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Oxidative stress and damage to macromolecules due to free radicals such as reactive oxygen species (ROS) are commonly considered factors that can impair health. This study investigated the potential antioxidant properties of of two subunit proteins associated with the pigment-protein complex phycocyanin derived from Nostoc sphaeroides (Gexianmi). Bacterial expression vectors were separately constructed to induce the two engineering subunit proteins, Ns-α and Ns-β. These engineering proteins were then examined for their potential to enhance antioxidative capacity in Caenorhabditis elegans . Firstly, a proper concentration of the proteins Ns-α and Ns-β in vitro exhibited 2, 2-azino-bis 3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging activity. Secondly, while there were no other observed effects on the nematodes, those treated with the proteins showed significant improvements in motility and reduced levels of lipofuscin compared to the control group. Furthermore, thirdly, the treated nematodes demonstrated increased resistance to oxidation, as evidenced by the higher survivals under oxidative conditions induced by 5 mM H 2 O 2 . Notably, the treated nematodes exhibited decline in endogenous ROS levels, and the redox-related genes, such as SOD-3 and CAT-1 , were down-regulated following consumption of the engineering proteins. Taken together, these findings suggest that engineering proteins Ns-α and Ns-β improve the antioxidative capacity of C. elegans by modulating ROS-related regulation, making them potential modulators in responding to oxidative stressors., Competing Interests: The authors declare that they have no competing interests., (© 2025 Wu et al.)

The study aimed to investigate the stability and anti-allergic efficacy of phycocyanin through the construction of microcapsules. Phycocyanin (PC), a blue pigment found in microalgae, has attracted significant attention due to its anti-allergic properties. However, it is susceptible to instability when exposed to light, heat, and changes in pH. To address this issue, phycocyanin microcapsules were prepared using sodium alginate (SA), calcium chloride and chitosan (CS) as wall materials. The structures of microcapsules were carried out using scanning electron microscopy (SEM), fourier transform infrared spectroscopy, and particle size measurements that confirmed the successful encapsulation of PC within the microcapsules. The optimal effect was achieved when the mass ratio of PC to SA was 1:3, resulting in an embedding rate of 70.92 %. Stability studies shown that phycocyanin microcapsules exhibited the highest pigment retention rate under conditions of pH 6, darkness and a temperature of 37 °C. Furthermore, in vivo testing on mouse revealed a strong anti-allergic effect. These findings indicate that microcapsules prepared with phycocyanin as the core material exhibit high stability and a favorable anti-allergic effect, suggesting significant potential. This study serves as a reference for the further development of anti-allergic foods that can effectively prevent or alleviate food allergies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Hydrogels have attracted extensive attention as wound dressing owing to their excellent multifunctionality, flexibility, and biocompatibility. Due to the frequent movement and stretching of skin as well as complex surface of wound, traditional wound dressings have difficulty to adapt to motion and irregular wounds. Furthermore, excessive reactive oxygen species (ROS) and bacterial infection can induce delayed wound healing. To this end, we developed a set of versatile phycocyanin-based dual network hydrogels (PPC hydrogels) with polyvinyl alcohol (PVA) and κ-carrageenan (CRG) as substrate via forming of borate ester bonds, hydrogen bonds, and electrostatic interaction. The PPC hydrogels not only possessed adaptivity, ultra-stretchability (7036.12 %), efficient self-healing and injectability, but also possessed antioxidative and antibacterial capacities conferred by C-phycocyanin (PC) and rhein. Moreover, the hydrogels also exhibited excellent hemostatic ability and high biocompatibility. More remarkably, the PPC-I hydrogel could accelerate wound healing by effect of anti-inflammation (downregulating TNF-α and IL-6) and promoting collagen deposition and angiogenesis (upregulating CD31), which may be utilized as hydrogel bandages and applied to motion and irregular wounds, thereby promising the application prospect of the hydrogels as wound dressing., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Physical activity, such as running, protects against cardiovascular disease and obesity but can induce oxidative stress. Athletes often consume antioxidants to counteract the overproduction of reactive oxygen and nitrogen species during exercise. Spirulina , particularly its phycocyanin content, activates the Nrf2 pathway, stimulating antioxidant responses. Studies show that phycocyanin enhances antioxidant defenses and reduces inflammation, potentially improving muscle adaptation and recovery. This study evaluates a Spirulina liquid extract (SLE) supplementation during endurance training, hypothesizing that phycocyanin improves oxidant status and performance in soleus and extensor digitorum longus muscles., Methods: Three-week-old male Wistar rats were divided into four groups: a sedentary control group (C), a sedentary group supplemented with SLE (SP), an endurance training group (T), and an endurance training group supplemented with SLE (SPT). After 8 weeks of treadmill training, blood and muscle were collected. Biochemical parameters and gene expression analyses were performed to assess the effects of training and supplementation., Results: The maximal aerobic speed improved significantly in the SPT group. Plasma lipid profiles showed a reduction in triglyceridemia, cholesterolemia, and atherogenic index in the trained groups, especially with SLE supplementation. Muscle malondialdehyde levels decreased in the SPT group compared to T. Gene expression analysis revealed upregulation of Nrf2 and mitochondrial biogenesis genes in both muscles, with differences between groups for genes related to glycogen storage and β-oxidation., Conclusions: This study demonstrated that SLE supplementation enhanced exercise performance and promoted muscle molecular adaptations. These findings suggest SLE as a promising functional food supplement for athletes, optimizing recovery and performance.

