Exploiting Natural Niches with Neuroprotective Properties: A Comprehensive Review.

Natural products from mushrooms, plants, microalgae, and cyanobacteria have been intensively explored and studied for their preventive or therapeutic potential. Among age-related pathologies, neurodegenerative diseases (such as Alzheimer's and Parkinson's diseases) represent a worldwide health and social problem. Since several pathological mechanisms are associated with neurodegeneration, promising strategies against neurodegenerative diseases are aimed to target multiple processes. These approaches usually avoid premature cell death and the loss of function of damaged neurons. This review focuses attention on the preventive and therapeutic potential of several compounds derived from natural sources, which could be exploited for their neuroprotective effect. Curcumin, resveratrol, ergothioneine, and phycocyanin are presented as examples of successful approaches, with a special focus on possible strategies to improve their delivery to the brain.

Microbial Community Response to Granular Peroxide-Based Algaecide Treatment of a Cyanobacterial Harmful Algal Bloom in Lake Okeechobee, Florida (USA).

Cyanobacterial harmful algal blooms (cyanoHABs) occur in fresh water globally. These can degrade water quality and produce toxins, resulting in ecological and economic damages. Thus, short-term management methods (i.e., algaecides) are necessary to rapidly mitigate the negative impacts of cyanoHABs. In this study, we assess the efficacy of a hydrogen peroxide-based algaecide (PAK® 27) on a Microcystis dominated bloom which occurred within the Pahokee Marina on Lake Okeechobee, Florida, USA. We observed a significant reduction in chlorophyll a (96.81%), phycocyanin (93.17%), and Microcystis cell counts (99.92%), and a substantial reduction in microcystins (86.7%) 48 h after treatment (HAT). Additionally, there was a significant shift in bacterial community structure 48 HAT, which coincided with an increase in the relative abundance of photosynthetic protists. These results indicate that hydrogen peroxide-based algaecides are an effective treatment method for cyanoHAB control and highlight their effects on non-target microorganisms (i.e., bacteria and protists).

C-phycocyanin improves the developmental potential of cryopreserved human oocytes by minimizing ROS production and cell apoptosis.

PURPOSE: The cryopreservation process damages oocytes and impairs development potential. As a potent antioxidant, C-phycocyanin (PC) regulates reproductive performance. However, its beneficial effects on vitrified human oocytes remain unknown. METHODS: In this study, human GV-stage oocytes obtained from controlled ovarian hyperstimulation (COH) cycles were randomly allocated to three groups: fresh oocyte without freezing (F group), vitrification in medium supplemented with PC (P group), and vitrification in medium without PC as control group (C group). After warming, viable oocytes underwent in vitro maturation. RESULTS: Our results showed that 3 µg/mL PC treatment increased the oocyte maturation rate after cryopreservation. We also found that PC treatment maintains the regular morphological features of oocytes. After PC treatment, confocal fluorescence staining showed a significant increase in the mitochondrial membrane potential of the vitrified oocytes, along with a notable decrease in intracellular reactive oxygen species and the early apoptosis rate. Finally, after in vitro maturation and parthenogenetic activation, vitrified oocytes had a higher potential for cleavage and blastocyst formation after PC treatment. CONCLUSION: Our results suggest that PC improves the developmental potential of cryopreserved human GV-stage oocytes by attenuating oxidative stress and early apoptosis and increasing the mitochondrial membrane potential.

The synergistic effect of dielectric barrier discharge plasma and phycocyanin on shelf life of Oncorhynchus mykiss rainbow fillets.

This study aimed to evaluate the efficacy of dielectric barrier discharge treatment (DBD) combined with phycocyanin pigment (PC) in extending the shelf life of Oncorhynchus mykiss rainbow fillets stored at 4 ± 0.1 °C. Microbiological, physicochemical, sensory and antioxidant properties were assessed over an 18-day storage period. The combined DBD and PC treatment significantly inhibited total viable counts and Psychrotrophic bacteria counts compared to the rest of the samples throughout storage. While Total Volatile Nitrogen concentrations remained below international standard until day 18, they exceeded this threshold in control sample by day 9. DBD treatment notably reduced Trimethylamine levels compared to controls (p < 0.05). PC and DBD combined inhibited DPPH and ABTS radical scavenging capacities by 80% and 85%, respectively, while demonstrating heightened iron-reducing antioxidant activity compared to controls. Analysis of 24 fatty acids indicated that PC mitigated DBD's adverse effects, yielding superior outcomes compared to controls. The ratio of n-3 to n-6 fatty acids in all samples met or fell below international standard. Thus, the combined use of DBD and PC shows promise in extending fillet shelf life by over 15 days at 4 °C.

