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Spirulina and C-phycocyanin reduce cytotoxicity and inflammation-related genes expression of microglial cells

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Abstract

OBJECTIVE: Our aim was to investigate the effects of Spirulina on BV-2 microglial cell cytotoxicity and inflammatory genes expression. METHODS: BV-2 microglial cells were treated with lipopolysaccharide (LPS) (1 µg/ml) and various concentrations of Spirulina platensis water extract or its active component (C-phycocyanin (C-PC)) for 24 hours. Cytotoxicity (lactate dehydrogenase (LDH) release) and expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) mRNAs were assayed. RESULTS: LPS increased LDH production and up-regulated expression of iNOS, COX-2, TNF-α, and IL-6 by BV-2 microglial cells. However, Spirulina platensis water extract and C-PC significantly reduced LPS-induced LDH release, and expression of iNOS, COX-2, TNF-α, and IL-6 mRNAs. CONCLUSION: Spirulina can reduce the cytotoxicity and inhibit expression of inflammation-related genes of LPS-stimulated BV-2 microglial cells.

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... Moreover, SPAE also protected against membrane hyperpermeability induced by LPS and/or LM. These findings agree with previous ones in other cellular models [57,58]. Furthermore, several investigations have indicated that LPS triggers an inflammatory signaling cascade to reduce tight junction protein expression, leading to increased intestinal permeability and disruption of intestinal epithelial barrier function [59]. ...
... It has also been shown that exposure to TNF-α increases the para-cellular permeability of a monolayer of differentiated Caco-2 cells [68]. Interestingly, Chen et al. (2012) [57] showed that c-phycocyanin results in inhibition of NO release, activation of NF-κB, and suppression of TNF-α formation. In another previous study, spirulina was shown to prevent LPS-induced up-regulation of iNOS, COX-2, TNF-α, and IL-6 in BV-2 cells [69]. ...
... It has also been shown that exposure to TNF-α increases the para-cellular permeability of a monolayer of differentiated Caco-2 cells [68]. Interestingly, Chen et al. (2012) [57] showed that c-phycocyanin results in inhibition of NO release, activation of NF-κB, and suppression of TNF-α formation. In another previous study, spirulina was shown to prevent LPS-induced up-regulation of iNOS, COX-2, TNF-α, and IL-6 in BV-2 cells [69]. ...
Article
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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.
... [2,18,21] Spirulina is an herbal supplement that contains various vitamins, minerals, and antioxidants that are beneficial for body health. [9] Spirulina is often referred to as a superfood because it has complete nutrition and high protein content. Spirulina is believed to provide various benefits, such as improving the immune system. ...
... Spirulina is believed to provide various benefits, such as improving the immune system. [9,38] Assessing TBI is challenging, but blood glial fibrillary acidic protein (GFAP) can predict intracranial pathologies undetectable on head computed tomography scans. [1,19] It is commonly used for prognostic and follow-up in patients with negative imaging results. ...
... In the study conducted by Chen et al. 2012, [9] the neuroprotective effects of Spirulina platensis and its active component, C-phycocyanin (C-PC), were explored in relation to their ability to modulate inflammatory responses in microglial cells. is research focused on BV-2 microglial cells treated with lipopolysaccharide (LPS) and different concentrations of Spirulina platensis water extract or C-PC for a period of 24 h. ...
Article
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Background Traumatic brain injury (TBI) is a global health problem with the potential to cause dangerous neurological problems. Based on histopathological findings in Sprague Dawley (SD) rats with TBI in the acute phase, the study seeks to discover the effect of Centella asiatica , cinnamon, and spirulina as neuroprotective. Methods We conducted an experimental study with 30 SD rats randomly divided into three groups. The intervention was the administration of C. asiatica , cinnamon, and spirulina to the control and the experimental groups. Histological features were assessed using hematoxylin and eosin (H&E) staining and immunohistochemical examination. The data were analyzed using statistical analysis through correlation tests. Results The test samples’ average body weights had P > 0.05, indicating no significant difference in the test sample body weights. Therefore, the variations in the expression level of the dependent variable were expected to be caused by the induction of brain injury and the administration of C. asiatica , cinnamon, and spirulina. In addition, the variables were not normally distributed. Thus, the Spearman test was carried out and showed the correlation was very strong, with a value of r = 0.818 and P < 0.05. Conclusion Based on histopathological findings from the brains of SD rats with TBI, pegagan, cinnamon, and spirulina will protect the brain (neuroprotective) in the acute phase.
... Furthermore, different studies have shown either anti-or proinflammatory effects of C-PC. For example, in macrophages and BV-2 microglia cells, C-PC reduced the expression of several inflammatory genes (e.g., iNOS, COX-2, TNF-α, and IL-1β) [22,23]. Conversely, Chen et al. [24] showed that C-PC induced secretion of TNF-α, IL-1β, and IL-6, increased expression of COX-2, and stimulated the phosphorylation of proteins implicated in inflammatory responses, including ERK, JNK, p38 and IκB in murine macrophages. ...
... In an attempt to explain the inconsistency between our results and some previous studies that have shown the anti-inflammatory properties of C-PC in macrophage and microglia cultures [23,24], we examined whether C-PC could be contaminated with LPS. Microglia were pretreated with polymyxin B (PMB, 50 µg/mL), a cyclic cationic polypeptide antibiotic able to bind to lipid A and neutralize LPS biological activity, widely used in vitro and in vivo to impede the effects of endotoxin contamination [40,41]. ...
... Spirulina platensis also synthetizes C-PC, a water-soluble pigment, known worldwide as a food additive and cosmetic colorant with potential biological activities and health benefits [52]. Antioxidant and antitumor activities, together with hepatic, renal, cardiovascular, and CNS protective properties of C-PC from Spirulina platensis have been extensively shown [19][20][21][22][23][24][25][53][54][55][56][57][58]. Moreover, it should be emphasized that Spirulina and C-PC, in particular, exert anti-inflammatory and immunomodulatory activities by stimulating the production of antibodies and up-or down-regulating the expression of different sets of key cytokines, such as IL-1β, IL-2, IL-4, IL-6, IL-10, and TNF-α [10][11][12][13][14]59]. ...
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The blue-green alga Spirulina platensis is rich in phycocyanins, that exhibit a wide range of pharmacological actions. C-phycocyanin (C-PC), in particular, possesses hepatoprotective, nephroprotective, antioxidant, and anticancer effects. Furthermore, several studies have reported both anti- and proinflammatory properties of this pigment. However, the precise mechanism(s) of action of C-PC in these processes remain largely unknown. Therefore, here we explored the C-PC effect in in vitro microglia activation. The effect of C-PC on the expression and release of IL-1β and TNF-α and the activation of NF-κB was examined in primary microglia by real-time PCR, ELISA, and immunofluorescence. Treatment with C-PC up-regulated the expression and release of IL-1β and TNF-α. C-PC also promoted the nuclear translocation of the NF-κB transcription factor. Then, to elucidate the molecular mechanisms for the immunoregulatory function of C-PC, we focused on investigating the role of Toll-like receptor 4 (TLR4). Accordingly, several TLR4 inhibitors have been used. Curcumin, ciprofloxacin, L48H37, and CLI-095 that suppresses specifically TLR4 signaling, blocked IL-1β and TNF-α. Overall, these results indicate the immunomodulatory effect of C-PC in microglia cultures and show for the first time that the molecular mechanism implicated in this effect may involve TLR4 activation.
... Some studies have demonstrated that polysaccharides biological activity can be improved by modifying their structure or combining them with nanoparticles, such as selenium or sulfate, as this surface modification can enhance cellular uptake (Table 1) (Yang et al., 2012;Fiorito et al., 2018;Zhou et al., 2020a). When combined with nanoparticles, PS bioavailability is influenced by the size, shape, and structure of the nanoparticles, being more easily absorbed and metabolized by the organism Zhou et al., 2020a). ...
... According to Reynolds et al. (2021), phycobiliproteins are a promising alternative due to their therapeutic properties to combat nonenveloped viruses, such as rhino-, polio-, and noroviruses. PC is the phycobiliprotein present in the greatest amount in Spirulina cells, reaching 40% of its protein composition and has proven antioxidant, anticancer, immunomodulatory, and anti-inflammatory activity (Cian et al., 2012;Shih et al., 2009;Chen et al., 2012;Bhat and Madyastha, 2000). Despite its high concentration, the extraction and isolation of PC from cyanobacterial cells is complicated due to the multilayer cell wall of these microalgae. ...
... The anti-inflammatory activity of CPC from A. platensis was demonstrated partly through inhibition of proinflammatory cytokines formation such as tumor necrosis factor α (TNF-α), inducible nitric oxide synthase (iNOS) and cyclooxygeanase-2 (COX-2) expression both in vitro and in vivo (Shih et al., 2009;Chen et al., 2012;Bhat and Madyastha, 2000). In addition, both A. platensis and CPC inhibited Complimentary Contributor Copy expression of inflammation-related genes by LPS-stimulated BV-2 microglial cells . ...
Chapter
Microalgae usually called “Spirulina” in the literature and in commercial packages have been studied as potential sources of protein for food and feed supplementation. These microalgae are produced industrially worldwide, being recognized as GRAS (Generally Recognized as Safe) by the Food and Drug Administration (USA) and accepted by the European Union for human consumption. Apart from a high protein content and balanced amino acid composition, its biomass contains compounds with antioxidant, anti-inflammatory, anti-tumor, anti-viral and anti-microbial activities. Some of these compounds have been determined to boost the immune system and prevent diseases such as hyperglycemia, cancer, diabetes, hypertension, cardiovascular and respiratory disorders. It has also been suggested that the supplementation with Spirulina biomass and/or its extracts could help immune systems to fight different viral infections, including those by SARS-CoV2, the etiologic agent of COVID-19. This immunity boosting activity has been related to the presence of some polysaccharides, carotenoids, phycobiliproteins, fatty acids and biopeptides in the biomass. In this context, this chapter will address the boosting effect of the immune system by Spirulina exploring its antiviral activity and respective mechanisms. The applications of the biomass as a supplement and nutraceuticals production will be also address.
... A protective effect of C-PC, as well as of the aqueous extract from Spirulina, was also demonstrated against an inflammatory condition in a lipopolysaccharide (LPS)-induced activation of BV-2 microglial cells [29]. This study showed that the expression of iNOS and COX-2 was inhibited and TNF-α and IL-6 were down-regulated in BV-2 microglial cells treated with C-PC (85, 125, and 150 µg mL −1 for 24h). ...
... The following supporting information can be downloaded at: https: //www.mdpi.com/article/10.3390/nu16111752/s1, Table S1: Effects of C-PC or PCB-B on different disease models [20,[24][25][26][27][28][29][30][31][32][33][34]36,[38][39][40][41][43][44][45][46][47][48][49][50][51][52][62][63][64][65][66][67][68]71,72,[76][77][78][79][80][81][82][85][86][87][88][90][91][92][93][94][95][96][97][98][99][100][101][102][103][104][105][106][107][108][109][111][112][113][114][115][116][117]. ...
Article
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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.
... Sp platensis has an active component C-phycocyanin, which seems to have a remarkable effect in controlling inflammatory conditions and maintaining cell membranes. In parallel with previous findings (Chen et al. 2012;Brito et al. 2020), lactate dehydrogenase (LDH), a cytosolic enzyme that is recognized as an indicator of cell membrane degradation, was reduced by Sp supplements (p < 0.05). In the study by Chen et al. (2012), derived C-phycocyanin was more effective in reducing LDH than Sp aqueous extract. ...
... In parallel with previous findings (Chen et al. 2012;Brito et al. 2020), lactate dehydrogenase (LDH), a cytosolic enzyme that is recognized as an indicator of cell membrane degradation, was reduced by Sp supplements (p < 0.05). In the study by Chen et al. (2012), derived C-phycocyanin was more effective in reducing LDH than Sp aqueous extract. ...
