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Selective Inhibition of Cyclooxygenase-2 by C-Phycocyanin, a Biliprotein from Spirulina platensis
Abstract
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.
... Reducing NF-κB nuclear translocation inhibits the production of proinflammatory genes, which is how S. platensis anti-inflammatory mechanism is exhibited (Chen et al. 2012;Hwang et al. 2013;Ku et al. 2013;Lee et al. 2017;Al-Qahtani & Binobead 2019). Phycocyanin from S. platensis, as an anti-inflammatory, selectively inhibits cyclooxygenase-2 (COX-2) and affects the negative regulation of NF-κB activity (Reddy et al. 2000;Poligone & Baldwin 2001;Shih et al. 2009;Khan & Khan 2018). ...
... Although there was no significant difference, this investigation revealed a decline in COX-2 in the treatment group compared to the control rats. The results of this study are in line with in vitro studies conducted by Reddy et al. 2000 andin vivo by Shih et al. 2009. Phycocyanobilin and phycocyanin from S. Vol. 31 No. 6, November 2024 platensis were reported that have anti-inflammatory potential through the inhibition of Cycloocgenase-2 (COX-2) (Reddy et al. 2000;Shih et al. 2009). ...
... The results of this study are in line with in vitro studies conducted by Reddy et al. 2000 andin vivo by Shih et al. 2009. Phycocyanobilin and phycocyanin from S. Vol. 31 No. 6, November 2024 platensis were reported that have anti-inflammatory potential through the inhibition of Cycloocgenase-2 (COX-2) (Reddy et al. 2000;Shih et al. 2009). Our earlier research verified that the ethanol-based extract of S. platensis utilized in this investigation contained phycocyanobilin . ...
Pro- and anti-inflammatory mediators need to be released in a balanced way to maintain a healthy state as we age. One important regulatory element in the equilibrium of pro- and anti-inflammatory mediators is NF-κB. The purpose of this study was to examine how S. platensis affected the control of inflammatory mediators in young, healthy, emerging adults and adults in rats. In this investigation, 200 mg/kg BW of S. platensis extract was administered to six groups of male Wistar rats, ages 12, 18, and 24 weeks, along with a control group. In both the treatment and control groups, NF-κB p65 protein expression was lower at 24 weeks than it was at 12 and 18 weeks. TNF-α and COX-2 proteins were lower in the treatment group than in the control group. All age groups in the treatment group had higher levels of IL-10 protein than the control group. The quantity of NF-κB p65 was positively correlated with COX-2 and TNF-α. By raising the concentration of NF-κB p65, the ethanolic extract of S. platensis altered a mediator of cellular immunity. A decrease followed this in TNF-α and COX-2 and a rise in IL-10 in the rat spleen at different ages.
... Spirulina is believed to provide various benefits, such as improving the immune system. [9,38] Assessing TBI is challenging, but blood glial fibrillary acidic protein (GFAP) can predict intracranial pathologies undetectable on head computed tomography scans. [1,19] It is commonly used for prognostic and follow-up in patients with negative imaging results. ...
... It also contains a variety of antioxidants, including flavonoids, provitamin A (betacarotene), Vitamin C, E, selenium, and phycocyanin, as well as SOD, which has been shown to have antioxidant potential in numerous in vivo and in vitro tests. [7,38,44] According to a study by aakur and Sravanthi [42] in male albino rats, pretreatment with spirulina (90, 180 mg/kg) considerably reduced the neurological deficit. Spirulina 45 and 90 mg/kg pretreatment results in neural cell degeneration, minor congestion, and slight vaculations, respectively, while spirulina 180 mg/kg results in neuronal cells with a normal nucleus. ...
Background
Traumatic brain injury (TBI) is a global health problem with the potential to cause dangerous neurological problems. Based on histopathological findings in Sprague Dawley (SD) rats with TBI in the acute phase, the study seeks to discover the effect of Centella asiatica , cinnamon, and spirulina as neuroprotective.
Methods
We conducted an experimental study with 30 SD rats randomly divided into three groups. The intervention was the administration of C. asiatica , cinnamon, and spirulina to the control and the experimental groups. Histological features were assessed using hematoxylin and eosin (H&E) staining and immunohistochemical examination. The data were analyzed using statistical analysis through correlation tests.
Results
The test samples’ average body weights had P > 0.05, indicating no significant difference in the test sample body weights. Therefore, the variations in the expression level of the dependent variable were expected to be caused by the induction of brain injury and the administration of C. asiatica , cinnamon, and spirulina. In addition, the variables were not normally distributed. Thus, the Spearman test was carried out and showed the correlation was very strong, with a value of r = 0.818 and P < 0.05.
Conclusion
Based on histopathological findings from the brains of SD rats with TBI, pegagan, cinnamon, and spirulina will protect the brain (neuroprotective) in the acute phase.
... Moreover, nutraceutical measures which can inhibit cox-2 induction in inflamed colonic epithelium, might be expected to have comparable activity. In this regard, spirulina, or its chief protein phycocyanin -which carries the chromophore phycocyanobilin, capable of mimicking the NADPH oxidase-inhibitory activity of bilirubin (McCarty et al., 2007;Zheng et al., 2013;Marín-Prida et al., 2022) has been found to down-regulate cox-2 activity or expression in various models of inflammation (Reddy et al., 2000;Reddy et al., 2003;Shih et al., 2009;Chen et al., 2012). And, not surprisingly, both phycocyanin and whole spirulina have been reported to be protective in dextran sodium sulfate induced colitis in rodents (Garcia et al., 2020;Gu et al., 2020;Morsy et al., 2019;El-Maadawy et al., 2022). ...
... ., 2011Cotterchio et al., 2006.;Jackson et al., 2020Khankari et al., 2020., Ko et al., 2018McCarty, 2006., Shin et al., 2015Tse et al., 2018., Yang et al., 2009Yu et al., 2016. Spirulina Chen et al., 2012., El-Maadawy et al., 2022Garcia et al., 2020.;Guo et al., 2020.;MarÃ-n-Prida et al.,2022.;McCarty , 2007;Morsy et al., 2019.;Reddy et al., 2003.;Reddy et al., 2000.;Shih et al., 2009. Quercetin Benito et al., 2021., Bondonno et al., 2020Kee et al., 2016.;Lolli et al., 2012., Makino et al. 2009McCarthy et al., 2020.;Murphy et al., 2011.;Murota et al., 2010.;Neamu et al., 2022.;Sánchez-Jaramillo et al., 2022.;Shan et al., 2009.;Valentová et al., 2014., Villota et al., 2022. Vitamin D Emmanouillidou ...
