Article

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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... [51] suggested a potential concerted modulation of nuclear factor-erythroid 2-related factor 2 (Nfr2)/antioxidant responsive elements (ARE) and nuclear factor-kappa Although Spirulina antioxidant and anti-inflammatory activities can be due to both phenolic compounds and phycocyanins, C-phycocyanin is contained in higher amounts (Table 1) and has been studied more in vitro [56][57][58][59][60][61][62][63] and in animal models [27,57,[64][65][66]. In addition to the scavenging property of C-phycocyanin [56, 57], in cellular models it exerted the antioxidant activity also regulating the antioxidant enzymes activity, such as SOD, CAT, and GPX [58] and inhibiting the cyclooxygenase-2 (COX-2) [63] and the inducible nitric oxide synthase (iNOS) gene expression [63]. ...
... [51] suggested a potential concerted modulation of nuclear factor-erythroid 2-related factor 2 (Nfr2)/antioxidant responsive elements (ARE) and nuclear factor-kappa Although Spirulina antioxidant and anti-inflammatory activities can be due to both phenolic compounds and phycocyanins, C-phycocyanin is contained in higher amounts (Table 1) and has been studied more in vitro [56][57][58][59][60][61][62][63] and in animal models [27,57,[64][65][66]. In addition to the scavenging property of C-phycocyanin [56, 57], in cellular models it exerted the antioxidant activity also regulating the antioxidant enzymes activity, such as SOD, CAT, and GPX [58] and inhibiting the cyclooxygenase-2 (COX-2) [63] and the inducible nitric oxide synthase (iNOS) gene expression [63]. Furthermore, a 50% inhibitory concentration (IC50) of 180 nM has been found in a COX-2 isolated enzyme assay [62]. ...
... [51] suggested a potential concerted modulation of nuclear factor-erythroid 2-related factor 2 (Nfr2)/antioxidant responsive elements (ARE) and nuclear factor-kappa Although Spirulina antioxidant and anti-inflammatory activities can be due to both phenolic compounds and phycocyanins, C-phycocyanin is contained in higher amounts (Table 1) and has been studied more in vitro [56][57][58][59][60][61][62][63] and in animal models [27,57,[64][65][66]. In addition to the scavenging property of C-phycocyanin [56, 57], in cellular models it exerted the antioxidant activity also regulating the antioxidant enzymes activity, such as SOD, CAT, and GPX [58] and inhibiting the cyclooxygenase-2 (COX-2) [63] and the inducible nitric oxide synthase (iNOS) gene expression [63]. Furthermore, a 50% inhibitory concentration (IC50) of 180 nM has been found in a COX-2 isolated enzyme assay [62]. ...
Article
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The highly nutritional and ecofriendly Spirulina ( Arthrospira platensis ) has hypolipidemic, hypoglycemic, and antihypertensive properties. Spirulina contains functional compounds, such as phenolics, phycocyanins, and polysaccharides, with antioxidant, anti-inflammatory, and immunostimulating effects. Studies conducted on Spirulina suggest that it is safe in healthy subjects, but attitude to eating probably affects the acceptability of Spirulina containing foods. Although the antioxidant effect of Spirulina is confirmed by the intervention studies, the concerted modulation of antioxidant and inflammatory responses, suggested by in vitro and animal studies, requires more confirmation in humans. Spirulina supplements seem to affect more effectively the innate immunity, promoting the activity of natural killer cells. The effects on cytokines and on lymphocytes’ proliferation depend on age, gender, and body weight differences. In this context, ageing and obesity are both associated with chronic low grade inflammation, immune impairment, and intestinal dysbiosis. Microbial-modulating activities have been reported in vitro, suggesting that the association of Spirulina and probiotics could represent a new strategy to improve the growth of beneficial intestinal microbiota. Although Spirulina might represent a functional food with potential beneficial effects on human health, the human interventions used only supplements. Therefore, the effect of food containing Spirulina should be evaluated in the future.
... 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]. ...
Article
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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 . ...
... SPI contains 62% amino acids, is the world's richest natural source of vitamin B12 and contains a whole spectrum of natural mixed carotenes and xanthophyll phytopigments. SPI is wrapped with a soft cell wall formed from complex sugars and proteins like rhamnose, xylose, glucose, galactose, and arabopyranose glucuronic acid [3] [4]. Algae of the genus Spirulina spp present approximately 15% of biliproteins (C-phycocyanin, allophycocyanin and phycoerythrin) [4], with C-phycocyanin being the major protein component of SPI. ...
... SPI is wrapped with a soft cell wall formed from complex sugars and proteins like rhamnose, xylose, glucose, galactose, and arabopyranose glucuronic acid [3] [4]. Algae of the genus Spirulina spp present approximately 15% of biliproteins (C-phycocyanin, allophycocyanin and phycoerythrin) [4], with C-phycocyanin being the major protein component of SPI. ...
... More recently SPI has been found to have additional pharmacological properties through a variety of active constituents. SPI exhibits antioxidant, anti-inflammatory, neuroprotective, immunomodulatory, antihyperlipidemic, cardiovascular and anti-diabetic properties, making it a potential drug candidate in the therapeutic management of chronic disorders such as diabetes and hypertension [4]- [9] [2] [25]- [32] [44] [45]. ...
Article
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Spirulina platensis (SPI) is a microalga with a high content of functional compounds, such as phenolics, phycocyanins and polysaccharides that has been shown to have antioxidant, anti-inflammatory, hypoglycemic, neuro-protective and immunomodulatory effects. The objectives of the present work were to study the possible effects of SPI treatment on the glycemic-lipid profile, oxidative stress, lipid peroxidation and cardiac performance in diabetic rats. Diabetes was induced by streptozotocin (STZ) in male Wistar rats. In diabetic animals SPI, at a dose of 50 mg/kg/day, reduced lipid peroxidation, nitrite levels and lipids in plasma and tissues. SPI exhibited an effective improvement on +dP/dT and −dP/dT in non-diabetic rats. This study showed that SPI significantly suppressed nitrite generation and lipoperoxidation in the hearts of diabetic animals, as well as an improvement in the cardiac function in control SPI-treated rats which is consistent with several studies that demonstrated the protective effect of antioxidants on oxidative stress-mediated injury caused by reactive oxygen species (ROS) produced in diabetic myocardial tissues.
... 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.
... This microalgae is legally permitted as a food supplement in Europe, Japan and in the United States, where the FDA recently issued the first Generally Recognized as Safe (GRAS) license for Spirulina, allowing its use in food (FDA, 2012). Spirulina platensis has anticholesterolemic action (Bertolin et al., 2009;Cheong et al., 2010;Gonzalez-Torres et al., 2015;Kim et al., 2010), antioxidant, anti-inflammatory (Pak et al., 2012), as well as neuroprotective properties (Bachstetter et al., 2010;Bermejo-Bescos, Pinero-Estrada, & Villar del Fresno, 2008;Chen et al., 2012;Pabon et al., 2012;Perez-Juarez, Chamorro, Alva-Sanchez, Paniagua-Castro, & Pacheco-Rosado, 2016;Stromberg, Gemma, Vila, & Bickford, 2005;Thaakur & Jyothi, 2007). Phycocyanin, from the extract of Spirulina platensis, is characterized as a natural, single blue color, water-soluble, and highly stable protein (Padyana, Bhat, Madyastha, Rajashankar, & Ramakumar, 2001). ...