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Considering the anti-viral effects of Spirulina platensis (Sp), this study investigated the impact of Sp on impaired blood biomarkers of patients hospitalized in the intensive care unit (ICU) with COVID-19. Therefore, 104 patients (aged 48–66; 61.5% male) were randomly assigned to the Sp (daily consumption of 5 g) or placebo group for 2 weeks. Linear regression analysis was employed to assess the differences in blood test results between the control and intervention groups among patients with COVID-19. Our results showed significant differences in certain hematological tests, including a higher level of hematocrit (HCT) and a lower platelet count (PLT) in the intervention group (p < 0.05). The percentage of lymphocytes (Lym%) in serology testing was significantly different between the control and intervention groups (p = 0.03). In terms of biochemical test analyses, Sp supplementation was associated with reduced levels of both blood urea nitrogen (BUN) and lactate dehydrogenase (LDH) (p = 0.01). Furthermore, on day 14, the intervention group displayed significantly higher medians of serum protein, albumin, and zinc compared to the control group (p < 0.05). Additionally, patients supplemented with Sp had a lower BUN–albumin ratio (BAR) (p = 0.01). No immunological and hormonal differences were observed between groups following 2 weeks. Our analysis indicates that Sp supplementation may be effective in regulating some blood test abnormalities associated with COVID-19. This study was registered at ISRCTN as IRCT20200720048139N1.
... Studies reported that the absence of COX-2 favored the proinflammatory response [100], and acetylation of COX-2 induced the production of anti-inflammatory mediators [101]. Chen et al. (2012) reported that the expression of iNOS, COX-2, TNF-α, and IL-6 was inhibited by C-phycocyanin (C-PC) present in S. platensis [102]. Since our ethanol extract did not inhibit the expression of COX-2, we can safely assume that C-PC is not the responsible bioactive compound in the ethanol extract. ...
... Studies reported that the absence of COX-2 favored the proinflammatory response [100], and acetylation of COX-2 induced the production of anti-inflammatory mediators [101]. Chen et al. (2012) reported that the expression of iNOS, COX-2, TNF-α, and IL-6 was inhibited by C-phycocyanin (C-PC) present in S. platensis [102]. Since our ethanol extract did not inhibit the expression of COX-2, we can safely assume that C-PC is not the responsible bioactive compound in the ethanol extract. ...
Article
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The disease burden of neurodegenerative diseases is on the rise due to the aging population, and neuroinflammation is one of the underlying causes. Spirulina platensis is a well-known superfood with numerous reported bioactivities. However, the effect of S. platensis Universiti Malaya Algae Culture Collection 159 (UMACC 159) (a strain isolated from Israel) on proinflammatory mediators and cytokines remains unknown. In this study, we aimed to determine the anti-neuroinflammatory activity of S. platensis extracts and identify the potential bioactive compounds. S. platensis extracts (hexane, ethyl acetate, ethanol, and aqueous) were screened for phytochemical content and antioxidant activity. Ethanol extract was studied for its effect on proinflammatory mediators and cytokines in lipopolysaccharide (LPS)-induced BV2 microglia. The potential bioactive compounds were identified using liquid chromatography-mass spectrometric (LC-MS) analysis. Ethanol extract had the highest flavonoid content and antioxidant and nitric oxide (NO) inhibitory activity. Ethanol extract completely inhibited the production of NO via the downregulation of inducible NO synthase (iNOS) and significantly reduced the production of tumor necrosis factor (TNF)-α and interleukin (IL)-6. Emmotin A, palmitic amide, and 1-monopalmitin, which might play an important role in cell signaling, have been identified. In conclusion, S. platensis ethanol extract inhibited neuroinflammation through the downregulation of NO, TNF-α and IL-6. This preliminary study provided insight into compound(s) isolation, which could contribute to the development of precision nutrition for disease management.
... The antioxidants present in spirulina, such as phycocyanin and beta-carotene, offer a wide range of potential health benefits, particularly in reducing inflammation, supporting heart health, and preventing chronic diseases. These antioxidants have been shown to possess potent antiinflammatory properties, contributing to their ability to mitigate inflammation-related conditions Chen et al. (2012)Brito et al., 2020Cheong et al., 2010;Pak et al., 2012;Bhattacharyya & Mehta, 2012;Ismail et al., 2015;Huang et al., 2022;Zhang & Zhang, 2013;Kusmardi et al., 2021;Mao et al., 2005). Additionally, the antioxidant and antiinflammatory effects of spirulina have been associated with its potential to support heart health by reducing oxidative stress and inflammation, which are key factors in the development of cardiovascular diseases (Cheong et al., 2010;Pak et al., 2012). ...
Article
This review article highlights the versatile health benefits of spirulina, a nutrient-rich dietary supplement. Spirulina has various advantages, including functioning to support the immune system, increase energy, and has antioxidant properties. Being high in protein, essential amino acids, and iron, spirulina can be added to the diet to improve nutritional intake and improve overall health. The versatility of spirulina as a dietary supplement makes it feasible to incorporate spirulina into different diets by simply adding it to a smoothie, salad, or a supplement. Spirulina is an alternative for people who want to conveniently and sustainably optimize their health.
... Moreover, lymphoid organs, such as the spleen and bursa, documented decreased inflammation and overall mitigation of histopathological alterations. The decreased nitric oxide levels were interpreted as the likely consequence of down-regulated expression of the iNOS enzyme, given the presence, among the bioactive Spirulina components, of substances like heptadecane and C-phycocyanin that are capable of inhibiting iNOS gene expression via inhibitory modulation of the nuclear factor kappa B (NF-kB) transcription factor pathway [111][112][113][114][115]. C-phycocyanin has been reported to also act as direct inhibitor of the activity of iNOs, as well as of the inducible pro-inflammatory enzyme cyclooxygenase 2 [2]. ...
Article
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The broiler industry is pivotal in meeting the growing global demand for highly nutritious animal protein foods. Hence, there is a continuous interest in identifying novel, alternative, and even unconventional feed resources that could help sustainably support chicken meat production and quality. In this view, the microalga Spirulina (Arthrospira, formerly Spirulina, platensis), due to its unique chemical composition and some ecological advantages offered by its cultivation over traditional agriculture, has attracted great attention in the poultry sector for potential application in broiler diet, either as a functional supplement or a replacer of conventional protein sources such as soybean meal. The studies conducted so far seem to have confirmed many of the initial expectations regarding the advantages that may derive from dietary Spirulina supplementation, documenting its capacity to positively influence the intestinal and general health status of broiler chickens, leading to improved or preserved productive performance (under normal or challenging conditions, respectively), as well as to increased disease resistance and survivability. Furthermore, dietary Spirulina supplementation has been shown to induce positive changes in some important traits of broiler meat quality. However, at present, the inclusion of Spirulina in broiler diet, especially but not solely in relation to the use as an alternative protein source, presents sever-al technical and economic limitations. To increase the overall awareness around the actual usefulness and practical usability of Spirulina as a novel natural component of the broiler diet, this review paper seeks to provide a comprehensive and integrated presentation of what is currently known about this topic, highlighting critical issues that are still pending and would require further research efforts.
... Therefore, it aids in the suppression of inflammation [76]. Chen et al. [77] observed that St and its active constituent, C-phycocyanin, lowered interleukin-6, Cyclooxygenase-2, TNF-α, and nitric oxide synthase, as well as reduced TNF-α release. According to Farag et al. [64], Cg inhibits the release of TNF-α, which may be explained by its antioxidant properties and ability to reduce reactive oxygen species (ROS), which are known to increase the levels of TNF-α and IL-1β. ...
Article
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This study assessed the possible pharmacological effects of Chlorella vulgaris (Cg), Spirulina platensis (St), and silymarin (Sl) against thioacetamide (TA)-induced cardiotoxicity in rats, with a focus on their antioxidant, cardioprotective, and anti-inflammatory properties. The following is the random grouping of sixty male rats into six groups of ten animals each: the control (negative control), TA-intoxicated group (positive control; 300 mg/kg body weight (BW)), Sl + TA group (100 mg Sl/kg BW + TA), St + TA group (400 mg St/kg BW + TA), Cg + TA (400 mg Cg/kg BW + TA), and St + Cg + TA group (400 St + 400 Cg mg/kg BW + TA) were all administered for 30 days. At the start of the study, groups 2 through 6 were administered TA intraperitoneally at a dosage of 300 mg/kg BW for two consecutive days, with a 24 h gap between each dose, to induce cardiac damage. Blood samples were obtained to measure hematological parameters and perform biochemical assays, including lipid profiles and cardiac enzymes. For histopathology and immunohistochemistry determination, tissue samples were acquired. The current findings showed that TA injection caused hematological alterations and cardiac injury, as evidenced by greater serum levels of troponin I, creatine kinase-MB, and total creatine kinase (p < 0.05), as well as significantly elevated serum malondialdehyde and decreased serum total antioxidant capacity (p < 0.05) concentrations. Moreover, an increase in blood low-density lipoprotein and total cholesterol concentration (p < 0.05) was recorded in the TA group. There were alterations in the heart tissue’s histological structure of the TA group compared to the control ones. These alterations were characterized by vacuolar degeneration of myocytes, loss of cross striation, coagulative necrosis, and fibrosis of interstitial tissue, which was ameliorated by the supplementation of SI, St, and Cg. The TA-intoxicated group showed weak expression of B-cell lymphoma protein 2 (p < 0.05) and strong immunoreactivity of tumor necrosis factor-α and B-cell lymphoma protein 2-associated X (p < 0.05). However, the groups receiving Sl, St, and Cg experienced the opposite. The administration of Sl, St, Cg, and St + Cg along with TA significantly improved and restored (p < 0.05) erythrogram indices, including RBCs, hemoglobin, total leukocytic count, lymphocytes, and monocyte, to the normal control values. The administration of Sl, St, and Cg alleviated the cardiotoxicity caused by TA via reducing oxidative stress, inflammatory markers, and apoptosis in heart tissue. In summary, the current findings suggest that the treatment with Sl, St, and Cg was beneficial in ameliorating and reducing the cardiotoxicity induced by TA in rats.
... These cytokines are linked to the ability of S. platensis to either stimulate or inhibit the transcription factor NF-κB (Mao & Gershwin 2005;Balachandran et al. 2006;Liu et al. 2017). Reducing NF-κB nuclear translocation inhibits the production of proinflammatory genes, which is how S. platensis anti-inflammatory mechanism is exhibited (Chen et al. 2012;Hwang et al. 2013;Ku et al. 2013;Lee et al. 2017;Al-Qahtani & Binobead 2019). Phycocyanin from S. platensis, as an anti-inflammatory, selectively inhibits cyclooxygenase-2 (COX-2) and affects the negative regulation of NF-κB activity (Reddy et al. 2000;Poligone & Baldwin 2001;Shih et al. 2009;Khan & Khan 2018). ...
Article
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Pro- and anti-inflammatory mediators need to be released in a balanced way to maintain a healthy state as we age. One important regulatory element in the equilibrium of pro- and anti-inflammatory mediators is NF-κB. The purpose of this study was to examine how S. platensis affected the control of inflammatory mediators in young, healthy, emerging adults and adults in rats. In this investigation, 200 mg/kg BW of S. platensis extract was administered to six groups of male Wistar rats, ages 12, 18, and 24 weeks, along with a control group. In both the treatment and control groups, NF-κB p65 protein expression was lower at 24 weeks than it was at 12 and 18 weeks. TNF-α and COX-2 proteins were lower in the treatment group than in the control group. All age groups in the treatment group had higher levels of IL-10 protein than the control group. The quantity of NF-κB p65 was positively correlated with COX-2 and TNF-α. By raising the concentration of NF-κB p65, the ethanolic extract of S. platensis altered a mediator of cellular immunity. A decrease followed this in TNF-α and COX-2 and a rise in IL-10 in the rat spleen at different ages.
... This study revealed Spirulina's immunomodulatory molecular pathways. Spirulina and C-phycocyanin may reduce neuroinflammatory processes by lowering microglial cell cytotoxicity and gene expression, according to Chen et al. [159]. De Mattos et al. examined how hypoxic Spirulina-fed gilthead seabream changed stress parameters. ...
Article
This comprehensive review of Spirulina encompasses biotechnology, phycocyanin production, and purification. Bioactive compounds and vital nutrients are investigated during the study. The literature examines the potential therapeutic advantages and clinical applications of Spirulina. This analysis assesses Spirulina consumption and its associated health risks. The current review offers a comprehensive synthesis of the therapeutic applications as well as technologies utilized for the extraction and purification of phycocyanin. Moreover, this discourse delves into the examination of various advantageous techniques for extracting and purifying phycocyanin, encompassing physical, chemical, and enzymatic methods. The data derived from a multitude of studies strongly indicate the potential therapeutic applications of phycocyanin, encompassing its notable attributes as an antioxidant, anti-inflammatory agent, anticancer agent, antiviral agent, antimicrobial agent, antiallergic agent, anti-obesity agent, antihypertensive agent, and an immunological agent.
