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Effect of phycocyanin in zymosan-induced arthritis in mice - Phycocyanin as an antiarthritic compound
Abstract
The antiinflammatory effect of a phycocyanin extract was studied in zymosan-induced arthritis model in mice. Four days after the intraarticular injection of zymosan, (15 mg/ml), phycocyanin (25, 50, and 100 mg/kg p.o) was administered to animals for 8 days. The mice were then killed and the synovial fluid measured for β-glucuronidase. Each knee joint was totally removed for histopathological and ultrastructural studies. Phycocyanin significantly reduced the levels of β-glucuronidase that had been increased by zymosan. Histopathological and ultrastructural studies showed inhibition in cellular infiltration and reduction of synovial hyperplasia and synovitis. The antiinflammatory activity exerted by phycocyanin may be due, at least in part, to its antioxidative properties, although inhibitory effects on both arachidonic acid metabolism and cytokine production such as tumor necrosis factor (TNF) may also be involved. To our knowledge, this is the first report on the antiinflammatory effect of phycocyanin in an experimental model of arthritis.
... Phycocyanin also showed anti-inflammatory effect in a zymosan-induced experimental arthritis model in mice [184], in acetic acid induced colitis in rats [185] and in carrageenan-induced thermal hyperalgesia model where both its pre-or post-administration influenced nociception (rat paw withdrawal) showing its additional antihyperalgesic activity in this model [186]. Phycocyanin also inhibited allergic inflammatory response in a dose dependent manner in ovalbumin-induced edema model in mice as well as in other in vivo and in vitro models probably due to its inhibitory effect on histamine release from mast cells [187]. ...
... In vitro studies in lipopolysaccharide-stimulated RAW 264.7 macrophages [188] or BV-2 microglial cells [189] indicated that phycocyanin inhibits nitrite production, tumor necrosis factor formation and NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) activation [188], decreases the cytotoxicity and inhibits the expression of inflammation-related genes [189]. In addition, the observed anti-inflammatory effects are probably due, at least in part, to the antioxidant and ROS scavenging effects of phycocyanin (see Section 6.3.2) [130,184,185], to its inhibitory effects on arachidonic acid metabolism and cytokine production, on tumor necrosis factor formation [184,188], leukotriene B 4 formation [181], and on prostaglandin E2 production and phospholipase A2 activity [182]. In vitro studies using isolated enzyme assays and whole blood assays have shown that even very low (nanomolar) concentrations of phycocyanin selectively inhibit cyclooxygenase type 2 (COX-2) [190] which is upregulated during inflammation and cancer (especially breast cancer cells), and which in addition may also reduce prostaglandin E2 production [191]. ...
... In vitro studies in lipopolysaccharide-stimulated RAW 264.7 macrophages [188] or BV-2 microglial cells [189] indicated that phycocyanin inhibits nitrite production, tumor necrosis factor formation and NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) activation [188], decreases the cytotoxicity and inhibits the expression of inflammation-related genes [189]. In addition, the observed anti-inflammatory effects are probably due, at least in part, to the antioxidant and ROS scavenging effects of phycocyanin (see Section 6.3.2) [130,184,185], to its inhibitory effects on arachidonic acid metabolism and cytokine production, on tumor necrosis factor formation [184,188], leukotriene B 4 formation [181], and on prostaglandin E2 production and phospholipase A2 activity [182]. In vitro studies using isolated enzyme assays and whole blood assays have shown that even very low (nanomolar) concentrations of phycocyanin selectively inhibit cyclooxygenase type 2 (COX-2) [190] which is upregulated during inflammation and cancer (especially breast cancer cells), and which in addition may also reduce prostaglandin E2 production [191]. ...
Background:
Open tetrapyrroles termed phycobilins represent the major photosynthetic accessory pigments of several cyanobacteria and some eukaryotic algae such as the Glaucophyta, Cryptophyta and Rhodophyta. These pigments are covalently bound to so-called phycobiliproteins which are in general organized into phycobilisomes on the thylakoid membranes.
Objective & methods:
In this work we first briefly describe the physico-chemical properties, biosynthesis, occurrence, in vivo localization and roles of the phycobilin pigments and the phycobiliproteins. Then the potential applications and uses of these pigments, pigment-protein complexes and related products by the food industry (e.g., as LinaBlue® or the so-called spirulina extract used as coloring food), by the health industry or as fluorescent dyes are critically reviewed.
Conclusion:
In addition to the stability, bioavailability and safety issues of purified phycobilins and phycobiliproteins, literature data about their antioxidant, anticancer, anti-inflammatory, immunomodulatory, hepatoprotective, nephroprotective and neuroprotective effects, and their potential use in photodynamic therapy (PDT) are also discussed.
... It effectively inhibited CCl 4 -induced lipid peroxidation in rat liver in vivo (13). Recently it was demonstrated that oral administration of phycocyanin exerted anti-inflammatory effects in arthritis induced by zymosan in mice (15). It was suggested that the anti-inflammatory activity of phycocyanin could be due to its ability to inhibit arachidonic acid metabolism and to scavenge oxygen free radicals (15,16). ...
... Recently it was demonstrated that oral administration of phycocyanin exerted anti-inflammatory effects in arthritis induced by zymosan in mice (15). It was suggested that the anti-inflammatory activity of phycocyanin could be due to its ability to inhibit arachidonic acid metabolism and to scavenge oxygen free radicals (15,16). In fact, oxygen free radicals are believed to be involved in rheumatoid arthritis (17) and inhibitors of arachidonic acid metabolism are commonly used in the treatment of arthritis (18). ...
... Inhibition of COX-2 activity is a favorable condition for treating inflammation, arthritis, and preventing cancer (29). Earlier studies have demonstrated the anti-inflammatory property of phycocyanin (15) and this property of phycocyanin can be explained, in part, by the specific inhibition of COX-2. The mechanism of inhibition of COX activity by phycocyanin appears to be similar to those reported for COX-2 selective inhibitors, occurring via a timedependent mechanism leading to a possible formation of a tightly bound inhibitor complex (26,30). ...
We report data from two related assay systems (isolated enzyme assays and whole blood assays) that C-phycocyanin a biliprotein from Spirulina platensis is a selective inhibitor of cyclooxygenase-2 (COX-2) with a very low IC(50) COX-2/IC(50) COX-1 ratio (0.04). The extent of inhibition depends on the period of preincubation of phycocyanin with COX-2, but without any effect on the period of preincubation with COX-1. The IC(50) value obtained for the inhibition of COX-2 by phycocyanin is much lower (180 nM) as compared to those of celecoxib (255 nM) and rofecoxib (401 nM), the well-known selective COX-2 inhibitors. In the human whole blood assay, phycocyanin very efficiently inhibited COX-2 with an IC(50) value of 80 nM. Reduced phycocyanin and phycocyanobilin, the chromophore of phycocyanin are poor inhibitors of COX-2 without COX-2 selectivity. This suggests that apoprotein in phycocyanin plays a key role in the selective inhibition of COX-2. The present study points out that the hepatoprotective, anti-inflammatory, and anti-arthritic properties of phycocyanin reported in the literature may be due, in part, to its selective COX-2 inhibitory property, although its ability to efficiently scavenge free radicals and effectively inhibit lipid peroxidation may also be involved.
... Pc was also evaluated in zymosan-induced arthritis in mice [58], an experimental model of rheumatoid arthritis in which complement is activated via alternative pathway and the secretion of lysosomal enzymes into the knee joint synovial fluid is induced. This activity correlates with histomorphological changes observed in the joint, such as vasculitis, synovitis and pannus formation. ...
... Furthermore, TNF-α and other cytokines are well known mediators of zymosan-induced arthritis and have been found in the synovial fluid [64,65]. In this context and using the experimental conditions described elsewhere [58], Pc (25, 50 and 100 mg/kg, p.o) administered on a daily dose for 8 days, suppressed the activity of the lysosomal enzyme βglucuronidase by 60, 80 and 93 % with respect to the mice treated with zymosan alone [58]. Furthermore, the histopathological and ultrastructural studies performed in the knee joints of mice treated with Pc or the reference drug, triamcinolone, showed a decrease in the inflammatory response. ...
... Furthermore, TNF-α and other cytokines are well known mediators of zymosan-induced arthritis and have been found in the synovial fluid [64,65]. In this context and using the experimental conditions described elsewhere [58], Pc (25, 50 and 100 mg/kg, p.o) administered on a daily dose for 8 days, suppressed the activity of the lysosomal enzyme βglucuronidase by 60, 80 and 93 % with respect to the mice treated with zymosan alone [58]. Furthermore, the histopathological and ultrastructural studies performed in the knee joints of mice treated with Pc or the reference drug, triamcinolone, showed a decrease in the inflammatory response. ...
Phycocyanin (Pc) is a phycobiliprotein that has been recently reported to exhibit a variety of pharmacological properties. In this regard, antioxidant, anti-inflammatory, neuroprotective and hepatoprotective effects have been experimentally attributed to Pc. When it was evaluated as an antioxidant in vitro, it was able to scavenge alkoxyl, hydroxyl and peroxyl radicals and to react with peroxinitrite (ONOO(-);) and hypochlorous acid (HOCl). Pc also inhibits microsomal lipid peroxidation induced by Fe(+2)-ascorbic acid or the free radical initiator 2,2' azobis (2-amidinopropane) hydrochloride (AAPH). Furthermore, it reduces carbon tetrachloride (CCl(4))-induced lipid peroxidation in vivo. Pc has been evaluated in twelve experimental models of inflammation and exerted anti-inflammatory effects in a dose-dependent fashion in all of these. Thus, Pc reduced edema, histamine (Hi) release, myeloperoxidase (MPO) activity and the levels of prostaglandin (PGE(2)) and leukotriene (LTB(4)) in the inflamed tissues. These anti-inflammatory effects of Pc can be due to its scavenging properties toward oxygen reactive species (ROS) and its inhibitory effects on cyclooxygenase 2 (COX-2) activity and on Hi release from mast cells. Pc also reduced the levels of tumor necrosis factor (TNF-alpha) in the blood serum of mice treated with endotoxin and it showed neuroprotective effects in rat cerebellar granule cell cultures and in kainate-induced brain injury in rats.
... They were administered orally on a daily basis, from days 4 to 12. Thereafter, mice were then killed by cervical dislocation and the synovial fluid of knee joints was sampled in order to measure the level of b glucuronidase enzyme. The knee joints were then totally removed for histological studies (Remirez et al., 1999). ...
... Arthritis was assessed semiquantitatively in standardized frontal section of the knee joint, which included the presence of subsynovial inflammation, destruction of articular cartilage, and general destruction of the joint with pannus formation and bone erosion (Beckman et al., 1998). These parameters were scored on a scale of 0-4 as described previously by Remirez et al. (1999). ...
... Zymosan is well known as a powerful releaser of arachidonic acid metabolites, which are very important for vasodilation and swelling as well as the release of chemotactic factors that recruit polymorphonuclear cells to the affected zone and that contribute actively to the early phase of inflammatory reaction (Remirez et al., 1999). ...