Although multifunctional drug delivery systems have shown significant potential in the treatment of diabetic nephropathy (DN), developing an efficient synergistic drug delivery strategy remains a major challenge. The purpose of this paper is to develop a nanoparticle-loaded microneedle (MN) patch transdermal drug delivery system aimed at achieving blood glucose control and reactive oxygen species (ROS) scavenging for the synergistic treatment of DN. MNs are composed of hyaluronic acid and phycocyanin (PC), both exhibiting excellent biocompatibility and degradation properties. Subsequently, insulin and celastrol (CEL)-based nanoparticles were incorporated into the MN to create the transdermal drug delivery platform (MN-IN&NPs). MN-IN&NPs can penetrate through the stratum corneum of skin and reach the dermis layer. Accompanied by the dissolution of MN, PC, insulin, and CEL-based NPs are continuously released. PC possesses anti-inflammatory and antioxidant properties that enable it to scavenge excessive ROS, thereby exerting synergistic effects alongside CEL nanoparticles. Furthermore, MN-IN&NPs significantly enhance drug transdermal delivery efficiency, while prolonging insulin's action duration. Therefore, MN-IN&NPs effectively integrate blood glucose control with ROS scavenging functions, presenting a promising therapeutic strategy for DN.

Radiation therapy is a primary modality for cancer treatment; however, it often leads to various degrees of skin injuries, ranging from mild rashes to severe ulcerations, for which no effective treatments are currently available. In this study, a multifunctional microsphere (PC@CuS-ALG) was synthesized by encapsulating phycocyanin-templated copper sulfide nanoparticles (PC@CuS) within alginate (ALG) using microfluidic technology. Phycocyanin, a natural protein derived from microalgae, shows abilities to scavenge reactive oxygen species, repair radiation-induced damage to skin cells, and ameliorate macrophage-related inflammatory responses. CuS contributes to photothermal conversion efficiency and exhibits antibacterial properties. The microspheres facilitate the sustained release of PC@CuS, retain moisture at the wound site, and provide a supportive environment for cell migration and growth. In a mouse model of infected radiation-induced skin injury, PC@CuS-ALG exhibited antibacterial and wound healing effects, resulting in accelerated epidermal tissue regeneration, increased thickness and maturation of dermal granulation tissue, and an ameliorated inflammatory response. This study presents a novel, effective, and safe approach for treating radiation-induced skin injuries complicated by bacterial infection., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Spirulina platensis (SP) provides humans with proteins and natural pigments. The effects of micro/nanoplastics (MNPs) on SP are of great interest. We focused on the effects of high concentrations (100-300 mg/L) of polystyrene MNPs on SP for 50 days. MNPs caused growth retardation, a decrease in peak concentration of algal cells, the emergence of surface cracks and pores, and stimulated the secretion of extracellular polymeric substances that promoted heterogeneous aggregation of SP. During the first 35 days, there were significant differences between the exposure groups in the phycocyanin concentration, yield and purity and the ratio of phycocyanin to phycobiliprotein, with the higher MNPs concentration resulting in lower values, whereas on day 50 there were no statistically significant differences in any of these metrics between the control or exposure groups. This study enriches the knowledge about the long-term effects of MNPs on SP for microalgae culture and food industry., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Hydrogels with antioxidant and antibacterial activities have received increasing attention in wound healing due to excessive reactive oxygen species (ROS) and bacterial infection are common issues associated with wounds. Herein, we constructed a series of hydrogels with C-phycocyanin (C-PC), quaternized chitosan (QCS) and silk fibroin protein (SF) as matrixes, which with tetrakis hydroxymethyl phosphonium sulfate (THPS) as crosslinking agent to form dynamic covalent bonds with C-PC and SF. The hydrogel exhibited excellent stretchability and compressibility, which with adhesion strength reached 15 ± 3 kPa and rapid self-healing properties. The hydrogel possessed strong antioxidant activity with assessments of DPPH radical-scavenging capacity and total reducing power. In addition, the hydrogel possessed obvious coagulation function and good blood compatibility, which also showed strong antibacterial activity against E. coli and S. aureus. To improve the therapeutic effect, polydeoxyribonucleotide (PDRN) with the ability of promote wound healing was introduced into the hydrogel. The results showed that the hydrogel loading with PDRN possessed high biocompatibility and can promote cell migration. More importantly, the hydrogel loaded with PDRN can effectively promote wound healing by exerting anti-inflammatory and antioxidant effects, which may offer promising potential application value in the field of wound dressing and tissue repair., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2025 Elsevier B.V. All rights reserved.)

In the present investigation, 13% ± 0.84 of the extracted and purified phycocyanin from Phormidium versicolor was obtained, with a purity of 0.69 following dialysis. FT-IR analysis of purified phycocyanin revealed stretching vibration peaks in the profiles of the functional groups of N-H, O-H, C = O, N-H, C = O, and C = NH + . The phycocyanin had a significant DPPH radical scavenging ability (IC 50  = 0.6 ± 0.02 mg mL -1 ) confirmed with FRAP assay, and it exhibited microbiological activity between 1.25 and 2.5 mg mL -1 against Candida albicans, Klebsiella pneumoniae, and Enterococcus faecalis. Phycocyanin showed no cytotoxic and improved the viability of HEK-293. It was added to skin cream at a rate of 6 mg g -1 because of its significant yield extraction and biological activity. At 10 mg mL -1 , a bactericidal activity has been noted, inhibiting the growth of bacteria responsible for inflammatory skin conditions. For 60 days, the emulsion's stability was monitored at room temperature, 25 °C, and 45 °C. The appearance of the batch kept at 45 °C was changed to beige after 7 days, while the others were kept for 15 days. Skin creams enhanced with phycocyanin were found to be stable over the course of storage at both room temperature and 25 °C, based on centrifugation stability analysis. But starting on the fifteenth day, the items kept at 45 °C were unstable. Thus, the current study's findings are in favor of using phycocyanin as an antioxidant in cosmetic products. However, further investigation is required before using it in clinical trials. KEY POINTS: • Phycocyanin extraction field (13%) is particularly significant compared to other cyanobacteria. • Phycocyanin at 0.6 μg g-1 in skin cream fights bacteria in skin inflammation. • Phycocyanin-enriched cream was stable at room temp, 25 °C, and unstable at 45 °C after day 15., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024. The Author(s).)