Progressive up-regulation of β-catenin signaling is very common in the transformation of colorectal epithelium to colorectal cancer (CRC). Practical measures for opposing such signaling hence have potential for preventing or slowing such transformation. cAMP/PKA activity in colon epithelium, as stimulated by COX-2-generated prostaglandins and β2-adrenergic signaling, boosts β-catenin activity, whereas cGMP/PKG signaling has the opposite effect. Bacterial generation of short-chain fatty acids (as supported by unrefined high-carbohydrate diets, berberine, and probiotics), dietary calcium, daily aspirin, antioxidants opposing cox-2 induction, and nicotine avoidance, can suppress cAMP production in colonic epithelium, whereas cGMP can be boosted via linaclotides, PDE5 inhibitors such as sildenafil or icariin, and likely high-dose biotin. Selective activation of estrogen receptor-β by soy isoflavones, support of adequate vitamin D receptor activity with UV exposure or supplemental vitamin D, and inhibition of CK2 activity with flavanols such as quercetin, can also oppose β-catenin signaling in colorectal epithelium. Secondary bile acids, the colonic production of which can be diminished by low-fat diets and berberine, can up-regulate β-catenin activity by down-regulating farnesoid X receptor expression. Stimulation of PI3K/Akt via insulin, IGF-I, TLR4, and EGFR receptors boosts β-catenin levels via inhibition of glycogen synthase-3β; plant-based diets can down-regulate insulin and IGF-I levels, exercise training and leanness can keep insulin low, anthocyanins and their key metabolite ferulic acid have potential for opposing TLR4 signaling, and silibinin is a direct antagonist for EGFR. Partially hydrolyzed phytate can oppose growth factor-mediated down-regulation of β-catenin by inhibiting Akt activation. Multifactorial strategies for safely opposing β-catenin signaling can be complemented with measures that diminish colonic mutagenesis and DNA hypomethylation - such as avoidance of heme-rich meat and charred or processed meats, consumption of phase II-inductive foods and nutraceuticals (e.g., Crucifera), and assurance of adequate folate status.
... The antioxidant capacity of PC explains many of the therapeutic properties attributed to this pigment [33][34][35]. Furthermore, PC is a potent anti-inflammatory compound, in part, through selective inhibition of the cyclooxygenase-2 (COX-2) enzyme, responsible for the production of pro-inflammatory prostaglandins at the site of inflammation [33,[36][37][38][39]. ...
... One of the metabolites with biological function present in the aqueous extracts evaluated was the phycobiliprotein phycocyanin. As was previously mentioned, phycocyanin has recognized anti-inflammatory property by means of selective inhibition of the enzyme COX-2 [38]; however, membrane protection effect has been also reported for this pigment and explained by a protective activity against oxidative damage in the heat induced human erythrocyte hemolysis model [87][88][89]. ...
... To the best of our knowledge, we are the first to report that blueberry can directly inhibit the enzymatic activity of COX-2, with the IC 50 as low as 18 µg/mL (equivalent to 12 mg/mL fresh berry). As a comparison, the IC 50 of celecoxib, a strong selective COX-2 inhibitor, is reported as 0.097 µg/mL [46]. While weaker than celecoxib, being food, blueberries can be consumed in larger quantities. ...
... To the best of our knowledge, we are the first to report that blueberry can directly inhibit the enzymatic activity of COX-2, with the IC50 as low as 18 µg/mL (equivalent to 12 mg/mL fresh berry). As a comparison, the IC50 of celecoxib, a strong selective COX-2 inhibitor, is reported as 0.097 µg/mL [46]. While weaker than celecoxib, being food, blueberries can be consumed in larger quantities. ...
Blueberries are rich in polyphenolic compounds and have shown improvement in cognitive function in several clinical trials. The molecular basis of the neuronal protection of blueberries, however, is not fully understood. The objective of this research is to understand the biochemistry basis of neuronal protection effects of blueberries through their impacts on several enzymes and pathways involved in Alzheimer’s disease (AD) and other neurodegenerative diseases. We examined the inhibition effects of blueberries on the enzymatic activity of cholinesterase (acetylcholinesterase, AChE; and butyrylcholinesterase, BuChE), tyrosinase, and cyclooxygenase-2 (COX-2). The effects of blueberries on the biosynthesis of acetylcholinesterase in a cellular model were also studied. Further, the effect of blueberries on amyloid fibril formation was evaluated. Our results showed that blueberries directly inhibit the enzymatic activity of AChE, BuChE, tyrosinase, and COX-2, with the IC50 at 48 mg/mL, 9 mg/mL, 403 mg/mL, and 12 mg/mL of fresh berry equivalent, respectively. Further, blueberries delay the amyloid fibril formation by 24 h at 39 mg fresh berry/mL. It also reduces the synthesis of acetylcholinesterase synthesis at 19 mg fresh berry/mL in a cellular model. Those results suggested that the neuroprotection effects of blueberries may involve different pathways, including enhancing cholinergic signaling through their effect on cholinesterase, reducing neuroinflammation through inhibition of COX-2, and reducing amyloid formation. Collectively, blueberries may play a vital role in neuronal protection beyond their antioxidant activity and our results provide more molecular mechanisms for their neuroprotective effects, and support blueberries being nutraceutical to improve cognitive function.
... 75,77,78 The anti-inflammatory activity of PBPs has been associated with the modulation of macrophage function and the inhibition of proinflammatory signaling. 61 In addition, PC from N. sphaeroides selectively inhibits COX-2 activity 104 and attenuates inflammation and dysfunction in mice with cystitis. 74 PC also has anti-inflammatory effects, such as the inhibition of albumin denaturation and anti-protease and antilipoxygenase activities. ...