A mixture of fatty acids obtained from sugar cane (Saccharum officinarum L.) wax oil (FAM), in which the main constituents are palmitic, oleic, linoleic, and linolenic acids, was evaluated in two models of inflammation: zymosan-induced arthritis and in the tail test for psoriasis, both on mice. In the first model, FAM significantly reduced zymozan-induced increase of beta glucuronidase (DE(50) 90+/-7 mg/kg). Histopathological studies showed inhibition in cellular infiltration and reduction of synovial hyperplasia and synovitis, whereas in the second test, histopathological and ultrastructural studies showed that topical application of FAM induced orthokeratosis with the presence of keratohyalin granules in the previously parakeratotic adult mouse tail, and without effects on epidermal thickness. The ED(50) of FAM in this model was 155+/-10 mg. The results of our studies showed that topical application of FAM exerts an important anti-inflammatory activity in both tests without evidence of irritant effects. The anti-inflamatory effects exerted by FAM may be due to its inhibitory effects on arachidonic acid metabolism. To our knowledge, this is the first report on the anti-inflammatory effect of sugar cane by-products in experimental models of arthritis and psoriasis.
... These effects have been related to the antioxidant activity of Am, while others are attributed to some of its active ingredients, such as phycobiliproteins, which decrease oxidative stress [19,24]. Various studies have shown that extracts of Am rich in phycobiliproteins exhibit relevant pharmacological properties, including anti-teratogenic and neuroprotective effects, antigenotoxic properties, anti-inflammatory, and antioxidant activities, and protection against colitis [19,[25][26][27][28]. However, to our knowledge, there are no reports on the anti-ulcerative activities of phycobiliproteins from Am. ...
... In rats with colitis treated with phycocyanin, Gonzales et al. [27] described a substantial reduction in neutrophil infiltration in colonic mucosal injury. Remirez et al. [28] evaluated the protective effect of the phycocyanin extract in the zymosan-induced arthritis model in mice, finding that treatment with phycocyanin displayed an inhibition of cellular infiltration. Further studies carried out by Romay et al. [75,76] demonstrated that phycocyanin is able to inhibit the inflammatory response and edema triggered by 12-O tetradecanoyl phorbol 13-acetate in mice, as well as reduce the LTB4 levels in arachidonic acid-induced mouse ear edema. ...
Phycobiliproteins of Arthrospira (Spirulina) maxima have attracted attention because of their potential therapeutic antioxidant properties. The aim of this study was to assess the possible antiulcerogenic activity of these phycobiliproteins (ExPhy) against ethanol-induced gastric ulcers in rats. To explore the possible mechanisms of action, we examined antioxidant defense enzymes (e.g., catalase, superoxide dismutase, and glutathione peroxidase), as well as the level of lipid peroxidation (MDA) and the histopathological changes in the gastric mucosa. Intragastric administration of ExPhy (100, 200, and 400 mg/kg body weight) significantly lowered the ulcer index value compared to the ulcer control group (p < 0.05). The greatest protection was provided by the concentration of 400 mg/kg. The histological study supported the observed gastroprotective activity of ExPhy, showing a reduced inflammatory response. Moreover, the alcohol-induced decrease in stomach antioxidant enzyme activity found in the ulcer control group was prevented by ExPhy pretreatment. Furthermore, ExPhy reversed the ethanol-induced increase in lipid peroxidation. In summary, the antiulcerogenic potential of ExPhy may be due, at least in part, to its anti-oxidant and anti-inflammatory effects.
... The knee joints were then totally removed for histological studies. (6). ...
... Zymosan is well known as a powerful releaser of arachidonic acid metabolites which are very important for vasodilation and swelling as well as the release of chemotactic factors that recruit polymorphonuclear cells to the affected zone and that contribute actively to the early phase of inflammatory reaction (6). ...
A mixture of fatty acids obtained from sugar cane (Saccharum officinarum L.) wax oil, (FAM) in which the main constituents are palmitic, oleic, linoleic and linolenic acids, was evaluated in two models of inflammation: zymosan-induced arthritis and in the tail test for psoriasis, both on mice. In the first model, FAM significantly reduced zymozan-induced increase of β glucuronidase (DE 50 90 ± 7 mg/kg). Histopathological studies showed inhibition in cellular infiltration and reduction of synovial hyperplasia and synovitis, whereas in the second test, histopathological and ultrastructural studies showed that topical application of FAM induced orthokeratosis with the presence of keratohyalin granules in the previously parakeratotic adult mouse-tail, and without effects on epidermal thickness The ED 50 of FAM in this model was 155 ± 10 mg. The results of our studies showed that topical application of FAM exerts an important anti-inflammatory activity in both tests without evidence of irritant effects. The antiinflamatory effects exerted by FAM may be due to its inhibitory effects on arachidonic acid metabolism. To our knowledge, this is the first report on the anti-inflammatory effect of sugar cane by-products in experimental models of arthritis and psoriasis.
... Recently it has been reported that phycocyanin, a biliprotein obtained from microalgae Spirulina (Arthospira) maxima, has antioxidant and ROS scavenging properties [7] and also exerts anti-inflammatory activity in in vivo experimental models of colitis in rats [8] and arthritis in mice [9], in which NO, TNF-α and arachidonic acid metabolites are strongly involved in the inflammatory response [10]. ...
... Thus, it was able to scavenge OH · and alkoxy (RO · ) radicals as well as to inhibit luminol-enhanced chemiluminescence from zymosan-activated human polymorphonuclear leukocytes (PMNL) and microsomal lipid peroxi- dation induced by Fe +3 -ascorbic acid. Also phycocyanin exerted inhibitory effects in various experimental models of inflammation in rodents [8,9,18] and evidence has been provided that besides ROS scavenging properties, the inhibition by phycocyanin of prostaglandin E 2 (PGE 2 ) and leukotriene B 4 (LTB 4 ) production is also involved in its mode of action as anti-inflammatory agent [19,20]. ...
Wirkung von Phycocyanin-Extrakt auf die Serumspiegel von Tumornekrosefaktor a und Nitrit bei Endotoxin-behandelten Mäusen
Phycocyanin, ein aus Mikroalgen gewonnenes Biliprotein, besitzt antioxidative und entzündungshemmende Eigenschaften, wie in verschiedenen In-vivound In-vitro-Modellen festgestellt werden konnte. In der vorliegenden Studie wurde die Wirkung von Phycocyanin auf Tumornekrosefaktor-α (TNFα)- und Nitrit-Spiegel im Serum von mit Lipopolysaccharid (LPS) behandelten Mäusen untersucht. TNFα wurde anhand der Zytotoxicität an L 929-Zellen gemessen, und die Nitrite wurden mit Hilfe der Griess-Reak-tion bestimmt, nachdem alle Nitrate un-ter Beteiligung der Nitratreduktase zu Nitriten reduziert worden waren. 1 h nach der Injektion von LPS (0.5 mg/kg i.p.) war ein signifikanter Anstieg der TNFα-Spiegel im Serum der Mäuse zu verzeichnen. Wurde Phycocyanin (50–300 mg/kg p.o.) 1 h vor der Verabreichung von LPS gegeben, nahm die TNFα-Serumkonzentration dosisabhängig ab. 18 h nach der Gabe von LPS (30 mg/kg i.p.) wurde ein Anstieg der Nitrit-Serumspiegel beobachtet, welche durch Vorbehandlung mit Phycocyanin (100–300 mg/kg p.o.) dosisabhängig reduziert werden konnten. Die Ergebnisse zeigen, daß Phycocyanin die Produktion von TNFα und NO hemmt, was vermutlich den antioxidativen Eigenschaften dieses Biliproteins zuzuschreiben ist.
... µg/mL), C-PC (638.98 µg/mL), and APC (649.52 µg/mL), which were significantly compared to diclofenac value (699.3 µg/mL). The antiarthritic effects of PBPs may be due to their ability to scavenge ROS as well as their efficiency in blocking the metabolism of arachidonic acid and the generation of cytokines like tumor necrosis factor (TNF) 37 . ...
Phycobiliproteins (PBPs) are a class of water-soluble pigments with a variety of biological functions that are present in red macroalgae and cyanobacterial species. The crude forms of phycocyanin (C-PC) from the blue green alga Arthrospira platensis and allophycocyanin (APC) from the red macroalga Corallina officinalis were extracted and purified by ammonium sulphate precipitation, anion exchange chromatography, and size exclusion chromatography methods, respectively. The obtained C-PC and APC from A. platensis and C. officinalis were 0.31 mg/mL and 0.08 mg/mL, respectively, with molecular masses of “17.0 KDa and 19.0 KDa” and “15.0 KDa and 17.0 KDa” corresponding to α and β subunits, respectively. FT-IR was used to characterize the purified APC and C-PC in order to look into their structures. Highly purified extracts (A620/A280 > 4.0) were obtained from subtractions’ PC3 and PC4 that were tested for their biological activities. APC and C-PC crude extracts plus their fractions exhibited potent anti-oxidant in different ratios by using three techniques. PC1 showed high anti-inflammatory (75.99 and 74.55%) and anti-arthritic (78.89 and 76.92%) activities for C. officinalis and A. platensis, respectively compared with standard drugs (72.02 and 71.5%). The methanolic and water extracts of both species showed greater antibacterial efficacy against Gram +ve than Gram −ve marine bacteria. Our study shed light on the potential medical uses of C-PC and APC extracted from the tested species as natural substances in a variety of foods and drugs. Further investigations are required to explore the diverse chemical natures of distinct PBPs from different cyanobacteria and red algae because their amino acid sequences vary among different algal species.
... Researchers concluded that bone erosion was accompanied by severe inflammation of articular tissues. They also suggest that zymosan is a potent releaser of arachidonic metabolites that contribute actively to the primary phase of the inflammatory response (38). In another study, when zymosan was injected intra-articularly (15 mg/ml) into the knee joints, it caused arthritis in mice, resulting in a significant increase in -glucuronidase levels when compared with the control group. ...
Inflammation triggers immune system-mediated actions that contribute to the development of multiple diseases. Zymosan, a polysaccharide derived from the Saccharomyces cerevisiae cell wall, is mainly made up of glucan and mannan residues and is used as an inflammatory agent. Zymosan is a fungal product that activates the immune system through the activation of inflammatory signaling pathways, and releases a variety of harmful chemicals including pattern recognition receptors, reactive oxygen species (ROS), and the excitatory amino acid glutamate, cytokines, adhesion molecules, etc. Furthermore, we will dive into the molecular mechanistic insights through which this fungal agent induces and influences various inflammatory diseases such as cardiovascular, neuroinflammation, diabetes, arthritis, and sepsis. Based on the evidence, zymosan appears to be a promising inflammatory-inducing agent. Nonetheless, more animal data is the need of the hour to catch a glimpse and unravel the capacity of zymosan.
... It was reported by Remirez et al. [94] that C-PC from Arthospira maxima exhibited an anti-inflammatory effect in azymosan-induced arthritis model in mice. C-PC reduced in a dose-dependent manner ear oedema induced by arachidonic acid and 12-O-tetradecanoyl phorbol-13-acetate in mice as well as carrageenan-induced rat paw oedema. ...
Phycobiliproteins (PBPs) are colored and water-soluble biliproteins found in cyanobacteria, rhodophytes, cryptomonads and cyanelles. They are divided into three main types: allophycocyanin, phycocyanin and phycoerythrin, according to their spectral properties. There are two methods for PBPs preparation. One is the extraction and purification of native PBPs from Cyanobacteria, Cryptophyta and Rhodophyta, and the other way is the production of recombinant PBPs by heterologous hosts. Apart from their function as light-harvesting antenna in photosynthesis, PBPs can be used as food colorants, nutraceuticals and fluorescent probes in immunofluorescence analysis. An increasing number of reports have revealed their pharmaceutical potentials such as antioxidant, anti-tumor, anti-inflammatory and antidiabetic effects. The advances in PBP biogenesis make it feasible to construct novel PBPs with various activities and produce recombinant PBPs by heterologous hosts at low cost. In this review, we present a critical overview on the productions, characterization and pharmaceutical potentials of PBPs, and discuss the key issues and future perspectives on the exploration of these valuable proteins.