... Phycocyanin is one of the natural biological molecules found in Spirulina platensis algae as a light-harvesting pigment, which possesses anti-inflammatory, anti-cancer, and antioxidant effects [15][16][17]. Phycocyanin has many advantages, including water solubility, non-toxic nature, and no staining effect as reported by other disinfectants [18]. Therefore, using phycocyanin is a better alternative as a safe photosensitizer to be used in disinfecting cavities before restoration especially in esthetic zone [19,20]. ...
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Purpose The study aimed to compare microshear bond strength of self-etch adhesive and resin cement to coronal and radicular dentin, respectively, after disinfection with two modalities using photodynamic therapy (c-phycocyanin) and chlorohexidine. Methods Premolar teeth extracted for orthodontic reasons (n = 48) were used. Twenty-four premolars were sectioned parallel to the occlusal surface above cemento-enamel junction to expose coronal dentin (group 1). While in (group 2), they were sectioned parallel to the occlusal surface below CEJ to expose radicular dentin. Each group was further subdivided into three groups (n = 8) according to the disinfection protocol: group A = (control group), group P = dentin disinfected with c-phycocyanin, and group C = dentin disinfected with chlorohexidine. After disinfection, flowable resin composite was bonded to coronal dentin using one step self-etch adhesive, and self-adhesive resin cement was bonded to radicular dentin. Microshear bond strength was then evaluated. Results Coronal dentin (group 1) has shown no significant difference between groups (1A and 1C), but both were significantly higher than group 1P. Regarding radicular dentin (group 2), both groups (2C and 2P) showed no statistical difference when compared to group 2A. Conclusions Coronal dentin disinfection with chlorhexidine did not affect its bond strength; however, c-phycocyanin irradiated with diode laser (aPDT) negatively affected the bond strength of coronal dentin to self-etch adhesive. Radicular dentin disinfection with chlorhexidine significantly increased its bond strength. C-phycocyanin irradiated with diode laser did not significantly affect the bond strength of radicular dentin.
... Due to its high water solubility, nontoxicity, and immune-modulating qualities, PC offers several benefits over photosensitizers generated from chlorophyll [73][74][75][76]. PC might be utilized in PDT for the elimination of cancer without causing any harm to normal cells since it is easily metabolized in normal cells as opposed to diseased cells [71]. ...
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Phycobiliproteins (PBPs) are accessory light-harvesting pigment complexes found in cyanobacteria, red algae, and certain types of cryptophytes. The unique spectral features (strong absorbance and fluorescence), proteinaceous nature, and some imperative properties such as the anti-oxidative, hepato-protective, anti-inflammatory, and anti-aging activity of PBPs allow their use in biomedical industries. However, basic research and technological innovations are required to explore their potential in biomedical applications. The techniques responsible for therapeutic effects need to be standardized for medical application purposes. This review focuses on the current status of PBPs, their structure, functions, methods of preparation, and applications. Additionally, the stability, bioavailability, and safety issues of PBPs, along with their use in therapeutics, are discussed.
... Chen et al. showed that Spirulina sp. could reduce the mRNAs levels of inflammation-related proteins in microglial cells (BV-2 cell line), including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6). Therefore, this microorganism can be a therapeutic candidate for microglia-associated neuronal damage (5). Spirulina sp., as a complementary drug, exhibited an ameliorative role in aspirin-induced gastric ulcers by alleviating oxidative stress and inflammation. ...
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Background Spirulina is a cyanobacteria species containing various bioactive compounds. Spirulina is a known source of nutrients in some traditional diets. Different activities have been reported for various extracts of S. platensis. Objectives In this study, the polysaccharide content of culture media and biomass extract of one species of Spirulina was partially purified, and its analgesic and anti-inflammatory effects were evaluated. Methods Spirulina platensis PCST5 was cultured in a sterile Zarouk medium at 27°C and 16/8h of light/ dark exposure cycle for 25 days. Then, the polysaccharide content of biomass and cell-free culture medium samples (BPSs and CFPSs, respectively) was partially purified. The analgesic and anti-inflammatory effects were evaluated using animal models. Results 16S rRNA gene analysis confirmed that the organism was genetically similar to Spirulina platensis. The CFPSs (30 and 100 mg/kg) and BPSs (30 mg/kg) significantly reduced pain-related behaviors in rats. Similarly, all samples could significantly reduce carrageenan-induced paw inflammation volume compared with the control group. Our results suggest Spirulina's polysaccharide fractions (CFPSs and BPSs) had significant analgesic and anti-inflammatory effects. Conclusions Since Spirulina is a readily available source of bioactive compounds, finding such potent anti-inflammatory and anti-nociceptive compounds can provide promising leads for novel drug development.
... Leptin-depending induction of COX-2 has likewise been shown to hinge on oxidant-mediated MAP kinase activation in various tissues [25][26][27][28][29][30][31][32]. Spirulina, likely owing to its phycocyanobilin (PCB) chromophore that can mimic bilirubin's ability to inhibit NOX2-dependent NADPH oxidase complexes, has been shown to suppress COX-2 induction in various contexts [33][34][35][36][37]. Although its impact on aromatase induction in the breast has not yet been studied, it is intriguing that spirulina feeding has been reported to markedly suppress DMBA-mediated breast cancer induction in rats [38]. ...
Article
Background: Visceral obesity and the metabolic syndrome that often accompanies it are robust and well-established risk factors for postmenopausal breast cancer. This increased risk is thought to be mediated, in large part, by increased aromatase expression in the breast. stromal adipocytes and in mammary epithelium; this results in a high local concentration of estrogen capable of supporting the cancerous transformation of estrogen receptor-positive (ER+) epithelial cells. Aromatase, a member of the cytochrome 450 family, is expressed in the endoplasmic reticulum. After menopause, it converts androgens produced within the adrenal cortex (androstenedione and testosterone) into estrogens (estrone and estradiol, respectively. Therefore, the main objective of this narrative article is to review dietary and nutraceutical remedies for the prevention of menopause. Breast cancer: leading strategies to suppress breast aromatase Methods: The research articles to carry out this work were focused based on many searches and reviews in the following databases: Google Scholar, MDPI, PubMed, ScienceDirect and using the following keywords and combined synonyms: (“nutraceuticals” or “supplements” or “aromatase inhibitors” or “aromatase” or "antioxidants”) AND (“breast cancer” or “vascular function” or “inflammation”). The keywords were also searched in the references of the original articles included in this study Conclusion: A number of nutraceutical, dietary, and lifestyle measures hold promise for breast cancer prevention and may be considered practical options by women seeking to minimize their risk. for this cancer, particularly as these measures appear to have few downsides and are likely to work in other ways to promote health.
... This finding could be explained by the presence of Spirulina bioactive components such Spirulina lipid extract and heptadecane, which have been shown to inhibit the NF-kB pathway Ku et al., 2013) and thus may diminish the iNOS and nitric oxide synthesis (Morris et al., 2003). It has also been reported that C-phycocyanin may inhibit the iNOS gene expression (Chen et al., 2012). ...
Article
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Avian influenza (AI) viruses pose a risk to the worldwide poultry industry. Ultimately, improving the efficiency of the H9N2 vaccine is necessary to better control low-pathogenic avian influenza-H9N2 by using natural immunostimulant. Therefore, the goal of the present study was to examine varying doses of the cyanobacterium Spirulina extract on the effectiveness of H9N2 vaccine. Thus, a total of 150 specific pathogen-free (SPF) chickens were allocated into 6 groups, 25 birds each, as follow: G1, G2, and G6 were supplemented with 200, 400, and 400 mg Spirulina extract/kg feed, respectively, whilst the feed in G3, G4, and G5 were not supplemented with Spirulina extract. At 21-days-old, only the chickens in G1, G2, and G3 were vaccinated with the H9N2 AI vaccine. After 4 wk postvaccination, the chickens in G1, G2, G3, G4, and G6 were challenged with H9N2 AI Egyptian strain. The challenged virus was selected from a recent circulating Egyptian strain during 2022, and it was related to A/quail/Hong Kong/G1/97-like virus lineage and clustered with G1-B sub-lineage EGY-2 group. It had a high amino acids identity percentage of 92.6% with the A/chicken/Iran/av1221/1998 (Boehringer Ingelheim) vaccine. The results of real-time reverse-transcriptase polymerase-chain-reaction (rRT-PCR) revealed that no shedding of the virus was reported in G1, G2, G3, and G5. The supplementation of Spirulina extract in low (200 mg/kg of feed) and high (400 mg/kg of feed) concentration with the birds vaccinated with H9N2 AI vaccine (G1 and G2) induced prominent immuno-stimulatory effect in a dose dependent manner where it strongly enhanced the phagocytic activities of broilers' peripheral blood monocytes, and lysozyme at all days postvaccination (dpv) and days postchallenge (dpc) compared to other groups with significant differences at all day of experiment and 21st dpv, 28th dpv, 7th dpc, and 14th dpc, respectively. The supplementation with Spirulina extract in G1 and G2 induced the highest hemagglutination inhibition antibody titer in a dose-dependent manner at all-time intervals. The antibody titer postvaccination was significantly increased in G1 and G2 at 14th, and 21st dpv, in comparison with G3. Furthermore, G1 and G2 showed higher significant antibody titers at 7th and 14th dpc, compared to other groups. Furthermore, Spirulina extract (200 and 400 mg/kg feed) in G1 and G2 showed anti-inflammatory effect in a dose dependant manner by downregulating nitric oxide levels at all times postchallenge with a significant difference at 3 to 7 dpc compared to G3, G4, and G6, with improved histopathological alterations in the trachea, lung, kidney, spleen, and bursa of Fabricius. G6 supplied with 400 mg/kg Spirulina extract feed only without vaccination had a similar effect as vaccinated groups on innate immunity. However, it delayed the production of antibodies and did not prevent viral shedding as in vaccinated groups. In conclusion, vaccination in conjunction with either dose of Spirulina extract (G1, and G2) prevents viral shedding, increases the immune response, and reduces inflammation and histopathological change caused by H9N2 AI infection in a dose dependent manner. We recommend the use of 400 mg Spirulina extract/kg feed as a natural immunostimulant in conjunction with the H9N2 vaccine to achieve the highest possible level of protection against H9N2 AI infection.
... The scientists came to the conclusion that both substances significantly inhibited the release of lactate dehydrogenase brought on by lipopolysaccharide. Inflammatory mediators such as inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), cyclooxygenase-2 (COX-2), and tumor necrosis factor-alpha (TNF-α) were able to be inhibited by the researchers [38]. ...
Article
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Algae and their food products are in a great interest worldwide because of their nutritional value and health benefits. These edible substances are an excellent supply of antioxidants, high-quality protein, and fibers. The present work therefore targeted assessing Arthrospira platensis (A. platensis) (Cyanobacteria) and Chlorella vulgaris (C. vulgaris) (Chlorophyta) nutritional value and exploring A. platensis and C. vulgaris effects on hepatic enzymes and antioxidants in diabetic rats. A total of 48 healthy adult albino male rats of the Sprague-Dawley strain were assigned into 8 groups (n = 6). They were gavaged with 0, 100, 200, and 300 mg/kg of Ap and Cv extract. The first group were healthy rats fed on basal diet only, also known as the control negative (−ve) group, and seven other groups which induced diabetes by 120 mg/kg alloxan were as follows: groups 3, 4, and 5 treated with Spirulina are given 100, 200, 300 mg/kg of body weight, respectively, for 30 days and groups 6, 7, and 8 treated with Chlorella are given 100, 200, 300 mg/kg of body weight, respectively, for 30 days. By the end, sampling of blood was done to evaluate some biochemical markers encompassing trace minerals, hepatorenal functional indexes, malondialdehyde (MDA), antioxidants, and total protein (TP). Current findings revealed significant increase of plasma concentration hepatic enzymes (AST, ALT), creatinine, urea, and MDA but decrease in antioxidant enzymes, GSH, and TP in diabetic rats. However, an oral supplement of A. platensis or C. vulgaris (100, 200 ,and 300 mg/kg of body weight) lowered the levels of AST, ALT, creatinine, urea, and MDA and increased antioxidants and Tp. Diabetes decreased the plasma levels of antioxidants and also increased hepatic enzymes. The inclusion of A. platensis and C. vulgaris supplementing 100, 200, and 300 mg/kg of body weight increased some antioxidant enzymes, Tp, and GLP while lowered the levels of MDA, AST, ALT, creatinine, and urea. Our findings suggest that A. platensis and C. vulgaris are promising natural sources with nutritional and functional properties that allowed them to be used for the nutritional management of diabetic patients.