Nostoc sphaeroides Kützing is a freshwater edible cyanobacterium that is rich in active substances such as polysaccharides, proteins and lipids; it has a variety of pharmacological effects such as antioxidant, anti‐inflammatory, antitumor and cholesterol‐lowering effects; and is often used as a traditional Chinese medicine with many potential applications in food, cosmetics, medical diagnostics and disease treatment. However, to meet the needs of different fields, such as medicine, there is an urgent need for basic research and technological innovation in culture technology, extraction and preparation of active substances, and the pharmacological mechanism of N. sphaeroides. This paper reviews the pharmacological effects of N. sphaeroides active substances, discusses current culture techniques and methods for extracting active components, and outlines the challenges encountered in cultivating and industrializing N. sphaeroides while discussing future development trends. © 2024 Society of Chemical Industry.
... According to Reddy. [32] when experimental rats were supplemented with Spirulina, helps in gaining body weight. Gosh et al., [9] have demonstrated the antihyperglycemic effect of Cyanobacterial pigments such as C-pycoerytherin (C-PE), phycocynin (C-PC), lycopene and myxoxanthophyl. ...
Blue-green algae (cyanobacteria) are considered the most primitive photosynthetic prokaryotes which appeared on this planet during the Precambrian period. The application of cyanobacteria showed immense potential in wastewater and industrial effluent treatment, bioremediation of aquatic and terrestrial habitats, chemical industries, biofertilizers, food, feed, and fuel, etc. Spanish local fishermen collected blue-green masses from the lakes that were prepared as a dry cake, known as 'tecuitlatl'. Spirulina, chlorella and Noctoc cyanobacterial species are being used as food supplements which are full of nutrients such as protein, and vitamins, and also have medicinal values like antiviral, antibacterial, anti-cancerous ECT. Besides, several Cyanobacterial species are also being used as biofertilizers in agriculture, and also for chelating toxic heavy metal ions for removing them from soil which is commonly known as bioremediation of soil pollutants. In viewing the "one platform" solution, nature has provided for all the environmental and medical problems in Cyanobacteria, there is a need to practically implement the use of cyanobacteria in the lives of common man. This chapter not only shades lite on the nutritional but also medicinal values of different species of cyanobacteria but also briefly discussed the new discovery of Exo-polysaccharides (metabolites) of cyanobacteria which are considered as one of the important group of biopolymers having significant ecological, industrial and biotechnological importance. Due to their structural complexity, versatility and valuable biological properties, they are now emerging as high-value compounds. However, poor understanding of their complex structural properties, and lack of concrete information regarding the genes encoding the proteins involved in the EPS biosynthetic pathways, their process of Research Perspectives of Microbiology and Biotechnology Vol. 4 Cyanobacteria: Harnessing Nature's Versatile Allies in Pharmaceuticals, Food, and Agriculture 186 production and the associated factors controlling their structural stability, strongly limit their commercialization and applications in the various fields of biotechnology.
... Furthermore, two different investigations demonstrated that C-PC also exerted antiinflammatory effects through the inhibition of the arachidonic cascade: one showed the inhibitor activity of the apoprotein C-PC on COX-2 via in vitro assays; the second one reported a reduced formation of leukotriene B4 via LOX in an in vivo mouse ear inflammation test [35,36]. ...
Arthrospira platensis, commonly known as Spirulina, is a photosynthetic filamentous cyanobacterium (blue–green microalga) that has been utilized as a food source since ancient times. More recently, it has gained significant popularity as a dietary supplement due to its rich content of micro- and macro-nutrients. Of particular interest is a water soluble phycobiliprotein derived from Spirulina known as phycocyanin C (C-PC), which stands out as the most abundant protein in this cyanobacterium. C-PC is a fluorescent protein, with its chromophore represented by the tetrapyrrole molecule phycocyanobilin B (PCB-B). While C-PC is commonly employed in food for its coloring properties, it also serves as the molecular basis for numerous nutraceutical features associated with Spirulina. Indeed, the comprehensive C-PC, and to some extent, the isolated PCB-B, has been linked to various health-promoting effects. These benefits encompass conditions triggered by oxidative stress, inflammation, and other pathological conditions. The present review focuses on the bio-pharmacological properties of these molecules, positioning them as promising agents for potential new applications in the expanding nutraceutical market.
... Additionally, the protective efficacies of TEL and Sp nanoparticles were ascertained against cardiotoxicity caused by Cyclo. Spirulina and its primary ingredients like C-phycocyanin, fatty acids, and phenolic and flavonoid compounds have antiinflammatory, neuroprotective, hepatoprotective, immunomodulatory, and anticancer properties (Reddy et al., 2000;Khan et al., 2005b). Given its apparent non-toxicity and significant multiorgan protection against a range of chemical and drug-induced toxic assaults, spirulina has attracted increasing interest (Zareba et al., 2007;Lu et al., 2010). ...
... Additionally, the protective efficacies of TEL and Sp nanoparticles were ascertained against cardiotoxicity caused by Cyclo. Spirulina and its primary ingredients like C-phycocyanin, fatty acids, and phenolic and flavonoid compounds have antiinflammatory, neuroprotective, hepatoprotective, immunomodulatory, and anticancer properties (Reddy et al., 2000;Khan et al., 2005b). Given its apparent non-toxicity and significant multiorgan protection against a range of chemical and drug-induced toxic assaults, spirulina has attracted increasing interest (Zareba et al., 2007;Lu et al., 2010). ...
Background
Cardiotoxicity is one of the limiting side effects of the commonly used anticancer agent cyclophosphamide (Cyclo).
Materials and methods
The possible protective effects of telmisartan and nanoformulated Spirulina platensis (Sp) methanolic extract against Cyclo-induced cardiotoxicity were examined in this study. Experimental groups of rats were randomly divided into nine groups as control vehicle, control polymer, telmisartan (TEL, 10 mg/kg), free Sp extract (300 mg/kg), nano Sp extract (100 mg/kg), Cyclo (200 mg/kg), TEL + Cyclo, free Sp + Cyclo, and nano Sp + Cyclo. The groups with Cyclo combinations were treated in the same manner as their corresponding ones without Cyclo, with a single dose of Cyclo on day 18.