... About 20% of papers related to PCY health effects are describing its anti-inflammatory properties. It was first reported by Remirez et al. [31] when zymosan-induced arthritis mice model was investigated. The early study suggested that PCY antiarthritic effect could be associated with ROS scavenging potential, and down-regulation of cytokine secretion and arachidonic acid metabolic mechanism. ...
Phycocyanins (PCYs) are a group of luxuriant bioactive compounds found in blue-green algae with an estimated global market of about US$250 million within this decade. The multifarious markets of PCYs noted by form (e.g. powder or aqueous forms), by grade (e.g. analytical, cosmetic, or food grades), and by application (such as biomedical, diagnostics, beverages, foods, nutraceuticals and pharmaceuticals), show that the importance of PCYs cannot be undermined. In this comprehensive study, an overview on PCY, its structure, and health-promoting features are diligently discussed. Methods of purification including chromatography, ammonium sulfate precipitation and membrane filtration, as well as characterization and measurement of PCYs are described. PCYs could have many applications in food colorants, fluorescent markers, nanotechnology, nutraceutical and pharmaceutical industries. It is concluded that PCYs offer significant potentials, although more investigations regarding its purity and safety are encouraged.
... Additional studies have shown that phycocyanin, a similar phycobiliprotein from cyanobacteria, is bioavailable and non-toxic when administered orally or via injection and may also have some powerful anti-inflammatory effects [122,123]. Thus, allophycocyanin is a promising virucidal compound from Arthrospira that merits further research. (Table 3) [90]. ...
Viruses are abiotic obligate parasites utilizing complex mechanisms to hijack cellular machinery and reproduce, causing multiple harmful effects in the process. Viruses represent a growing global health concern; at the time of writing, COVID-19 has killed at least two million people around the world and devastated global economies. Lingering concern regarding the virus' prevalence yet hampers return to normalcy. While catastrophic in and of itself, COVID-19 further heralds in a new era of human-disease interaction characterized by the emergence of novel viruses from natural sources with heretofore unseen frequency. Due to deforestation, population growth, and climate change, we are encountering more viruses that can infect larger groups of people with greater ease and increasingly severe outcomes. The devastation of COVID-19 and forecasts of future human/disease interactions call for a creative reconsideration of global response to infectious disease. There is an urgent need for accessible, cost-effective antiviral (AV) drugs that can be mass-produced and widely distributed to large populations. Development of AV drugs should be informed by a thorough understanding of viral structure and function as well as human biology. To maximize efficacy, minimize cost, and reduce development of drug-resistance, these drugs would ideally operate through a varied set of mechanisms at multiple stages throughout the course of infection. Due to their abundance and diversity, natural compounds are ideal for such comprehensive therapeutic interventions. Promising sources of such drugs are found throughout nature; especially remarkable are the algae, a polyphyletic grouping of phototrophs that produce diverse bioactive compounds. While not much literature has been published on the subject, studies have shown that these compounds exert antiviral effects at different stages of viral pathogenesis. In this review, we follow the course of viral infection in the human body and evaluate the AV effects of algae-derived compounds at each stage. Specifically, we examine the AV activities of algae-derived compounds at the entry of viruses into the body, transport through the body via the lymph and blood, infection of target cells, and immune response. We discuss what is known about algae-derived compounds that may interfere with the infection pathways of SARS-CoV-2; and review which algae are promising sources for AV agents or AV precursors that, with further investigation, may yield life-saving drugs due to their diversity of mechanisms and exceptional pharmaceutical potential.
... It exhibited several pharmacological effects, including reactive oxygen species (ROS)-scavenging actions, anti-oxidant 18 , hepatoprotective 17 , and anti-arthritic 19 . Furthermore, C-PC has shown anti-inflammatory effects in several experimental models, in vitro and in vivo [19][20][21][22] . Inhibition of cyclooxygenase-2 activity has been reported as one of the significant anti-inflammatory effects of C-PC 23 . ...
Excessive bone loss occurs in inflammatory disorders such as periodontitis and osteoporosis. The underlying mechanism is related to the differentiation of macrophages into multinucleated giant osteoclasts and their bone resorptive activity. C-Phycocyanin (C-PC) is a phycobiliprotein extracted from the blue-green algae, which has been shown to have various pharmacological effects. The role of C-PC on bone metabolism needs revelation. In this study, we determined the effectiveness of C-PC as an inhibitor of osteoclast differentiation, activity, and survival in vitro. We found that C-PC strongly inhibited the differentiation of macrophages to TRAP-positive osteoclasts, distinctive osteoclast specific podosomal organization, and dentine matrix resorption without any cytotoxicity. Also, it suppressed the expression of osteoclast specific markers, such as cathepsin K and integrin β3 at mRNA and protein levels. RANKL mediated signaling utilizes reactive oxygen species (ROS) for the differentiation of osteoclasts. C-PC attenuated RANKL stimulated ROS. Mechanistic studies indicate that C-PC has the potential to reduce osteoclast formation via blocking the degradation of cytosolic IκB-α and hence, the activation of downstream markers such as c-Fos and NFATc1. However, it does not have any effect on osteoblast-mediated bone formation in vitro. Collectively, our data suggest that C-PC may be utilized as a therapeutic agent that can target bone loss mediated by excessive osteoclastic bone resorption without affecting osteoblastic activity in bone.
... Pc extracted from Spirulina platensis, has been demonstrated previously, that it possesses a broad spectrum of therapeutic effects notably hepatoprotective [28], anti-inflammatory [48,49] and antioxidant [50,51]. Besides, previous studies have also shown that Pc has several anti-mutagenic [52], antiarthritic [53], antiviral [54] and anticancer effects [55]. ...
... R-PE and R-PC, respectively) (Sampath-Wiley and Neefus 2007; Oh et al. 2013). In general, phycobiliproteins (phycocynin and phycoerythrin) content has antioxidant properties which have been shown to be beneficial in the treatment of Alzeimer's and Parkinson's diseases, gastric ulcers, and cancers in humans Padula and Boiteux 1999;Remirez et al. 1999). Seaweeds, including Pyropia and Porphyra are rich source of minerals (Rupérez 2002). ...
Genus Pyropia is one of the nutritionally rich marine algae. Among Indian Pyropia species, Pyropia acanthophora has been documented as a new addition with its new variety robusta. Biodiversity assessment revealed that P. acanthophora var. robusta reported only on the central west coast of India during monsoon (June to September). The nutritional composition of the collected samples was evaluated for proximate analysis along with vitamin C, dietary fiber, pigments, minerals, and fatty acid composition. The protein content was in the range of 14.11 ± 0.62 to 18.36 ± 0.90 g (100 g)−1 dry wt. Lipid content ranged from 1.65 ± 0.25 to 2.56 ± 0.40 g (100 g)−1 dry wt., and the concentrations of PUFA among these lipids were found in considerable quantity. Dietary fiber was also obtained in high concentration and ranged from 45.13 ± 1.30 to 63.0 ± 4.40 g (100 g)−1 dry wt. In this study, the level of K, Na, Mg, Fe, I, and P were appreciably high. Thus, the nutritional analysis of P. acanthophora var. robusta confirmed that it has potential to be used as an ingredient for nutritional supplements.
... The anti-inflammatory effects of crude Arthrospira products, as well as phycocyanin-enriched extracts, are well documented. 8,9,[23][24][25][27][28][29] However, to the best of our knowledge, this study is the first to establish an association with consumption of an aqueous Arthrospira extract enriched in phycocyanin and other aqueous compounds to pain relief in a human population. The overall speed and magnitude of resolution of some aspects of chronic pain suggests an underlying effect on oxidative stress and inflammation. ...
Objectives
The aim of this study was to evaluate the effects of consumption of an aqueous cyanophyta extract (ACE) from Arthrospira platensis on chronic pain in humans, in two clinical pilot studies.
Design and interventions
The two pilot studies each involved 12 subjects experiencing chronic pain. The initial study followed an open-label 4-week study design involving consumption of 1 g ACE per day. A subsequent placebo-controlled, single-blind, crossover study involved consumption of 500 mg ACE, 250 mg ACE, or 0 mg ACE (placebo) per day for 1-week duration, separated by 1-week washout period.
Subjects
Adult subjects of both sexes, with chronic joint-related pain for at least 6 months prior to enrollment, were recruited after obtaining written informed consent.
Outcome measures
Visual analog scales were used to score pain at rest and during physical activity for each person’s primary and secondary areas of chronic pain. An activities of daily living questionnaire was used to collect data on physical functioning.
Results
The data showed rapid reduction of chronic pain in people consuming ACE, where the reduction in pain scores for each person’s primary pain area reached a high level of statistical significance after 2 weeks of consumption (P<0.01), both when at rest and when being physically active. Secondary pain areas when physically active showed highly significant improvements within 1 week of consumption of 1 g/d (P<0.001) and borderline significant improvements within 1 week of consuming 500 mg/d (P<0.065) and 250 mg/d (P<0.05). This was accompanied by an increased ability to perform daily activities (P<0.05). A small but significant weight loss was observed during the 4-week study, as the average body mass index dropped from 31.4 to 29.4 (P<0.01).
Conclusion
Consumption of ACE was associated with reduction of chronic pain, as well as a dose-dependent increased ability to perform activities of daily living.
... La C-FC inhibe el edema producido en modelos de inflamación de la pata inducida por carragenina y glucosa oxidasa 33 , así como en el modelo de inflamación de la oreja del ratón inducida con ácido araquidónico 34 . En un modelo de artritis inducida por zimosano en ratones, la C-FC (25, 50, 100 mg/kg), administrada por vía oral, una vez al día a partir del cuarto y hasta el duodécimo día posterior a la aplicación del zimosano, disminuyó la actividad de la enzima β-glucuronidasa en el líquido sinovial, así como las lesiones tisulares de la rodilla 35 . En ratones tratados intratraquealmente con lipopolisacárido (LPS), la C-FC administrada tres horas después, logró disminuir en los pulmones los niveles de citocinas proinflamatorias (TNF-α, IL-6, IL-1β) y quimiocinas (CINC-3), de especies reactivas del oxígeno y del nitrógeno (nitrito/nitrato, O 2 • -), así como la expresión de óxido nítrico sintasa inducible (iNOS, en inglés), COX-2 y del factor nuclear de transcripción κB (NF-κB, en inglés), y la actividad de la enzima mieloperoxidasa. ...