... These mediators stimulate astrocytes to activate further reactions that can impair synaptic function, the blood-brain barrier, metabolic function, and glutamate metabolism, further exacerbating neurodegeneration [38,39]. Cyanobacteria possess strong anti-inflammatory properties that have been shown to impact microglial activation and response, decrease inflammatory mediators, and modulate inflammatory genes [40][41][42][43][44]. ...
Article
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Neurodegenerative diseases (NDs) are characterized by progressive and irreversible neuronal loss, accompanied by a range of pathological pathways, including aberrant protein aggregation, altered energy metabolism, excitotoxicity, inflammation, and oxidative stress. Some of the most common NDs include Alzheimer’s Disease (AD), Parkinson’s Disease (PD), Multiple Sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS), and Huntington’s Disease (HD). There are currently no available cures; there are only therapeutic approaches that ameliorate the progression of symptoms, which makes the search for new drugs and therapeutic targets a constant battle. Cyanobacteria are ancient prokaryotic oxygenic phototrophs whose long evolutionary history has resulted in the production of a plethora of biomedically relevant compounds with anti-inflammatory, antioxidant, immunomodulatory, and neuroprotective properties, that can be valuable in this field. This review summarizes the major NDs and their pathophysiology, with a focus on the anti-neurodegenerative properties of cyanobacterial compounds and their main effects.
... Studies concluded that Spirulina can suppress tumorigenesis and critical viral infections, apparently due to its capacity to stimulate and progress the immune system [126]. Several studies showed its neuroprotective properties of Spirulina against neuroinflammation, Parkinson's disease, ischemic brain damage, and schizophrenia [127][128][129]. Oral administration of the phycocyanin component of Spirulina platensis can prevent the diabetic nephropathy by inhibiting NADPH dependent superoxide production [130]. ...
Article
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There are various herbicides which were used in the agriculture industry. Atrazine (ATZ) is a chlorinated triazine herbicide that consists of a ring structure, known as the triazine ring, along with a chlorine atom and five nitrogen atoms. ATZ is a water-soluble herbicide, which makes it capable of easily infiltrating into majority of the aquatic ecosystems. There are reports of toxic effects of ATZ on different systems of the body but, unfortunately, majority of these scientific reports were documented in animals. The herbicide was reported to enter the body through various routes. The toxicity of the herbicide can cause deleterious effects on the respiratory, reproductive , endocrine, central nervous system, gastrointestinal, and urinary systems of the human body. Alarmingly, few studies in industrial workers showed ATZ exposure leading to cancer. We embarked on the present review to discuss the mechanism of action of ATZ toxicity for which there is no specific antidote or drug. Evidence-based published literature on the effective use of natural products such as lycopene, curcumin, Panax ginseng, Spirulina platensis, Fucoidans, vitamin C, soyabeans, quercetin, L-carnitine, Telfairia occidentalis, vitamin E, Garcinia kola, melatonin, selenium, Isatis indigotica, polyphenols, Acacia nilotica, and Zingiber officinale were discussed in detail. In the absence of any particular allopathic drug, the present review may open the doors for future drug design involving the natural products and their active compounds.
... One study revealed the fact that Lu had directly inhibited the zinc-induced hypo phosphorylation not just because of its anti-oxidant activity but also through the regulatory mechanism of the tyrosine phosphokinase system. It was also reported that the BBB crossing activity of the Lu greatly enhanced when transported along with the Vitamin E Tocopherol [28][29][30][31][32]. ...
Article
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Phytochemicals or natural products have been studied extensively for their potential in the treatment of neurodegenerative diseases (NDs) like Parkinson’s disease, Alzheimer’s disease, etc. The neuronal structure loss and progressive dysfunction are the main characteristics of these diseases. In spite of impressive and thorough knowledge of neurodegenerative molecular pathways, little advancement has been found in the treatment of the same. Moreover, it was proved that natural products can be used efficiently in the treatment of NDs while certain issues regarding the patient's safety and clinical data are still existing. As ND is a bunch of diseases and it will start the myriad of pathological processes, active targeting of the molecular pathway behind ND will be the most efficient strategy to treat all ND-related diseases. The targeting pathway must prevent cell death and should restore the damaged neurons. In the treatment of ND and related diseases, natural products are playing the role of neuroprotective agents. This review will target the therapeutic potential of various phytochemicals which shows neuroprotective action.
... S. (Arthrospira) platensis is a filamentous and multicellular Gram-negative cyanobacterium (blue-green algae) that is a member of the Phormidiaceae family (Seyidoglu et al. 2017;Zahran and Emam 2018). It is increasing in popularity through its high nutritional content (i.e., proteins, carbohydrates, lipids, minerals, vitamins and pigments) (Saranraj and Sivasakthi 2014;Seyidoglu et al. 2017) as well as bioactive components which conduce to its therapeutic potential (cancer, diabetes, arthritis, cardiovascular diseases, anaemia, allergic diseases) (Ramamoorthy and Premakumari 1996;Løbner et al. 2008;Juárez-Oropeza et al. 2009;Chen et al. 2012). S. platensis shows antioxidant and immunomodulatory properties through some biochemical constituents such as c-linolenic acid (precursor of arachidonic acid), carotenes, tocopherol and minerals (e.g. ...
Article
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Spirulina platensis has gradually gained more attention for its therapeutic, antioxidant, and anti-inflammatory potential worldwide. However, the current molecular knowledge about the effects of spirulina on stress-related genes is rather limited. The effects of dietary intake of spirulina on the HSP70 gene expression were assessed in a controlled in vivo experimental design. Moreover, alterations in serum corticosterone levels, IL-2, IL-4, IFN-γ, triglyceride, ALT, AST, relative gene expression values, and the correlations between them were evaluated. A total of 36 rats were divided into four groups: control group, stress-only group, spirulina group, and spirulina+stress group. To control the dose administration, S. platensis was applied by a gastric gavage in stress groups. Crowded environment stress and hosting alone stress were applied to the stress-only group and spirulina + stress group. RNA was extracted from brain samples using TRIpure and the relative gene expression assessment was performed using Roche-LightCycler-480-II real-time PCR-System. Gene expression values were remarkably different among the four experimental groups. The differences between stress-only and the spirulina groups were statistically significant (P<0.05). The correlation between the HSP70 gene expression and the IFN-γ was found to be statistically significant (P<0.05; r=0.50). Results indicate a novel effect of spirulina on the HSP70 expression related to the stress-response. Data presented in this study may be useful for further studies to define not only the molecular genetic aspects through dietary S. platensis but also the effects of spirulina on stress-response and animal welfare.Graphical abstract
... In particular, C-phycocyanin, contained in large amounts in the microalgae, may inhibit the cyclooxygenase-2 gene expression, regulate the antioxidant enzymes activity, such as glutathione peroxidase, superoxide dismutase and catalase, having scavenging property (Shih and Kubo 2005;Chen et al. 2012). ...
Article
The goal of this review was to critically evaluate the research on the effects of Spirulina (SP) supplementation on pathological conditions in the general population, considering its antioxidant, immunomodulatory, and anti-inflammatory properties. On a total of 1621 records screened, eighteen studies published between 2001 and 2020 met the inclusion criteria. Despite variability in research methodology and patient conditions, the findings of these studies generally support the benefits of supplementing diet with SP in subjects with both transmittable and non-transmittable diseases. Improvements were found for all the conditions studied, with the only exception of male infertility. However, the number of clinically controlled trials examining the effects of SP on specific health conditions is still very low, and some studies show medium quality. Further research in this field is needed to confirm the possible clinical role of Spirulina supplementation in parallel with medical therapies.
... Originally, TNF-α is thought to be produced mainly by immune cells as lymphocytes, and activated macrophages but further studies reported its expression also in smooth muscle cells, endothelial, and epithelial cells [35]. Likewise studied mice by Hwang et al. [36] and Chen et al. [37] who found that dietary supplementation with c-pc or Spirulina platensis water extract significantly down-regulated the mRNAs expression of TNF-α gene. On the other side some researches showed up-regulation of TNF-α level in mouse model with tumor [38]. ...
Research
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Background: Treatment of prostate cancer (PCa) is facing many challenges; one of them is androgen deprivation therapy relapse. These outcomes raising the need to In-vivo study of new modalities and substances alone or in combination. Silver Nano-particles (AgNPs) and Spirulina are promising substances for control PCa alone or in combination. Method: PCa in rats were induced using bicalutamide and Testosterone followed by (7, 12-dimethylbenz[a]anthracene), then Testosterone was injected s.c. for 3 months. Rats were divided into six groups, 12 rats in each group. Results: Spirulina therapy, or (AgNPs/Sp), or bicalutamide (Casodex®) groups exhibited substantial decreases in PSA relative to (PCa) group and achieved the normal level as same as control (co) group, however AgNPs treatment showed no change in PSA level as PCa group. AgNPs up-regulated the expression of BAX, while Spirulina could up-regulate Caspase 3, and down-regulated TNF-α. The combination of AgNPs/Spirulina up-regulated the P53, BAX, and BCL2 compared with PCa group. The up-regulation in Bcl2 gene was within the normal range, still significantly down the level compared with (co) animals. High-grade prostatic intraepithelial neoplasia was removed according to a histopathological analysis, and varied percentages of each treatment group eventually returned to normal prostatic acini. Conclusion: AgNPs alone have low effect in High-grade prostatic intraepithelial neoplasia, while Spirulina plus AgNPs combination treatment improved its effects. Each Spirulina and bicalutamide normalized prostate cells architectures, reduced PSA level, and down-regulated TNF-α gene expression.
... The anti-inflammatory capacity of PCB is also related to inhibiting the expression of inflammation-related genes and suppressing the cytotoxicity of microglia in some neurodegenerative diseases [64]. Microglial cells play a crucial role in host defence and tissue recovery in the central nervous system. ...
Article
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Phycocyanobilin (PCB) is a linear open-chain tetrapyrrole chromophore that captures and senses light and a variety of biological activities, such as anti-oxidation, anti-cancer, and anti-inflammatory. In this paper, the biological activities of PCB are reviewed, and the related mechanism of PCB and its latest application in disease treatment are introduced. PCB can resist oxidation by scavenging free radicals, inhibiting the activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, and delaying the activity of antioxidant enzymes. In addition, PCB can also be used as an excellent anti-inflammatory agent to reduce the proinflammatory factors IL-6 and IFN-γ and to up-regulate the production of anti-inflammatory cytokine IL-10 by inhibiting the inflammatory signal pathways NF-κB and mitogen-activated protein kinase (MAPK). Due to the above biological activities of phycocyanobilin PCB, it is expected to become a new effective drug for treating various diseases, such as COVID-19 complications, atherosclerosis, multiple sclerosis (MS), and ischaemic stroke (IS).
... Both cytokines (IL-6 and IFN-γ) are produced by activated microglia [57], thereby confirming that the deleterious activation of these glial cells after the ischemic event, is restricted by the C-PC application. It is noteworthy that C-PC inhibited the expression of IL-6 and other inflammation-related genes in lipopolysaccharide-stimulated BV-2 microglial cells in vitro [58]. ...