Unraveling the Anti-Aging Properties of Phycocyanin from the Cyanobacterium Spirulina (Arthrospira platensis).

In recent years, marine natural products have become one of the most important resources of novel lead compounds for critical diseases associated with age. Spirulina, a dietary supplement made from blue-green algae (cyanobacteria: scientific name Arthrospira platensis), is particularly rich in phycocyanin, a phycobiliprotein, which accounts for up to 20% of this cyanobacterium's dry weight and is considered responsible for its anti-cancer, anti-inflammatory and antioxidant activities. Although the anti-aging activity of phycocyanin has been investigated, how exactly this compound works against aging remains elusive. The aim of our research is to use the yeast Saccharomyces cerevisiae as a model organism to investigate the anti-aging properties of phycocyanin from A. platensis. Our results show that phycocyanin has a powerful anti-aging effect, greatly extending the chronological life span of yeast cells in a dose-dependent way, as the effect was also pronounced when cells were grown in SD medium under calorie restriction conditions (0.2% glucose). Both ROS and accumulation of dead cells were followed by staining chronologically aged cells with dihydrorhodamine 123 (DHR123) and propidium iodide (PI). Interestingly, we found that most of the aged phycocyanin-treated cells, which were unable to form colonies, were actually ROS+/PI-. Finally, we show that the moment in which phycocyanin is added to the culture does not substantially influence its effectiveness in counteracting chronological aging.

C-Phycocyanin improves the quality of goat oocytes after in vitro maturation and vitrification.

In vitro maturation (IVM) and cryopreservation of goat oocytes are important for establishing a valuable genetic bank for domesticated female animals and improving livestock reproductive efficiency. C-Phycocyanin (PC) is a Spirulina extract with antioxidant, antiinflammatory, and radical scavenging properties. However, whether PC has positive effect on goat oocytes IVM or developmental competence after vitrification is still unknown. In this study, we found that first polar body extrusion (n = 293), cumulus expansion index (n = 269), and parthenogenetic blastocyst formation (n = 281) were facilitated by adding 30 µg/mL PC to the oocyte maturation medium when compared with the control groups and that supplemented with 3, 10, 100 or 300 µg/mL PC (P < 0.05). Although PC supplementation did not affect spindle formation or chromosome alignment (n = 115), it facilitated or improved cortical granules migration (n = 46, P < 0.05), mitochondria distribution (n = 39, P < 0.05), and mitochondrial membrane potential (n = 46, P < 10-4). Meanwhile, supplementation with 30 µg/mL PC in the maturation medium could significantly inhibit the reactive oxygen species accumulation (n = 65, P < 10-4), and cell apoptosis (n = 42, P < 0.05). In addition, PC increased the oocyte mRNA levels of GPX4 (P < 0.01), and decreased the mRNA and protein levels of BAX (P < 0.01). Next, we investigated the effect of PC supplementation in the vitrification solution on oocyte cryopreservation. When compared with the those equilibrate in the vitrification solution without PC, recovered oocytes in the 30 µg/mL PC group showed higher ratios of normal morphology (n = 85, P < 0.05), survival (n = 85, P < 0.05), first polar body extrusion (n = 62, P < 0.05), and parthenogenetic blastocyst formation (n = 107, P < 0.05). Meanwhile, PC supplementation of the vitrification solution increased oocyte mitochondrial membrane potential (n = 53, P < 0.05), decreased the reactive oxygen species accumulation (n = 73, P < 0.05), promoted mitochondria distribution (n = 58, P < 0.05), and inhibited apoptosis (n = 46, P < 10-3). Collectively, our findings suggest that PC improves goat oocyte IVM and vitrification by reducing oxidative stress and early apoptosis, which providing a novel strategy for livestock gamete preservation and utilization.