Background: Recently, the use of natural products as skin photoprotective agents has been in increasing demand. This study investigated the bioactivity of phycocyanin (PC) extracted from Spirulina sp. on human skin fibroblast cell line (CCD-966SK), specifically focusing on apoptosis, necrosis, anti-inflammatory effects, and enzymatic reactions., Methods: The first step of this study was cyanobacterial cell culture and the extraction and purification of PC. After that, CCD-966SK cell line was cultivated under normal and UV irradiation. The bioassays included the cytotoxicity measurement, cell viability assay, morphology determination, tumour necrosis factor-α and Interleukin 6 release assays, enzyme activity for superoxide dismutase and glutathione peroxidase as well as malondialdehyde content and the cell-free extract of cyanobacterial stains were assessed., Results: The cell viability results showed that as the concentration of the PC increased, the viability of CCD-966SK cell line was reduced, which suggested that the effect of PC on the growth of fibroblast cells was dose dependent. The morphological results indicated that presence of PC in the fibroblast cell culture medium led to a transformation in cell morphology from spindle-shaped to spherical. PC released anti-inflammatory IL-6 and TNF-a cytokines, indicating high inflammation resistance. Furthermore, the findings revealed that PC dramatically reduced the release of superoxide dismutase, glutathione peroxidase, and malondialdehyde from inflammatory cells, with the reduction being more apparent at increasing doses., Conclusions: In conclusion, the results indicated that PC inhibit the CCD-966SK cell line by membrane destructor, which led to the increase the leakage of cell constituent and increase enzymes activities.

Introduction: The prevention and treatment of chronic obstructive pulmonary disease (COPD) is closely tied to antioxidation and anti-inflammation. Phycocyanin (PC) has numerous pharmacological effects, such as antioxidation and anti-inflammation. However, it remains unclear whether PC can play a therapeutic role in COPD., Objective: As inflammation and oxidative stress can aggravate COPD, this study is to explore the effect of PC on COPD mice and its mechanisms., Methods: The COPD mice model was established by exposing them to lipopolysaccharide (LPS) and cigarette smoke (CS); PC was administrated in a concentration of 50 mg/kg for 30 days. On the last day, lung function was measured, and bronchoalveolar lavage fluid (BALF) was obtained and classified for cells. Lung tissue pathological change was analyzed, and organ indices statistics were measured. Based on molecular docking, the mechanism was explored with Western blotting, immunohistochemical, and immunofluorescence in vivo and in vitro., Results: PC significantly ameliorated the pulmonary function of COPD mice and reduced inflammation of the lung (p < 0.05), and hematoxylin and eosin (H&E) staining showed PC depressed lung inflammatory cell accumulation and emphysema. Periodic acid Schiff (PAS) and Masson staining revealed that PC retarded goblet cells metaplasia and collagen deposition (p < 0.05). In addition, in vivo PC regulated Heme oxygenase 1 (HO-1) (p < 0.05) and NAD(P)H dehydrogenase quinone 1 (NQO1) level (p < 0.01) in the lung, as well as NOX2 level in pulmonary macrophages. Molecular docking results indicate that phycocyanobilin (PCB) in PC had a good binding site in Keap1 and NOX2 proteins; the phycocyanobilin-bound phycocyanin peptide (PCB-PC-peptide) was obtained for further studies. In vitro, PCB-PC-peptide could depress the phospho-NF-E2-related factor 2 (p-Nrf2) and NQO1 protein expression in RAW264.7 cells induced by cigarette smoke extract (CSE) (p < 0.05)., Conclusion: PC exerts beneficial effects on COPD via anti-inflammatory and antioxidative stress, which may be achieved through PCB., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background: The aim of this study is to investigate the effect of antimicrobial photodynamic therapy (aPDT) using three different concentrations of phycocyanin and two different laser powers on Streptococcus mutans., Materials and Methods: In this study, Streptococcus mutans was investigated using three different concentrations of phycocyanin (2.5, 5, and 10 mg/mL), in the presence and absence of 635 nm diode laser at two power levels (400 and 500 mW). The treatments were as follows: the control group received no treatment. The next 3 groups received only the phycocyanin at 2.5, 5, and 10 mg/mL. The remaining groups received both phycocyanin and laser treatment. Finally, bacteria were counted using the colony forming units (CFUs)/mL method. Data analysis was performed using IBM SPSS 26 software and ANOVA statistical test., Results: All groups except for the phycocyanin group at a concentration of 10 mg/mL showed a statistically significant difference compared to the control group (p-Value < 0.05). Additionally, the least effect was observed in the control and the phycocyanin at a concentration of 10 mg/mL groups, while the greatest effect was found in the group receiving phycocyanin at 2.5 mg/mL concentration and laser with a power of 500 mW (2.5 + DL500)., Conclusion: aPDT can be used as a complementary and non-invasive method to reduce bacterial load. The effectiveness of aPDT decreased with increasing phycocyanin concentration. Moreover, higher laser irradiation power resulted in reduced Streptococcus mutans bacterial load. Thus, the most pronounced effects were observed in the group receiving phycocyanin at 2.5 mg/mL concentration and 635 nm diode laser with a power of 500 mW (2.5 + DL500)., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Damage to intestinal epithelial cells is present in obesity and other diseases because of inflammatory and oxidative processes. This damage compromises the gastrointestinal barrier, killing enterocytes, altering intestinal permeability, and eliciting abnormal immune responses that promote chronic inflammation. Recent evidence shows that spirulina is a potent natural agent with antioxidant and anti-inflammatory properties., Objectives: This study was conducted to evaluate the effect of spirulina aqueous extract (SPAE) on the alterations of the intestinal epithelium induced by lipid micelles (LMs) and/or inflammation induced by lipopolysaccharides (LPSs) in the Caco-2 cell line., Methods: In the current research, we assessed the protective actions of SPAE against cytotoxicity, oxidative stress, inflammation, and epithelial barrier perturbation by using an in vitro model, the intestinal Caco-2 cells, treated with LPSs and/or LMs. We also performed an in silico molecular docking analysis with spirulina's bioactive compound, phycocyanobilin., Results: Our results showed that SPAE has no cytotoxic effect on Caco-2 cells. On the contrary, it improved cell viability and exhibited anti-inflammatory and antioxidant actions. SPAE also protected against endoplasmic reticulum stress and tight junction proteins, thus improving the epithelial barrier. The in silico study revealed a strong binding affinity of the phycocyanobilin compound with human SOD and NADPH oxidase and a good binding affinity towards COX-2 and iNOS., Conclusions: Taken together, these findings demonstrate the beneficial actions of SPAE on Caco-2 cells, suggesting it may be useful in preserving the epithelial intestinal barrier in human conditions involving oxidative stress and inflammation such as obesity.