Article
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Background Ischemic stroke produces a large health impact worldwide, with scarce therapeutic options. Objective This study aimed to reveal the role of NADPH oxidase and neuroinflammatory genes on the cerebral anti-ischemic effects of C-Phycocyanin (C-PC), the chief biliprotein of Spirulina platensis. Methods : Rats with either focal cerebral ischemia/reperfusion (I/R) or acute brain hypoperfusion, received C-PC at different doses, or a vehicle, for up to 6 h post-stroke. Neurological, behavioral and histochemical parameters were assessed in I/R rats at 24 h. Cerebral gene expression and hippocampal neuron viability were evaluated in hypoperfused rats at acute (24 h) or chronic phases (30 days), respectively. A molecular docking analysis between NOX2 and C-PC-derived Phycocyanobilin (PCB) was also performed. Results C-PC, obtained with a purity of 4.342, significantly reduced the infarct volume and neurologic deficit in a dose-dependent manner, and improved the exploratory activity of the I/R rats. This biliprotein inhibited NOX2 expression, a crucial NAPDH oxidase isoform in the brain, and the superoxide increase produced by the ischemic event. Moreover, C-PC-derived PCB showed a high binding affinity in silico with NOX2. C-PC downregulated the expression of pro-inflammatory genes (IFN-γ, IL-6, IL-17A, CD74, CCL12) and upregulated immune suppressive genes (Foxp3, IL-4, TGF-β) in hypoperfused brain areas. This compound also decreased chronic neuronal death in the hippocampus of hypoperfused rats. Conclusion These results suggest that the inhibition of cerebral NADPH oxidase and the improvement of neuroinflammation are key mechanisms mediating the neuroprotective actions of C-PC against brain ischemia.
... inflammatory-related signaling molecules and inhibited pro-inflammatory cytokines formation in in vitro and animal studies. 6,28,29 Immulina is a high molecular weight polysaccharide extract from spirulina that has been shown to have anti-inflammatory effects. 7,30 GLA is the most abundant fatty acid in spirulina, and an increased ratio of GLA to arachidonic acid is capable of attenuating biosynthesis of arachidonic acid metabolites (i.e., prostaglandins series 2, leukotrienes series 4) and exerts an anti-inflammatory effect. ...
Article
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Background: Spirulina is an interesting nutritional supplement that has attracted a lot of attention. The aim of the present study was to examine the effect of spirulina supplementation on oxidative stress, inflammatory factors and plasma markers of exercise-induced muscle damage in male taekwondo athletes. Results: A total of 18 trained taekwondo male athletes took part in a double-blind, placebo-controlled crossover study. Each subject received either spirulina (8 g/day) or placebo for 3 weeks. The study had two periods separated by a 14-day washout. Blood samples were taken after finishing a training checklist program (4 times in total). There were no significant carryover effects; therefore, the two-week washout period was adequate. Compared to the placebo, a dose of 8 g / d of spirulina supplement over 21 days resulted in a significant decrease in plasma levels of lactate dehydrogenase (LDH), creatine kinase (CK) and interleukin 6 (IL6) and a significant increase in plasma levels of total antioxidant capacity (TAC), superoxide dismutase (SOD) and glutathione peroxidase (GPX) (p<0.05). There was not any statistically significant change in the plasma malondialdehyde (MDA) (p>0.05). Conclusion: Due to the improvement of antioxidant and anti-inflammatory conditions as well as an appropriate protein content, spirulina supplementation can produce a preventive effect on exercise-induced muscle damage in taekwondo athletes. Trial registration: Iranian Registry of Clinical Trials, IRCT20121110011421N4. Registered 12 July 2021 - Retrospectively registered, https://irct.ir/trial/11692.
... (18) Phycocyanin has many advantages, including water solubility, a non-toxic nature. (19) Therefore, using phycocyanin is a better alternative as a safe photosensitizer to be used in disinfecting cavities before restoration especially in esthetic zone. ...
Preprint
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Antimicrobial photodynamic therapy (aPDT) can be adopted as a modality for bacterial decontamination before cavity restoration to decrease the risk of secondary caries development. Trials to eliminate the microbial load using cavity disinfectants with no adverse effect on the bond strength of adhesive restoration geared toward the long-term success. C-phycocyanin is a safe photosensitizer to be used in disinfecting cavities before restoration especially in esthetic zone as it does not stain the tooth or the restoration as does the toluidine blue. ⁽¹⁶⁾ However no studies had evaluated the bond strength of resin to dentin disinfected with C-phycocyanin extracted from spirulina platensis. The teeth (n=48) will be allocated into 2 groups (n=24) according to the type of exposed dentin surface (coronal dentin and radicular dentin). Artificial caries affected dentin of coronal dentin (ACAD) will be induced after pH cycling for 14 days. Dentin surfaces will be disinfected either by using C-phycocyanin as photosensitizer activated using 635-nm diode laser or 2 % chlorohexidine or not disinfected (control group). Then one step self-etch adhesive will be bonded to coronal dentin followed by resin composite packing into the tygon tube applied perpendicular onto the coronal dentin.Self-adhesive resin cement will be bonded to radicular dentin by packing it into the tygon tubes applied perpendicular onto the radicular dentin. Microshear bond strength of self-etch adhesive to coronal dentin; and resin cement to radicular dentin will be tested. One sample from each group will be prepared for scanning electron microscope (SEM) examination.
... For example, phycocyanin, a water-soluble and non-toxic protein isolated from Spirulina, can decrease the plasma levels of total cholesterol, triglycerides, and malondialdehyde in diabetic mice [66]. Phycocyanin exhibits anti-inflammatory activities through inhibiting cyclooxygenase-2 expression and cytokines production in lipopolysaccharide-activated macrophages [67,68]. Furthermore, microalgae are also one source of ω3 PUFAs, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). ...
Article
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β-carotene, a member of the carotenoid family, is a provitamin A, and can be converted into vitamin A (retinol), which plays essential roles in the regulation of physiological functions in animal bodies. Microalgae synthesize a variety of carotenoids including β-carotene and are a rich source of natural β-carotene. This has attracted the attention of researchers in academia and the biotech industry. Methods to enrich or purify β-carotene from microalgae have been investigated, and experiments to understand the biological functions of microalgae products containing β-carotene have been conducted. To better understand the use of microalgae to produce β-carotene and other carotenoids, we have searched PubMed in August 2021 for the recent studies that are focused on microalgae carotenoid content, the extraction methods to produce β-carotene from microalgae, and the bioactivities of β-carotene from microalgae. Articles published in peer-reviewed scientific journals were identified, screened, and summarized here. So far, various types and amounts of carotenoids have been identified and extracted in different types of microalgae. Diverse methods have been developed overtime to extract β-carotene efficiently and practically from microalgae for mass production. It appears that methods have been developed to simplify the steps and extract β-carotene directly and efficiently. Multiple studies have shown that extracts or whole organism of microalgae containing β-carotene have activities to promote lifespan in lab animals and reduce oxidative stress in culture cells, etc. Nevertheless, more studies are warranted to study the health benefits and functional mechanisms of β-carotene in these microalgae extracts, which may benefit human and animal health in the future.
... Phycocyanin is one of the natural biological molecules found in Spirulina platensis [13] as a light-harvesting pigment, which possess anti-inflammatory, anti-cancer, and antioxidant effects [14]. Phycocyanin has many advantages, including water solubility, a non-toxic nature [15], and immune system boosting properties [16]. The anionicity or cationicity of these photosensitizers after binding process to the calcium atoms or the phosphate atoms respectively which present in hydroxyapatite crystals produces precipitates that act as a physical barrier, thus interfering with the dentin surface-resin contact [17]. ...
Article
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Objectives The aim of this study is to evaluate the influence of the antimicrobial photodynamic therapy with phycocyanin and toluidine blue on the bond strength of resin composite to the sound dentin. Materials and methods The samples include 120 tooth blocks taken from 60 human extracted sound third molar teeth. They were randomly divided into 12 groups and disinfected with two different photosensitizers (Phycocyanin and Toluidine blue) activated by 635 nm diode laser for aPDT procedure. Then two different protocols (total-etch and self-etch) of universal adhesive system (G-Premio BOND, GC Dental Products CORP. Japan) were applied. The samples then filled with resin composite (Gradia® Direct, GC Dental Products CORP. Japan). After 10000 cycles of thermocycling, all samples were subjected to the micro shear bond strength (μSBS) test using a universal testing machine (1 mm/min). The data were analyzed with One Way ANOVA. Results The effect of aPDT using both photosensitizers (phycocyanin and toluidine blue O) on the bonding strength to dentin was not significant (P>0.05). However, the bonding strength of total etch groups was reduced significantly (P<0.05) after aPDT using both photosensitizers. Phycocyanin self-etch group showed the greatest bonding strength (19.48 ± 3.89 MPa) in comparison to other aPDT groups. No significant reduction after thermocycling in dentin bond strength was observed in all groups (P>0.05), with exception of control total etch groups, which showed significant difference (P<0.05). Conclusion aPDT using toluidine blue O and phycocyanin has no adverse effect on bonding to sound dentin when using universal adhesive in self-etch protocol. Clinical relevance Phycocyanin is more recommended to be used in aPDT in comparison to toluidine blue as a natural photosensitizer.
... In addition, spirulina is a rich source of the pigment phycocyanin, which is a very powerful antioxidant and has the property of destroying free radicals (hydroxyl and proximal radicals) [10]. The effects of spirulina on IL6 concentration and activation have been demonstrated in various studies [11][12][13]. ...
... Phenolic compounds are a source of bioactive molecules with several beneficial health effects 6 due to their ability to act as antioxidants 7 , antibacterial 8 , and antidiabetes agents 9 . Phycobiliproteins, carotenoids and phenol present in S. platensis have anti-inflamatory activities 10 , thus making them a potential functional food product 11 . ...
Article
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Background: Spirulina platensis contains several bioactive molecules such as phenol, flavonoid and phycocyanin pigments. This study unveils total phenol, flavonoid, antioxidant activity, phycocyanin content and evaluated encapsulation efficiency from Ocimum basilicum intervention on S. platensis . O. basilicum intervention aims to reduce unpleasant odors from S. platensis that will increase consumption and increase bioactive compounds. Methods: The intervention was carried out by soaking a S. platensis control sample (SP) in O. basilicum with a ratio of 1:4 (w/v) and it was then dried (DSB) and microencapsulated by freeze drying methods (MSB) using a combination of maltodextrin and gelatin. Total flavonoid and phenolic analysis with curve fitting analysis used a linear regression approach. Antioxidant activity of samples was analysed with the 2,2’-azino-bis-3-3thylbenzthiazoline-6-sulphonic acid (ABTS) method. Data were analysed using ANOVA at significance level (p < 0.05) followed by Tukey test models using SPSS v.22. Results: The result of this study indicated that O. basilicum intervention treatment (DSB) has the potential to increase bioactive compounds such as total phenol, antioxidant activity and phycocyanin, and flavonoid content. Intervention of O. basilicum on S. platensis (DSB) significantly increases total phenol by 49.5% and phycocyanin by 40.7%. This is due to the phenol and azulene compounds in O. basilicum which have a synergistic effect on phenol and phycocyanin in S. platensis . Microencapsulation using a maltodexrin and gelatin coating is effective in phycocyanin protection and antioxidant activity with an encapsulation efficiency value of 71.58% and 80.5%. Conclusion: The intervention of O. basilicum on S. platensis improved the total phenol and phycocyanin content and there is potential for a pharmaceutical product for a functional food and pharmaceutical product.
... For example, it's been clear that Spirulina sp. extract had protective effects on mouse BV-2 normal microglial cells Chen et al. [27], normal 3T3 mouse fibroblasts Chu et al. [28], murine bone marrow Hayashi et al. [29], and human stem cells Bachstetter et al. [30]. According to the results of the present study along with the previous studies, it seems that Spirulina extract has significant inhibitory effects on cancer cells and at the same time protects the normal cells. ...
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In order to study the effects of Spirulina, Arthrospira platensis, two cell lines of A549 and HFF were treated with the concentration of IC50 for 24 h. MTT analysis showed that the highest decrease in viability of cells happened at the concentration of 500 μg/ml. The necrosis, releases of LDH, produced DCFH, and Lipid peroxidation were higher in the cancer cell lines in comparison to normal cells. Results showed that the extract affected the cell cycle of the A549 cell line. Also, the algal extract had concentration-dependent antioxidant activity. Also, the production of malonyl dialdehyde was significantly higher in treated cells and there was a significant relationship between produced MDA and ROS. Results showed that A. platensis extract had a remarkable effect on the lung cancer cell cycle and arrest the cell cycle in phase G2; so the cells didn't enter phase M and the proliferation of cancer cells prevented. Furthermore, according to the higher production of ROS and MDA in treated A549 cancer cell lines, it could be concluded that this algal extract could be considered as a natural product with anticancer activity against lung cancer cells.