Results
The results indicate that Cyclo causes significant cardiotoxicity, manifesting in the form of notable increases of 155.49%, 105.74%, 451.76%, and 826.07% in the serum levels of glutamic oxaloacetic transaminase (SGOT), lactate dehydrogenase (LDH), creatine kinase MB (CK-MB), and cardiac troponin I (cTnI) enzyme activities, respectively, as compared to the control. In addition, the cardiac glutathione (GSH) content and activity of glutathione peroxidase-1 (GPX-1) enzyme decreased by 65.94% and 73.85%, respectively. Treatment with nano Sp extract showed the most prominent restorations of the altered biochemical, histopathological, and immunohistochemical features as compared with those by TEL and free Sp; moreover, reductions of 30.64% and 43.02% in the p-AKT content as well as 60.43% and 75.30% of the endothelial nitric oxide synthase (eNOS) immunoreactivity were detected in the TEL and free Sp treatment groups, respectively. Interestingly, nano Sp boosted the autophagy signal via activation of beclin-1 (36.42% and 153.4%), activation of LC3II (69.13% and 195%), downregulation of p62 expressions (39.68% and 62.45%), and increased gene expressions of paraoxonase-1 (PON-1) (90.3% and 225.9%) compared to the TEL and free Sp treatment groups, respectively.
Conclusion
The findings suggest the protective efficiency of telmisartan and nano Sp extract against cardiotoxicity via activations of the antioxidant, antiapoptotic, and autophagy signaling pathways.
... Lastly, the search for compounds with antioxidant activity (astaxanthin, fucoxanthin, phycocyanin, β-carotene etc.), protecting against certain diseases associated with the formation of free radicals and improving the quality of farmed fish (Bermejo et al. 2008) receives a lot of attention. Generally, these works are also associated with the study of cyanobacteria from the genus Arthrospira (Bhat and Madyastha 2000; Reddy et al. 2000;Wang et al. 2007) or microalgae Haematococcus pluvialis (Chlorophyceae) (Sheikhzadeh et al. 2012). ...
Search for novel best-performing starter feed ingredients is one of the main challenges of modern aquaculture industry. The goal of this article is to evaluate the effect of microalgae supplementation enriched with omega-3 polyunsaturated eicosapentaenoic acid and the powerful antioxidant fucoxanthin on growth performance of Red tilapia fry (Oreochromis mossambicus × Oreochromis niloticus). We formulated three experimental diets, using two strains of microalgae from our culture collection – Vischeria magna SBV-108 (Eustigmatophyceae), rich in eicosapentaenoic acid and Mallomonas furtiva SBV-13 (Chrysophyceae), rich in fucoxanthin – and their combination. Vischeria magna SBV-108 is a new strain which biochemical properties and growth characteristics have not been previously studied. Coppens Supreme-15 was used as a control diet. The best growth performance was recorded in eicosapentainoic acid enriched Diet 1 (10% w/w V. magna), that significantly (P<0.05) overperformed control feed on absolute growth, average growth, specific growth rate, feed conversion rate, protein efficiency ratio, protein productive value and energy productive value. Diet 3 (5% w/w V. magna and 5% w/w M. furtiva) and Diet 2 (10% w/w M. furtiva) were not significantly different from control at most parameters. Generally, supplementation of feed with microalgae rich in omega-3 eicosapentaenoic acid significantly improved Red tilapia fry growth parameters and overall feed performance, while supplementation of feed with microalgae rich in antioxidant fucoxanthin was not beneficial compared to the control.
... Pagels and co-workers [32] found that a PBP-rich extract of Cyanobium sp. was capable of reducing COX-1 and COX-2 activity in a dosage of 100 µg/mL. Similarly, Reddy and his team [33] observed that PC from Spirulina platensis also reduced COX-2 activity in a dosage between 1-30 µg/mL. Altogether, the present results demonstrate that acetonic extracts are more promising than aqueous ones regarding LOX inhibition, thus being worthy of further exploitation. ...
Cyanobacteria are among the oldest organisms colonizing Earth. Their great biodiversity and ability to biosynthesize secondary metabolites through a variety of routes makes them attractive resources for biotechnological applications and drug discovery. In this pioneer study, four filamentous cyanobacteria (Cephalothrix lacustris LEGE 15493, Leptolyngbya boryana LEGE 15486, Nodosilinea nodu-losa LEGE 06104 and Leptothoe sp. LEGE 11479) were explored for their anti-inflammatory potential in cell and cell-free in vitro bioassays, involving different inflammatory mediators and enzymes. Extracts of different polarities were sequentially prepared and chemically characterized for their content of phycobiliproteins (PBPs) and carotenoids. HPLC-PDA analysis of the acetone extracts revealed β-carotene to be the dominant carotenoid (18.4-44.3 mg/g) and zeaxanthin as the dominant xanthophyll (52.7-192.9 mg/g), with Leptothoe sp. LEGE 11479 and Nodosilinea nodulosa LEGE 06104, respectively, being the richest strains. The PBP profile was in accordance with the color presented by the aqueous extracts, with Leptolyngbya boryana LEGE 15486 being the richest in phycocyanin (204.5 µg/mg) and Leptothoe sp. LEGE 11479 the richest in phycoerythrin (78.5 µg/mg). Aqueous extracts were more effective in superoxide anion radical scavenging, while acetone ones were more effective in scavenging nitric oxide radical (• NO) and in inhibiting lipoxygenase. Acetone extracts also reduced • NO production in lipopolysaccharide-stimulated RAW 264.7 macrophages, with the mechanistic study suggesting a downregulation of the inducible nitric oxide synthase expression. Nodosilinea nodulosa LEGE 06104 and Leptothoe sp. LEGE 11479 acetone extracts presented the lowest IC 50 values for the mentioned assays, pointing them out as promising resources for the development of new multi-target anti-inflammatory therapies.
... Thus, CPC must be metabolized into peptides and chromo-peptides containing phycocyanobilin (PCB) and PCB. CPC and PCB have the potential to avoid endothelial dysfunction due to their antioxidant, anti-inflammatory [13,24], and signaling pathway modulators on NADPH oxidase [25], COX2 [26], VEGF [27], and eNOS expression [13]. ...