... Phycocyanin, from the extract of Spirulina platensis, is characterized as a natural, single blue color, water-soluble, and highly stable protein (Padyana, Bhat, Madyastha, Rajashankar, & Ramakumar, 2001). It has been reported to be beneficial in wound healing (Madhyastha, Radha, Nakajima, Omura, & Maruyama, 2008), hypertension (Ichimura et al., 2013), oxidative stress (Pleonsil, Soogarun, & Suwanwong, 2013), neuroinflammation (Chen et al., 2012), and in ironinduced neuronal toxicity (Bermejo-Bescos et al., 2008). In many countries it is used as a supplement in food and in pharmacology because of its nutraceutical potential. ...
... The toxicity caused by the aggregation of aSyn is strongly associated with increased levels of oxidative stress, which is also a central feature in PD (Blesa, Trigo-Damas, Quiroga-Varela, & Jackson-Lewis, 2015). Phycocyanin, which is the main component of the cyanobacterium S. platensis, has emerged as an interesting food supplement due to its biological properties (Bermejo-Bescos et al., 2008;Chen et al., 2012;Farooq et al., 2014;Nagaoka et al., 2005). In our study, we found that phycocyanin reduces aSyn inclusion formation, and increases cell viability. ...
Article
Parkinson’s disease (PD) is an age-related neurodegenerative disorder associated with the misfolding and aggregation of alpha-synuclein (aSyn) in proteinaceous inclusions. These inclusions are common to a wider spectrum of disorders known as synucleinopathies. While the molecular bases of PD are still unclear, oxidative stress and impairment of protein quality-control systems play an important role, and are regarded as valuable targets for therapeutic interventions. We employed a yeast model of synucleinopathies to test the cytoprotective potential of phycocyanin, a biliprotein used as a nutritional supplement. We found that phycocyanin effectively protected against aSyn toxicity in yeast and, importantly, the mechanism of action involves the reduction of aSyn inclusions and superoxide levels, through the regulation of genes and enzymes involved in oxidative stress response, glutathione metabolism, and cellular protein quality-control systems. Overall, this study highlights the potential of phycocyanin as a nutraceutical in neurodegenerative diseases associated with proteotoxicity, such as synucleinopathies.
... It has been reported that S. platensis protein extract was a potent antioxidant which was able to scavenge free radicals with its chelating capacity and prevent radical-mediated cell death in vitro [294]. A follow-up study revealed that the aqueous extract of S. platensis and its active component C-phycocyanin could reduce cytotoxicity and inhibit the expression of inflammation-related genes like COX-2, TNF-α, IL-6, and iNOS in vitro, suggesting its AD preventive effects [295]. Another cyanobacterium, Spirulina maxima, contains many physiologically active chemicals including carotenoids, polysaccharides, chlorophylls, C-phycocyanin, and vitamins [296]. ...
... In vitro [293][294][295] Spirulina maxima Ethanolic Extract ...
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Alzheimer’s disease (AD) is the number one neurovegetative disease, but its treatment options are relatively few and ineffective. In efforts to discover new strategies for AD therapy, natural products have aroused interest in the research community and in the pharmaceutical industry for their neuroprotective activity, targeting different pathological mechanisms associated with AD. A wide variety of natural products from different origins have been evaluated preclinically and clinically for their neuroprotective mechanisms in preventing and attenuating the multifactorial pathologies of AD. This review mainly focuses on the possible neuroprotective mechanisms from natural products that may be beneficial in AD treatment and the natural product mixtures or extracts from different sources that have demonstrated neuroprotective activity in preclinical and/or clinical studies. It is believed that natural product mixtures or extracts containing multiple bioactive compounds that can work additively or synergistically to exhibit multiple neuroprotective mechanisms might be an effective approach in AD drug discovery.
... Additionally, from another perspective, the effect of SP on normal cell models has been previously investigated using mouse BV-2 normal microglial cells (Chen et al., 2012), T3 mouse fibroblasts (Chu, Lim, Radhakrishnan, & Lim, 2010), murine bone marrow (Hayashi et al., 2006), and human stem cells (Bachstetter et al., 2010). The findings of these studies verified those protective properties in normal cells in vitro. ...
... To palliate the toxic effects of CDDP, several strategies have been proposed by numerous natural products (Desai et al., 2008). Also, the effect of spirulina on normal cell models has been previously investigated using mouse BV-2 normal microglial cells (Chen et al., 2012), T3 mouse fibroblasts (Chu et al., 2010), murine bone marrow (Hayashi et al., 2006), and human stem cells (Bachstetter et al., 2010). The findings of these studies verified those protective properties in normal cells in vitro. ...
Article
Herein two experiments were conducted. The first experiment evaluated the antitumor activity of Arthrospira platensis (Spirulina platensis, SP) alone or in combination with cisplatin (CDDP) in Ehrlich ascites carcinoma (EAC) bearing mice. The second experiment assessed the outcomes of SP and/or CDDP administration on renal, hepatic, and bone marrow function in normal mice. The results showed that the EAC evoked a significant decrease in the mice survival rate, life span percentage, antioxidant defense system, and Caspase-3 immunoexpression but a significant increase in the viable cancer cells count, tumor and lipid peroxidation biomarkers concentrations, and Ki-67 immunoexpression. The EAC induced alterations improved to various degrees following SP and/or CDDP administration. SP minimized the oxidative hepatic and renal DNA-damaging and hematotoxic effect of CDDP. Overall, SP has a potent anticancer activity and could be used effectively as a hematinic and hepato-renal protective agent with anticancer drugs like CDDP.
... It has been shown that in allergic inflammation, PC can significantly inhibit the release of TNF-α, IL-6, IL-1β, and neutrophil infiltration. PC can reduce the increase of TNF-α, IL-1β, and IL-6 caused by LPS-induced microglia [19]. In addition, PC can also have an important protective effect on inflammatory bowel diseases and macrophage activation [20]. ...
... In allergic inflammation, PC can significantly inhibit the release of inflammatory factors and the infiltration of neutrophils [19,20]. These results indicate that PC can reduce lung tissue damage caused by chest irradiation by inhibiting inflammation. ...
Article
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Objective Radiation pneumonia and fibrosis are major clinical complications of radiotherapy for thoracic tumor patients, and may significantly reduce survival and quality of life. At present, no safe and effective radiation protection measures have been approved for clinical use. Phycocyanin, a protein responsible for photosynthesis from Spirulina, has been shown to have a variety of biological activities and to be beneficial for a variety of diseases, including pulmonary fibrosis. However, the preventive and protective effects of phycocyanin on radiation-induced pulmonary fibrosis have not been studied. Design X-ray single dose irradiation was used on the chest of mice to prepare a mouse model of pulmonary fibrosis, from which the effect of phycocyanin on pulmonary histopathologic change, pulmonary fibrosis, the microbiota in lung and gut, LPS, TNF-α, and IL-6 at different time after irradiation were evaluated. Results Phycocyanin alleviated the radiation-induced lung injury and reduced the level of inflammatory factors. Thorax irradiation led to the disorder in microbiota of the lung and gut. The variation trend of the diversity of the two tissues was opposite, but that of the microbiota composition was similar. The phycocyanin intervention regulated the composition of the lung and gut microbiota, transformed them into normal state, and reduced the level of LPS, which significantly reduced the abundance of inflammation-related bacteria, and increased the abundance of probiotics that produce short-chain fatty acids. Conclusion Phycocyanin could regulate the radiation-induced disorder in lung and gut microbiota of mice, and reduce the radiation-induced lung inflammation and fibrosis.