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Science has been showing the great impact that diet represents on man’s health. The diversified consumption of food is deficient throughout the world. The academy and the food industry need, in line with the consumer, to introduce new foods and new substances and seek prevention and therapy for different chronic noncommunicable diseases (NCDs). Neurodegenerative diseases, especially Alzheimer’s and Parkinson’s disease, are age-related disorders and are closely associated with stochastic factors that denote the choices of each individual for himself and the environment. These behaviors potentiate the oxidative stress and the inflammatory processes that culminate in the appearance of these pathologies. Spirulina platensis, due to its content of proteins, pigments, and vitamins, plays an important role because these elements are considered valuable targets for therapeutic interventions in neurodegenerative diseases.
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Chapter
Neurodegenerative diseases are diverse in nature and are characterized by the continuous loss of neurons, glial cells, and neural networks in the brain and spinal cord, as well as selective malfunctioning of these tissues. Dementia pathologies such as Alzheimer’s disease are reaching epidemic proportions, yet they are not successfully managed by effective symptomatic treatments. Even with a high prevalence, neurogenerative diseases are treated with drugs that alleviate the symptoms of patients, but which develop adverse events and still do not inhibit the progression of the disease. Only five drugs have been developed to alleviate cognitive symptoms and behavioral and psychological symptoms of dementia. As two of these licensed drugs, cholinesterase inhibitors are natural derived galantamine and rivastigmine, the potential for plants to yield new therapeutic agents has stimulated extensive research to discover new cholinesterase inhibitors together with plant extracts, phytochemicals and their derivatives with other mechanistic effects relevant to dementia treatment. Consequently, algae pave way for exploring potential compounds with therapeutic uses. In the search of neuroprotective natural product, algae have been recognised as an alternative to explore advanced bioactive natural materials because algae contain a wide range of bioactive compounds. Thus, within a new pharmacological perspective, this chapter aimed to discuss the therapeutic potential of natural compounds of algae against neurogenerative diseases.
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Glaucium grandiflorum extracts have traditionally been used to treat brain-related disorders. G. grandiflorum extracts also exhibited inhibitory effects on cholinesterase enzymes, as well as antigenotoxic activity. However, no research has been done on the effect of G. grandiflorum alkaloid extracts on the anti-oxidative and anti-inflammatory mechanisms. In this study we aimed to evaluate the anti-oxidative and anti-inflammatory activities of the alkaloid extract obtained from G. grandiflorum as well as the mechanisms responsible for their neuroprotective effects in neuronal damage caused by LPS in BV2 cells. We used LC-MS/MS and 1H, 13C NMR analysis to determine the presence of major alkaloids (allocryptopine, tetrahydropalmatine, and tetrahydroberberine N-oxide (trans-cannadine-N-oxide) in the alkaloid extracts. We used flow cytometry to study the alkaloid extracts' effects on ROS production; we also employed qRT-PCR and Western Blot to analyze the effects of oxidative stress and inflammation-related genes and proteins. ROS production within the cell was inhibited by chloroform alkaloid extract (CAE). There occurred marked CAE-induced reductions in IL-1β, Cox-2, and iNOS mRNA expressions. We also observed marked reductions in IL-6 and TNF-α mRNA expressions with methanol alkaloid extract (MAE). CAE effectively suppressed IL-1β and iNOS protein levels, especially as in qRT-PCR studies, while MAE effectively reduced IL-6 and TNF-α protein levels. Additionally, MAE was found to be prominent in suppressing the levels of Cox-2 protein, unlike qRT-PCR studies. According to our study findings, oxidative stress brought about by inflammation was suppressed by alkaloid extracts from G. grandiflorum which can be attributed to their suppressor effects on the pro-inflammatory cytokines-mediators, and p38 MAPK. As a result, a drug active substance that suppresses oxidative stress and inflammation has been brought to the neuropharmacological field.
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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.
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Aim The current study aimed to evaluate the efficacy of chlorhexidine (CHX), phycocyanin photosensitizer (PC), green tea extract (GTE), and propolis (PP) on the adhesive bond integrity and microleakage of caries-affected dentin (CAD) using etch and rinse adhesive system. Material and Methods A sum of 80 extracted human mandibular molars was collected and assessed using ICDAS criteria. Randomly CAD samples were treated with different disinfectants (n = 20) each CHX, PC, GTE, and PP. After ensuring disinfection, specimens were rehabilitated with bulk-fill composite resin employing etch and rinse adhesive system. SBS testing was performed by engaging (n=10) specimens in a universal testing machine. Microleakage analysis was performed by using the dye penetration technique.A stereomicroscope under 40× magnification was utilized for analyzing failure modes. Statistical analysis was accomplished by using the ANOVA and Tukey's post hoc tests (p<0.05). Results Highest bond strength was displayed by CAD disinfection with CHX and bonded to resin cement (15.33 ± 0.14 MPa). Whereas, the lowest SBS bond value was presented by Group 2 dentin surface disinfection with PC. CAD disinfected with GTE, PP and CHX demonstrated comparable SBS(p>0.05). The maximum microleakage score was exhibited when CAD bonded to resin cement disinfected with PP. While the minimum microleakage score was unveiled CAD bonded to resin cement sanitized with CHX Conclusion Caries-affected dentin bonded to resin cement, chlorhexidine exhibited the highest adhesive shear bond strength with a minimal microleakage score using etch and rinse adhesive system.
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Microalgae and microalgae-derived compounds have great potential as supplements in the human diet and as a source of bioactive products with health benefits. Spirulina (Arthrospira platensis (Nordstedt) Gomont, or Spirulina platensis) belongs to the class of cyanobacteria and has been studied for its numerous health benefits, which include anti-inflammatory properties, among others. This work was aimed at comparing some spirulina products available on the Italian market. The commercial products here analyzed consisted of spirulina cultivated and processed with different approaches. Single-component spirulina products in powder and flake form, free of any type of excipient produced from four different companies operating in the sector, have been analyzed. The macro- and micromorphological examination, and the content of pigments, phycobiliproteins, phenols, and proteins have shown differences regarding the morphology and chemical composition, especially for those classes of particularly unstable compounds such as chlorophylls and carotenoids, suggesting a great influence of both culture conditions and processing methods.
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Nostoc sphaeroides is an edible Cyanobacterium which has high nutritional value and is widely used in dietary supplements and therapeutic products. N. sphaeroides contains protein, fatty acid, minerals and vitamins. Its polysaccharides, phycobilin, phycobiliproteins and some lipids are highly bioactive. Thus, N. sphaeroides possesses anti-oxidation, anti-inflammation and cholesterol reducing functions. This paper reviews and evaluates the literature on nutritionally and functionally important compounds of N. sphaeroides. It also reviews and evaluates the processing of technologies used to process N. sphaeroides from fresh harvest to dry particulates including pretreatment, sterilization and drying, including their impact on sensorial and nutritional values. This review shows that a suitable combination of ultrasound, radio frequency and pulse spouted microwave with traditional sterilization and drying technologies greatly improves the sensorial and nutritive quality of processed N. sphaeroides and improves their shelf life; however, further research is needed to evaluate these hybrid technologies. Once suitably processed, N. sphaeroides can be used in food, cosmetics and pharmaceutical drugs as an ingredient.
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Background: Spirulina platensis contains several bioactive molecules such as phenol, flavonoid and phycocyanin pigments. This study unveils total phenol, flavonoid, antioxidant activity, phycocyanin content and evaluated encapsulation efficiency from Ocimum basilicum intervention on S. platensis . O. basilicum intervention aims to reduce unpleasant odors from S. platensis that will increase consumption and increase bioactive compounds. Methods: The intervention was carried out by soaking a S. platensis control sample (SP) in O. basilicum with a ratio of 1:4 (w/v) and it was then dried (DSB) and microencapsulated by freeze drying methods (MSB) using a combination of maltodextrin and gelatin. Total flavonoid and phenolic analysis with curve fitting analysis used a linear regression approach. Antioxidant activity of samples was analysed with the 2,2’-azino-bis-3-3thylbenzthiazoline-6-sulphonic acid (ABTS) method. Data were analysed using ANOVA at significance level (p < 0.05) followed by Tukey test models using SPSS v.22. Results: The result of this study indicated that O. basilicum intervention treatment (DSB) has the potential to increase bioactive compounds such as total phenol, antioxidant activity and phycocyanin, and flavonoid content. Intervention of O. basilicum on S. platensis (DSB) significantly increases total phenol by 49.5% and phycocyanin by 40.7%. This is due to the phenol and azulene compounds in O. basilicum which have a synergistic effect on phenol and phycocyanin in S. platensis . Microencapsulation using a maltodexrin and gelatin coating is effective in phycocyanin protection and antioxidant activity with an encapsulation efficiency value of 71.58% and 80.5%. Conclusion: The intervention of O. basilicum on S. platensis improved the total phenol and phycocyanin content and there is potential for a pharmaceutical product for a functional food and pharmaceutical product.
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Spirulina platensis treatment (400 mg kg(-1) for 25 days) effectively suppressed peripheral sensitization via modulation of glial activation and improved motor coordination and restoration of functional motor activity in collagen-induced arthritic rats. Spirulina treatment also resulted in an appreciable reduction of the NF200 accumulation in the spinal cord neurons of arthritic rats. This is indicative of neuroprotective action of S. platensis against glutamate excitotoxicity-induced central sensitization produced by the peripheral joint inflammation in the collagen-induced arthritis. The results suggest that effects of S. platensis may be due to its counter regulation of spinal glial activation and could be a potential strategy for the treatment of arthritis.
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Changes in the gene expressions for tumor necrosis factor-α (TNF-α) and/or interleukin-1β (IL-1β) during tinnitus have not been previously reported. We evaluated tinnitus and mRNA expression levels of TNF-α, IL-1β, and N-methyl D-aspartate receptor subunit 2B (NR2B) genes in cochlea and inferior colliculus (IC) of mice after intraperitoneal injections of salicylate. Forty-eight 3-month-old male SAMP8 mice were randomly and equally divided into two groups: salicylate-treated and saline-treated. All mice were trained to perform an active avoidance task for 5 days. Once conditioned, an active avoidance task was performed 2 hours after daily intraperitoneal injections of saline, either alone or containing 300 mg/kg sodium salicylate. Total numbers of times (tinnitus score) the mice climbed during the inter-trial silent period for 10 trials were recorded daily for 4 days (days 7 to 10), and then mice were euthanized for determination of mRNA expression levels of TNF-α, IL-1β, and NR2B genes in cochlea and IC at day 10. Tinnitus scores increased in response to daily salicylate treatments. The mRNA expression levels of TNF-α increased significantly for the salicylate-treated group compared to the control group in both cochlea (1.89 ± 0.22 vs. 0.87 ± 0.07, P < 0.0001) and IC (2.12 ± 0.23 vs. 1.73 ± 0.22, p = 0.0040). mRNA expression levels for the IL-1β gene also increased significantly in the salicylate group compared to the control group in both cochlea (3.50 ± 1.05 vs. 2.80 ± 0.28, p < 0.0001) and IC (2.94 ± 0.51 versus 1.24 ± 0.52, p = 0.0013). Linear regression analysis revealed a significant positive association between tinnitus scores and expression levels of TNF-α, IL-1β, and NR2B genes in cochlea and IC. In addition, expression levels of the TNF-α gene were positively correlated with those of the NR2B gene in both cochlea and IC; whereas, the expression levels of the IL-1β gene was positively correlated with that of the NR2B gene in IC, but not in cochlea. We conclude that salicylate treatment resulting in tinnitus augments expression of the TNF-α and IL-1β genes in cochlea and IC of mice, and we suggest that these proinflammatory cytokines might lead to tinnitus directly or via modulating the NMDA receptor.
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Seungma-galgeun-tang (SGT) has been used for treatment of chronic diseases in the folk medicine recipe. Since nitric oxide (NO) is one of the major inflammatory parameters, we first studied the effects of SGT on NO production in lipopolysaccharide (LPS)-stimulated BV-2 microglia. SGT inhibited the secretion of NO in BV-2 microglia, without affecting cell viability. The protein level of inducible nitric oxide synthase (iNOS) was decreased by SGT and SGT also inhibited production of PGE2 and expression of Cox-2. Proinflammatory cytokines, such as TNF-α, IL-1β and IL-12, were inhibited by SGT in a dose-dependent manner and SGT blocked the activation of NF-κB, which was considered to be a potential transcription factor for the expression of iNOS, COX-2 and proinflammatory cytokines. SGT also blocked the degradation of IκB and activation (decrease of cytosolic p65) of NF-κB, p65. These results suggest that SGT could exert its anti-inflammatory actions by suppressing the synthesis of NO through inhibition of NF-B activity.