Cyanobacterial phycobiliproteins, such as phycoerythrin (PE) and phycocyanin (PC), are colored potential bioactive proteins that have antioxidant and antimicrobial properties. In this study, we formulated a new food prototype based on PE and PC-fortified low-fat yogurt and cream cheese. Four distinct low-fat yogurt and cream cheese products were manufactured, including a control group (No PE and PC), samples produced with phycoerythrin (+ PE), samples produced with phycocyanin (+ PC), and samples produced with both phycoerythrin and phycocyanin (PC + PE). Afterwards statistically compared the physicochemical composition, colorimetric properties, antioxidant and antimicrobial activities, and sensory profile of the fortified foods at 4 °C and 8 °C for 28 and 42 days. Additionally, we confirmed that PE and PC are not toxic to Caenorhabditis elegans at concentrations up to 1 mg/mL. The results showed that the MIC of PE and PC against E. coli was significantly higher than against S. aureus (3.12 ± 0.05 µg/mL vs. 1.56 ± 0.01 µg/mL, respectively; p ≤ 0.05). Additionally, the maximum diameter of the inhibition zone of PE and PC against S. aureus was significantly higher than against E. coli (6.6 ± 0.011 mm vs. 11.66 ± 0.02 mm, respectively; p ≤ 0.05). Results of color parameters showed that the control group had significantly higher L* values than the samples enriched with PE and PC. Moreover PE and PC significantly increased the a* and b* values respectively. The amount of ΔE in the control yogurts and cream cheese was higher than in the samples with PE and PC. Overall, the results showed that adding PE and PC had a significant effect on all measured factors (p < 0.01). Cream cheeses and low-fat yogurts enriched with either PE or PE + PC had the greatest antioxidant activity and the lowest number of psychrophilic bacteria and mold, and yeast counts at the end of the test period. Therefore, low-fat yogurt and cream cheese containing cyanobacterial PE and PC can be considered an innovative dairy product for the food industry. This study marks the initial effort to employ PE and PC derived from Nostoc sp. and Spirulina sp. as antioxidant and antimicrobial agents in the food industry., Competing Interests: Competing interests The authors declare no competing interests. Ethical statement All methods were carried out following relevant guidelines and regulations. The authors did not do any experiments on humans and/or the use of human tissue samples. All experimental protocols and panelists involved in the study were approved by the ethics committee of Tehran Medical Sciences, Islamic Azad University, Tehran, Iran. Participants gave their consent to take part and use their information. The full name of the ethics committee that approved the study is Dr Fahimeh Nemati and Dr Sarvenaz Falsafi., (© 2024. The Author(s).)

The P53 gene is commonly mutated in breast cancer, protein based the gene as anticancer drugs could provide efficient and stable advantages by restoring the function of the wild-type P53 protein. In this study, we describe the creation and utilization of a micelle composed by natural phycocyanin and paclitaxel and grafting anti-HER2 (PPH), which effectively packages and transports recombinant P53 protein with anti-ER (PE), resulting in a new entity designated as PE@PPH, to address localization obstacles and modify cellular tropism to the cell membrane or nucleus. The results indicate that PE@PPH has strong antitumor properties, even at low doses of PTX both in vitro and in vivo . These findings suggest that PE@PPH could be an enhancing micelle for delivering therapeutic proteins and promoting protein functional recovery, particularly in addressing the challenges posed by tumor heterogeneity in breast cancer.