C-phycocyanin (CPC) is a photosynthetic protein found in Arthrospira maxima with a nephroprotective and antihypertensive activity that can prevent the development of hemodynamic alterations caused by chronic kidney disease (CKD). However, the complete nutraceutical activities are still unknown. This study aims to determine if the antihypertensive effect of CPC is associated with preventing the impairment of hemodynamic variables through delaying vascular dysfunction. Twenty-four normotensive male Wistar rats were divided into four groups: (1) sham + 4 mL/kg/d vehicle (100 mM of phosphate buffer, PBS) administered by oral gavage (og), (2) sham + 100 mg/kg/d og of CPC, (3) CKD induced by 5/6 nephrectomy (CKD) + vehicle, (4) CKD + CPC. One week after surgery, the CPC treatment began and was administrated daily for four weeks. At the end treatment, animals were euthanized, and their thoracic aorta was used to determine the vascular function and expression of AT1, AT2, and Mas receptors. CKD-induced systemic arterial hypertension (SAH) and vascular dysfunction by reducing the vasorelaxant response of angiotensin 1-7 and increasing the contractile response to angiotensin II. Also, CKD increased the expression of the AT1 and AT2 receptors and reduced the Mas receptor expression. Remarkably, the treatment with CPC prevented SAH, renal function impairment, and vascular dysfunction in the angiotensin system. In conclusion, the antihypertensive activity of CPC is associated with avoiding changes in the expression of AT1, AT2, and Mas receptors, preventing vascular dysfunction development and SAH in rats with CKD.
... Spirulina represents a growing special food in the nutrition sector as it is rich in macroand micronutrients, with high nutritional values: about 60-70% of its dry weight consists of proteins and essential amino acids [1], while the remaining part contains minerals, fatty acids, vitamins, and fat-soluble antioxidants [2]. It also contains polypeptides called phycobiliproteins (e.g., phycocyanin and allophycocyanin) to which the antioxidant activity of the seaweed seems to be linked; moreover, it also appears to have antibacterial activity [3,4]. ...
Spirulina, a filamentous microalga, is used all over the world as a nutraceutical dietary supplement. Recent studies have focused on examining its chelating activity and antioxidant properties, especially as a candidate for protection against neurotoxicity caused by heavy metals. The MTT test and LDH assay were used to examine the viability of the SH-SY5Y cells for 24, 48, and 72 h, to Cd, Hg, and Pb, individually or in combination with Spirulina, and the effects of necrotic cell death. In comparison to the control group, the viability of SH-SY5Y cells decreased after 24 h of exposure, with Cd being more toxic than Hg and Pb being less lethal. The effects of heavy metal toxicity on cell survival were ranked in order after 72 h under identical experimental circumstances as follows: Hg, Pb, and Cd. The viability of the cells was then tested after being exposed to Spirulina at doses of 5 at 50 (%v/v) for 24, 48, and 72 h, respectively. SH-SY5Y cells that had been treated with mixtures of heavy metals and Spirulina underwent the same assay. Cell viability is considerably increased by using Spirulina treatments at the prescribed periods and doses. Instead, the same procedure, when applied to SH-SY5Y cells, caused the release of LDH, which is consistent with the reduction in cell viability. We demonstrated for the first time, considering all the available data, that Spirulina 5, 25, and 50 (%v/v) enhanced the number of viable SH-SY5Y cells utilized as a model system for brain cells. Overall, the data from the present study provide a first insight into the promising positive role of Spirulina against the potentially toxic effects of metals.
... Leptin-depending induction of COX-2 has likewise been shown to hinge on oxidant-mediated MAP kinase activation in various tissues [25][26][27][28][29][30][31][32]. Spirulina, likely owing to its phycocyanobilin (PCB) chromophore that can mimic bilirubin's ability to inhibit NOX2-dependent NADPH oxidase complexes, has been shown to suppress COX-2 induction in various contexts [33][34][35][36][37]. Although its impact on aromatase induction in the breast has not yet been studied, it is intriguing that spirulina feeding has been reported to markedly suppress DMBA-mediated breast cancer induction in rats [38]. ...
Background: Visceral obesity and the metabolic syndrome that often accompanies it are robust and well-established risk factors for postmenopausal breast cancer. This increased risk is thought to be mediated, in large part, by increased aromatase expression in the breast. stromal adipocytes and in mammary epithelium; this results in a high local concentration of estrogen capable of supporting the cancerous transformation of estrogen receptor-positive (ER+) epithelial cells. Aromatase, a member of the cytochrome 450 family, is expressed in the endoplasmic reticulum. After menopause, it converts androgens produced within the adrenal cortex (androstenedione and testosterone) into estrogens (estrone and estradiol, respectively. Therefore, the main objective of this narrative article is to review dietary and nutraceutical remedies for the prevention of menopause. Breast cancer: leading strategies to suppress breast aromatase Methods: The research articles to carry out this work were focused based on many searches and reviews in the following databases: Google Scholar, MDPI, PubMed, ScienceDirect and using the following keywords and combined synonyms: (“nutraceuticals” or “supplements” or “aromatase inhibitors” or “aromatase” or "antioxidants”) AND (“breast cancer” or “vascular function” or “inflammation”). The keywords were also searched in the references of the original articles included in this study Conclusion: A number of nutraceutical, dietary, and lifestyle measures hold promise for breast cancer prevention and may be considered practical options by women seeking to minimize their risk. for this cancer, particularly as these measures appear to have few downsides and are likely to work in other ways to promote health.
... Lastly, increasing attention is paid to the search for compounds with antioxidant activity (astaxanthin, fucoxanthin, phycocyanin, β-carotene etc.) to protect against certain diseases associated with the formation of free radicals and to improve the quality of farmed fish (Bermejo et al., 2008). Generally, these works are also associated with the study of cyanobacteria from the genus Arthrospira Reddy et al., 2000;Wang et al., 2007) or microalgae Haematococcus pluvialis (class Chlorophyceae) (Sheikhzadeh et al., 2012). ...