Effects of the algae derivatives on performance, intestinal histomorphology, ileal microflora, and egg yolk biochemistry of laying Japanese quail.

We examined the effect of the Persian Gulf algae derivates, phycocyanin (PC) and fucoidan (FUC), on production performance, egg quality, intestinal histomorphology, ileal microflora, and egg yolk biochemistry of laying Japanese quail. A total of 250 six-wk-old Japanese quails with an average body weight of 215 ± 10 g were allocated to 5 treatments, 5 replicates and 10 birds in each replicate in a completely randomized design. The treatment groups received PC (from Spirulina platensis) and FUC (from brown seaweed) in their drinking water while control groups did not. Treatment groups received PC and FUC at 20 or 40 mg/L levels (denoted as PC20, PC40, FUC20, and FUC40, respectively). All birds were fed the same diet. All treatments significantly improved the percentage of hen day egg production (HDEP) (P = 0.002), egg mass (P = 0.002), and feed conversion ratio (FCR) (P = 0.022) but no difference was noted in egg weight (EW) and feed intake (FI). Different levels of PC and FUC significantly increased the thickness of eggshells (P = 0.022); however, the weight of the digestive tract (liver, spleen, proventriculus, gizzard, and pancreas) and oviduct was not affected. Algal derivates improved the villus height (P = 0.007) and crypt depth (P = 0.007) of the duodenum, as well as, the villus height (P = 0.005) and crypt depth (P = 0.026) of the jejunum. Both algal derivates positively affected the intestinal microflora (populations of Lactobacillus (P = 0.017), Coliform (P = 0.005), and Clostridium (P = 0.000)) whereas aerobic bacteria were unaffected. Yolk cholesterol P = 0.012) and yolk malondialdehyde P = 0.050) content were significantly reduced in experimental treatments compared to the control group. In conclusion, our results showed that the treatment of laying Japanese quails with algal derivates positively affects quail performance, intestinal morphology, intestinal microflora, and yolk cholesterol and malondialdehyde. Additional studies exploring optimal dosages and mechanisms of action is warranted to fully understand the scope of the algae derivates in poultry production.

Collagen/chitosan/genipin hydrogel loaded with phycocyanin nanoparticles and ND-336 for diabetic wound healing.

Diabetic wound healing remains a healthcare challenge due to the overexpression of matrix metalloproteinase-9 (MMP-9) and the imbalance between angiogenic factors and vascular inhibitory factors. In this study, we developed a nanocomposite injectable collagen/chitosan hydrogel for the treatment of delayed diabetic wound healing, which can promote cell migration to the wound site (through the addition of phycocyanin) and reduce the expression of MMP-9 (through the use of ND-336) to improve the therapeutic effect of diabetic wound healing. Furthermore, different weight ratios of collagen and chitosan hydrogels were prepared to select the hydrogel with proper mechanical properties. In vitro experiments confirmed that all hydrogels have favorable biocompatibility and hemocompatibility. Notably, Gel 2, with a weight ratio of collagen and chitosan at 25:75, was found to have an excellent capability to facilitate cell migration and in vivo studies further proved that Gel 2 nanocomposite hydrogel had the best ability to improve diabetic wound healing by promoting cell migration and decreasing MMP-9 expression. The collagen/chitosan/genipin hydrogel loaded phycocyanin and ND-336 can be harnessed for non-toxic and efficient treatment of wound healing management of diabetes.

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.

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.

Cooperative antioxidative defense of the blue-green alga Arthrospira (Spirulina) platensis under oxidative stress imposed by exogenous application of hydrogen peroxide.