La C-Ficocianina (C-FC), principal biliproteína de la cianobacteria Spirulina platensis, posee múltiples propiedades farmacológicas. Su proceso de purificación puede estar influido por factores relacionados con el crecimiento de la cianobacteria, tales como la intensidad luminosa y la agitación, la forma de suministrar los nutrientes y su concentración, el pH y la temperatura. La combinación de métodos con diferentes principios de separación, tales como las cromatografías de intercambio iónico, por filtración en gel y la precipitación con sulfato de amonio, ha permitido obtener la C-FC con grados de pureza adecuados para aplicaciones biofarmacéuticas. Entre las propiedades antioxidantes descritas para esta proteína se encuentran su potente capacidad secuestradora de radicales alcoxilos, hidroxilos y peroxilos, además de reaccionar con el peroxinitrito. La C-FC es un inhibidor selectivo de la ciclooxigenasa-2. En varios modelos experimentales, la C-FC ha mostrado efectos antiinflamatorios y ha reducido el daño en el tejido inflamado. Entre sus acciones se encuentran la disminución de los niveles de citocinas y quimiocinas proinflamatorias, la inhibición de la actividad de la mieloperoxidasa y de la activación del factor NF-κB. La C-FC ha mostrado efectos citoprotectores en modelos de daño isquémico cerebral y cardíaco, y de daño tisular inducido por tóxicos, tales como lesiones hepáticas, vasculares, renales, pancreáticas, oculares o frente a la hipertensión asociada al síndrome metabólico. Esta proteína también ejerce efectos cicatrizantes en heridas de la piel. Se han descrito, además, acciones antitumorales de la C-FC en diversas líneas celulares y modelos animales de cáncer colorectal, epidérmico, de leucemia mieloide y de hepatocarcinoma. Estas evidencias
Revista de Ciencias Farmacéuticas y Alimentarias. RNPS: 2396 - Vol.1 / Nº.1 - 2015 pág.29-43
Artículo de Revisión Recibido: 9 de enero 2015 - Aceptado: 20 de febrero 2015
30
sugieren que la C-FC podría constituir una promisoria alternativa terapéutica en el tratamiento de diferentes enfermedades humanas.
... The intensity of infiltrate was significantly higher in group induced with amoebic antigen that acted alone and along with known inducing agent CFA thus caused more severe inflammation in comparison to arthritic control. This activity is correlated with the histomorphological changes observed in the joint, such as vasculitis, synovitis and pannus formation [30]. ...
Today it is well known about mechanisms of cell communication, how the cells that mediate immune response and tissue injury accumulate in tissues but the aetiology of rheumatoid arthritis (RA) is still unknown. This study was to evaluate immunomodulatory effects of crude Entamoeba histolytica (HM1 IMS strain) antigen in complete freund's adjuvant female wistar rats by studying the alterations in humoral and cell mediated immune responses and also the inflammatory effects by evaluating the changes in body weight, paw thickness, biochemical, serological, interleukin-6 (IL-6), IL-10 and tumor necrosis factor-α (TNF-α) and histopathology activities. Animals were randomly divided into six groups (n=6). CFA was induced in arthritic, drug and AA+CFA group whereas, 0.5ml amoebic antigen was induced subplantal in AA group while 0.5ml dose of amoebic antigen was given orally to AA+CFA group for 7-28th days. Indomethacin was used as a standard drug. Effects of amoebic antigen were associated with increased paw thickness and decreased body weight when compared to healthy control showed a significant difference. Oral administration of amoebic antigen has showed increased severe symptoms of arthritis in AA+CFA on comparison to healthy control rats. Significant increase in serum level of IL-6 and α TNF were found in AA group followed by AA+CFA group whereas, decrease in concentration of IL-10 was appear in AA+CFA group on comparison to arthritic and healthy control group (P<0.05). Histopathology of AA group showed severe signs of necrotic and degenerative changes on comparison to healthy control group. Thus the results demonstrated that E. histolytica alone or in combination with CFA increased bone damage, with alterations in antioxidant level in liver and kidney tissue homogenates as well as showed immunomodulatory arthritogenic properties which may contribute and raise joint inflammation.
... 15 In addition to their fundamental roles in global carbon cycling and nitrogen fixation, cyanobacteria such as Arthrospira platensis and A. maxima have become increasingly important economically in the production of human dietary supplements. Due to their diverse biological activities, in vitro and in vivo studies have been conducted to study selective COX-2 inhibition, 16 antioxidant, 17 and anti-inflammatory activity, 18 as well as neuroprotectant 19 and hepatoprotectant 20 properties. Therefore, due to the well-documented properties of bluegreen algae, A. platensis and A. maxima are gaining acceptance as nutritional support in the prevention of various chronic metabolic and inflammatory conditions. ...
The goal for this work was to characterize basic biological properties of a novel Arthrospira platensis-based aqueous cyanophyta extract (ACE), enriched in the known anti-inflammatory cyclooxygenase-2 (COX-2) inhibitor phycocyanin (PC), but also containing a high level of non-PC bioactive compounds. Antioxidant properties were tested in parallel in the Folin-Ciocalteu assay (chemical antioxidant capacity) and in the cellular antioxidant protection (CAP-e) bioassay, where both the PC and the non-PC fractions contributed to the antioxidant capacity and CAP of ACE. In contrast to the COX-2 inhibition seen in the presence of PC, the inhibition of enzymatic activity of the inflammatory mediator Lipoxygenase was associated specifically with the non-PC fraction of ACE. Inhibition of formation of reactive oxygen species (ROS) was evaluated using polymorphonuclear cells from healthy human donors. The inhibition of ROS formation was seen for both the PC and non-PC fractions, with ACE showing the most robust effect. The effects of PC, non-PC, and ACE on clotting and clot lysing was tested using a modified Euglobulin fibrinolytic assay in vitro. In the presence of PC, non-PC, and ACE, the time for clot formation and lysis was not affected; however, the clots were significantly more robust. This effect was statistically significant (p<.05) at doses between 125-500 μg/mL, and returned to baseline at lower doses. Both PC and the non-PC fraction contributed to the antioxidant properties and anti-inflammatory effects, without a negative impact on blood clotting in vitro. This suggests a potential benefit for the consumable ACE extract in assisting the reduction of inflammatory conditions.
... 15 In addition to their fundamental roles in global carbon cycling and nitrogen fixation, cyanobacteria such as Arthrospira platensis and A. maxima have become increasingly important economically in the production of human dietary supplements. Due to their diverse biological activities, in vitro and in vivo studies have been conducted to study selective COX-2 inhibition, 16 antioxidant, 17 and anti-inflammatory activity, 18 as well as neuroprotectant 19 and hepatoprotectant 20 properties. Therefore, due to the well-documented properties of bluegreen algae, A. platensis and A. maxima are gaining acceptance as nutritional support in the prevention of various chronic metabolic and inflammatory conditions. ...
Oligonol is a low-molecular-weight polyphenol that possesses antioxidant and anti-inflammatory properties. This study investigated the effects of Oligonol supplementation on sweating response, plasma volume (PV), and osmolality (Osm) after heat load in human volunteers. We conducted a placebo-controlled crossover trial. Participants took a daily dose of 200 mg Oligonol or placebo for 1 week. After a 2-week washout period, the subjects were switched to the other study arm. As a heat load, half-body immersion into hot water (42°C±0.5°C for 30 min) was performed in an automated climate chamber. Tympanic and mean body temperature (Tty, mTb) and whole-body sweat loss volume (WBSLV) were measured. Changes in PV, Osm, and serum levels of aldosterone and sodium were analyzed. Oligonol intake attenuated increases in Tty, mTb, and WBSLV after heat load compared with the placebo (P<.01, P<.05, and P<.01, respectively). In addition, serum aldosterone was maintained at a relatively low degree and serum sodium was maintained at a relatively high degree with Oligonol compared to the placebo (P<.01 and P<.05, respectively). However, PV decreased and Osm increased significantly with Oligonol compared to the placebo (P<.05 and P<.05, respectively). This study demonstrates that Oligonol supplementation for 1 week can attenuate elevation of body temperature and excessive sweating under heat load in healthy humans, but interpretation of the results requires caution due to the potent diuretic effect of Oligonol.
... In an earlier human feeding study conducted in this regard, Spirulinabased dietary supplement was found effective in suppressing the level of interleukin-(IL-) 4 [23]. Zymosan-induced upsurge in the level of beta-glucuronidase of experimental mice was significantly reduced following the administration of phycocyanin [97]. This antiarthritic action may be due to the combination of various mechanisms such as free radical scavenging, inhibition of arachidonic acid metabolism as well as inhibition of TNF-í µí»¼ within the mice. ...
Cyanobacteria are aquatic and photosynthetic organisms known for their rich pigments. They are extensively employed as food
supplements due to their rich contents of proteins. While many species, such as Anabaena sp., produce hepatotoxins (e.g.,
microcystins and nodularins) and neurotoxins (such as anatoxin a), Spirulina (Arthrospira) displays anticancer and antimicrobial
(antibacterial, antifungal, and antiviral) activities via the production of phycocyanin, phycocyanobilin, allophycocyanin, and other
valuable products.This paper is an effort to collect these nutritional and medicinal applications of Arthrospira in an easily accessible
essay from the vast literature on cyanobacteria.
... In an earlier human feeding study conducted in this regard, Spirulinabased dietary supplement was found effective in suppressing the level of interleukin-(IL-) 4 [23]. Zymosan-induced upsurge in the level of beta-glucuronidase of experimental mice was significantly reduced following the administration of phycocyanin [97]. This antiarthritic action may be due to the combination of various mechanisms such as free radical scavenging, inhibition of arachidonic acid metabolism as well as inhibition of TNF-within the mice. ...
Cyanobacteria are aquatic and photosynthetic organisms known for their rich pigments. They are extensively employed as food
supplements due to their rich contents of proteins. While many species, such as Anabaena sp., produce hepatotoxins (e.g.,
microcystins and nodularins) and neurotoxins (such as anatoxin a), Spirulina (Arthrospira) displays anticancer and antimicrobial
(antibacterial, antifungal, and antiviral) activities via the production of phycocyanin, phycocyanobilin, allophycocyanin, and other
valuable products.This paper is an effort to collect these nutritional and medicinal applications of Arthrospira in an easily accessible
essay from the vast literature on cyanobacteria.
... 3 -5 C-phycocyanin (C-PC) is of great interest because of its therapeutic value due to the protective effect and anticarcinogenic activity. 6,7 C-PC is a blue pigment with strong antioxidative and anti-inflammatory activities. 8,9 C-PC has been used for the treatment of Alzheimer's disease and Parkinson's disease, 10 and the prevention of experimental oral and skin cancers. ...
BACKGROUND: Phycobiliproteins are water soluble proteins useful as fluorescent markers of cells and macromolecules, and as natural colorants, and are anticarcinogenic. Although phycobiliproteins have many applications, their use is limited by the high cost of the purified macromolecules, mainly related with the cost of extraction and purification. In this study a fast and scalable method for preparative extraction and purification of C-phycocyanin (C-PC) from Anabaena marina is developed.
RESULTS: The method developed consists in the extraction of phycobiliproteins using repeated single contact strategy, separation being performed by expanded bed adsorption (EBA) chromatography using Streamline-DEAE. Optimal conditions for EBA were obtained at small scale, using a 15 mm internal diameter column, these being a sample load of 0.9 mg C-PC mL−1 adsorbent, an expanded bed volume twice the settled bed volume and a sample viscosity of 1.109 mP. The process was then scaled up 36 times, the success of the scale-up process being verified. Finally, to obtain pure C-PC conventional ion-exchange chromatography was utilized.
CONCLUSION: Small diameter columns was shown to be useful to simulate the behavior of larger diameter columns for use in scaled up systems. Expanded bed adsorption was demonstrated to be a scalable technology allowing large quantities of C-PC to be obtained, maintaining high protein recovery while reducing both processing cost and time. The proposed methodology allows recovery of more than 62% of the C-PC contained in the biomass in the form of pure C-PC concentrates. Copyright
... These compounds are made up of biline (tetrapyrolic open core) linked in a covalant way to a proteic chain. Recent studies showed that phycobiliproteins present antioxidant properties, which could be beneficial in the prevention or treatment of neuro-degenerative diseases caused by oxidative stress (Alzeimer's and Parkinson's) as well as in the cases of gastric ulcers and cancers (Gonzales et al. 1999, Padula et Boiteux 1999, Remirez et al. 1999). ...