Search for novel best-performing starter feed ingredients is one of the main challenges of modern aquaculture industry. The goal of this article was to evaluate the effect of microalgae supplementation enriched with omega-3 polyunsaturated eicosapentaenoic acid and powerful antioxidant fucoxanthin on grows and performance of Red tilapia fry ( Oreochromis mossambicus × Oreochromis niloticus ). We formulated three experimental diets, using two strains of microalgae from our culture collection – Vischeria magna (Petersen) Kryvenda, Rybalka, Wolf & Friedl SBV-108 (class Eustigmatophyceae), rich with eicosapentaenoic acid and Mallomonas furtiva Gusev, Certnerová, Škaloudová & Škaloud SBV-13 (class Chrysophyceae), rich with fucoxanthin – and their combination. Vischeria magna SBV-108 is a new strain whose biochemical properties and growth characteristics have not been previously studied. Coppens Supreme-15 was used as control diet. The best performing was omega-3 enriched Diet 1 (10% w/w Vischeria magna ), that significantly (P < 0.05) overperformed control feed on absolute growth, average growth, specific growth rate, feed conversion rate, protein efficiency ratio, protein productive value and energy productive value. Diet 3 (5% w/w Vischeria magna and 5% w/w Mallomonas furtiva ) and Diet 2 (10% w/w Mallomonas furtiva ) were not significantly different from control at most parameters. Generally, supplementation of feed with microalgae rich in omega-3 eicosapentaenoic acid significantly improved Red tilapia fry growth parameters and overall feed performance, while supplementation of feed with microalgae rich in antioxidant fucoxanthin was not beneficial compared to control.
... SP includes natural antioxidants and free radical scavengers, including phenolic compounds, tocopherol, γ-linolenic acid, β-carotene, and phycocyanin (Khan et al. 2005). Moreover, both SP and its primary component, C-phycocyanin, possess immunomodulatory, anti-inflammatory, neuroprotective properties, and anticancer (Reddy et al. 2000;Romay et al. 2003). SP has become increasingly popular due to its safety profile and remarkable neuroprotective properties against toxicity caused by various chemicals and pollutants, such as lead (Khalil et al. 2018;Galal et al. 2019), manganese (Ibrahim et al. 2020), acrylamide (Bin-Jumah et al. 2021), and microcystin-LR (Germoush et al. 2022). ...
The objective of this study was to investigate whether the neurotoxic effects caused by methotrexate (MTX), a frequently used chemotherapy drug, could be improved by administering Spirulina platensis (SP) and/or thymoquinone (TQ). Seven groups of seven rats were assigned randomly for duration of 21 days. The groups consisted of a control group that was given saline only. The second group was given 500 mg/kg of SP orally; the third group was given 10 mg/kg of TQ orally. The fourth group was given a single IP dose of 20 mg/kg of MTX on the 15th day of the experiment. The fifth group was given both SP and MTX, the sixth group was given both TQ and MTX, and the seventh group was given SP, TQ, and MTX. After MTX exposure, the study found that AChE inhibition, depletion of glutathione, and increased levels of MDA occurred. MTX also decreased the activity of SOD and CAT, as well as the levels of inflammatory mediators such as IL-1, IL-6, and tumor necrosis factor-α. MTX induced apoptosis in brain tissue. However, when MTX was combined with either SP or TQ, the harmful effects on the body were significantly reduced. This combination treatment resulted in a faster return to normal levels of biochemical, oxidative markers, inflammatory responses, and cell death. In conclusion, supplementation with SP or TQ could potentially alleviate MTX-induced neuronal injury, likely due to their antioxidant, anti-inflammatory, and anti-apoptotic effects.
... Spirulina,(Arthrospiraplatensis)is a freshwater bluegreen filamentous alga, and it is receiving increasing attention for its bioactive components such as vitamins (especially vitamin A and B12), minerals, polyunsaturated fatty acids, carotenes and other pigments that have antioxidants activity [4,5]. ...
... Polysaccharide extract of Spirulina has chemo-protective and radioprotective capability and may be a potential adjunct to cancer therapy (Zhang et al. 2011). Reddy et al. (2000) found that C-phycocyanin selectively inhibits COX-2, but has no effect on COX-1. The COX enzymes which are involved in prostaglandin synthesis are over-expressed in many breast cancer cells. ...
Spirulina species are photosynthetic and filamentous bacteria, commonly called 'blue-green microalgae'. Spirulina has a high nutrient content. It contains 60-70% protein with all essential amino acids present, and is rich in several vitamins, minerals, and bioactive compounds. Spirulina is also rich in essential fatty acids, and antioxidants. This rich nutritional content provides to Spirulina several health benefits including antioxidant, anti-inflammatory, immunomodulation, and insulin-sensitizing properties as well as positive effects in various diseases which could be also interesting for athletes. This paper mainly aims to review the interest and effects of Spirulina supplementation in athletes at rest, and in relation to exercise/training. Spirulina's biochemical composition, health properties/effects in humans, and effects in athletes including nutritional status, body composition, physical performance and intense exercise-related disorders were discussed in this review. Literature data showed that Spirulina seems to have positive effects on body composition especially in overweight and obese subjects which could not be the case in other pathologies and athletes. Spirulina appears to be also effective in improving aerobic fitness especially in untrained and moderately trained subjects. Results reported in the literature suggest that Spirulina may improve strength and power performance despite the minor or no significant effects in highly trained subjects. Most studies have shown that Spirulina improves antioxidant status, prevents and accelerates the recovery of exercise-induced lipid peroxidation, muscle damage and inflammation in trained and untrained subjects. Taken together, the results from these studies are encouraging and may demonstrate the potential benefits of Spirulina supplementation in athletes despite methodological differences.
... The expression of COX-2 increases in the case of damage to the gastric mucosa [55]. However, although a COX-dependent protective mechanism of PhyEx was not explored in the present study, it is known that C-PC is a natural COX-2 inhibitor [56] which decreases the synthesis of PGE2 which, depending on the context, actively participates in the inflammatory response. This allows us to assume that the decrease in the inflammatory infiltrate and edema in the group treated with PhyEx could have been influenced by a decrease in PGE2 levels derived from possible COX-2 inhibition. ...