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An inflammatory response in the central nervous system mediated by the activation of microglia is a key event in the early stages of the development of neurodegenerative diseases. LPS has been reported to cause marked microglia activation. It is very important to develop drugs that can inhibit microglia activation and neuroinflammation. Here, we investigated the inhibitory effect of YC-1, a known activator of soluble guanylyl cyclase, against LPS-induced inflammatory responses in microglia. To understand the inhibitory effects of YC-1 on LPS-induced neuroinflammation, primary cultures of rat microglia and the microglia cell line BV-2 were used. To examine the mechanism of action of YC-1, LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production, iNOS, COX-2 and cytokine expression were analyzed by Griess reaction, ELISA, Western blotting and RT-PCR, respectively. The effect of YC-1 on LPS-induced activation of nuclear factor kappa B (NF-kappaB) was studied by NF-kappaB reporter assay and immunofluorocytochemistry. YC-1 inhibited LPS-induced production of NO and PGE2 in a concentration-dependent manner. The protein and mRNA expression of iNOS and COX-2 in response to LPS application were also decreased by YC-1. In addition, YC-1 effectively reduced LPS-induced expression of the mRNA for the proinflammatory cytokines, TNF-alpha and IL-1beta. Furthermore, YC-1 inhibited LPS-induced NF-kappaB activation in microglia. YC-1 was able to inhibit LPS-induced iNOS and COX-2 expression and NF-kappaB activation, indicating that YC-1 may be developed as an anti-inflammatory neuroprotective agent.
Article
The expression of the genes for cyclooxygenase (COX) and NMDA receptor (NR) has seldom been reported in tinnitus. We hypothesized that expression of COX-2 and NR was altered in the cochlea and midbrain in salicylate-induced tinnitus. Experimental study on mice. We evaluated the tinnitus score and mRNA expression levels of COX-2 and NR subtype 2B (NR2B) in the cochlea and midbrain in response to intraperitoneal injections of salicylate for 4 days. At day 4 of tinnitus induction, the mean weights of the whole body and midbrain did not change greatly in both control and salicylate groups. The tinnitus score was not elevated from day 1 to day 4 in the control group, but increased day by day in the salicylate group. The mRNA expression level of COX-2 decreased slightly in the salicylate group in the cochlea (1.1 ± 0.33 vs. 1.3 ± 0.49, P = .0752) and in the midbrain (0.9 ± 0.10 versus 1.0 ± 0.35, P = .0489). Inversely, the expression levels of the NR2B gene increased moderately in the salicylate group in the cochlea (3.7 ± 0.47 versus 2.3 ± 1.13, P < 0.0001) and in the midbrain (1.6 ± 0.64 versus 1.0 ± 0.44, P = .0007). Salicylate induced tinnitus and altered the expression of the COX-2 and NR2B genes in the cochlea and midbrain of mice. These findings might contribute to further understanding of pathophysiology and therapy of tinnitus.
Article
This review provides a complete overview over a spectrum of areas where value-added applications of algae are in sight, from conventional food, feed, dietary supplement, and cosmetics to novel technologies for environmental and biofuel applications. In most cases macro- and microalgae are discussed separately due to their inherent differences from cultivation. Comparison of various cultivation systems are made in relation to specific value-added products. The potential uses of algal biomeal, the sizable waste stream generated after extraction of targeted compounds such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from the biomass of cultivated microalgae, are also discussed based on the concept of waste-recovery and biorefinery. The article presents some promising patents on potential industrial applications of macro- and microalgae.
Article
Epidemiological studies indicate that the intake of Mediterranean-style diet is inversely associated with risk of stroke, cardiovascular diseases, and cancer. Spirulina is widely used nutritional supplement rich in proteins and antioxidants. Evidence demonstrates that the impaired energy metabolism and the excessive generation of reactive oxygen radicals contribute to the brain injury associated with cerebral ischemia. In the present study, the protective effect of Spirulina was investigated in transient middle cerebral artery occlusion (MCAO)-induced focal cerebral ischemia-reperfusion injury in rats. Male albino rats were divided into six groups: control, sham-operated group, ischemic control group, and Spirulina-pretreated groups (45, 90 and 180 mg/kg/p.o.). Spirulina was administered once a day, for 7 days. The rats were subjected to a 2-h right MCAO via the intraluminal filament technique and 22 h of reperfusion. Pretreatment with Spirulina significantly reduced the histological changes and neurological deficits. Spirulina at a dose of 180 mg/kg significantly reversed the elevated brain malondialdehyde (MDA) content and restored the decreased activities of brain superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH) indicating that Spirulina has the protective potential against cerebral ischemia injury and its protective effects may be due to its antioxidant property.
Article
In this study, we investigated the signaling pathways involved in inflammatory production caused by peptidoglycan (PGN), a cell wall component of the gram-positive bacterium, in BV-2 microglia. PGN caused a concentration- and time-dependent increase in inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) mRNA and protein levels. In addition, PGN also induced IL-1β, TNF-α and IL-6 mRNA up-regulation in a concentration-dependent manner. Moreover, PGN also increased Toll-like receptor 2 (TLR2) expression in BV-2 microglia. Administration of TLR2 neutralizing antibody effectively inhibited PGN-induced iNOS and COX-2 expression. On the other hand, PGN-induced iNOS and COX-2 up-regulation were attenuated by PI3-kinase inhibitors (LY294002 and wortmannin), and an AKT inhibitor. Treatment of BV-2 microglia with PGN caused a time-dependent activation of PI3-kinase (p85) and AKT. PGN-induced PI3-kinase/AKT activation, iNOS and COX-2 expression were also inhibited by MyD88 inhibitory peptide. Treatment of cells with NF-κB inhibitor (pyrrolidine dithiocarbamate), IκBα phosphorylation inhibitor (Bay 117082), or IκB protease inhibitor (l-1-tosylamido-2-phenylethyl chloromethyl ketone) inhibited PGN-induced iNOS and COX-2 expression. Furthermore, stimulation of cells with PGN also activated IKKκ/α, IκBα phosphorylation, IκBα degradation, p65 phosphorylation at Ser536, and increased κB-luciferase activity. PGN-induced IKKα/κ phosphorylation, IκB7α phosphorylation, and IκBα degradation were further inhibited by pre-treatment with PI3-kinase inhibitors. Moreover, PGN-mediated increase of κB-luciferase activity was also inhibited by pre-transfection with dominant-negative mutants of p85, AKT, IKKα or IKKβ. Our data demonstrate that PGN-induced iNOS, COX-2 and proinflammatory cytokine expression was mediated through the TLR2/MyD88/PI3-kinase/AKT pathway, which in turn initiates IKKα/β and NF-κB activation in BV-2 microglia.
Article
There is considerable evidence that activated microglia play a central role in the pathogenesis of many prominent neurodegenerative disorders, including Parkinson's and Alzheimer's diseases. The elevated NADPH oxidase activity of these microglia contributes importantly to their pathogenic impact, collaborating with increased iNOS activity to generate the cytotoxic oxidant peroxynitrite. Phycocyanobilin (PCB), a chromophore derived from biliverdin that constitutes up to 1% of the dry weight of spirulina, has recently been shown to be a potent inhibitor of NADPH oxidase. The possibility that orally administered PCB could reach the brain parenchyma in sufficient concentrations to influence microglial function is consistent with the findings of two rodent studies: orally administered C-phycocyanin (the spirulina holoprotein that includes PCB) suppresses the neurotoxic impact of the excitotoxin kainite in rats, and a diet high in spirulina ameliorates the loss of dopaminergic neurons in the MPTP-induced Parkinsonian syndrome in mice. Hence, supplemental PCB may have considerable potential for preventing or slowing the progression of a range of neurodegenerative disorders. Some of the central physiological effects of PCB may also reflect inhibition of neuronal NADPH oxidase, which is now known to have a modulatory impact on neuron function, and can mediate neurotoxicity in certain circumstances. Neuronal NADPH oxidase activation is an obligate mediator of the central pressor effect of angiotensin II, and there is suggestive evidence that it may also play a role in inflammatory hyperalgesia; these findings point to possible antihypertensive and analgesic applications for PCB. The likely favorable effects of PCB on vascular health may also protect the brain by decreasing stroke risk, and inhibition of NADPH oxidase in rodents has been shown to lessen the neurotoxic impact of temporary cerebral ischemia. PCB may thus have versatile potential for preserving the healthful function of the central nervous system into advanced old age--albeit optimal neuroprotection may require more complex regimens that incorporate PCB along with other well tolerated nutraceuticals and drugs, in conjunction with prudent lifestyle modifications.
Article
The scientific dogma that multiple sclerosis (MS) is a disease caused by a single pathogenic mechanism has been challenged recently by the heterogeneity observed in MS lesions and the realization that not all patterns of demyelination can be modeled by autoimmune-triggered mechanisms. To evaluate the contribution of local tumor necrosis factor (TNF) ligand/receptor signaling pathways to MS immunopathogenesis we have analyzed disease pathology in central nervous system-expressing TNF transgenic mice, with or without p55 or p75TNF receptors, using combined in situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling and cell identification techniques. We demonstrate that local production of TNF by central nervous system glia potently and selectively induces oligodendrocyte apoptosis and myelin vacuolation in the context of an intact blood-brain barrier and absence of immune cell infiltration into the central nervous system parenchyma. Interestingly, primary demyelination then develops in a classical manner in the presence of large numbers of recruited phagocytic macrophages, possibly the result of concomitant pro-inflammatory effects of TNF in the central nervous system, and lesions progress into acute or chronic MS-type plaques with axonal damage, focal blood-brain barrier disruption, and considerable oligodendrocyte loss. Both the cytotoxic and inflammatory effects of TNF were abrogated in mice genetically deficient for the p55TNF receptor demonstrating a dominant role for p55TNF receptor-signaling pathways in TNF-mediated pathology. These results demonstrate that aberrant local TNF/p55TNF receptor signaling in the central nervous system can have a potentially major role in the aetiopathogenesis of MS demyelination, particularly in MS subtypes in which oligodendrocyte death is a primary pathological feature, and provide new models for studying the basic mechanisms underlying oligodendrocyte and myelin loss.
Article
Nurr1, an orphan nuclear receptor, plays an essential role in the generation and maintenance of dopaminergic neurons in the brain. Rare mutations in Nurr1 are associated with familial Parkinson's disease, but the underlying basis for this relationship has not been established. Here, we demonstrate that Nurr1 unexpectedly functions to inhibit expression of pro-inflammatory neurotoxic mediators in both microglia and astrocytes. Reduced Nurr1 expression results in exaggerated inflammatory responses in microglia that are further amplified by astrocytes, leading to the production of factors that cause death of tyrosine hydroxylase-expressing neurons. Nurr1 exerts anti-inflammatory effects by docking to NF-kappaB-p65 on target inflammatory gene promoters in a signal-dependent manner. Subsequently, Nurr1 recruits the CoREST corepressor complex, resulting in clearance of NF-kappaB-p65 and transcriptional repression. These studies suggest that Nurr1 protects against loss of dopaminergic neurons in Parkinson's disease in part by limiting the production of neurotoxic mediators by microglia and astrocytes.
Article
Parkinson's disease is characterized by a loss of dopaminergic neurons in the mesencephalon. Although the mechanism of this neuronal loss is still unknown, oxidative stress is very likely involved in the cascade of events leading to nerve cell death. Since nitric oxide could be involved in the production of free radicals, we analysed, using immunohistochemistry and histochemistry, the production systems of nitric oxide in the mesencephalon of four patients with idiopathic Parkinson's disease and three matched control subjects. Using specific antibodies directed against the inducible isoform of nitric oxide synthase (the enzyme involved in the synthesis of nitric oxide), we found evidence to suggest that this isoform was present solely in glial cells displaying the morphological characteristics of activated macrophages. Immunohistochemical analysis performed with antibodies against the neuronal isoform of nitric oxide synthase, however, revealed perikarya and processes of neurons but no glial cell staining. The number of nitric oxide synthase-containing cells was investigated by histoenzymology, using the NADPH-diaphorase activity of nitric oxide synthase. Histochemistry revealed (i) a significant increase in NADPH-diaphorasepositive glial cell density in the dopaminergic cell groups characterized by neuronal loss in Parkinson's disease and (ii) a neuronal loss in Parkinson's disease that was two-fold greater for pigmented NADPH-diaphorase-negative neurons than for pigmented NADPH-diaphorase-positive neurons.