... Such multiplicity of combined actions results in a highly efficient control of the inflammatory process. Spirulina biomass reduces oxidative stress, the expression of inflammatory mediators such as cytokines, as well as the activity of inflammatory enzymes (Chen et al., 2012;Hwang, Chen, & Chan, 2013;Xia et al., 2016). Its anti-inflammatory action has been demonstrated in many experimental models (Remirez, González, Merino, Rodriguez, & Ancheta, 2002;Rasool, Sabina, & Lavanya, 2006;Joventino et al., 2012;Somchit et al., 2014) and clinical trials have shown that it can be safely used to modulate cytokines and oxidative stress in humans (Mao, Water & Gershwin, 2005;Park et al., 2008). ...
... Phycocyanins and β-carotene stand out as potential analgesic substances found in Spirulina biomass because they have shown consistent anti-inflammatory properties under several conditions (Bai et al., 2015;Chen et al., 2012;Hwang et al., 2013;Shalaby & Shanab, 2013;Mallikarjun-Gouda, Udaya-Sankar, Sarada, & Ravishankar, 2015;Teng et al., 2016;Xia et al., 2016). However, further research is needed to determine whether those compounds are relevant for the intrinsic antinociceptive effect of SP-LEB18. ...
Article
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The management of pain is a world health issue. Available painkillers induce undesired side effects and are sometimes inefficient. Spirulina biomass has promoted anti-inflammatory activity in preclinical and clinical trials. This work characterizes the antinociceptive properties of Spirulina platensis LEB-18 biomass (SP-LEB18) and their mechanisms of action. In the CFA model in mice, SP-LEB18 reduced paw edema and mechanical allodynia, confirming its anti-inflammatory action and showing its antinociceptive activity. Cytokines levels were evaluated by ELISA; SP-LEB18 promoted an increase of IL-10 levels and a reduction of TNF-α and IL-1β levels. SP-LEB18 promoted centrally mediated antinociception, as indicated by the tail flick test. When the same set of experiments was conducted with IL-10 knockout mice, the antinociception was still detected in the tail flick test, but not in the CFA model. Pretreatment with naloxone abolished the effect of SP-LEB18, demonstrating a pure antinociceptive action of Spirulina biomass via the opioid system.
... Furthermore, many studies have evidenced the neuroprotective properties of Spirulina in multiple models of CNS diseases, such as Parkinson's disease, schizophrenia, ischemic brain damage and in lipopolysaccharide (LPS)-induced neuroinflammation (Strömberg et al., 2005;Chen et al., 2012;Pabon et al., 2012;Lima et al., 2017;Haider et al., 2021). However, the protective properties of Spirulina have been shown mainly after a pretreatment (i.e., prophylactic effect), whereas its effect after inflammatory stimuli has been only partially investigated. ...
... Additionally, pre-treatment with E1 showed a significant effect on the inflammatory signaling also by decreasing the LPS-induced over-expression of iNOS, an important regulator of inflammation. These results confirm previous studies that have suggested the use of Spirulina as a natural product to prevent inflammatory diseases, based on the anti-inflammatory effect of organic or water extracts of the microalga (Chen et al., 2012;Ku et al., 2013;Pham et al., 2017). We recently showed very similar results obtained with the use of an acetone extract from the microalga Euglena gracilis on the same in vitro model of neuroinflammation, despite some differences in the composition of the two extracts. ...
Article
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Background: Uncontrolled neuroinflammation and microglia activation lead to cellular and tissue damage contributing to neurodegenerative and neurological disorders. Spirulina ( Arthrospira platensis (Nordstedt) Gomont, or Spirulina platensis ), a blue-green microalga, which belongs to the class of cyanobacteria, has been studied for its numerous health benefits, which include anti-inflammatory properties, among others. Furthermore, in vivo studies have highlighted neuroprotective effects of Spirulina from neuroinflammatory insults in different brain areas. However, the mechanisms underlying the anti-inflammatory effect of the microalga are not completely understood. In this study we examined the effect of pre- and post-treatment with an acetone extract of Spirulina (E1) in an in vitro model of LPS-induced microglia activation. Methods: The effect of E1 on the release of IL-1β and TNF-α, expression of iNOS, nuclear factor erythroid 2–related factor 2 (Nrf2), and heme oxygenase-1 (HO-1), and the activation of NF-κB was investigated in primary microglia by ELISA, real-time PCR, and immunofluorescence. Results: Pre- and early post-treatment with non-cytotoxic concentrations of E1 down-regulated the release of IL-1β and TNF-α, and the over-expression of iNOS induced by LPS. E1 also significantly blocked the LPS-induced nuclear translocation of NF-κB p65 subunit, and upregulated gene and protein levels of Nrf2, as well as gene expression of HO-1. Conclusions: These results indicate that the extract of Spirulina can be useful in the control of microglia activation and neuroinflammatory processes. This evidence can support future in vivo studies to test pre- and post-treatment effects of the acetone extract from Spirulina.
... Spirulina has been consumed as food for centuries by Mexicans during Aztec civilisation and also in Central Africa (Dillon et al. 1995). It has received much attention as a functional food due to its widely-demonstrated antioxidant effects (Bermejo-Besc os et al. 2008, Gargouri et al. 2016) and anti-inflammatory effects in several studies (Chen et al. 2012, Abdel-Daim et al. 2015. These therapeutic properties enable the use of spirulina in the treatment of many chronic ailments such as arthritis (Remirez et al. 2002) and cardiovascular disease (Khan et al. 2006, Riss et al. 2007. ...
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The present study evaluates the protective effect of spirulina against diet-induced obesity and metabolic disorders in Psammomys obesus, an animal model of metabolic syndrome. Psammomys obesus lives on a low-energy diet, in order to remain healthy. However, under a standard laboratory chow diet (SLCD), this animal exhibits insulin resistance, which occurs as a result of obesity. Psammomys obesus was maintained on SLCD, in order to evaluate the effect of spirulina on obesity development with a particular focus on glucose and lipid metabolism, as well as the mRNA expression of some pro-inflammatory cytokines. After 12 weeks of treatment with spirulina, there was a significant reduction in body weight gain, plasma glucose, insulin and triglyceride levels. There was also a significant reduction in the mRNA expression of genes involved in lipogenesis and inflammation. Spirulina improved insulin sensitivity, glucose and lipid metabolism. These findings highlight the positive effect of spirulina on weight maintenance.
... is protective effect could be also contributed by the presence of the biliprotein C-phycocyanin [222,223]. e protective effect of Spirulina platensis and C-phycocyanin was further expanded by the study [224] that demonstrated Spirulina platensis water extract and its active compound C-phycocyanin reduced cytotoxicity and inhibited the inflammation-related gene expressions (COX-2, TNF-α, IL-6, and iNOS) of BV-12 microglial cells induced by lipopolysaccharides. ...