Gastric ulcers (GU) constitute a disease with a global prevalence ≈ 8.09 million. Of their causes, non-steroidal anti-inflammatory drugs (NSAIDs) such as indomethacin (IND) rank as the second most frequent etiologic agent. The pathogenic process of gastric lesions is given by the overproduction of oxidative stress, promotion of inflammatory processes, and inhibition of prostaglandin synthesis. Spirulina Arthrospira maxima (SP) is a cyanobacterium with a wide variety of substances with high nutritional and health values such as phycobiliproteins (PBPs) that have outstanding antioxidant activity, anti-inflammatories effects, and accelerate the wound healing process. This study aimed to determine the protective effect of PBPs in GU induced by IND 40 mg/kg. Our results show that the PBPs protected against IND-induced damage with a dose-dependent effect. At a dose of 400 mg/kg, a marked decrease in the number of lesions is observed, as well as the recovery of the main markers of oxidative stress damage (MDA) and antioxidant species (SOD, CAT, GPx) at close to baseline levels. The evidence derived from the present investigation suggests that the antioxidant effect of PBPs, together with their reported anti-inflammatory effects to accelerate the wound healing process, is the most reliable cause of their antiulcerogenic activity in this GU model.
... CPC can restrain cell proliferation, invoke apoptosis in cancerogenic cell lines, and affect gene regulation in mammalian cell lines (Liu et al. 2000;Cherng et al. 2007). CPC inhibits cyclooxygenase (COX), particularly COX-2, which is over-expressed in breast cancer cells but has no or minimal effect on COX-1 (Rimbau et al. 2001); it also works as an inhibitor of cytochrome oxidase II (Reddy et al. 2000). It is applicable in curing diseases like Parkinson's and Alzheimer's and averts cataracts, constipation, degenerative diseases, pancreatitis, and experimental oral and skin cancers (Rimbau et al. 2001). ...
Cyanobacteria are photosynthetic prokaryotes that have a variety of biological activities and can be used as dietary supplements. Because of its high nutritional, protein, and digestibility content, it is utilized as a meal supplement. Spirulina sp., Anabaena sp., Microcystis sp., Nostoc sp., Lyngbya sp., Oscillatoria sp., and other cyanobacteria create a wide range of secondary bioactive
metabolites with diverse biological functions. Cyanobacteria produce various physiologically active and chemically diverse compounds such as saccharides, fatty acid amides, lipopeptides, cyclic and acyclic peptides, and alkaloids. More than half of marine cyanobacteria could be used to extract bioactive compounds that can destroy cancer cells by causing apoptosis. Their effectiveness as an antiviral, antitumor, antibacterial, anti-HIV, and dietary additive is extensively documented. However, such drugs are in various phases of clinical studies, and only a few have made it to the market. This chapter examines the bioactive chemicals in cyanobacteria with antiprotozoal, antibacterial, anti-inflammatory, anticancer, antioxidant, and antiviral properties.
... Spirulina has high nutritional value, as it contains vitamins, pigments, proteins, minerals, lipids, and polysaccharides. 12 Spirulina is known for its antioxidant, anti-in ammatory, neuroprotective, hepatoprotective, immunomodulatory, and anticancer activities [13,14]. ...
Background
Gastritis is a collective name for disorders resulting from inflammatory changes in the gastric mucosa. Caesalpina sappan and Spirulina has various pharmacological activities, including the alleviation of gastritis.The study aimed to evaluate the protective effect of Caesalpina sappan and Spirulina against gastritis and determine changes in the expression of CD8, CD68, and major histocompatibility complex (MHC) molecules.
Methods
Gastritis was induced in 24 female Wistar albino rats on the first day using ethanol. The treatment groups were given C. sappan (250 mg/kg) and Spirulina (400 mg/kg) using oral gavage for 5 days. Blood and stomach tissue samples of the mice were analyzed.
Results
This study was found that C. sappan and Spirulina increased CD8 and CD68 expression levels, thereby decreasing the severity of inflammation. A simultaneous decrease in MHC I and MHC II expressing cells was observed in the treatment group. It was found that superoxide dismutase levels increased, whereas tumor necrosis factor-alpha, malondialdehyde, and myeloperoxidase levels decreased in the treatment group.
Conclusion
This study revealed that C. sappan and Spirulina can protect gastric mucosa by reducing oxidative stress and inflammation.
... The anti-in ammatory effect derives from its characteristic as an eliminator of reactive oxygen species, which is dependent on the increasing dismutase superoxide enzyme's activity (DSE), whose function plays a key role for the defense mechanism of gingival cells against oxidation reactions [43]. The phycocyanin also plays a key role in the suppression of COX-2's activity, having a CI 50 value of 180 nM, a concentration level at which drugs or substances can suppress biological processes by 50% and that is signi cantly lower than those values obtained for celecoxib (225nM) and other drugs, with a lower release of prostaglandins in the in ammation site [44]. Furthermore, spirulina has an inhibitory role in in ammatory response by blocking histamine from mast cells, thus becoming established as a strong natural anti-in ammatory [45]. ...
Background: This study aims to assess the clinical effectiveness of spirulina as an adjuvant to non-surgical periodontal therapy (NSPT) in contrast with the use of NSPT alone for the treatment of periodontitis.
Method: A systematic search was conducted in MEDLINE, EMBASE, Scopus, Central Cochrane Library, Scielo, Epistemonikos, and Google Scholar databases until April, 1st 2022. Adults with periodontitis who received NSPT were included. The intervention group consisted of subjects that were administered spirulina as an adjuvant to NSPT; the control group received NSPT alone. The search terms included randomized controlled clinical trials (RCT), with no language restrictions, and the following clinical periodontal parameters were established as primary change results: bleeding on probing index, probing depth, clinical attachment levels and gingival index. The risk of bias (RoB) was assessed by the RoB-2 tool. The mean differences were calculated and grouped through a meta-analysis, by using a random effects model.
Results: The risk of bias in the selected articles varied from “serious” to “very serious”. It was detected that there was a higher reduction in probing depth stemming from the use of spirulina as an adjuvant to NSPT, as compared with the probing depth values seen when receiving NSPT alone.
Conclusion: The evidence on the reduction of probing depth experienced by those participants who were treated with spirulina as an adjuvant to NSPT, compared to the one observed in those receiving NSPT alone, is weak. However, its clinical relevance can be argued upon given the scarce number of articles with high certainty and the high heterogeneity of the studies analyzed.
Systematic Review Registration: The study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under the reference number CRD42022318265.