Hydrogen peroxide (H2O2) is an environmentally-safe algaecide used to control harmful algal blooms and as a disinfectant in various domestic and industrial applications. It is produced naturally in sunny-water or as a by-product during growth, and metabolism of photosynthetic organisms. To assess the impact of H2O2 on Arthrospira platensis, several biochemical components, and antioxidant enzymes were analysed. The growth and biomass of A. platensis were decreased under the effect of H2O2. Whereas, the concentration up to 40 µM H2O2 non-significantly induced (at P < 0.05) the Chl a, C-phycocyanin (C-PC), total phycobiliprotein (PBP), and the radical scavenging activity of A. platensis. The half-maximal effective concentrations (EC50) for H2O2 were 57, 65, and 74 µM H2O2 with regards to the biomass yield, Chl a, and C-PC content, respectively. While, the total soluble protein, and soluble carbohydrates contents were significantly induced. However, the higher concentrations (60 and 80 µM) were lethal to these components, in parallel to the initiation of the lipid peroxidation process. Surprisingly, the carotenoids content was non-significantly increased by H2O2. Despite the relative consistency of catalase (CAT), the activities of superoxide dismutase (SOD) and peroxidase (POD) enzymes were boosted by all of the tested concentrations of H2O2. The relative transcript abundance of selected regulatory genes was also investigated. Except for the highest dose (80 µM), the tested concentrations had almost inhibitory effect on the relative transcripts of heat shock protein (HSP90), glutamate synthase (GOGAT), delta-9 desaturase (desC), iron-superoxide dismutase (FeSOD) and the Rubisco (the large subunit, rbcL) genes. The results demonstrated the importance of the non-enzymatic and enzymatic antioxidants for the cumulative tolerance of A. platensis.

Effect of C-phycocyanin purified from Spirulina platensis on cooled ram semen quality and in vivo fertility.

This research sought to purify C-phycocyanin (C-PC) from Spirulina platensis and investigate its potential in enhancing the quality parameters and in vivo fertility of ram semen subjected to cooled storage at 5 °C, when using a skim milk (SM) based semen extender. The purification process of C-PC involved cold maceration, pre-purification using chitosan and activated charcoal, followed by purification through aqueous two-phase extraction (ATPE) and ion-exchange chromatography. Afterward, fifty ejaculates were collected from 4 fertile Boujaâd rams and extended using the SM extender at 37 °C, enriched with 0 µg/mL (control), 1.2 µg/mL, 2.4 µg/mL, 3.6 µg/mL, or 4.8 µg/mL of C-PC. The diluted semen was subsequently cooled to 5 °C using a controlled cooling process, with a gradual cooling rate of approximately 0.5 °C per minute, and its quality parameters were evaluated after 0, 4, 8, and 24 h of cooling storage. Then, its fertilization ability after 4 h of cooling storage was evaluated using artificial insemination. The adopted purification process yielded a grade analytical purity of 4.06. Additionally, semen extended in SM with a 2.4 µg/mL C-PC supplement displayed significant (P < 0.0001) enhancement in total motility, progressive motility, curvilinear velocity, straight-line velocity, average path velocity, viability and lipid peroxidation of ram semen at 0, 4, 8, and 24 h of cooling storage. These improvements were observed in direct comparison to both the control group and the other C-PC concentrations. Regarding fertility rates, semen extended in SM with a 2.4 µg/mL C-PC recorded a 76 % rate, a notable increment from the 63 % observed in ewes inseminated by semen extended in SM alone, although the difference was not statistically significant (p > 0.05). These findings underscore the promising potential of C-PC as a natural supplement for enhancing semen quality, warranting further investigations.

Selenium enhances photodynamic therapy of C-phycocyanin against lung cancer via dual regulation of cytotoxicity and antioxidant activity.

As a natural photosensitizer, phycocyanin (PC) has high efficiency and uses low-intensity irradiation. To enhance the photodynamic therapy (PDT) of PC, we extract selenium-enriched phycocyanin (Se-PC) from Se-enriched Spirulina platensis and examine the synergistic effect of PC combined with selenium against lung tumors. In vitro experiments reveal that Se-PC PDT more efficiently reduce the survival rate of mouse lung cancer cells (LLC cell line) than PC PDT treatment by increasing the level of ROS and decreasing the level of GPx4, which is confirmed by the Chou-Talalay assay. In vivo imaging system analysis reveal that tumor volume is more markedly decreased in both the Se-PC PDT and PC PDT plus Na 2SeO 3 groups than in the PC PDT group, with inhibition rates reaching 90.4%, 68.3% and 53.1%, respectively, after irradiation with 100 J/cm 2 laser light at 630 nm. In normal tissues, Se-PC promotes the synthesis of antioxidant enzymes and the immune response by the IL-6/TNF-α pathway against tumor proliferation and metastasis. Using Se-PC as a photosensitizer in tumors, apoptosis and pyroptosis are the primary types of cell death switched by Caspases-1/3/9, which is confirmed by TEM. Based on the transcriptome analysis, Se-PC PDT treatment inhibits angiogenesis, regulates inflammation by the HIF-1, NF-κB and TGF-ß signaling pathways and dilutes tumor metabolism by reducing the synthesis of glucose transporters and transferrin. Compared to PC PDT, Se-PC increases the expression levels of some chemokines in the tumor niche, which recruits inflammatory cells to enhance the immune response. Our study may provide evidence for Se-PC as an effective photosensitizer to treat lung cancer.