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In recent years, natural products, which originate from plants, animals, and fungi, together with their bioactive compounds have been intensively explored and studied for their therapeutic potentials for various diseases such as cardiovascular, diabetes, hypertension, reproductive, cancer, and neurodegenerative diseases. Neurodegenerative diseases, including Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis are characterized by the progressive dysfunction and loss of neuronal structure and function that resulted in the neuronal cell death. Since the multifactorial pathological mechanisms are associated with neurodegeneration, targeting multiple mechanisms of actions and neuroprotection approach, which involves preventing cell death and restoring the function to damaged neurons, could be promising strategies for the prevention and therapeutic of neurodegenerative diseases. Natural products have emerged as potential neuroprotective agents for the treatment of neurodegenerative diseases. This review focused on the therapeutic potential of natural products and their bioactive compounds to exert a neuroprotective effect on the pathologies of neurodegenerative diseases.
... In the case of anti-inflammatory activity (Table 2), the best results were obtained with SMA, whilst the worst were registered for MD, and all tested samples showed significant differences in EC 50 values. Studies by Chen, Liu, Yang, Hwang, Chan, and Lee (2012) also showed antiinflammatory effects of the S. platensis aqueous extract, and of the phycocyanin pigment in LPS-stimulated microglia cells . In another study, Al-qahtani and Binobead (2018) analysed the anti-inflammatory effect in vivo, using the induction of hepatotoxicity in mice and inclusion of different concentrations of S. platensis in the diet during one week, observing that the ingestion of S. platensis led to a decrease in pro-inflammatory cytokines. ...
Article
The consumption of foods functionalized with spirulina might have positive health effects. However, spirulina-based food products are usually associated with unpleasant flavor and odor, and can present non-homogeneous appearance, impairing consumers’ acceptance. Moreover, it is important to assure bioactivity maintenance. To develop a novel food ingredient, spirulina was chemically characterized, and spray-dried using two encapsulating materials: i) maltodextrin and ii) maltodextrin crosslinked with citric acid. Thereafter, free and encapsulated spirulina were evaluated for their bioactive properties. Microencapsulated spirulina presented higher thermal stability than the base materials, while showing better anti-inflammatory activity without exerting cytotoxicity. Free and encapsulated spirulina were further added to yogurts to validate their suitability as functionalizing agents. Yogurts added with encapsulated spirulina presented a more homogeneous appearance, and the best solution was spirulina encapsulated in maltodextrin crosslinked with citric acid, considering the nutritional profile, attractive color, and improved antioxidant activity throughout storage time.
... Spirulina has been used since ancient times both as a source food, for its protein (up to 70%, w/w) and vitamin (4%, w/w) content, and as an important source of valuable natural biologically active molecules, such as essential amino acids, minerals, long-chain polyunsaturated fatty acids and antioxidants [1]. Especially the phycobiliproteins, carotenoids and phenols contribute to antioxidant, immunomodulatory, and anti-inflammatory properties of this microalgae, playing protective roles on human health [2,3]. If chlorophyll and carotenoids are naturally occurring pigments present in all photosynthetic organisms, the phycocyanins are cyanobacteria pigments, involved in photosynthesis. ...
Article
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Arthrospira platensis (spirulina) is considered a source of natural molecules with nutritional and health benefits. As the different storage forms can affect the quantity and quality of bioactive ingredients, the aim of the present work was to evaluate the effects of freezing, oven-drying and freeze-drying on chemical composition of spirulina biomass. Total proteins, photosynthetic pigments and antioxidants, were analyzed and compared to respective quantities in fresh biomass. The frozen sample exhibited the highest content of phycocyanin-C, phenols, and ascorbic acid, also respect to the fresh biomass. The highest total flavonoid amount was in the freeze-dried biomass. HPLC-DAD analysis of phenolic acids revealed the presence of the isoflavone genistein, known for its therapeutic role, in all the spirulina samples. The phosphomolybdenum method (TAC) and DPPH scavenging activity were applied to determine the antioxidant activity of different samples. The highest DPPH scavenging activity was detected in fresh and freeze-dried biomass and it was positively related to carotenoid content. A positive correlation indicated that carotenoids, chlorophyll, ascorbic acid and all phenolic compounds were the major contributors to the TAC activity in spirulina biomass. The results highlighted a different functional value of spirulina biomass, depending on the processing methods used for its storage.
... 1-4) Microglial cells, as the resident macrophage-like immune cells in the brain, are important contributors to neuroinflammation. [5][6][7][8] However, under inflammatory conditions, microglia are over-activated and therefore release various pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, tumor necrosis factor-alpha (TNF-α), interferon-γ (IFN-γ), and free radical mediators including reactive oxygen species (ROS) and nitric oxide (NO). [9][10][11] In turn, the redundant pro-inflammatory mediators will activate microglia and aggravate the pathogenesis of neurodegenerative diseases. ...
Article
Neuroinflammation manifested by over-activation of microglial cells plays an essential role in neurodegenerative diseases. Short-term activation of microglia can be beneficial, but chronically activated microglia can aggravate neuronal dysfunction possibly by secreting potentially cytotoxic substances such as tumor necrosis factor-alpha (TNF-α) and nitric oxide (NO), which can result in dysfunction and death of neurons. Therefore inhibiting over-activation of microglia and the production of cytotoxic intermediates may become an effective therapeutic approach for neuroinflammation. In this paper, we review our continuous research on natural inhibitors of over-activated microglia from traditional herbals, including flavonoids, lignans, sesquiterpene coumarins, and stilbenes. Graphical Abstract Fullsize Image
... This observation is consistent with other studies showing that Spirulina does not affect but even protects other normal cells. It has been demonstrated that Spirulina reduces the cytotoxicity of LPS in mouse BV-2 normal microglial cells [41], protects normal 3T3 mouse fibroblasts against oxidative stress-induced apoptosis [42], or promotes proliferation of murine bone marrow [43] and human stem cells [44]. Therefore, it seems likely that Spirulina exhibits high cytotoxic activity against cancer cells and trophic or protective properties in normal cells at the same time. ...
Article
Spirulina is a well-described and popular dietary supplement derived from Arthrospira algae. In the present study, the anticancer potential of a water extract of a commercial Spirulina product (SE) against the human non-small-cell lung carcinoma A549 cell line was evaluated. After qualitative analysis, we investigated the effect of SE on cell viability, proliferation, and morphology. Furthermore, the influence of SE on regulation of the cell cycle, induction of apoptosis in lung cancer cells, and expression of cell cycle/apoptosis-related proteins was evaluated. Additionally, we examined the cytotoxic effect of SE on normal human skin fibroblasts (HSF). Our studies revealed that SE significantly reduced cancer cell viability and proliferation, which was accompanied by cell cycle inhibition in the G 1 phase, induction of apoptosis, and prominent morphological changes. Moreover, we detected no cytotoxic effect of the tested Spirulina extract on normal skin fibroblasts. Our molecular studies demonstrated that SE reduced the phosphorylation of Akt and Rb proteins, reduced the expression of cyclin D1 and CDK4, and increased the Bax to Bcl-2 ratio in the A549 cells. In conclusion, the results obtained provide evidence of the anti-cancer activity of the commercial Spirulina product against lung cancer cells and strongly support the knowledge of the chemopreventive properties of Spirulina.
... Many photosensitizers have been characterized such as chlorophyll-derived protoporphyrin IX and chlorin e6, but due to its hydrophobic nature, it aggregates easily in physiological solution that reduces the efficacy of PDT mechanism (Ormond and Freeman 2013). PC has many advantages over chlorophyll-derived photosensitizer due to its high water solubility nature, nontoxicity, and immune-modulating properties (Muthulakshmi et al. 2012;Chen et al. 2012Chen et al. , 2014a. PC is easily metabolized in normal cells as compared to cancerous cells; therefore, it could be used in PDT for eradication of cancer without any harm to normal cells (Bharathiraja et al. 2016). ...