Cyanobacteria, especially Arthrospira, are valuable resources of nutrients and natural pigments with many beneficial health-related properties. This study optimized the extraction conditions of Arthrospira to achieve high phenolic contents and antioxidant activities. Under optimized extraction conditions, the bioactive compounds (phenolics and pigment components), antioxidant activities, and inhibitions of the key enzymes relevant to some non-communicable diseases were compared between Arthrospira platensis and Arthrospira maxima. Optimized extraction conditions were determined as 2 h shaking time, 50 °C extraction temperature, and 1% (w/v) solid-to-liquid ratio, giving effective phenolic and phycocyanin contents using aqueous extraction, while 80% (v/v) aqueous ethanolic extraction provided high total chlorophyll content. Most antioxidant activities were higher using 80% (v/v) aqueous ethanolic extracts. Both Arthrospira species inhibited the key enzymes involved in controlling non-communicable diseases including hyperlipidemia (lipase), diabetes (α-amylase, α-glucosidase, and dipeptidyl peptidase-IV), Alzheimer's disease (acetylcholinesterase, butyrylcholinesterase and β-secretase), and hypertension (angiotensin-converting enzyme). High inhibitory activities were detected against β-secretase (BACE-1), the enzyme responsible for β-amyloid plaque formation in the brain that acts as a significant hallmark of Alzheimer's disease. Arthrospira extract and donepezil (Alzheimer's disease drug) synergistically inhibited BACE-1, suggesting the potential of Arthrospira extracts as effective BACE-1 inhibitors. Interestingly, A. maxima exhibited higher bioactive compound contents, antioxidant activities, and key enzyme inhibitions than A. platensis, indicating high potential for future food and medicinal applications., (© 2024. The Author(s).)

Objectives: This study compared the effects of conventional, ultrasonic, and laser-activated irrigation (LAI) on penetration depth of three photosensitizers (PSs) in the root canal system., Materials and Methods: In this in vitro, experimental study, 120 extracted anterior teeth were decoronated such that the remaining root length was standardized at 12 mm. After root canal instrumentation with the ProTaper rotary system and irrigation with 5.25% NaOCl, the roots were assigned to 12 groups for the application of toluidine blue (TB), curcumin, and phycocyanin PSs combined with the LAI using erbium laser with 0.4 mm and 0.6 mm tips, ultrasonic activation, and conventional irrigation. The specimens were sectioned apicocoronally, and the dye penetration depth was quantified in the coronal, middle, and apical thirds under a stereomicroscope at x20 magnification. Data were analyzed by the Kruskal-Wallis and Dunn test (alpha=0.05)., Results: The effects of irrigation technique, PS type, and their interaction on dye penetration depth were significant at the apical, middle, and coronal thirds (P < 0.0001). TB + LAI with 0.4- and 0.6-mm laser tips showed the highest penetration depth while phycocyanin + LAI or conventional irrigation showed the lowest penetration depth at all areas. Dye penetration depth was the highest in the coronal, and the lowest in the apical third., Conclusion: The LAI technique with erbium laser (0.4- and 0.6-mm tips) enhanced the penetration depth of TB. The tested irrigation techniques had no significant efficacy for enhancement of the penetration depth of curcumin and phycocyanin., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: Evaluation of the effect of phycocyanin (PC) and toluidine blue (TBO) along with sodium fluoride varnish (FV) or titanium tetrafluoride (TiF 4 ) under the conditions of antimicrobial photodynamic therapy (PDT) on a dual-species cariogenic biofilm and on remineralization process., Design: After the development of Streptococcus mutans and Lactobacillus acidophilus dual-species biofilms on the human enamel disks, they were divided into 11 groups (n = 9): Control (0.9 % saline), PC, TBO, FV, and TiF 4 alone, PC and TBO in combination with a 635 nm diode laser (PDT treatment), PC-PDT + (PC + FV or TiF 4 + 635 nm diode laser), and TBO-PDT + (TBO + FV or TiF 4 + 635 nm diode laser). After the treatment, crystal violet assay was performed to determine the reduction of cariogenic biofilms. Enamel remineralization changes were analyzed using energy dispersive X-ray spectroscopy (EDX) and field emission scanning electron microscopy (FESEM) for the calcium and phosphorus (Ca/P) ratio., Results: Only TBO-PDT + showed superior antibiofilm activity when TiF 4 was applied. Furthermore, the highest Ca/P ratio was found after treatment of enamel surfaces with TiF 4 -TBO-PDT + . The FESEM images showed that the enamel disks treated with TiF 4 plus TBO-mediated PDT exhibited surface coating. However, TiF 4 plus PC-mediated PDT cannot repair demineralized enamel., Conclusions: These data suggest that TBO-PDT along with TiF 4 can effectively reduce cariogenic biofilms and significantly remineralize enamel disks, opening new avenues in caries prevention., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Prolonged strenuous exercise induces oxidative stress, leading to oxidative damage, skeletal muscle fatigue, and reduced exercise performance. The body compensates for oxidative stress through antioxidant actions, while related enzymes alone may not overcome excessive oxidative stress during prolonged strenuous exercise. Phycocyanin is an important antioxidant supplement derived from blue-green algae, which may be helpful in this type of situation. This study determined the effects of phycocyanin on exercise performance from prolonged strenuous exercise. Forty Sprague Dawley male rats were divided into 5 groups (n = 8 /group); Control group (C), Exercise group (E), and Exercise with supplement groups receiving low dose (Phycocyanin = 100 mg/kg BW; ELP) and high dose (Phycocyanin = 200 mg/kg BW; EHP) or vitamin C (Vitamin C = 200 mg/kg BW; VC). Phycocyanin was found to decrease oxidative damage markers, muscle fatigue, and muscle atrophy through the activated AKT/mTOR pathway. This was also found to have greater increases in antioxidants via Nrf2 signaling and increases ATP synthesis, GLUT4 transporters, and insulin signaling due to increased IRS-1/AKT signaling. In conclusion, phycocyanin was found to reduce oxidative damage and muscle atrophy, including an increase in insulin signaling in skeletal muscles leading to increased exercise performance in rats., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Puengpan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Spirulina maxima is a cyanobacterium considered a "superfood" due to its metabolites and nutrient content. These include a complex mixture of minerals, vitamins, fatty acids, proteins, and accessory pigments. In recent years, it has positioned itself as a promising source of bioactive molecules for the treatment of several diseases, including metabolic syndrome, coronary diseases, cancer, and the improvement of health modulating oxidative stress. C-Phycocyanin (C-PC) is a photosynthetic pigment from green-blue cyanobacterium and the most abundant phycobiliprotein in the Spirulina genus with various pharmacological properties attributed due to its antioxidant capacity but has no specific cellular target. This has made it a molecule of great interest in biomedical research. This review focuses on the pharmacological effects and the benefits on metabolic syndrome and oxidative stress of C-PC.

