C-Phycocyanin Attenuates Noise-Induced Cochlear Synaptopathy via the Inhibition of Oxidative Stress and Intercellular Adhesion Molecule-1 in the Cochlea.

The synapses between inner hair cells (IHCs) and spiral ganglion neurons (SGNs) are the most vulnerable structures in the noise-exposed cochlea. Cochlear synaptopathy results from the disruption of these synapses following noise exposure and is considered the main cause of poor speech understanding in noisy environments, even when audiogram results are normal. Cochlear synaptopathy leads to the degeneration of SGNs if damaged IHC-SGN synapses are not promptly recovered. Oxidative stress plays a central role in the pathogenesis of cochlear synaptopathy. C-Phycocyanin (C-PC) has antioxidant and anti-inflammatory activities and is widely utilized in the food and drug industry. However, the effect of the C-PC on noise-induced cochlear damage is unknown. We first investigated the therapeutic effect of C-PC on noise-induced cochlear synaptopathy. In vitro experiments revealed that C-PC reduced the H2O2-induced generation of reactive oxygen species in HEI-OC1 auditory cells. H2O2-induced cytotoxicity in HEI-OC1 cells was reduced with C-PC treatment. After white noise exposure for 3 h at a sound pressure of 118 dB, the guinea pigs intratympanically administered 5 µg/mL C-PC exhibited greater wave I amplitudes in the auditory brainstem response, more IHC synaptic ribbons and more IHC-SGN synapses according to microscopic analysis than the saline-treated guinea pigs. Furthermore, the group treated with C-PC had less intense 4-hydroxynonenal and intercellular adhesion molecule-1 staining in the cochlea compared with the saline group. Our results suggest that C-PC improves cochlear synaptopathy by inhibiting noise-induced oxidative stress and the inflammatory response in the cochlea.

Hepatoprotective Effect Assessment of C-Phycocyanin on Hepatocellular Carcinoma Rat Model by Using Photoacoustic Spectroscopy.

Hepatocellular carcinoma (HCC) is the most common primary neoplasia of the liver with elevated mortality. Experimental treatment with antioxidants has a beneficial effect on the experimental models of HCC. Arthrospira maxima (spirulina) and its phycocyanin have antitumoral action on different tumoral cells. However, it is unknown whether phycocyanin is the responsible molecule for the antitumoral effect on HCC. Photoacoustic spectroscopy (PAS) stands out among other spectroscopy techniques for its versatility of samples analyzed. This technique makes it possible to obtain the optical absorption spectrum of solid or liquid, dark or transparent samples. Previous studies report that assessing liver damage in rats produced by the modified resistant hepatocyte model (MRHM) is possible by analyzing their blood optical absorption spectrum. This study aimed to investigate, by PAS, the effect of phycocyanin obtained from spirulina on hepatic dysfunction. The optical absorption spectra analysis of the rat blood indicates the damage level induced by the MRHM group, being in concordance with the carried out biological conventional studies results, indicating an increase in the activity of hepatic enzymes, oxidative stress, Bax/Bcl2 ratio, cdk2, and AKT2 expression results, with a reduction in p53 expression. Also, PAS results suggest that phycocyanin decreases induced damage, due to the prevention of the Bax, AKT2, and p53 altered expression and the tumor progression in a HCC rat model.

Assessment of the Anticancer Potentials of the Free and Metal-Organic Framework (UiO-66) - Delivered Phycocyanobilin.

Phycocyanin (C-PC) is a constitutive chromoprotein of Arthrospira platensis, which exhibits promising efficacy against different types of cancer. In this study, we cleaved C-PC's chromophore phycocyanobilin (PCB) and demonstrated its ability as an anti-cancer drug for Colorectal cancer (CRC). PCB displayed an anti-cancer effect for CRC (HT-29) cells with IC50 of 108 µg/ml. Assessing the transcripts levels of some biomarkers revealed that the PCB caused an upregulation in the anti-metastatic gene NME1 level and downregulation of the COX-2 level. The flow cytometric results showed the effect of PCB on the arrest of the cell cycle's G1 phase. In addition, we successfully synthesized the UiO-66 (Zr-MOF). We incorporated the PCB into UiO-66 nanoparticles with a loading percentage of 46 %. Assessment of the cytotoxic effects of UiO-66@PCB showed a 2-fold improvement in the IC50 compared to the free PCB. In conclusion, we have shown that PCB displayed a promising potential as an anti-cancer agent. Yet, it is considered a safe and natural substance that can help to mitigate cancer spread and symptoms. In the meantime, UiO-66 can be used as a safe nano-delivery tool for PCB.

Chitosan/Cellulose-Based Porous Nanofilm Delivering C-Phycocyanin: A Novel Platform for the Production of Cost-Effective Cultured Meat.

Cultured meat is artificial meat produced via the mass culture of cells without slaughtering livestock. In the production process of cultured meat, the mass proliferation for preparing abundant cells is a strenuous and time-consuming procedure requiring expensive and excess serum. Herein, C-phycocyanin (C-PC) extracted from blue algae was selected as a substitute for animal-derived serum and a polysaccharide film-based platform was developed to effectively deliver C-PC to myoblast while reducing the cost of cell medium. The polysaccharide platform has a sophisticated structure in which an agarose layer is capped on a porous multilayer film formed by molecular reassembly between chitosan and carboxymethylcellulose (CMC). The porous multilayer film provides an inner structure in which C-PC can be incorporated, and the agarose layer protects and stabilizes the C-PC. The completed platform was easily applied to a cell culture plate to efficiently release C-PC, thereby improving myoblast proliferation in a serum-reduced environment during long-term culture. We developed a cell sheet-based meat model using this polysaccharide platform to evaluate the improved cost-efficiency by the platform method in the mass proliferation of cells. This strategy and innovative technology can simplify the production system and secure price competitiveness to commercialize cultured meat.

Assessment of C-phycocyanin effect on astrocytes-mediated neuroprotection against oxidative brain injury using 2D and 3D astrocyte tissue model.

Drugs are currently being developed to attenuate oxidative stress as a treatment for brain injuries. C-phycocyanin (C-Pc) is an antioxidant protein of green microalgae known to exert neuroprotective effects against oxidative brain injury. Astrocytes, which compose many portions of the brain, exert various functions to overcome oxidative stress; however, little is known about how C-Pc mediates the antioxidative effects of astrocytes. In this study, we revealed that C-Pc intranasal administration to the middle cerebral artery occlusion (MCAO) rats ensures neuroprotection of ischemic brain by reducing infarct size and improving behavioral deficits. C-Pc also enhanced viability and proliferation but attenuated apoptosis and reactive oxygen species (ROS) of oxidized astrocytes, without cytotoxicity to normal astrocytes and neurons. To elucidate how C-Pc leads astrocytes to enhance neuroprotection and repair of ischemia brain, we firstly developed 3D oxidized astrocyte model. C-Pc had astrocytes upregulate antioxidant enzymes such as SOD and catalase and neurotrophic factors BDNF and NGF, while alleviating inflammatory factors IL-6 and IL-1ß and glial scar. Additionally, C-Pc improved viability of 3D oxidized neurons. In summary, C-Pc was concluded to activate oxidized astrocytes to protect and repair the ischemic brain with the combinatorial effects of improved antioxidative, neurotrophic, and anti-inflammatory mechanisms.