Chapter
Phycobiliproteins (PBPs) have widespread biotechnological applications including nutraceuticals, pharmaceuticals, food industry, cosmetics, agriculture, bioremediation, aquaculture, biofuels, and bioenergy. PC is water-soluble, brilliantly blue colored, and most widely used as natural fluorescent and pharmaceutical agents in various biotechnological applications. However, PE and APC are mainly used for fluorescent, cosmetics, and certain other biotechnological applications. Although numerous applications have been found on commercial production of PBPs from various cyanobacteria species, however, certain cyanobacterium like Spirulina sp. (Arthrospira) is much exploited for large-scale production. To enhance the diversity of PBP-based bioproduct, biotechnological companies of leading country have followed a wide range of extraction and purification technology to obtain higher product quality. Thus, modern research and development about novel structural configuration biliproteins have expanded the further application of PBPs in many therapeutic sciences. PC also acts as natural photosensitizer that is used for light-oriented therapy for tumor cells called as photodynamic therapy. PBP-based drugs are still in progress for use in various clinical applications. In this chapter, we have focused on therapeutic significance and probable mechanism of action of PBPs in various human diseases.
... The high value of gamma-linolenic acid inhibits the work of prostaglandin and the progression of inflammation. On the other hand, some researchers reported that S. platensis and its extract C-phycocyanin, can regulate the cytotoxicity and inflammation-associated factors such as ions, COX-2, tumor necrosis factor (TNF)-α, and IL-6 with BV-2 microglial cell during the inflammatory process [98]. ...
... Shih et al. reported that PC significantly inhibited TNF-α, IL-1β, IL-6 secretion and neutrophil infiltration in inflammatory sites resulting from experimental hyperalgesia 26 . The increased levels of TNF-α, IL-1β and IL-6 after LPS stimulation in microglial cells could also be reversed by PC 27 . These results suggest that PC has a strong property to inhibit inflammatory cytokines release that alleviates multiple conditions, including BLM-induced lung injury. ...
Article
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Our aim was to investigate the effects of phycocyanin (PC) on bleomycin (BLM)-induced pulmonary fibrosis (PF). In this study, C57 BL/6 wild-type (WT) mice and toll-like receptor (TLR) 2 deficient mice were treated with PC for 28 days following BLM exposure. Serum and lung tissues were collected on days 3, 7 and 28. Data shows PC significantly decreased the levels of hydroxyproline (HYP), vimentin, surfactant-associated protein C (SP-C), fibroblast specific protein-1 (S100A4) and α-smooth muscle actin (α-SMA) but dramatically increased E-cadherin and podoplanin (PDPN) expression on day 28. Moreover, PC greatly decreased the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and myeloperoxidase (MPO) at the earlier time. Reduced expression of key genes in the TLR2 pathway was also detected. Compared with WT mice, TLR2-deficient mice exhibited less injury, and the protective effect of PC was partly diminished in this background. These data indicate the anti-fibrotic effects of PC may be mediated by reducing W/D ratio, MPO, IL-6, TNF-α, protecting type I alveolar epithelial cells, inhibiting fibroblast proliferation, attenuating epithelial-mesenchymal transitions (EMT) and reducing oxidative stress. The TLR2-MyD88-NF-κB pathway plays an important role in PC-mediated reduction in pulmonary fibrosis.
... In contrast, the enzyme concentrations were normalized following the treatment with SP particularly at coexposure and therapeutic treatment. The cytoprotective effect of SP could be responsible for the former findings (Chen et al., 2012). The amount of oxygen is very low in the testes because of weak vascularity. ...
Article
Furan is a common food contaminant and environmental pollutant. Spirulina platensis (SP) is a blue-green algae extensively used as therapeutic and health supplements. This study aimed to explore the probable beneficial role of SP against the influence of furan on reproductive system of male rats. Adult male rats were divided into control, vehicle control, SP (300 mg/kg bwt/ day, 7 days), furan (16 mg/kg bwt/ day,30 day), SP/furan, furan/SP and furan+SP groups. Hematology, sperm count, sperm morphology, serum testosterone (TES), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and estradiol (E2) levels, reduced glutathione (GSH), malondialdehyde (MDA), testicular enzymes, and pro inflammatory cytokines were estimated. In addition, histopathology of testis and seminal vesicles and apoptosis were evaluated. Anaemia, leukocytosis, and reduced gonadosomatic index were observed in the furan treated group. TES, LH, FSH, E2, and GSH were significantly decreased following furan treatment. MDA, testicular enzymes, and pro inflammatory cytokines were significantly incremented in testis of furan treated rats. Furan induced apoptic changes in testis. SP significantly counteracted furan reprotoxic impacts, particularly at co-exposure. Conclusively, these findings verified that SP could be candidate therapy against furan reprotoxic impacts.
... Previous studies from other authors have demonstrated that C-PC is an efficient scavenger of peroxynitrite [64] and significantly inhibits the LPS-induced nitrite production and iNOS (inducible isoform) protein expression in LPS-stimulated RAW264.7 macrophages [65]. Furthermore, C-PC was also able to significantly reduce the LPS-induced up-regulation of iNOS, along with a decrease in the expression of COX-2 and proinflammatory cytokines TNF-α and IL-6 mRNAs in LPS-stimulated BV-2 microglial cells [66]. Taken together, this evidence strongly points into remyelination actions of C-PC in MS by enabling OPCs survival, proliferation and maturation, through a versatile arsenal of biological abilities. ...
Article
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Myelin loss has a crucial impact on behavior disabilities associated to Multiple Sclerosis (MS) and Ischemic Stroke (IS). Although several MS therapies are approved, none of them promote remyelination in patients, limiting their ability for chronic recovery. With no available therapeutic options, enhanced demyelination in stroke survivors is correlated with a poorer behavioral recovery. Here, we show the experimental findings of our group and others supporting the remyelinating effects of C-Phycocyanin (C-PC), the main biliprotein of Spirulina platensis and its linked tetrapyrrole Phycocyanobilin (PCB), in models of these illnesses. C-PC promoted white matter regeneration in rats and mice affected by experimental autoimmune encephalomyelitis. Electron microscopy analysis in cerebral cortex from ischemic rats revealed a potent remyelinating action of PCB treatment after stroke. Among others biological processes, we discussed the role of regulatory T cell induction, the control of oxidative stress and pro-inflammatory mediators, gene expression modulation and COX-2 inhibition as potential mechanisms involved in the C-PC and PCB effects on the recruitment, differentiation and maturation of oligodendrocyte precursor cells in demyelinated lesions. The assembled evidence supports the implementation of clinical trials to demonstrate the recovery effects of C-PC and PCB in these diseases.
... Many photosensitizers have been characterized such as chlorophyll-derived protoporphyrin IX and chlorin e6, but due to its hydrophobic nature, it aggregates easily in physiological solution that reduces the efficacy of PDT mechanism (Ormond and Freeman 2013). PC has many advantages over chlorophyll-derived photosensitizer due to its high water solubility nature, nontoxicity, and immune-modulating properties (Muthulakshmi et al. 2012;Chen et al. 2012Chen et al. , 2014a. PC is easily metabolized in normal cells as compared to cancerous cells; therefore, it could be used in PDT for eradication of cancer without any harm to normal cells ). ...