In the Far East and Pacific, there has been a long tradition of consuming seaweeds as sea vegetables, while in Western countries the principal use of seaweeds has been as source of phycocolloids (alginate, carrageenan and agar), thickening and gelling agents for various industrial applications, including uses in foods. In addition, seaweeds constitute an interesting source of compounds with health protective effects. This paper is a short review on the biochemical composition and the nutritional value of seaweeds.
... Parmi les protéines algales, il faut citer la présence chez les algues rouges et bleues de molécules particulières : les phycobiliprotéines, qui sont les principaux pigments de ces algues et font partie du système de collecte de l'énergie lumineuse [6]. Les phycobiliprotéines (phycocyanine de spiruline et phycoerythrine des algues rouges) possèdent par ailleurs des propriétés antioxydantes qui pourraient être mises à profit dans la prévention ou le traitement de maladies dégénératives : certaines formes de cancer, maladies cardiovasculaires ou ophtalmiques liées au stress oxydatif [10,19,20]. ...
La quantité de macro-algues transformées annuellement dans le monde est de plus de 9 millions de tonnes (poids frais). Premier
débouché mondial en valeur et volume, les applications alimentaires directes (algue légume) concernent 75 % de cette production.
L’algue est un aliment traditionnel qui présente un intérêt nutritionnel connu et exploité depuis de nombreuses années par
les populations du Sud-Est asiatique. La valeur nutritionnelle des algues peut s’expliquer en grande partie par la présence
conjointe de trois grandes catégories de composants (fibres, minéraux et protéines), mais également par la présence de métabolites
présentant des propriétés antioxydantes et antiradicalaires tels que caroténoïdes, polyphénols, vitamines ou acides gras polyinsaturés.
In the Far East and Pacific Islands, there has been a long tradition of consuming seaweed as sea vegetables, while in Western
countries the main use of seaweed has been as source of phycocolloids (alginate, carrageenan and agar) used as thickening
and gelling agents in various industrial applications, including food processing. Seaweed is also a source of compounds with
protective health effects. The beneficial effects of seaweed on human health appear to derive from the presence of three categories
of constituents (fibre, proteins and minerals) as well as metabolites with antioxidant properties, including carotenoids,
polyphenols, vitamins and polyunsaturated fatty acids.
... The inhibitory effect of phycocyanin from Spirulina was also studied in zymosan induced arthritis in mice, an experimental model of RA in which complement is activated via alternative pathway and the secretion of lysosomal enzymes into the knee joint synovial fluid is induced. This activity is correlated with the histomorphological changes observed in the joint, such as vasculitis, synovitis and pannus formation (Remirez et al. 1999). In our opinion, the mechanism by which Spirulina exerts its anti-chemoattractant action on synovial cell infiltration or pannus formation in joints may be due to its inhibitory effects on the biosynthesis of the neutrophil chemotactic mediator LTB 4 . ...
To assess the protective efficacy of Spirulina platensis against collagen-induced arthritis (CIA) in female Wistar rats based on the changes in paws thickness, serum albumin, cholesterol, lipid peroxidation, alkaline phosphatase and acid phosphatase activities and histology of paw joints.
Arthritis was induced by intradermal injection of Collagen and Freund's adjuvant incomplete suspension at several sites on the back with a dose of 2 mg kg(-1) of body weight and boosted with 0.1 ml intradermally at the base of the tail. CIA rats were orally treated with 200 and 400 mg kg(-1) per oral of S. platensis from 0 to 45th day.
S. platensis at 400 mg kg(-1) per oral significantly elevates serum albumin and decreases the serum cholesterol, alkaline phosphatase and acid phosphatase activities, lipid peroxidation, paw thickness as well as normalize the joint histopathology of CIA rats.
S. platensis (400 mg kg(-1)) significantly normalizes changes observed in arthritic rats to near normal conditions, indicates that S. platensis has promising protective efficacy against CIA rats.
... 14,15 In previous studies, we have demonstrated the antioxidant and anti-inflammatory properties of phycocyanin in various in vitro and in vivo experimental models. 1,[16][17][18] It was thus also shown that phycocyanin extract reduces LTB 4 and prostaglandin E 2 levels in the arachidonic acid-induced mouse ear inflammation test. 2,3 In the present work, we have found that phycocyanin also exerts an anti-inflammatory effect in mouse ear swelling response to ovalbumin in which the various mediators quoted earlier are released in a IgEmediated reaction in sensitized mice (Table 1). ...
It has recently been reported that phycocyanin, a biliprotein found in the blue-green microalgae Spirulina, exerts anti-inflammatory effects in some animal models of inflammation. Taking into account these findings, we decided to elucidate whether phycocyanin might exert also inhibitory effects in the induced allergic inflammatory response and on histamine release from isolated rat mast cells. In in vivo experiments, phycocyanin (100, 200 and 300mg/kg post-orally (p.o.)) was administered 1 h before the challenge with 1 microg of ovalbumin (OA) in the ear of mice previously sensitized with OA. One hour later, myeloperoxidase activity and ear edema were assessed. Phycocyanin significantly reduced both parameters. In separate experiments, phycocyanin (100 and 200 mg/kg p.o.) also reduced the blue spot area induced by intradermal injections of histamine, and the histamine releaser compound 48/80 in rat skin. In concordance with the former results, phycocyanin also significantly reduced histamine release induced by compound 48/80 from isolated peritoneal rat mast cells. The inhibitory effects of phycocyanin were dose dependent. Taken together, our results suggest that inhibition of allergic inflammatory response by phycocyanin is mediated, at least in part, by inhibition of histamine release from mast cells.
... Collectively, data presented indicate that (i) C-phycocyanin significantly decreases Kupffer cell phagocytosis and the associated respiratory burst activity, and (ii) this latter effect may contribute to the suppression of oxidative stress-induced TNF-a response and NO production by hyperthyroid state. The studies may also explain the inhibitory effect of C-phycocyanin on the TNF-a response induced by lipopolysaccharide in mice [32], a response known to depend mainly upon Kupffer cell functioning [33], thus supporting the anti-inflammatory potential of the biliprotein [2,4,5,34]. ...
Kupffer cells, liver macrophages involved in immunomodulation, phagocytosis, and biochemical attack, can induce cytotoxicity and inflammation when their activity is exacerbated. The aim of this study was to evaluate the effects of C-phycocyanin on Kupffer cell functioning considering its antioxidant and anti-inflammatory properties.
Actions of C-phycocyanin on colloidal carbon phagocytosis, carbon-induced respiratory burst activity, and sinusoidal lactate dehydrogenase (LDH) release were studied in isolated perfused mouse liver. The influence of C-phycocyanin on tumor necrosis factor-a (TNF-alpha) and nitrite levels in serum and liver nitric oxide synthase (NOS) activity was assessed in rats subjected to thyroid hormone (T3) administration, a condition known to underlie hepatic oxidative stress comprising an increased Kupffer cell activity.
C-phycocyanin elicited a concentration-dependent inhibition of carbon phagocytosis and carbon-induced O2 uptake (IC50 = 0.2 mg/ml) by perfused livers, with a 52% diminution in the carbon-induced sinusoidal release of LDH being found at a concentration of 0.25 mg/ml. Thyroid calorigenesis induced an 82-fold increase in serum TNF-alpha levels, an effect that was suppressed by pretreatment with C-phycocyanin, the antioxidant alpha-tocopherol, and by the Kupffer cell inactivator gadolinium chloride. C-phycocyanin also suppressed the T3-induced increases in serum nitrite levels (234%) and in the activity of hepatic NOS (75%).
C-phycocyanin significantly decreases Kupffer cell phagocytosis and the associated respiratory burst activity, effects that may contribute to the abolition of oxidative stress-induced TNF-alpha response and NO production by hyperthyroid state.
... Dietary foods that possess antioxidant activity may play a role in human health, particularly in diseases believed to be involved, at least in part, with oxidation, such as coronary heart disease, inflammation, and mutagenesis leading to carcinogenesis (6). On the other hand, it was also demonstrated that oral administration of C-PC exerted an antiinflammatory effect in arthritis induced by zymosan in mice (7). Owing to its fluorescence properties, it has gained importance in the development of phycofluor probes for immunodiagnostics (8). ...
The aim of this study was to systematically examine the inhibitory mechanisms of C-phycocyanin (C-PC), one of the major phycobiliproteins of Spirulina platensis (a blue-green alga), in platelet activation. In this study, C-PC concentration-dependently (0.5-10 nM) inhibited platelet aggregation stimulated by agonists. C-PC (4 and 8 nM) inhibited intracellular Ca2+ mobilization and thromboxane A2 formation but not phosphoinositide breakdown stimulated by collagen (1 microg/mL) in human platelets. In addition, C-PC (4 and 8 nM) markedly increased levels of cyclic GMP and cyclic GMP-induced vasodilator-stimulated phosphoprotein (VASP) Ser(157) phosphorylation. Rapid phosphorylation of a platelet protein of Mw 47,000 (P47), a marker of protein kinase C activation, was triggered by phorbol-12,13-dibutyrate (150 nM). This phosphorylation was markedly inhibited by C-PC (4 and 8 nM). In addition, C-PC (4 and 8 nM) markedly reduced the electron spin resonance (ESR) signal intensity of hydroxyl radicals in collagen (1 microg/mL)-activated platelets. The present study reports on a novel and very potent (in nanomolar concentrations) antiplatelet agent, C-PC, which is involved in the following inhibitory pathways: (1) C-phycocyanin increases cyclic GMP/VASP Ser157 phosphorylation and subsequently inhibits protein kinase C activity, resulting in inhibition of both P47 phosphorylation and intracellular Ca2+ mobilization, and (2) C-PC may inhibit free radicals (such as hydroxyl radicals) released from activated platelets, which ultimately inhibits platelet aggregation. These results strongly indicate that C-PC appears to represent a novel and potential antiplatelet agent for treatment of arterial thromboembolism.
... C-phycocyanin (cpc), a biliprotein found in Spirulina platensis, is often used as a dietary nutritional supplement in many countries due to its therapeutic values including hepatoprotective, neuroprotective and reactive oxygen species-scavenging actions (Kay, 1991;Vadiraja et al. 1998;Romay et al. 2003). It has been demonstrated that oral administration of cpc exhibits an anti-inflammatory effect in several animal models, such as in mice with arthritis or sepsis (Romay et al. 1998(Romay et al. , 2001Remirez et al. 1999). The cpc is composed of two dissimilar a and b protein subunits of 17 000 and 19 500 Da, respectively, with one bilin chromophore attached to the a subunit (a 84) and two to the b subunit (b 84, b 155) (Romay et al. 2003). ...