Phycocyanin (PC) is a naturally occurring green pigment in Spirulina. It was extracted by ultrasonic extraction using green technology, and its structure was studied using IR- and NMR-spectroscopy. Spectral data confirmed the PC structure. This study also involves an in silico assessment of the diverse applications of green pigment PC. Utilizing QSAR, PreADME/T, SwissADME, and Pro-Tox, this study explores the safety profile, pharmacokinetics, and potential targets of PC. QSAR analysis reveals a favorable safety profile, with the parent structure and most metabolites showing no binding to DNA or proteins. PreADME/T indicates low skin permeability, excellent intestinal absorption, and medium permeability, supporting oral administration. Distribution analysis suggests moderate plasma protein binding and cautious blood-brain barrier permeability, guiding formulation strategies. Metabolism assessments highlight interactions with key cytochrome P450 enzymes, influencing drug interactions. Target prediction analysis unveils potential targets, suggesting diverse therapeutic effects, including cardiovascular benefits, anti-inflammatory activities, neuroprotection, and immune modulation. Based on the in silico analysis, PC holds promise for various applications due to its safety, bioavailability, and potential therapeutic benefits. Experimental validation is crucial to elucidate precise molecular mechanisms, ensuring safe and effective utilization in therapeutic and dietary contexts. DFT calculations, including geometry optimization, MEP analysis, HOMO-LUMO energy surface, and quantum reactivity parameters of the PC compound, were obtained using the B3LYP/6-311G(d,p) level. This integrated approach contributes to a comprehensive understanding of PC's pharmacological profile and informs future research directions., Competing Interests: The authors declare no conflicts of interest.

We investigated suitable culture conditions for the production of the blue pigment phycocyanin (PC) from the unique filamentous cyanobacteria Pseudanabaena sp. ABRG5-3 and Limnothrix sp. SK1-2-1. White, green, or red LED irradiation at 30 μmol photons/m 2 /s was effective for phycocyanin production when compared with Arthrospira platensis (Spirulina) sp. NIES-39, which is generally grown under high light irradiation. To investigate the safety of the cyanobacteria, ABRG5-3 cells were subjected to Ames (reverse mutation) tests and single oral-dose rat studies, which revealed non-mutagenic and non-toxic properties. When three purified phycocyanins (abPC, skPC, and spPC) were subjected to agarose gel electrophoresis, they showed different mobility, indicating that each phycocyanin has unique properties. abPC exhibited strong antiglycation activities as novel function., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Currently, sonodynamic therapy (SDT) has limited therapeutic outcomes and immune responses, highlighting the urgent need for enhanced strategies that can stimulate robust and long-lasting antitumor effects. Microcystis, a notorious microalga, reveals the possibility of mediating SDT owing to the presence of gas vesicles (GVs) and phycocyanin (PC). Herein, a nontoxic strain of Microcystis elabens (labeled Me) is developed as a novel agent for SDT because it generates O 2 under red light (RL) illumination, while GVs and PC act as cavitation nuclei and sonosensitizers, respectively. Moreover, algal debris is released after ultrasound (US) irradiation, which primes the Toll-like receptor pathway to initiate a cascade of immune responses. This sono-immune strategy inhibits CT26 colon tumor growth largely by promoting dendritic cell (DC) maturation and cytotoxic T-cell activation. After combination with the immune checkpoint blockade (ICB), the therapeutic outcome is further amplified, accompanied by satisfactory abscopal and immune memory effects; the similar potency is proven in the "cold" 4T1 triple-negative breast tumor. In addition, Me exhibits good biosafety without significant acute or chronic toxicity. Briefly, this study turns waste into wealth by introducing sono-immunotherapy based on Microcystis that achieved encouraging therapeutic effects on cancer, which is expected to be translated into the clinic., (© 2024 Wiley‐VCH GmbH.)

Pulmonary fibrosis is a chronic and irreversible progressive lung disease caused by various factors, such as age and environmental pollution. With countries stepping into an aging society and the seriousness of environmental pollution caused by global industrialization, the incidence of pulmonary fibrosis is annually increasing. However, no effective drug is available for pulmonary fibrosis treatment. C-phycocyanin (C-PC), extracted from blue-green algae, has good water solubility and antioxidation. This study elucidated that C-PC reinforces autophagy to block pulmonary fibrogenesis by inhibiting long noncoding RNA (lncRNA) biogenesis in vivo and in vitro. Cleavage under targets and release using nuclease (CUT & RUN)-PCR, co-immunoprecipitation (Co-IP), and nuclear-cytoplasmic separation experiments clarified that C-PC blocked the nuclear translocation of activating transcription factor 3 (ATF3) to prevent the binding between ATF3 and transcription factor Smad3, thereby hindering lncIAPF transcription. Human antigen R (HuR) truncation experiment and RNA binding protein immunoprecipitation (RIP) were then performed to identify the binding domain with lncIAPF in the 244-322 aa of HuR. lncIAPF exerted its profibrogenic function through the binding protein HuR, a negative regulator of autophagy. In summary, C-PC promoted autophagy via down-regulating the lncIAPF-HuR-mediated signal pathway to alleviate pulmonary fibrosis, showing its potential as a drug for treating pulmonary fibrosis. Exploring how C-PC interacts with biological molecules will help us understand the mechanism of this drug and provide valuable target genes to design new drugs., (© 2024. The Author(s).)