Book
Phycobiliproteins are water soluble, brilliantly colored accessory light-harvesting macromolecules organized in a supramolecular complexes on photosynthetic apparatus in cyanobacteria, red algae and cryptomonads. The objective of this book is to provide state of the art knowledge and highlight the recent developments and future biotechnological and biomedical applications of phycobiliproteins. This book will be highly useful for students, researchers, professionals and experts in the field of Life Sciences and Biomedical Sciences as well as industries for potential applications of phycobiliproteins.
... 62 The promising beneficial properties of Spirulina may be due to its CPC content. 63 In addition, although b-carotene is best known, Spirulina contains an antioxidant rich complex of at least ten Vitamin C -Protects the skin by sequentially donating electrons to neutralize free radicals -Serves as a co-factor for prolysyl and lysyl hydroxylase enzymes, which are responsible for stabilizing and cross-linking the collagen molecules -Interacts with copper ions at the tyrosinase-active site and inhibits action of the tyrosinase, which decreases melanin formation -Promotes wound healing and prevents post-inflammatory hyperpigmentation in cases such as acne vulgaris and rosacea -Improves skin hydration -Vitamins C and E synergistically work against UV-induced damage by reducing both cell apoptosis and thymine dimer formation carotenoids. The daily intake of 2.5 g of Spirulina would be sufficient to provide a remarkable 5,750 IU (3.5 mg) of b-carotene, corresponding to 115% of the daily recommendation of vitamin A. 57 Carotenoids are often applied in the food and pharmaceutical industries because of its pigmentation ability and antioxidant properties. ...
Article
Nutrition is one of the most important parameters involved in modulating skin health and condition. In this regard, the demand for natural compounds capable of promoting skin health and beauty has been attracting the attention of researchers and companies around the world. An interesting option to meet this demand is the use of Spirulina microalga, which has biotechnological potential, including several functional and nutritional applications. Although this microalga has been used in human nutrition since ancient times, it now has new applications and is being studied as a promising ingredient for nutricosmetics. The present review article summarizes Spirulina's most relevant activities, mainly its biologically active metabolites, which are interesting ingredients for nutricosmetic formulations and an important advance for skin care.
... Photoactive+ is a mixture of chlorophyllin-phycocyanin that is effective against biofilms of Gram-positive and Gram-negative bacteria, when activated by red (620-660 nm) and blue (400-450 nm) photonic energy wavelengths [11]. chlorophyllin is used as a coloring agent in food industry with several characteristics including antimicrobial and antitumoral effects [12] and phycocyanin extracted from Spirulina as an FDA-approved agent for coloring food is a water-soluble nontoxic agent with anticancer, antioxidant, antimicrobial and anti-inflammatory effects [13]. These natural products possess pharmacological activity with no toxic side effects [14]. ...
Article
Full-text available
The purpose of this study was to evaluate the in vitro effect of the chlorophyllin–phycocyanin mixture (Photoactive+) as a photosensitizer (PS) during antimicrobial photodynamic therapy (aPDT) on the count of Enterococcus faecalis (E. faecalis) using different light sources. The antimicrobial effect of aPDT with chlorophyllin–phycocyanin mixture using different light sources including diode laser (λ = 660 nm), diode laser (λ = 635 nm), LED (λ = 450 ± 30 nm) alone or in combination was assessed using microbial cell viability assay against E. faecalis. In addition, the cell cytotoxicity of Photoactive+ was assessed on human gingival fibroblast (HuGu) cells by MTT assay; E. faecalis growth when treated by both red wavelengths (635 nm, 660 nm) and combination of LED (420–480 nm) and red wavelengths (635 nm, 660 nm), significantly reduced compared to the control group (p < 0.05). There was no significant reduction in the number of viable cells exposed to Photoactive+ compared to the control group (p < 0.05). This study shows that the application of chlorophyllin–phycocyanin mixture and irradiation with emission of red light achieved a better result for bacterial count reduction, compared to a control. This component can be applied safely due to very negligible cytotoxicity.
... Platensis: Spirulina is a superfood, and C-Phycocyanin is a key ingredient, and it is believed to protect the liver and kidneys during detoxification 18 . Several properties like antioxidation, detoxification, and importantly, inhibition of viral replication are some of the vital functions attributed to C-Phycocyanin present in Spirulina 19,20 . It consists of four cyclopentane rings with two double-bonded oxygen and two carboxyl groups attached to it Fig. 4. 3D structure of C-phycocyanin in relation to its chemical structure 25 was obtained with chem sketch software. ...
Article
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SARS-CoV-2 or COVID-19 is one of the deadly pandemics faced by the world population, which has infected 7 million and claimed the lives of 0.4 million people. In spite of a few drugs available to control the pandemics, a formal vaccine is the least that the world expects under the current scenario. However, the release of a vaccine is expected to come at the cost of its own time. SARS-CoV-2 replicates in the host cells with the aids of the molecular machinery of a complex formed by three non-structural proteins (NSPs) viz., nsp12, nsp8, and nsp7. Recent studies reveal that among the three NSPs, nsp12 is vital for viral replication and is the target for drugs. Several studies have linked the viral infection to a weaker immune system, which is quite likely to be targeted by the virus. In search of such a natural compound that might increase the immunity and block the viral replication within the host, we selected C-Phycocyanin of Spirulina plantesis to study its anti-viral property in-silico. Spirulina is a free-floating filamentous microalgae growing in alkaline water bodies. It is a well-known source of valuable food supplements, such as proteins, vitamins, amino acids, minerals, etc. In the present study, we focused on the possibility of C-Phycocyanin to inhibit the active site of nsp12, which is very much needed for viral replication. Auto Dock, Auto Grid, and Discovery Studios tools reveal that C-Phycocyanin inhibits the active site of nsp12 thereby interfering with the replication of the virus itself.
... 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
Full-text available
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).
... Especially Spirulina has been investigated in detail with in vitro and in vivo studies (107). Next to antioxidant (108,109), hypolipemic (110), antihypertensive (111), and other effects, Spirulina and its component C-phycocyanin show immunomodulatory and anti-inflammatory activity (109,112). Upon Spirulina consumption, a reduction of pro-inflammatory cytokines via inhibition of NFκB has been reported in mice (113). On the other hand, the high molecular weight polysaccharide immunila that has been isolated from Spirulina platensis, possesses immunostimulatory activity (114,115). ...