Osteogenic differentiation of human amniotic mesenchymal stem cells by phycocyanin and phycoerythrin pigments isolated from Spirulina platensis and Gracilaria gracilis algae.

Bone regeneration is a multistep and regular physiological process that occurs normally in fracture repair and bone defects. However, some factors such as aging, particular diseases and some drugs prevent or slowdown bone natural healing. Cell therapy using stem cells and differentiation activating factors is an effective treatment method for bone regeneration triggering in unusual conditions. Therefore, in the present study the effect of phycocyanin and phycoerythrin pigments which isolated from Spirulina platensis and Gracilaria gracilis algae was investigate on osteogenic differentiation potency of human Amniotic Mesenchymal Stem Cells (hAMSCs). For this purpose, hAMSCs were exposed to 300, 500, and 700 µg/ml concentrations of phycocyanin and phycoerythrin pigments and then the cells viability was measured with MTT assay in 48 and 72 h after treatment. The osteo-differentiation level of cells was studied by measuring ALP activity using calorimetric method and Alizarin red staining for calcium deposition in 7 and 21 days after treatment. Also, total RNA of cells was extracted in different time periods and then cDNA synthesized with specific primers, and relative expression of Runx2, ß-catenin and Osteocalcin genes were investigated using SYBR Green RT-qPCR technique. Osteogenic differentiation of hAMSCs that treated with pigments was confirmed by mineral deposits staining and increased level of ALP activity. Furthermore, these pigments elevated significantly the expression of osteogenic marker genes compared to control samples and caused hAMSCs to differentiate into osteoblast cells. According to these results, phycocyanin and phycoerythrin may suggest as suitable osteogenic supplements with low toxicity, low cost and high efficiency, although the molecular mechanism of its efficacy is not available yet.

Phycocyanin as a nature-inspired antidiabetic agent: A systematic review.

BACKGROUND: Nutraceuticals have been important for more than two decades for their safety, efficacy, and outstanding effects. Diabetes is a major metabolic syndrome, which may be improved using nutritional pharmaceuticals. Some microalgae species, such as spirulina, stand out by providing biomass with exceptional nutritional properties. Spirulina has a wide range of pharmacological effects, mostly related to phycocyanin. Phycocyanin is a protein compound with antidiabetic properties, known as a nutraceutical. OBJECTIVE: This review delves into phycocyanin applications in diabetes and its complications and ascertains the mechanisms involved. METHODS: Scopus, PubMed, Cochrane Library, Web of Science, and ProQuest databases were systematically reviewed (up to April 30, 2023), in which only animal and cellular studies were found. RESULTS: According to animal studies, the administration of phycocyanin affected biochemical parameters (primary outcome) related to diabetes. These results showed an increase in fasting insulin serum and a decrease in fasting blood glucose, glycosylated serum protein, and glycosylated hemoglobin. In cellular studies, though, phycocyanin prevented methylglyoxal and human islet amyloid polypeptide-induced dysfunction in ß-cells and induced apoptosis through different molecular pathways (secondary outcome), including activation of Nrf2, PI3K/Akt, and suppression of JNK and p38. Also, phycocyanin exerted its antidiabetic effect by affecting the pathways regulating hepatic glucose metabolism. CONCLUSIONS: Thus, based on the available information and literature, targeting these pathways by phycocyanin may unleash an array of benefits, including positive outcomes of the antidiabetic effects of phycocyanin as a nutraceutical. OTHER: This systematic review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) at the National Institute of Health. The registration number is CRD42022307522.