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., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Asthma is a chronic immunological disease related to oxidative stress and chronic inflammation; both processes promote airway remodeling with collagen deposition and matrix thickening, causing pulmonary damage and lost function. This study investigates the immunomodulation of C-phycocyanin (CPC), a natural blue pigment purified from cyanobacteria, as a potential alternative treatment to prevent the remodeling process against asthma. We conducted experiments using ovalbumin (OVA) to induce asthma in Sprague Dawley rats. Animals were divided into five groups: (1) sham + vehicle, (2) sham + CPC, (3) asthma + vehicle, (4) asthma + CPC, and (5) asthma + methylprednisolone (MP). Our findings reveal that asthma promotes hypoxemia, leukocytosis, and pulmonary myeloperoxidase (MPO) activity by increasing lipid peroxidation, reactive oxygen and nitrogen species, inflammation associated with Th2 response, and airway remodeling in the lungs. CPC and MP treatment partially prevented these physiological processes with similar action on the biomarkers evaluated. In conclusion, CPC treatment enhanced the antioxidant defense system, thereby preventing oxidative stress and reducing airway inflammation by regulating pro-inflammatory and anti-inflammatory cytokines, consequently avoiding asthma-induced airway remodeling.

Gastrointestinal cancer is the most fatal cancer worldwide. The etiology of gastrointestinal cancer has yet to be fully characterized. Alcohol consumption, obesity, tobacco, Helicobacter pylori and gastrointestinal disorders, including gastroesophageal reflux disease, gastric ulcer, colon polyps and non-alcoholic fatty liver disease are among the several risks factors for gastrointestinal cancers. Phycocyanin which is abundant in Spirulina. Phycocyanin, a member of phycobiliprotein family with intense blue color, is an anti-diabetic, neuroprotective, anti-oxidative, anti-inflammatory, and anticancer compound. Evidence exists supporting that phycocyanin has antitumor effects, exerting its pharmacological effects by targeting a variety of cellular and molecular processes, i.e., apoptosis, cell-cycle arrest, migration and Wnt/β-catenin signaling. Phycocyanin has also been applied in treatment of several gastrointestinal disorders such as, gastric ulcer, ulcerative colitis and fatty liver that is known as a risk factor for progression to cancer. Herein, we summarize various cellular and molecular pathways that are affected by phycocyanin, its efficacy upon combined drug treatment, and the potential for nanotechnology in its gastrointestinal cancer therapy., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

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. C-PC is a fluorescent protein, with its chromophore represented by the tetrapyrrole molecule phycocyanobilin B (PCB-B). 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 . Indeed, the comprehensive C-PC, and to some extent, the isolated PCB-B, has been linked to various health-promoting effects. These benefits encompass conditions triggered by oxidative stress, inflammation, and other pathological conditions. The present review focuses on the bio-pharmacological properties of these molecules, positioning them as promising agents for potential new applications in the expanding nutraceutical market.

Aims: To assess the impact of various cavity disinfectants PC-PDT (Phycocyanin activated by Photodynamic therapy), PC@AgNPs-PDT (Phycocyanin and silver nanoparticles activated by PDT), and Nd: YAG laser on the survival rate of S.mutans and the bond integrity of composite restoration METHODS: Sixty human mandibular molars that scored 4 and 5 based on ICDAS criteria were included. The infected dentin was removed while the CAD was preserved based on visual, tactile, and staining assessment. S.mutans were cultured on the CAD of twenty samples. All the specimens were indiscriminately distributed into four groups based on cavity disinfection (n=20 each includes n = 5 each group incubated with S.mutans) Group 1: CHX, Group 2: Nd:YAG laser, Group 3: PC-PDT and Group 4: PC@AgNPs-PDT. S.mutans survival rate was assessed for each group(n = 5). Forty samples underwent composite bonding for SBS and failure mode assessment using universal testing machine (UTM) and stereomicroscope. The calculations for the mean and standard deviation (SD) and their comparison among different groups were performed using a one-way analysis of variance (ANOVA) and the Tukey post hoc test (p ≤ 0.05) RESULTS: CAD surface treated disinfected with PC@AgNPs-PDT yielded the lowest survival rates (0.13 ± 0.05 CFU/ml) and highest SBS (17.23 ± 1.45 MPa). Group 1 (CHX) unveiled the highest survival rate of S.mutans (0.33 ± 0.12 CFU/ml). However, Group 2 (Nd:YAG Laser) (11.87 ± 0.67 MPa) presented the lowest SBS CONCLUSION: The combination of Phycocyanin loaded with silver nanoparticles and activated with Photodynamic therapy demonstrates the highest antimicrobial potential and bond strength of composite restorations., (Copyright © 2024. Published by Elsevier B.V.)

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 H 2 O 2 -induced generation of reactive oxygen species in HEI-OC1 auditory cells. H 2 O 2 -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.

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., Competing Interests: Declaration of competing interest There are no conflicts to declare., (Copyright © 2024. Published by Elsevier B.V.)

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., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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.

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).

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., (© 2024. The Author(s).)

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.