Thesis
In this thesis, the immunomodulatory effects of selected natural products that are applied in complementary medicine were investigated. The European mistletoe, Viscum album, is used as an additive anticancer therapy, and it can be observed that mistletoe induces the maturation of dendritic cells (DCs). In this work, it was investigated if the tumor-induced immunosuppression of DC maturation could be counteracted via mistletoe treatment. Moreover, the role of mistletoe lectins in this process was analyzed. Using monocyte-derived DCs, the effects of two different mistletoe preparations (Iscador® Qu Spez and abnobaVISCUM® Fraxini) on DC maturation were measured by quantifying CD83, CD86, and HLA-DR expression using flow cytometry and confocal microscopy. Additionally, changes in DC cytokine release were measured using bead array assays. A co-culture with T cells was carried out to assess the impact of mistletoe-treated DCs on T cell proliferation and function using CFSE staining and cytokine ELISA. The role of mistletoe lectins in this process was evaluated via the incubation of DCs with ML-depleted mistletoe preparations or anti-ML antibodies. The effects of mistletoe on DCs in an immunosuppressive tumor microenvironment were highlighted via the simultaneous incubation with a tumor supernatant. The results showed that DC maturation was induced by mistletoe treatment and that this process was dependent on MLs; however, the effects were not strong enough to produce a measurable activation of the T cells. The tumor supernatant effectively inhibited DC maturation and this process could be, in part, counteracted by mistletoe treatment in a ML-dependent manner. From these results it can be concluded that the recovery of DC maturation after tumor-induced immunosuppression is a possible mode-of-action of mistletoe in cancer treatment. Equisetum arvense, the common horsetail, has also been traditionally used in the treatment of inflammatory diseases and is one of the plants with the highest silica amounts. First, preparation methods were tested to obtain high silica yields. To investigate if the immunomodulatory effects of Equisetum arvense are mediated by silica, the effects of Equisetum decoctions on certain immune parameters were interpreted in regard to their silica concentration. A silica standard solution was used as well. A flow cytometric analysis of the influences on T cell proliferation, apoptosis, and CD25/CD69 expression were measured, and influences on T cell function were assessed using IL-2 and IFN-γ ELISA. The data revealed that T cell activation and function was impaired in an IL-2 dependent mechanism by Equisetum decoctions and the silica standard solution. Using HPLC-UV-MS, isoquercitrin could be identified as the most abundant flavonoid and bioactivity testing revealed inhibitory effects on T cell proliferation as well. It could therefore be concluded that the immunosuppressive activity of Equisetum arvense preparations is mediated by both silica and isoquercitrin. Cyanobacteria represent an interesting source for novel drug creations. Screening its effects on T cell proliferation and apoptosis revealed various interesting strains exhibiting immunosuppression but not cytotoxicity. Using bioactivity-guided fractionation, hapalindoles could be identified as active compounds in one strain, namely Hapalosiphon sp. Influences of different cyanobacteria strains on the IL-2 signaling pathways AP-1, NFAT, and NFκB have been measured using reporter cell lines and intracellular staining. Moreover, the effects of two cyanobacteria strains on the THP-1 cancer cell line have been measured, and both were able to inhibit proliferation via induction of apoptosis. The results revealed that cyanobacteria can be potent immune modulators and that further research should be conducted to describe their effects and active compounds as well as to evaluate possible applications in more detail. Moreover, further elucidation of the immunomodulatory effects of Tricholoma populinum, green tea catechins, the active mutant of the plant cyclotide kalata B1 T20K, and Rosmarinus officinalis was carried out. Tricholoma populinum, a mushroom described to alleviate inflammatory diseases, led to a reduction in IL-8 secretion by HMC-1 mast cells while affecting cell viability only at high concentrations. The green tea catechins ECG and F- ECG reduced the viability of LNCaP and PC-3 prostate cancer cell lines, which was measured using the WST-1 assay. Additionally, the effects of ECG, F-ECG, and various other green tea catechins on T cell proliferation, the induction of apoptosis, and cell viability were measured. Some catechins were able to reduce T cell proliferation, and the effects of ECG on T cells were intensified by fluorination. These results support the use of green tea in the prevention of prostate cancer via its inhibition of tumorigenesis and reduction of inflammation. Moreover, the active mutant of plant cyclotide kalata B1 T20K and Rosmarinus officinalis, two natural products with known immunomodulatory effects, were screened for their potential to affect IL-2 signaling in T cells. The investigations reported in this thesis describe the procedure for evaluating the immunomodulatory effects of natural products. The results revealed that natural products can be potent modulators of the human immune system, which provides a rationale for their use in complementary medicine.
... 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
Full-text available
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.
... 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
Full-text available
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
Full-text available
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.
... Moreover, Spirulina and C-phycocyanin inhibit toxic effects and inflammatory genes expression of neuronal supporting cells which explains the reduction of neurotoxicity in neuronal cells. 23 We observed the anti-nociception effect of Spirulina platensis in our diabetic neuropathic rat model. ...
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Introduction: Diabetic neuropathy is a common consequence of diabetes. Hyperalgesia is one of the main symptoms of diabetic neuropathy. In response to noxious stimuli, streptozotocin (STZ)-induced diabetic rats show exaggerated hyperalgesic behavior, while Spirulina platensis has anti-inflammatory, antioxidant, and insulin-like effects. To assess the antinociceptive effect of oral Spirulina platensis (SP) powder on formalin-induced nociceptive responses in STZ-induced diabetic rats. Methods: Sixty mature male albino rats were randomly allocated into six equal groups (10 in each group). Group 1 (control non-diabetic group) received 0.9% saline; group 2 was given oral pure SP powder-treated as a non-diabetic control group, group 3 was sodium salicylate-treated rats and used as a positive non-diabetic control group, group 4 managed as vehicle-treated diabetic rats, group 5 considered as SP-treated-diabetic group, and sodium salicylate-treated-diabetic rats used as a diabetic positive control group (group 6). STZ-diabetic rats were orally given SP in a dose of 500 mg kg/day for 1 month. The formalin test was implemented in two phases: the early phase in the first 10-min post-formalin injection, and the late phase was considered in the 15-60 min post-formalin injection time interval. Results: Pain scores were increased in the diabetic groups during both phases of the experiment. Blood glucose was significantly reduced in diabetic rats that received oral SP, P < 0.01. Besides, SP-treated rats had lower pain scores during both phases of the experiment than untreated diabetic ones. However, in the sodium salicylate group, the pain score was reduced only during the second phase. An exaggerated nociceptive response occurred in diabetic rats after the formalin test. A significant antinociceptive effect appeared in SP-treated control and diabetic rats. Discussion: The findings suggest that oral Spirulina platensis could have a potential therapeutic role for managing induced painful diabetic neuropathy in rats.
... 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 . ...
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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 48.7% 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 with an encapsulation efficiency value of 71.58%. Conclusion: The intervention of O. basilicum on S. platensis improved the total phenol and phycocyanin content and there is potential for a pharmaceutical product.
... A cela s'accompagnent les taux de TNFα qui sont eux aussi relativement faibles. La diminution des macrophages pro-inflammatoires ainsi que du TNFα sont accompagnés par une prévention significative de l'insulinorésistance chez les animaux ayant reçu une supplémentation en spiruline Grâce à ses composés actifs (phycocyanine et β-carotène), la spiruline diminue l'activité iNOS(Chen et al., 2012) (Yigit et al., 2016), ce qui suggère une activité prédominante de l'arg1 dans les macrophages M2 chez les animaux du groupe SP de notre étude.Comme pour l'inflammation aigüe, la spiruline pourrait exercer son effet antiinflammatoire par le biais de ses composés anti-oxydants, principalement la phycocyanine, qui inhiberait les effets duTNFα (yin et al., 1998). En effet, l'administration de spiruline chez les Psammomys SP s'accompagne d'une diminution de l'activité de l'iNOS indiqué par un ratio NO/urée normal, auquel est associé un faible taux de TNFα .Ces résultats plaident en faveur d'une activité prédominante de l'arg1 dans les macrophages M2 de ces animaux.La spiruline pourrait aussi exercer son effet anti-inflammatoire par le biais de ses composés antioxydants. ...