C-phycocyanin (cpc), a biliprotein isolated from Spirulina platensis, has been reported to exert many therapeutic and nutritional values. In the present study, we examined whether cpc has an antiplatelet activity in vitro and further investigated the possible anti-aggregatory mechanisms involved. Our results showed that preincubation of cpc (1-50 microg/ml) with rabbit washed platelets dose-dependently inhibited the platelet aggregation induced by collagen (10 microg/ml) or arachidonic acid (100 microm), with an IC50 of about 10 microg/ml. Furthermore, the thromboxane B2 formation caused by collagen or arachidonic acid was significantly inhibited by cpc due to suppression of cyclooxygenase and thromboxane synthase activity. Similarly, the rise of platelet intracellular calcium level stimulated by arachidonic acid and collagen-induced platelet membrane surface glycoprotein IIb/IIIa expression were also attenuated by cpc. In addition, cpc itself significantly increased the platelet membrane fluidity and the cyclic AMP level through inhibiting cyclic AMP phosphodiesterase activity. These findings strongly demonstrate that cpc is an inhibitor of platelet aggregation, which may be associated with mechanisms including inhibition of thromboxane A2 formation, intracellular calcium mobilization and platelet surface glycoprotein IIb/IIIa expression accompanied by increasing cyclic AMP formation and platelet membrane fluidity.
Prostate cancer (PCa) is the most diagnosed cancer in 112 countries and the second leading cause of death in men in 48 countries. We studied the outstanding agents silver nanoparticles (AgNPs) and Spirulina algae (Sp) for the management of PCa once as monotherapy or last as a combination. PCa in rats was induced using bicalutamide (Casodex®) and testosterone, followed by (7, 12-dimethylbenz[a]anthracene). Then, testosterone was injected s.c. for 3 months. Rats were divided into six groups, with 12 rats in each group. Group I was assigned as the control (co), group II as the PCa model, group III treated with AgNPs, group IV treated with Spirulina extract, group V treated with a combination of AgNPs plus Spirulina, and group VI treated with bicalutamide. The results show that AgNPs could normalize IL-6 levels and could overcome the hormonal disturbance induced in PCa rats along the hypothalamic–pituitary–testis axis. Spirulina revealed a significant reduction in the level of total and free prostatic specific antigen (PSA) to the same level as bicalutamide treatment, which was the same as the control group. Histopathological study revealed regression (75%) of the histological pattern of high-grade prostatic intraepithelial neoplasia (HGPIN) for Spirulina alone, and (50%) for bicalutamide. The best effect on IL-6 decline was reached with the AgNPs/Spirulina combination as well as bicalutamide treatment compared with the PCa group. Bicalutamide treatment significantly decreased the PSA concentration relative to the PCa group and reached the normal level. Adding Spirulina to AgNPs as a combination enhanced its effect on all mentioned drawbacks associated with PCa except hormonal imbalance that needs more adjustments.
An overview of the biological properties of phycocyanin (PC) amply illustrates that it may not have any specific functional feature towards any system at which it may elicit a specific function, but for the molecular interactions. Nevertheless, based on existing evidences, it is hypothesized that PC has more than one functional target with the interacting systems; therefore, it has diversity of effects. The mechanism of PC action remains elusive of a comprehensive idea. The present investigation focuses on the pro inflammatory enzyme, lipoxygenase (LOX) inhibiting property of PC purified from Oscillatoria sp. Enzyme kinetics studies show that the molecular composite of PC is required for its inhibition shown on LOX. Isothermal titration calorimetric study proves that one molecule of PC interacts with two molecules of LOX. Molecular dynamics simulation study pertaining to PC-LOX interactions shows it to be appropriate as a model to give molecular mechanistic insight into the varied biological properties of PC, demonstrated elsewhere in experimental studies including animal model studies. It explains that the PC-LOX interaction is of a function-freezing, protein-protein interaction in nature. The wide spectrum of properties of PC might be due to its function as a powerful protein hub showing non-specific protein-protein interactions.
Seaweeds or macroalgae are generally grouped into three taxa: green, brown, and red algae. (A more comprehensive review of seaweed systematics can be found in chapter: Macroalgae Systematics.) They are important bioresources of the oceans and play a major role in the maintenance of its ecosystem. These marine algae are utilized for food, fodder, polysaccharide extraction, biofertilizers, cosmetics, papermaking, and biobased fuels. In this chapter, numerous topics on seaweed biology are covered including: the role in maintenance of ocean ecology, herbivory and predation defense mechanisms, life history of important seaweeds, and their commercial applications.
Objective: The effects of gastroprotective properties of Spirulina platensis was investigated in acetic acid and ethanol induced ulcers in rats. Methods: Administration of 2 and 4mg/kg Spirulina platensis extract for 7 days. After day 7, oral administration of either 80% (v/v) ethanol or 6% (v/v) acetic acid. Control rats received saline or anti-ulcer drug omeprazole (20 mg/kg) prior to ulcer induction. Results: The extract inhibited the mean lesion score of acetic acid, 4.333 to 3.000. Whereas, for ethanol induced ulcers, the extract reduced the lesion scoring from 2.833 to 1.677. However, this activity was statistically less potent than the anti-ulcer drug, omeprazole. Spirulina platensis alone did not induce any ulcers in rats. Conclusions: These results suggested that Spirulina platensis has gastroprotective activity against ulcers induced by acetic acid and ethanol.
Despite many technological and clinical advances in wound healing using chemical and natural agents, mechanism of action of these agents during wound healing remains a major bottleneck. C-Phycocyanin (C-pc), a natural chromo-fluroprotein from cyanobacteria Spirulina fussiformis, was found to be effective in curative aspects of wound healing. Here, we envisage the systematic mechanism of action and its relationship with plasminogen activators namely urokinase type plasminogen activator (uPA). C-pc that was isolated from Spirulina fussiformis showed pro-fibrinolytic activity in bovine and human cell lines. Dose dependent increase in fibrinolysis was noticed in both cell lines, implying that the observed activity was not cell type specific. Zymography assay confirmed that uPA was responsible for the fibrinolytic properties of C-pc. Collectively, results suggest that uPA induction by C-pc is transcriptionally regulated and does not require de novo protein synthesis for mRNA stability. Further studies suggest that the activity is via a cAMP mediated mechanism that is dependent on PKA pathway. Fibroblast proliferation and migration is a hallmark of wound healing. C-pc promoted fibroblast proliferation by inducing cyclin-dependent kinases Cdk1 and Cdk2, in a uPA-independent manner. In vitro wound healing and fibroblast migration assays revealed the pro-migratory properties of C-pc. C-pc also induced the expressions of GTPases Rac 1 and Cdc42, via PI-3K mjhsignal pathway. Short interference RNA studies demonstrated that uPA was necessary for C-pc induced GTPase expression and fibroblast migration. In vivo wound healing experiments in mice validated in vitro findings that C-pc accelerates wound healing. In conclusion, we expose the wound healing property of C-pc and the related molecular pathway mechanisms associated with the event.
Spirulina is an unbranched, helicoidal, and filamentous blue-green algae or cyanobacterium that has been found in various aquatic environments. Although it has been a common dietary substance around the world since ancient times, its nutritional values and health benefits have not been scientifically proven. Recently, several lines of studies have provided insight into its nutritive and health beneficial effects. Hence, Spirulina's unusually high protein content and its richness in vitamins, minerals, carotenoids, and essential fatty acids are now well recognized. Notably, it has been found to possess various bioactivities, including antioxidant, anti-infammatory, antiallergic, anticancer, antiobesity, antidiabetic, antiviral, antibacterial, and antihepatopathic activities. This chapter presents a brief overview of the general characteristics of Spirulina, as well as its biochemical components and pharmaceutical properties.
IntroductionBiomedical applications of seaweedsIndustrial applications of seaweedsConclusion
AcknowledgmentReferences
Phycocyanins (PCs) are water-soluble phycobiliproteins, with extraordinary fluorescent properties (high quantum yield, high Stokes shift, and an important insensitivity to quenching). They have therapeutic value due to their protective effect against various conditions and their anticarcinogenic activity, their antioxidative and anti-inflammatory activities, and in the treatment of Alzheimer's and Parkinson's disease. PCs are composed of two relatively homologous subunits: the a and — chains. Three isomeric bilins – phycocyanobilin (PCB), phycobiliviolin (PVB), and phycoerythrobilin (PEB) – are found attached to PCs. PCs can be extracted from cyanobacteria using different methodologies, which combine breakage of cell walls and extraction of the water-soluble PCs into aqueous media. The recent research and developments in PC synthesis and functionality have further expanded the potential applications of these macromolecules in the areas of biotechnology, diagnostics, food, and medicine.
Currently, our society lives under a misleading apprehension of there being food abundance…..etc, etc…… Many people of the west are surrounded by fast food rich in calories and unsaturated fats, high powered advertising and over-consumption. The mass market has actually become accustomed to the expression of "junk food" to designate such offerings, but yet this highly processed ―food‖ is consumed in large amounts. The consequences of consumption of these offerings for the mass (western) the lack of essential nutrients, obesity and diseases related to excessive intake of sugars (diabetes) and fat (arteriosclerosis), among others. It is worrying that the fast food trends of the west are being adopted seemingly without concern in developing countries as they become more prosperous, hence rates of associated disease are increasing. What roles have the seaweeds in this picture? Represent exactly the opposite: a natural food that gives us a highly nutritious but low in calories. Algae are therefore the best way to address the nutritional deficiencies of the current food, due to its wide range of constituents: minerals (iron and calcium), protein (with all essential amino acids), vitamins and fiber [1,2]. Contrary to what happens in East Asia, the West is more involved with use of seaweed as a source in thickeners and gelling properties of hydrocolloids extracted from seaweeds: carrageenan, agar and alginate (E407, E406 and E400, respectively), which are widely used in food industry, especially in desserts, ice cream, the fresh vegetable gelatin. Perhaps in most cases, the consuming public are blissfully unaware they are consuming seaweed derived products. However attitudes are quite different in Asian cultures where seaweeds are highly valued and regarded for their appearance, texture, flavour and in a number of cases, beneficial health properties.
Cancer research illustrated that combinatorial studies can provide significant improvement in safety and effectiveness over the monotherapy regimens. A combination of two drugs may restrain precancerous colon polyps, opening a new possible opportunity for chemoprevention of colon cancer. In this context, chemopreventive efficacy of a combination regimen of C-phycocyanin, a biliprotein present in Spirulina platensis, a cyanobacterium, which is a selective cycloxygenase-2 (COX-2) inhibitor and piroxicam, a traditional non-steroidal anti-inflammatory drug was considered in 1,2 dimethylhyadrazine (DMH)-induced colon carcinogenesis in rats. Western blotting, immunohistochemistry, DNA fragmentation, fluorescent staining, PGE(2) enzyme immunoassay, and carrageenan-induced paw edema test were performed along with morphological and histological analysis. DMH treatment showed a rich presence of preneoplastic lesions such as multiple plaque lesions, aberrant crypt foci, and well-characterized dysplasia. These features were reduced with piroxicam and C-phycocyanin administration. The number of apoptotic cells was featured prominently in all the groups compared with DMH. DMH treatment revealed intact high molecular weight genomic DNA with no signs of laddering/DNA fragmentation while it was noticeable significantly in control and DMH + piroxicam + C-phycocyanin. DMH group showed highest COX-2 expression and PGE(2) level in comparison with other groups. Doses of piroxicam and C-phycocyanin used in the present study were established at an anti-inflammatory range. A combination regimen of piroxicam and C-phycocyanin, rather than individually has the much greater potential for reduction of DMH-induced colon cancer development and COX-2 being the prime possible target in such chemoprevention.