R-phycocyanin from porphyra haitanensis influences drosophila melanogaster lifespan in a sex-specific manner.

Aging has become a major global public health challenge. Our previous research showed that R-phycocyanin (R-PC) possessed anti-aging activity. Notably, studies already revealed that gender may affect the responses to the anti-aging drug. Therefore, it is worth investigating whether the anti-aging effects and their underlying molecular mechanisms of R-PC differ between genders. Firstly, R-PC was isolated from porphyra haitanensis and its anti-aging mechanisms were explored using the nature aging male and female drosophila melanogaster as model. Next, the regulation pathway of longevity was analyzed by KEGG pathway analysis. The longevity pathways-associated molecules were also examined to explore anti-aging mechanisms of R-PC. The results showed that R-PC increased AMPK activity, thus enhanced the key regulatory factors of autophagy (Atg1, Atg8, Atg5), and consequently induced autophagy. Hence, the longevity activity of R-PC life was related with AMPK/mTOR/S6K autophagic signaling pathways in aging female drosophila melanogaster. Meanwhile, R-PC significantly down-regulated TNF-α, MMP3, IL-1ß, IL-6, IL-8 expression levels, and the anti-inflammatory and longevity was associated with R-PC-induced regulation of pI3k/AKT/FOXO3 signaling pathway in aging male drosophila melanogaster. These finding showed that R-PC from porphyra haitanensis might exert the anti-aging actions via different mechanisms in male and female drosophila melanogaste.

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.

Mechanisms of action of non-enzymatic antioxidants to control oxidative stress during in vitro follicle growth, oocyte maturation, and embryo development.

In vitro follicle growth and oocyte maturation still has a series of limitations, since not all oocytes matured in vitro have the potential to develop in viable embryos. One of the factors associated with low oocyte quality is the generation of reactive oxygen species (ROS) during in vitro culture. Therefore, this review aims to discuss the role of non-enzymatic antioxidants in the control of oxidative stress during in vitro follicular growth, oocyte maturation and embryonic development. A wide variety of non-enzymatic antioxidants (melatonin, resveratrol, L-ascorbic acid, L-carnitine, N-acetyl-cysteine, cysteamine, quercetin, nobiletin, lycopene, acteoside, mogroside V, phycocyanin and laminarin) have been used to supplement culture media. Some of them, like N-acetyl-cysteine, cysteamine, nobiletin and quercetin act by increasing the levels of glutathione (GSH), while melatonin and resveratrol increase the expression of antioxidant enzymes and minimize oocyte oxidative stress. L-ascorbic acid reduces free radicals and reactive oxygen species. Lycopene positively regulates the expression of many antioxidant genes. Additionally, L-carnitine protects DNA against ROS-induced damage, while acteoside and laminarin reduces the expression of proapoptotic genes. Mogrosides increases mitochondrial function and reduces intracellular ROS levels, phycocyanin reduces lipid peroxidation, and lycopene neutralizes the adverse effects of ROS. Thus, it is very important to know their mechanisms of actions, because the combination of two or more antioxidants with different activities has great potential to improve in vitro culture systems.

The Cyanobacterial "Nutraceutical" Phycocyanobilin Inhibits Cysteine Protease Legumain.

The blue biliprotein phycocyanin, produced by photo-autotrophic cyanobacteria including spirulina (Arthrospira) and marketed as a natural food supplement or "nutraceutical," is reported to have anti-inflammatory, antioxidant, immunomodulatory, and anticancer activity. These diverse biological activities have been specifically attributed to the phycocyanin chromophore, phycocyanobilin (PCB). However, the mechanism of action of PCB and the molecular targets responsible for the beneficial properties of PCB are not well understood. We have developed a procedure to rapidly cleave the PCB pigment from phycocyanin by ethanolysis and then characterized it as an electrophilic natural product that interacts covalently with thiol nucleophiles but lacks any appreciable cytotoxicity or antibacterial activity against common pathogens and gut microbes. We then designed alkyne-bearing PCB probes for use in chemical proteomics target deconvolution studies. Target identification and validation revealed the cysteine protease legumain (also known as asparaginyl endopeptidase, AEP) to be a target of PCB. Inhibition of this target may account for PCB's diverse reported biological activities.