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Background: Eradication of endodontic biofilms from the infected root canal system is still the main concern in endodontics. In this study, the role of the power density parameter in the efficacy of antimicrobial photodynamic therapy (PDT) with toluidine blue O (TBO) and phycocyanin (PC) activated by a 635 nm diode laser (DL) against Enterococcus faecalis biofilm in the root canal model was investigated., Materials and Methods: The E. faecalis biofilm in the root canal was treated with TBO and PC with different power densities (636, 954, 1273, and 1592 W/cm 2 ). The untreated biofilm represented the control group. After the treatments, the biofilms were analyzed based on the number of colonies per milliliter., Results: TBO and PC activated with 635 nm DL with a power density of 1592 W/cm 2 were more efficient in removing E. faecalis biofilms within the root canals than those with a power density of 636 W/cm 2 (p = 0.00)., Conclusion: The light power density optimized the bacterial reduction of E. faecalis biofilms in the root canal spaces. These results provide information on the decisive parameters for performing PDT on intracanal biofilms., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

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., Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential no conflicts of interest with respect to the research, authorship, and/or publication of this article: The researchers are fellows of EDI, COFAA, and SNI.

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., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of competing interest Authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Hydrogen peroxide (H 2 O 2 ) 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 H 2 O 2 on Arthrospira platensis, several biochemical components, and antioxidant enzymes were analysed. The growth and biomass of A. platensis were decreased under the effect of H 2 O 2 . Whereas, the concentration up to 40 μM H 2 O 2 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 (EC 50 ) for H 2 O 2 were 57, 65, and 74 μM H 2 O 2 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 H 2 O 2 . 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 H 2 O 2 . 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

One of the promising sources for creating specialized foods is the biomass of Arthrospira platensis food microalgae. Biomass of A. platensis and its aqueous extracts are used as a source of bioactive compounds, primarily phycocyanins which are protein macromolecules that largely determine the antioxidant, immunomodulatory and anti-inflammatory properties of this cyanobacterium. The chromophore part of phycocyanin is photo- and thermolabile and can undergo restructuring, as a result of which phycocyanin loses its biological value. Various food proteins can be used to protect chromophoric compounds. In this work, two types of proteins (whey and egg proteins) were studied in the complex with phycocyanin. The aim of the study was to identify the heat-protective effect of egg and milk proteins in relation to phycocyanin by using colorimetric method and differential scanning calorimetry. Material and methods . Food sodium caseinate, whey protein concentrate, unfractionated edible egg white and phycocyanin concentrate were used as research objects. Combinations of phycocyanin with proteins were prepared by mixing equal volumes of 1% aqueous solutions, followed by thermostatting the mixtures at a temperature of (28±0.5) °C for 60 minutes in an incubator shaker at a stirring speed of 100 rpm. Studies of the thermodynamic characteristics of the samples separately and in combination with phycocyanin were carried out using differential scanning calorimetry by heating of the samples from 25 to 200 °C at a rate of 5 °C/min. The color change of phycocyanin solutions during storage for 20 min at a temperature of 50 °C was assessed by spectrocolorimetry. Results . The most pronounced low-temperature endothermic effect (peak at 60 °C) was detected in the whey protein concentrate. The ovalbumin had a small thermal effect at 70 and 100 °C, while the sodium caseinate had a small thermal effect at 132 °C. The dry phycocyanin sample had two peaks at 80 and 121 °C and the onset of thermal degradation at 65 °C. The destruction temperature of the sodium caseinate solution was 100.8±1.3 °C, for the whey protein concentrate solution - 113.7±0.8 °C. The aqueous solution of phycocyanin had a thermal effect peak at 103.3±1.7 °C. Mixing phycocyanin with the studied edible proteins resulted in changes in the peak degradation temperatures. The most noticeable decrease was observed for ovalbumin in complex with phycocyanin (at 101.9±1.9 °C), indicating a decrease in the thermal stability of phycocyanin in the presence of this protein. The combination of phycocyanin with whey protein concentrate led to a significant increase in the destruction temperature (at 112.0±2.1 °C). In terms of color index, solutions of phycocyanin complexes with proteins differed significantly from an aqueous solution of phycocyanin. The samples had threshold values for color tolerance (ΔE) in the range of 2 units, that is they were visually distinguishable immediately after preparation. All samples tended to darken when heated to 50 °C. Conclusion . Increasing the thermal stability of phycocyanin is possible when it is combined with whey protein concentrate. The observed effect significantly exceeds the effect of combining phycocyanin with sodium caseinate and egg protein. The change in color of solutions of the studied complexes when heated to 50 °C occurred to a lesser extent in the presence of whey protein concentrate, which may indicate greater preservation of the chromophoric groups of phycocyanin. The results obtained indicate the prospects of using whey protein concentrates for the development of new forms of functional food ingredients containing phycocyanin., Competing Interests: The author declares no conflicts of interest., (Copyright© GEOTAR-Media Publishing Group.)

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 2 SeO 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-β 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.

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, β-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., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The aim of this study was to investigate a potential preventive effect of phycocyanin extract from Spirulina platensis against ethanol- induced hepatorenal toxicity and cognitive behavior impairment in male Wistar rats. The animals were randomly and equally divided into four groups (six animals each): control group received saline solution, ethanol (EtOH) group was injected intraperitoneally with 1 ml/kg of ethanol solution 38% (w/v), phycocyanin groups were treated with 25 (PC1) or 50 (PC2) mg/kg phycocyanin extract followed by ethanol administration. All treatments were conducted for 14 successive days. Results revealed that ethanol induced oxidative stress in brain, liver, and kidney by increasing lipid peroxidation level and SOD and CAT activities. Serum biochemical perturbations were also observed in EtOH group, which was indicated by a significant elevation in ALT, AST, cholesterol, triglycerides, creatinine, and urea levels. Combined exposure to EtOH with phytocyanin contracted these biochemical alterations. Phycocyanin decreased also EtOH-induced anxiety and ameliorated exploratory behavior assessed by the elevated-plus maze and open field tests respectively.

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 β-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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier GmbH.)

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-1β, 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., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

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.