidase, NBT: nitro blue tetrazolium, NF-kB: nuclear factor-kappa B, NQO: NAD(P)H quinone oxidoreductase, PGE2: Prostaglandin E₂, PI3K/AKT: phosphatidylinositol-3-kinase/serine threonine protein kinase B, PPA: porcine pancreatic amylase, PPARγ; peroxisome proliferator-activated receptor gamma, PTEN: phosphatase and tensin homolog, qRT-PCR quantitative real-time-polymerase chain reaction, ROS: reactive oxygen species, SGOT/AST: serum glutamic oxaloacetic transaminase/aspartate aminotransferase, SGPT/ALT: serum glutamic pyruvate transaminase/alanine aminotransferase, SOD: superoxide dismutase, SMA: smooth muscle actin, SREBP: sterol regulatory element-binding protein, TC: total cholesterol, TEM: transmission electron microscopy, TIMP: tissue inhibitor matrix metalloproteinase, TNF: tumor necrosis factor, TGs: triglycerides, TGF-β1: transforming growth factor-beta1, uPA: urokinase-type plasminogen activator, VCAM: vascular cell adhesion molecule, VEGF-A: vascular endothelial growth factor A, WB: western blot, 7-AAD: 7-amino-actinomycin D.