In this paper a large and scaleable method for purification of C-phycocyanin (C-PC) from the cyanobacteria Synechocystis aquatilis has been developed. Phycobiliproteins are extracted from the cells by osmotic shock and separated by passing the centrifuged cell suspension through an expanded bed adsorption chromatography (EBAC) column using Streamline-DEAE as adsorbent. The eluted C-PC rich solution is finally purified by packed-bed chromatography using DEAE-cellulose. Optimal extraction is achieved using phosphate 0.05 M buffer pH 7.0 twice. The operation of EBAC is optimized on a small scale using a column of 15 mm internal diameter (I.D.). The optimal conditions are a sample load of 4.9 mg C-PC/mL adsorbent, an expanded bed volume twice the settled bed volume and a sample viscosity of 1.020 mP. The EBAC process is then scaled up by increasing the column I.D. (15, 25, 40, 60 and 90 mm) and the success of the scale-up process is verified by determining the protein breakthrough capacity and product recovery. The yield of the EBAC step is in the range of 90-93% for every column diameter. To obtain pure C-PC, conventional ion-exchange chromatography with DEAE-cellulose is utilized and a yield of 74% is obtained. The overall yield of the process, comprising all steps, is 69%. The purification steps are monitored using SDS-PAGE and the purity of recovered C-PC is confirmed by absorption and emission spectroscopy and RP-HPLC. Results show that EBAC method is a scalable technology that allows large quantities of C-PC to be obtained without product loss, maintaining a high protein recovery while reducing both processing cost and time.
C-Phycocyanin (C-Pc) is one of the major biliprotein pigments of unicellular cyanbacterium of Spirulina platenesis, it has nutritional, medicinal, and hepatoprotectant application. The growth and multiplication of human hepatoma cell lines (HepG2) under the effect of different concentrations of C-PC (0.8, 1.75, 3.5 and 7.0 microg/ml) against untreated cells as control for 24h were investigated. The results showed that the proliferating cells in presence of C-PC reached 70, 51, 44, and 39%, respectively. The results revealed that the greatest reduction in proliferation of cells was recorded at 7.0 microg/ml and LC50 at 1.75 microg/ml of C-PC. In parallel, to the previous results HCl-denatured MG-P revealed that in mass of cells there is a pattern of apoptosis because the expanded cytoplasmic area (bluish-green) reduced and appeared faintly red as C-PC concentration increased. Moreover, the cells lost all the nuclear entities then, become fragmented and having no nuclear remnants. The C-PC may be a new potential anti-cancer drug for therapy of human hepatoma cells.
Hydrochlorous acid bleaches c-phycocyanin visible absorbance with a second-order rate constant (pH 7.4) of 1.3x10(3) M(-1) s(-1). In excess of protein, ca. 0.16 bilin moieties are disrupted by each reacted HOCl molecule. This indicates that the main reaction takes place at the apoprotein level, with a total rate constant (in monomeric units concentration) of 2.5x10(4) M(-1) s(-1). This rate constant is too low to provide protection to other biomolecules under physiological conditions. The reported antiinflammatory properties of phycocyanin are not then related to the removal of HOCl. On the other hand, the rather slow reaction rate with HOCI could be beneficial to its role as antiinflammatory agent since it will allow the protein to maintain its integrity at the inflammation locus.
Peroxynitrite (ONOO(-)) is known to inactivate important cellular targets and also mediate oxidative damage in DNA. The present study has demonstrated that phycocyanin, a biliprotein from spirulina platensis and its chromophore, phycocyanobilin (PCB), efficiently scavenge ONOO(-), a potent physiological inorganic toxin. Scavenging of ONOO(-) by phycocyanin and PCB was established by studying their interaction with ONOO(-) and quantified by using competition kinetics of pyrogallol red bleaching assay. The relative antioxidant ratio and IC(50) value clearly indicate that phycocyanin is a more efficient ONOO(-) scavenger than PCB. The present study has also shown that PCB significantly inhibits the ONOO(-)-mediated single-strand breaks in supercoiled plasmid DNA in a dose-dependent manner with an IC(50) value of 2.9 +/- 0.6 microM. These results suggest that phycocyanin, has the ability to inhibit the ONOO(-)-mediated deleterious biological effects and hence has the potential to be used as a therapeutic agent.
The anti-inflammatory effect of microalgae Spirulina was studied in zymosan-induced arthritis in mice. Four days after the intra-articular injection of zymosan (15 mg/ml), Spirulina (100 and 400 mg/kg perorally) was administered to animals for 8 days. The mice were than killed and beta-glucuronidase was measured in the synovial fluid. Each knee joint was totally removed for histopathological studies. Spirulina significantly reduced the levels of beta-glucuronidase that had been increased by zymosan. Histopathological and ultrastructural studies showed inhibition of the inflammatory reaction, whereas no destruction of cartilage, well-preserved chondrocytes, and normal rough endoplasmic reticulum and mitochondria were seen. The anti-arthritic effect exerted by Spirulina as shown in this model may be at least partly due to the previously reported antiinflammatory and antioxidative properties of its constituent, phycocyanin. To our knowledge, this is the first report on the anti-inflammatory effect of Spirulina in an experimental model of arthritis.
C-Phycocyanin (C-PC) is one of the major biliproteins of Spirulina platensis, a blue green algae, with antioxidant and radical scavenging properties. It is also known to exhibit anti-inflammatory and anti-cancer properties. However, the mechanism of action of C-PC is not clearly understood. Previously, we have shown that C-PC selectively inhibits cyclooxygenase-2 (COX-2), an inducible isoform that is upregulated during inflammation and cancer. In view of the reported induction of apoptosis in cancer cells by cyclooxygenase-2 inhibitors, the present study is undertaken to test the effect of C-PC on LPS stimulated RAW 264.7 mouse macrophage cell line. These studies have shown a dose dependent reduction in the growth and multiplication of macrophage cell line by C-PC. This decrease in cell number appears to be mediated by C-PC induced apoptosis as evidenced by flow cytometric and confocal microscopic studies. Cells treated with 20 micro M C-PC showed typical nuclear condensation and 16.6% of cells in sub-G(o)/G(1) phase. These cells also showed DNA fragmentation in a dose dependent manner. The studies on poly(ADP ribose) polymerase (PARP) cleavage showed typical fragmentation pattern in C-PC treated cells. This C-PC induced apoptosis in RAW 264.7 cells appears to be mediated by the release of cytochrome c from mitochondria and independent of Bcl-2 expression. These effects of C-PC on RAW 264.7 cells may be due to reduced PGE(2) levels as a result of COX-2 inhibition.
C-phycocyanin (C-PC), found in blue green algae, is often used as a dietary nutritional supplement. C-PC has been found to have an anti-inflammatory activity and exert beneficial effect in various diseases. However, little is known about its mechanism of action. Overproduction of nitric oxide (NO) derived from inducible nitric oxide synthase (iNOS) plays an important role in the pathogenesis of inflammation. The aim of this study was to determine whether C-PC inhibits production of nitrite, an index of NO, and iNOS expression in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. Our results indicated that C-PC significantly inhibited the LPS-induced nitrite production and iNOS protein expression accompanied by an attenuation of tumor necrosis factor-alpha (TNF-alpha) formation but had no effect on interleukin-10 production in macrophages. Furthermore, C-PC also suppressed the activation of nuclear factor-kappaB (NF-kappaB) through preventing degradation of cytosolic IkappaB-alpha in LPS-stimulated RAW 264.7 macrophages. Thus, the inhibitory activity of C-PC on LPS-induced NO release and iNOS expression is probably associated with suppressing TNF-alpha formation and nuclear NF-kappaB activation, which may provide an additional explanation for its anti-inflammatory activity and therapeutic effect.
Phycocyanin is a pigment found in blue-green algae which contains open chain tetrapyrroles with possible scavenging properties. We have studied its antioxidant properties.
Phycocyanin was evaluated as a putative antioxidant in vitro by using: a) luminol-enhanced chemiluminescence (LCL) generated by three different radical species (O2-, OH., RO.) and by zymosan activated human polymorphonuclear leukocytes (PMNLs), b) deoxyribose assay and c) inhibition of liver microsomal lipid peroxidation induced by Fe+2-ascorbic acid. The antioxidant activity was also assayed in vivo in glucose oxidase (GO)-induced inflammation in mouse paw.
The results indicated that phycocyanin is able to scavenge OH. (IC50 = 0.91 mg/mL) and RO. (IC50 = 76 microg/mL) radicals, with activity equivalent to 0.125 mg/mL of dimethyl sulphoxide (DMSO) and 0.038 microg/mL of trolox, specific scavengers of those radicals respectively. In the deoxyribose assay the second-order rate constant was 3.56 x 10(11) M(-1) S(-1), similar to that obtained for some non-steroidal anti-inflammatory drugs. Phycocyanin also inhibits liver microsomal lipid peroxidation (IC50 = 12 mg/mL), the CL response of PMNLs (p < 0.05) as well as the edema index in GO-induced inflammation in mouse paw (p < 0.05).
To our knowledge this is the first report of the antioxidant and anti-inflammatory properties of c-phycocyanin.
To examine the effects of C-phycocyanin, a pigment found in blue-green algae which acts as an antioxidant in vitro and in vivo, in different animal models of inflammation.
Male Sprague Dawley rats and OF1 mice were used.
Oedema was induced by: a) AA (0.5 mg/ear) or TPA (4 microg/ear) in the mouse ear b) carrageenan injection (0.1 mL of 1% suspension) in the rat paw (+/-adrenalectomy) and c) cotton pellet implantation in the rat axilla. Phycocyanin (50-300mg/kg, p.o.) or indomethacin (1 mg/ear or 3-10mg/kg, p.o.) as control were tested in the four animal models.
Measurement of the increase in the weight (mg) of 6 mm ear punch biopsies from treated ears were made in comparison to control ears, together with myeloperoxidase (MPO) activity as an index of neutrophil infiltration. The increase in the paw thickness (mm) was measured with a dial caliper. Cotton pellet was implanted and seven days afterwards the granuloma was removed and the dry weight was determined. Acute toxicity was studied in mice and rats. Statistics were performed using one-way analysis of variance with the Duncan Multirange test.
Phycocyanin reduced significantly (p < 0.05) and in a dose-dependent manner ear oedema induced by AA and TPA in mice as well as carrageenan-induced rat paw oedema (both in intact and adrenalectomized animals). In the TPA test, phycocyanin also reduced MPO content. Phycocyanin also exerted an inhibitory effect in the cotton pellet granuloma test. In the acute toxicity test in rats and mice, even at the highest dose tested (3000 mg/kg, p.o.), no toxicity was found.
Phycocyanin shows anti-inflammatory activity in four experimental models of inflammation. Its antioxidative and oxygen free radical scavenging properties may contribute, at least in part, to its anti-inflammatory activity.
Camphor, capsaicin, ketoprofen, lavender oil, cineole, β-pinene and methyl nicotinate which are used in topical formulations for the relief of pain associated with rheumatic and musculo-skeletal disorders were assessed for hydroxyl radical scavenging properties. The compounds tested were irradiated with simulated sunlight in a model aqueous system containing dequalinium chloride and hydrogen peroxide. The rate of degradation of the dequalinium chloride by the photogenerated hydroxyl radicals was measured and found to follow second-order kinetics. Ketoprofen, a clinically used antirheumatic agent, gave the optimal results. The hydroxyl radical scavenging properties of the other compounds are discussed in terms of their chemical structure and possible reactivity.