Article
The most characteristic feature of microglial cells is their rapid activation in response to even minor pathological changes in the CNS. Microglia activation is a key factor in the defence of the neural parenchyma against infectious diseases, inflammation, trauma, ischaemia, brain tumours and neurodegeneration. Microglia activation occurs as a graded response in vivo. The transformation of microglia into potentially cytotoxic cells is under strict control and occurs mainly in response to neuronal or terminal degeneration, or both. Activated microglia are mainly scavenger cells but also perform various other functions in tissue repair and neural regeneration. They form a network of immune alert resident macrophages with a capacity for immune surveillance and control. Activated microglia can destroy invading micro-organisms, remove potentially deleterious debris, promote tissue repair by secreting growth factors and thus facilitate the return to tissue homeostasis. An understanding of intercellular signalling pathways for microglia proliferation and activation could form a rational basis for targeted intervention on glial reactions to injuries in the CNS.
Article
The cytokines interleukin (IL)-1 and tumor necrosis factor (TNF)-alpha, produced by glial cells within the brain, appear to contribute to the neuropathogenesis of several inflammatory neurodegenerative diseases; however, little is known about the mechanism underlying cytokine-induced neurotoxicity. Using human fetal brain cell cultures composed of neurons and glial cells, we investigated the injurious effects of IL-1beta and TNF-alpha, cytokines which are known to induce nitric oxide (NO) production by astrocytes. Although neither cytokine alone was toxic, IL-1beta and TNF-alpha in combination caused marked neuronal injury. Brain cell cultures treated with IL-1beta plus TNF-alpha generated substantial amounts of NO. Blockade of NO production with a NO synthase inhibitor was accompanied by a marked reduction (about 45%) of neuronal injury, suggesting that NO production by astrocytes plays a role in cytokine-induced neurotoxicity. Addition of N-methly-D-aspartate (NMDA) receptor antagonists to brain cell cultures also blocked IL-1beta plus TNF-alpha-induced neurotoxicity (by 55%), implicating the involvement of NMDA receptors in cytokine-induced neurotoxicity. Treatment of brain cell cultures with IL-1beta plus TNF-alpha was found to inhibit [3H]-glutamate uptake and astrocyte glutamine synthetase activity, two major pathways involved in NMDA receptor-related neurotoxicity. These in vitro findings suggest that agents which suppress NO production or inhibit NMDA receptors may protect against neuronal damage in cytokine-induced neurodegenerative diseases.
Article
At the interface between the innate and adaptive immune systems lies the high-output isoform of nitric oxide synthase (NOS2 or iNOS). This remarkable molecular machine requires at least 17 binding reactions to assemble a functional dimer. Sustained catalysis results from the ability of NOS2 to attach calmodulin without dependence on elevated Ca2+. Expression of NOS2 in macrophages is controlled by cytokines and microbial products, primarily by transcriptional induction. NOS2 has been documented in macrophages from human, horse, cow, goat, sheep, rat, mouse, and chicken. Human NOS2 is most readily observed in monocytes or macrophages from patients with infectious or inflammatory diseases. Sustained production of NO endows macrophages with cytostatic or cytotoxic activity against viruses, bacteria, fungi, protozoa, helminths, and tumor cells. The antimicrobial and cytotoxic actions of NO are enhanced by other macrophage products such as acid, glutathione, cysteine, hydrogen peroxide, or superoxide. Although the high-output NO pathway probably evolved to protect the host from infection, suppressive effects on lymphocyte proliferation and damage to other normal host cells confer upon NOS2 the same protective/destructive duality inherent in every other major component of the immune response.
Article
The cytokine interleukin-6 (IL-6) is an important mediator of inflammatory and immune responses in the periphery. IL-6 is produced in the periphery and acts systemically to induce growth and differentiation of cells in the immune and hematopoietic systems and to induce and coordinate the different elements of the acute-phase response. In addition to these peripheral actions, recent studies indicate that IL-6 is also produced within the central nervous system (CNS) and may play an important role in a variety of CNS functions such as cell-to-cell signaling, coordination of neuroimmune responses, protection of neurons from insult, as well as neuronal differentiation, growth and survival. IL-6 may also contribute to the etiology of neuropathological disorders. Elevated levels of IL-6 in the CNS are found in several neurological disorders including AIDS dementia complex, Alzheimer's disease, multiple sclerosis, systemic lupus erythematosus, CNS trauma, and viral and bacterial meningitis. Moreover, several studies have shown that chronic overexpression of IL-6 in transgenic mice can lead to significant neuroanatomical and neurophysiological changes in the CNS similar to that commonly observed in various neurological diseases. Thus, it appears that IL-6 may play a role in both physiological and pathophysiological processes in the CNS.
Article
Interleukin-6 (IL-6) appears to be an important modulator of the inflammatory response associated with CNS ischemia. Clinically, IL-6 values obtained in the first week post-stroke have been shown to correlate with infarct size and outcome. In this study we used a focal reversible stroke model to investigate the time course and relationship to outcome of IL-6 production in plasma, brain and CSF. Reversible middle cerebral artery occlusion or sham surgery was produced in 50 adult Swiss Webster mice by advancing an 8-0 filament into the internal carotid artery for 2 h (sham 1 min). At 3, 6, 12, 24, and 72 h (8 each ischemia; 2 each sham) groups of animals were evaluated on a 28 point clinical scale, blood and CSF obtained, and the brains were evaluated for infarct volume and IL-6 mRNA levels. Serum levels of IL-6 (ELISA mean +/- SD; undetectable in controls) overall sham group, 102 +/- 87; 3 h, 908 +/- 494* pg ml-1; 6 h, 1079 +/- 468* pg ml-1; 12 h, 980 +/- 221* pg ml-1; pg ml-1; 24 h, 320 +/- 314* pg ml-1; 72 h, 20 +/- 30* pg ml-1 (*p < or = 0.05 to sham). CSF levels (ELISA) overall sham group, 10 +/- 18; 3 h, 379 +/- 210* pg ml-1; 6 h, 157 +/- 61* pg ml-1; 12 h, 136 +/- 88* pg ml-1; 24 h, 127 +/- 99 pg ml-1; 72 h, 72 +/- 9* pg ml-1 (*p < or = 0.05 to sham). Brain IL-6 mRNA levels overall sham group, 20; 3 h, 480; 6 h, 599; 12 h, 7960; 24 h, 20267; 72 h, 0. There was an overall R2 of 0.20 between plasma and CSF IL-6. There was an overall R2 of 0.13 and 0.20 between infarct size and serum and CSF IL-6 level respectively, and an overall R2 of 0.10 and 0.17 between neurologic function and serum and CSF IL-6 level respectively. These findings confirm that IL-6 values increase following CNS ischemia with peak serum and CSF levels occurring before brain values. CSF IL-6 levels had a stronger correlation with neurologic function and infarct size than serum.
Article
15-deoxy-Delta(12,14)-PGJ(2), a cyclopentenone derivative of PGD(2), was recently reported [Petrova et al., Proc. Natl. Acad. Sci. USA 96 (1999) 4668-4673] to suppress inducible nitric oxide synthase (iNOS) production in microglia and mixed glial cultures stimulated with lipopolysaccharide (LPS). We report here that in addition to suppressing iNOS production, 15d-PGJ(2) also decreases the production of tumor necrosis factor alpha (TNFalpha), interleukin-1 beta (IL-1beta) and cyclooxygenase-2 (COX-2) in LPS-stimulated BV-2 microglial cells, thereby acting as a general inhibitor of microglial activation. Concomitantly, 15d-PGJ(2) itself up-regulates the production of the antioxidant enzyme heme oxygenase-1 (HO-1) and increases intracellular total glutathione levels. To test if increased HO-1 levels were involved in the ability of 15d-PGJ(2) to block microglial activation, we used a HO-1 inhibitor that could block the activity of HO-1. The presence of the HO-1 inhibitor did not alter the 15d-PGJ(2)-induced inhibition of LPS-stimulated iNOS and TNFalpha protein levels, and led to only a partial reduction in the protection offered by 15d-PGJ(2) against LPS-induced nitrite production. These results suggest that HO-1 upregulation by 15d-PGJ(2) is not the primary pathway responsible for the anti-inflammatory action of 15d-PGJ(2) in microglial cells.
Article
Sesame antioxidants have been shown to inhibit lipid peroxidation and regulate cytokine production. In this study, we focused on the effect of sesamin and sesamolin, on nitric oxide (NO) induction by lipopolysaccharides (LPS) in the murine microglial cell line BV-2 and rat primary microglia. The results showed that sesamin and sesamolin significantly inhibited NO production, iNOS mRNA and protein expression in LPS-stimulated BV-2 cells. Sesamin or sesamolin significantly reduced LPS-activated p38 MAPK of BV-2 cells. Furthermore, SB203580, a specific inhibitor of p38 MAP kinase, dose-dependently inhibited NO production in LPS-stimulated BV-2 cells. Taken together, the inhibition of NO production might be due to the reduction of LPS-induced p38 MAPK signal pathway by sesamin and sesamolin.
Article
Free radicals are involved in neurodegenerative disorders, such as ischemia and aging. We have previously demonstrated that treatment with diets enriched with blueberry, spinach, or spirulina have been shown to reduce neurodegenerative changes in aged animals. The purpose of this study was to determine if these diets have neuroprotective effects in focal ischemic brain. Adult male Sprague-Dawley rats were fed with equal amounts of diets (blueberry, spinach, and spirulina) or with control diet. After 4 weeks of feeding, all animals were anesthetized with chloral hydrate. The right middle cerebral artery was ligated with a 10-O suture for 60 min. The ligature was later removed to allow reperfusional injury. Animals were sacrificed and brains were removed for caspase-3 enzymatic assays and triphenyltetrazolium chloride staining at 8 and 48 h after the onset of reperfusion. A subgroup of animals was used for locomotor behavior and biochemical assays. We found that animals which received blueberry, spinach, or spirulina enriched diets had a significant reduction in the volume of infarction in the cerebral cortex and an increase in post-stroke locomotor activity. There was no difference in blood biochemistry, blood CO2, and electrolyte levels among all groups, suggesting that the protection was not indirectly mediated through the changes in physiological functions. Animals treated with blueberry, spinach, or spirulina had significantly lower caspase-3 activity in the ischemic hemisphere. In conclusion, our data suggest that chronic treatment with blueberry, spinach, or spirulina reduces ischemia/reperfusion-induced apoptosis and cerebral infarction.
Article
Microglia are a major neuroglial component of the CNS, playing an important role as resident immunocompetent and phagocytic cells in the CNS in the event of injury and disease. To understand the role of microglia in the CNS in health and diseases, we have recently established an immortalized clonal cell line of human microglia, HMO6, from human embryonic telencephalon tissue by using a retroviral vector encoding v-myc. This immortalized microglia HMO6 cell line exhibits cell-type-specific antigens for microglia, including CD11b (Mac-1), CD68, CD86 (B7-2), HLA-ABC, HLA-DR, and RCA-1 lectin, and actively phagocytoses latex beads.
Article
Inflammation during the perinatal period has become a recognized risk factor for developmental brain injuries over the past decade or more. To fully understand the relationship between inflammation and brain development, a comprehensive knowledge about the immune system within the brain is essential. Microglia are resident immune cells within the central nervous system and play a critical role in the development of an inflammatory response within the brain. Microglia are critically involved with both the innate and adaptive immune system, regulating inflammation and cell damage within the brain via activation of Toll-like receptors, production of cytokines, and a myriad of other intracellular and intercellular processes. In this article, microglial physiology is reviewed along with the role of microglia in developmental brain injuries in humans and animal models. Last, microglial functions within the innate and adaptive immune system will be summarized. Understanding the processes of inflammation and microglial activation is critical for formulating effective preventative and therapeutic strategies for developmental brain injuries.