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The edible cyanobacterium Spirulina platensis and its chief biliprotein C-Phycocyanin have shown protective activity in animal models of diverse human health diseases, often reflecting antioxidant and anti-inflammatory effects. The beneficial effects of C-Phycocyanin seem likely to be primarily attributable to its covalently attached chromophore Phycocyanobilin (PCB). Within cells, biliverdin is generated from free heme and it is subsequently reduced to bilirubin. Although bilirubin can function as an oxidant scavenger, its potent antioxidant activity reflects its ability to inactivate some isoforms of NADPH oxidase. Free bilirubin can also function as an agonist for the aryl hydrocarbon receptor (AhR); this may explain its ability to promote protective Treg activity in cellular and rodent models of inflammatory disease. AhR agonists also promote transcription of the gene coding for Nrf-2, and hence can up-regulate phase 2 induction of antioxidant enzymes such as HO-1. Hence, it is proposed that C-Phycocyanin/PCB chiefly exert their protective effects via inhibition of NADPH oxidase activity, as well as by AhR agonism that both induces Treg activity and up-regulates phase 2 induction. This simple model may explain their potent antioxidant/anti-inflammatory effects. Additionally, PCB might mimic biliverdin in activating anti-inflammatory signaling mediated by biliverdin reductase. This essay reviews recent research in which C-Phycocyanin and/or PCB, administered orally, parenterally, or intranasally, have achieved marked protective effects in rodent and cell culture models of Ischemic Stroke and Multiple Sclerosis, and suggests that these agents may likewise be protective for Alzheimer’s disease, Parkinson’s disease, and in COVID-19 and its neurological complications.
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Phycocyanin (PC) is a light-harvesting protein isolated from Spirulina and has health benefits for a range of diseases including pulmonary fibrosis (PF). In this study, a bleomycin-induced pulmonary fibrosis model was used to determine whether PC attenuates PF and modulates the intestinal microbiota. The results showed that PC intervention attenuated the pulmonary fibrosis, demonstrated by hematoxylin-eosin staining (HE), Masson’s trichrome staining, and lung dry-wet weight ratio, and PC significantly inhibited the production of interleukin-1 beta (IL-1β), tumor necrosis factor-α (TNF-α), and lipopolysaccharide (LPS). Additionally, intestinal microbiota analysis revealed that PC intervention significantly increased the bacterial diversity and richness. Correlation analysis indicated that 9 families and 17 genes were significantly associated with at least 1 physiological index. And PC intervention significantly decreased the bacteria which is related to inflammation and dramatically increased the SCFAs-producing bacteria and probiotics. These data indicated that PC can decrease the pro-inflammatory cytokines and regulate the intestinal microbiota in BLM-induced PF mice.
Chapter
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Context: Marine microorganisms represent a promising source of bioactive molecules for biomedical applications. Increasing scientific literature is describing novel metabolites isolated from marine microbes with attractive pharmacological properties, such as anti-inflammatory, immunomodulatory, and anticancer. Aims: To reveal a background of the main marine microbial-derived products that have been isolated and characterized, including recent examples. The main mechanisms of action of these compounds in different models are also discussed. Methods: This research was structured based on a four phases design. 1) the identification of research questions, 2) selection of relevant studies, 3) filtering of studies based on inclusion and exclusion criteria, and 4) collection and organization of the data. For the web search, were used PubMed, Web of Science, Science Direct and ProQuest. For the selection and classification of the papers was used PRISMA software. Results: A wide variety of marine microbial metabolites with important pharmacological properties have been discovered and characterized so far. The main sources of these compounds are marine actinomycetes, bacilli, fungi from Aspergillus and Penicillium genus, microalgae, and some marine symbiotic bacteria and fungi. Most of these metabolites exhibit cytotoxic, pro-apoptotic, anticancer, anti-inflammatory, and immunomodulatory activities. Complex structural moieties, such as multiple aromatic rings and heteroatoms, seem to be related to these properties. The mechanisms of action of most of these molecules target apoptosis-related proteins, enzymes, transcription factors, DNA binding proteins and some cell surface receptors. Conclusions: The marine environment offers an efficient and attractive way to obtain novel natural products. Marine microorganisms are a prolific source of new molecules and extracts with therapeutic potential in the treatment of chronic inflammatory diseases. They represent and ecofriendly and feasible option to obtain drug candidates with multiple mechanisms of action and important biomedical applications.
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Human history has witnessed various pandemics throughout, and these cause disastrous effects on human health and country's economy. Once again, after SARS (Severe Acute Respiratory Syndrome) and MERS (Middle East Respiratory Syndrome), the world is observing a very tough time fighting an invisible enemy, the novel COVID-19 coronavirus. Initially observed in the Wuhan province of China, now, it has spread across 210 countries. Number of corona affected confirmed cases have reached > 3 million globally and death toll has reached to 258,481 as on 6 th May,2020. Researchers are working round the clock, forming collaborative efforts and sharing their data to come up with a cure for this disease. The new coronavirus genome was quickly sequenced and clinical and epidemiological data are continuously being collected and analyzed. This data is crucial for forming better public health policies and developing antiviral drugs and vaccines. As there is no vaccine available in market against COVID-19, personal health, immunity, social distancing and basic protection measures are extremely important. It is critical to avoid the virus infection and to strengthen the immune system as the coronavirus can be fatal for those with weak immunity. This article reviews the nutritional and therapeutic potential of Spirulina, which is considered as superfood and a natural supplement to strengthen the immune system. Spirulina is highly nutritious and has hypolipidemic, hypoglycemic and antihypertensive properties. Spirulina contains several bioactive compounds, such as phenols, phycobiliproteins and sulphated polysaccharides and many more with proven antioxidant, anti-inflammatory and immunostimulant/ immunomodulatory effects.
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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.
Thesis
Ce travail concerne l’élaboration, l’étude physico-chimique et l’évaluation biologique de verres bio-actifs purs et associés à des éléments chimiques ou à des molécules à usage thérapeutique. Les différents matériaux synthétisés par fusion et par voie sol-gel présentent un caractère amorphe à longue distance, et des propriétés thermiques caractéristiques des verres. Deux éléments dopants (Zn et Sr) ainsi qu’une molécule (phycocyanine) et une cyanobactérie (Spirulina Platensis) ont été introduits dans la matrice des bio-verres élaborés. Leur réactivité chimique a été étudiée in vitro suite aux échanges solide/liquide physiologique (SBF) sans cellules. De plus, leur cytotoxicité (prolifération et adhésion cellulaire) a été évaluée lors des tests avec cellules. La bio-activité des verres et nano-verres bio actifs a été investiguée pour élucider la formation d’une couche d’hydroxyapatite carbonatée, cristal majoritaire de la matrice osseuse à la surface des verres bio-actifs. La synthèse par voie sol-gel et l’utilisation de la technique de l’émulsion ont permis l’élaboration de nanoparticules de verre bio actif de tailles maîtriser comprises entre 20 et 200 nm. Cette maîtrise ouvre de nombreuses possibilités d’applications dans le domaine de la nanotechnologie médicale. Ces particules ont été utilisées dans 2 applications différentes. Notre première expérimentation a été de créer deux types de bio implants osseux composés du nano-verre seul et du nano-verre associé à une cyanobactérie. Cette étude a pour objectif de comparer les effets de la cyanobactérie lors de tests in vitro puis in vivo. Notre deuxième approche a porté sur le recouvrement d’un alliage biocompatible et l’étude des effets de la taille des particules sur les caractéristiques physico-chimiques de la couche ainsi formée.
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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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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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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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,