In the present work the time course of collagen-induced arthritis and the effect of Sandimmune Neoral in this model of arthritis were followed in the rat over an extended period of time (70 days) using high resolution three-dimensional (3D) magnetic resonance imaging (MRI). High resolution 3D gradient-echo (TR = 100 ms; TE = 3.8 ms) images with a voxel size of 94 x 81 x 60 micron3 were acquired from the hind paw of DA rats (n = 21) at various time points after injection of type II bovine collagen into the tail. Eleven rats were treated with Neoral (15 mg/kg/day p.o. together with vehicle) for 42 days starting at day 14 after collagen injection. The remaining controls received vehicle. Pathomorphological changes associated with the collagen-induced arthritic process, e.g., increase of joint space and cartilage and bone erosion, could be observed in vivo in the control group. In contrast, no changes in the joint architecture were detected in Neoral-treated animals. Indeed, Neoral showed strong anti-inflammatory effects and marked protection against cartilage and bone destruction in this model. Qualitative information derived from the MR images correlated significantly with histological findings.
A number of stimuli known to induce acid hydrolase secretion from cultured macrophages were examined for their ability to activate C3 via the alternative pathway of the complement system. Loss of haemolytically active C3 was checked in normal and C4-deficient guinea-pig serum. For comparison the interactions of cultured macrophages with other agents well known as potent activators of the alternative pathway of the complement system have been investigated. As judged by their activity in these assays, group A streptococcal cell walls, different carrageenan preparations, dental plaque and Actinomyces viscosus were all capable of initiating the alternative pathway but differed with respect to their potency and their ability to inhibit C3 turnover at high concentrations. Zymosan, some carrageenans, polyanethol sulphonate, and Corynebacterium parvum all induce the release of hydrolytic enzymes from macrophages in culture, even in the absence of serum in the medium. The release is time- and dose-dependent and is not associated with loss of the cytoplasmic enzyme lactate dehydrogenase or any other sign of cell death. The parallelism between the capacity of several agents to activate the complement system via the alternative pathway and to induce inflammatory responses in vivo and selective lysosoma enzyme secretion from cultures of macrophages is discussed.
The paralelism between the capacity of various agents to elicit chronic inflammatory responses in vivo and to induce the selective release of lysosomal enzymes from cultures of mouse peritoneal macrophages in vitro is discussed. Zymosan elicits an intense inflammatory response when injected i.m. in mice. Chrysotile asbestos produces a response of a similar nature and intensity as is seen with zymosan, while injections of acid-leached asbestos and polystyrene latex are not followed by inflammation. It is also shown that zymosan and asbestos induce a dose-dependent increase in the total enzyme activity of an inflamed muscle. On the other hand latex and acid-leached asbestos caused no significant increases in lysosomal enzyme levels. Agents eliciting inflammatory responses, such as zymosan and chrysotile asbestos induce a selective release of acid hydrolases from cultured macrophages; in contrast agents lacking the capacity to induce inflammation, such as latex and acid-leached chrysotile asbestos, do not induce the release of lysosomal enzymes from cultured macrophages.
Zymosan particles, which are able to activate complement by the alternative pathway and to induce enzyme secretion from macrophages, were injected into knee joints of mice. After various time intervals, synovia were assessed histologically for various markers of inflammation. Within 7 days after intraarticular injection of zymosan, a chronic inflammatory arthritis with mononuclear cell infiltration, synovial hypertrophy and pannus formation was observed. Latex particles, which do not activate complement or macrophages, produced only mild, transient inflammatory reactions.
A novel and very useful technique was developed to assay a lysosomal enzyme released into the joint synovial fluid during zymosan-induced arthritis in mice.
This β-glucuronidase activity correlated with histomorphological changes observed in the joint: vasculitis, synovitis and pannus formation.
The antiarthritic drug triamcinolone acetonide improved both biochemical and histological parameters.
A low-viscosity embedding medium based on ERL-4206 is recommended for use in electron microscopy. The composition is: ERL-4206 (vinyl cyclohexene dioxide) 10 g, D.E.R. 736 (diglycidyl ether of polypropylene glycol) 6 g, NSA (nonenyl succinic anhydride) 26 g, and S-1 (dimethylaminoethanol or DMAE) 0.4 g. The medium is easily and rapidly prepared by dispensing the components, in turn by weight, into a single flask. The relatively low viscosity of the medium (60 cP) permits rapid mixing by shaking and swirling. The medium is infiltrated into specimens after the use of any one of several dehydrating fluids, such as ethanol, acetone, dioxan, hexylene glycol, isopropyl alcohol, propylene oxide, and tert.-butyl alcohol. It is compatible with each of these in all proportions. After infiltration the castings are polymerized at 70°C in 8 hours. Longer curing does not adversely affect the physical properties of the castings. Curing time can be reduced by increasing the temperature or the accelerator, S-1, or both; and the hardness of the castings is controlled by changes in the D.E.R. 736 flexibilizer. The medium has a long pot life of several days and infiltrates readily because of its low viscosity. The castings have good trimming and sectioning qualities. The embedding matrix of the sections is very resistant to oxidation by KMnO4 and Ba(MnO4)2, compared with resins containing NADIC methyl anhydride. Sections are tough under the electron beam and may be used without a supporting membrane on the grids. The background plastic in the sections shows no perceptible substructure at magnifications commonly used for biological materials. The medium has been used successfully with a wide range of specimens, including endosperms with a high lipid content, tissues with hard, lignified cell walls, and highly vacuolated parenchymatous tissues of ripe fruits.
As zymosan-induced arthritis in rats combines dual activation of early prostaglandin-dependent processes (edema, fever, pain) and IL-1 related effects on cartilage metabolism, we compared the respective influences of indomethacin (IMT) and dexamethasone (DEX) on its course. Different parameters were assessed: knee swelling, febrile response, loss of activity, cartilage metabolism and histology. DEX improved all these parameters, while IMT exerted only light beneficial effects on fever and knee swelling without obvious beneficial influence on cartilage metabolism and histological lesions. These results suggest that anti-inflammatory activities of DEX and IMT are due to interferences with different pathways during zymosan-induced arthritis in rats.
Sera of patients with various inflammatory and autoimmune rheumatic diseases were screened for the presence of xanthine oxidase (XOD) and compared to sera from healthy donors and patients with nonrheumatic diseases including AIDS, internal diseases, and different carcinomas. Up to 50-fold higher levels of XOD were detected in rheumatic sera (P < 0.001). In addition, serum sulfhydryls (SH) were determined as sensitive markers of oxidative stress. The SH status in rheumatic patients was diminished by 45–75% (P < 0.001) and inversely correlated to the concentration of serum XOD (R=0.73), suggesting a causal interrelation. The depletion of serum sulfhydryls by the oxyradical-producing XOD/acetaldehyde system was mimicked successfully ex vivo in human serum from healthy donors. Cortisone treatment of patients suffering from systemic lupus erythematosus and rheumatoid arthritis impressively normalized elevated XOD concentrations in rheumatic sera to those of healthy controls. The participation of xanthine oxidase in the depletion of serum antioxidants in rheumatic patients is discussed in the light of substrate availability andK
m values.
Rheumatoid arthritis patients have defective neuroendocrine-immune responses to the stress of inflammation, and currently available data shows that this contributes to the pathophysiology of the disease. The advances in neuroendocrine immunology have improved our understanding of the pathophysiological mechanisms involved in RA. These observations raise important therapeutic questions which are certainly worth further investigation as they may open up novel avenues for the management of the disease.
1. Rheumatoid arthritis (RA) is probably the most common source of treatable disability. A major problem in modern rheumatology is that the mechanism(s) of action of the currently used disease-modifying antirheumatic drugs (DMARDs) remain unclear. Many of these drugs entered rheumatology mainly through clinical intuition and have been used for decades. 2. The former T-cell-centered paradigm of rheumatoid inflammation has given way to a model of inflammation highlighting the macrophage and its proinflammatory cytokines. In particular, tumor necrosis factor alpha (TNF-alpha) has gained prominence as a central proinflammatory mediator in RA, and antibodies against TNF-alpha have been successfully used in patients with RA. 3. This review will summarize the recent advances in determining the mechanisms of action of the currently used DMARDs, with particular emphasis on their effects on the induction of TNF-alpha and interleukin 1 (IL-1) in mononuclear phagocytes. Although some DMARDs, such as auranofin, antimalarials and tenidap, act as inhibitors of the induction of these cytokines in monocytes or macrophages or both, other drugs, such as methotrexate, D-penicillamine and aurothiomalate, do not seem to affect either TNF-alpha or IL-1. 4. The drugs' effects on proinflammatory cytokine induction are correlated to those on other macrophage responses.
1. The antiarthritic and anti-inflammatory efficacy of N-acetyl-L-cysteine (NAC) was tested in male DBA/1 hybrid mice suffering from type II collagen-induced arthritis. Parameters including the arthritis index and the phagocytic responses recorded by chemiluminescence in unseparated blood were used for the assessment of disease activity. 2. Mice were immunized by subdermal injection of bovine type II collagen in Freund's complete adjuvant. The treatment with NAC started at day 42 after immunization and was continued over a period of six weeks: in doses ranging up to 50 mg/kg, a dose-dependent suppression of arthritis was noted; between 50 and 200 mg/kg, the inhibition curve had a plateau [ED50 = 50 mg/(kg x day)]. 3. The arthritis index correlated positively with the generation of chemiluminescence by reactive oxygen species (ROS) produced in neutrophils and monocytes activated by 12-O-tetradecanoylphorbol 13-acetate. 4. After treatment with 100 mg/kg of NAC from day 42 after immunization over a period of six weeks, the ROS production was reduced to levels occurring in whole blood of healthy animals. 5. It is concluded that low-molecular-weight antioxidants such as NAC may be adequate for controlling oxidative stress-derived damage in rheumatic diseases by modulation of ROS-dependent signal transduction pathways.
The ingress of inflammatory leucocytes into the synovium is a crucial step in the pathogenesis of rheumatoid arthritis (RA). Cytokines are mediators involved in the inflammatory events, adhesive mechanisms, angiogenesis and osteopenia associated with RA. Pro- and anti-inflammatory cytokines, growth factors and chemokines all have an important role in these processes. Because the efficacy of currently used antirheumatic therapy is often limited, there is a need for more specific intervention strategies. Anticytokine therapy may include the use of monoclonal antibodies, antagonistic cytokines, soluble cytokine receptors, cytokine receptor antagonists, somatic gene transfer or other approaches. Hopefully, the study of cytokines and their interactions will lead to the development of new immunomodulatory strategies that will benefit patients with RA.
The anti-inflammatory effect of c-phycocyanin extract was studied in acetic acid-induced colitis in rats. Phycocyanin (150, 200 and 300 mg kg-1 p.o.) was administered 30 min before induction of colitis with enema of 1 ml of 4% acetic acid per rat. Twenty-four hours later myeloperoxidase (MPO) activity was determined as well as histopathological and ultrastructural studies were carried out in colonic tissue. Phycocyanin substantially reduced MPO activity which was increased in the control colitis group. Also, histopathological and ultrastructural studies showed inhibition in inflammatory cell infiltration and reduction to some extent in colonic damage in rats treated with phycocyanin. The probable role of antioxidative and the scavenging properties of phycocyanin against reactive oxygen species in the anti-colitic effect is discussed in this paper. To our knowledge this is the first report on the anti-inflammatory effect of phycocyanin in an experimental model of colitis.(c) 1999 The Italian Pharmacological Society.