... Based on a number of experimental findings, PC is used as an adjuvant because of its several beneficial properties, including reactive oxygen species (ROS) inhibitory effects and it's antimicrobial properties (Romay and Gonzalez, 2000). Furthermore, it has the capacity to slow down inflammatory processes (Reddy et al., 2000), including a decrease in nuclear factor activation in RAW 264.7 macrophages, which attenuated lipopolysaccharideinduced iNOS expression and TNF production. In vitro evidence of the suppression of COX-2 activity (Cherng et al., 2007). ...
Almost all of the current hair dye products today contain synthetic chemicals which may cause allergic reactions in some users. Phycocyanin (PC), a non-toxic cyanobacterial pigment, has been used in the food and cosmetics sectors. There are however, been a few reports on the application of phycocyanin as a hair colorant. This study aimed to assess the biological qualities of phycocyanin for use in natural hair dye product. Phycocyanin was tested for use against anti skin-pathogen (Staphylococcus aureus ATCC 25923, Staphylococcus epidermidis ATCC 14990, Methicillin-resistant Staphylococcus aureus (MRSA) DMST 20625, Propionibacterium acnes DMST 14916, Candida albicans DMST 21424, and Malassezia furfur M21), cytotoxicity of human immortalized keratinocyte (HaCaT) cells and tested for color fastness when used as a shampoo wash. According to the findings, Arthrospira (Spirulina) platensis phycocyanin has not shown the potential for use against anti-skin pathogenic microorganisms. While testing phycocyanin at the maximum doses of 2.5 mg/mL, the cytotoxicity test revealed that it is not hazardous to HaCaT cells. Bleached hair was dyed with a mixture of phycocyanin, natural developers, and mordants. A chroma meter was used to monitor color changes after shampoo washing. The findings revealed that phycocyanin has dyeability potential. 50% of the dyed hair color remained after 5 shampoo washes. The stability and color degradation of phycocyanin in hair dye powder formulation demonstrated good physical stability along with four cycles of heating/cooling. As a result, we can see that this pigment has the potential to be used as an active ingredient in natural hair dyes.
... PC is a dietary protein that reduces inflammatory cytokines such as interleukin-6 (IL-6), NO, MMP-3, TNF, and sulfated glycosaminoglycans in osteoarthritis patients. In a mouse ear inflammation test, PC inhibits cyclooxygenase-2 activity and stimulates the production of leukotriene B4 (Reddy et al. 2000).The catalytic control of nitric oxide synthase (NOS) produces nitric oxide (NO), which is vital in regulating the healthy and pathological inflammatory response of cells (Table 4) (Moncada et al. 1991). The presence of a large quantity of NO induced the production of proinflammatory cytokines, lipopolysaccharide (LPS), and free radicals which is a key mediator in the pathophysiology of inflammatory disorders (Szabo and Thiemermann 1995). ...
Ecological studies have helped to understand the diverse nature of cyanobacteria and to uncover its long history due to morphological plasticity and ecological flexibility. Cyanobacteria are found flourishing all over different habitats on earth, including the extreme environments. They are major players in the biogeochemical cycling of carbon, nitrogen, and oxygen. Cyanobacteria are oxygenic autotrophs and are major nitrogen fixers. The inherent ability to fix atmospheric nitrogen makes them extremely important in maintaining the stability and equilibrium of the ecosystem, thereby providing them a better competitive advantage in environments where nitrogen concentration is comparatively low. The adaptations to different kinds of environmental conditions including extreme pH, salinity, and temperature, make them the most diverse group of organisms on the earth. This feature of adaptability has helped to cultivate cyanobacteria successfully in laboratory conditions as well. Not only ecologically, but cyanobacteria are morphologically diverse too and this morphological complexity makes the taxonomy of this group very difficult and confusing. This complicacy impedes the accurate identification and classification of cyanobacteria, thus making it interesting but challenging. The taxonomic identity is complicated because of confusions due to morphological plasticity and the role of ecology in classification, thus leading to
erroneous identifications. The gradual shift from classical morphological taxonomy to molecular taxonomy has led to the development of a combined “polyphasic approach” which has resulted into the amalgamation of morphological, ecological, genetic, molecular and phylogenetic traits. Thus, cyanobacterial taxonomy has been substantially enhanced by combining different fields and taking into account the analysis of all approaches to establish a united, unambiguous and uncomplicated system of classification.
... PC is a dietary protein that reduces inflammatory cytokines such as interleukin-6 (IL-6), NO, MMP-3, TNF, and sulfated glycosaminoglycans in osteoarthritis patients. In a mouse ear inflammation test, PC inhibits cyclooxygenase-2 activity and stimulates the production of leukotriene B4 (Reddy et al. 2000).The catalytic control of nitric oxide synthase (NOS) produces nitric oxide (NO), which is vital in regulating the healthy and pathological inflammatory response of cells (Table 4) (Moncada et al. 1991). The presence of a large quantity of NO induced the production of proinflammatory cytokines, lipopolysaccharide (LPS), and free radicals which is a key mediator in the pathophysiology of inflammatory disorders (Szabo and Thiemermann 1995). ...
Cyanobacteria are photosynthetic, oxygenic prokaryotes that first arose during the Precambrian period (2.8-3.5 billion years ago) and set the stage for the evolution of aerobic life today. As photosynthetic organisms, cyanobacteria contain a light-harvesting complex that absorbs light energy. These harvesting complexes are split into three chemical groups: chlorophylls, carotenoids, and phycobiliproteins.
The principal pigments for light absorption in cyanobacteria are phycobiliproteins, whereas carotenoids play an important role in nonphotochemical quenching (NPQ) as a defense against saturating light and a reactive oxygen species quencher (ROS). For photosynthesis, phototrophic organisms must generate not just carotenoids but also chlorophylls. Chl a is required for practically all oxygenic photosynthetic organisms, although Chl d and Chl f have recently gained popularity due to their unique ability to absorb light in the far-red region.
Interestingly, in recent years, scientists and industrialists throughout the world have been working to produce natural products that are both sustainable for the future and less detrimental to human civilization. Cyanobacterial photopigments have been significant in the development of a wide range of biotechnological applications, including food,
cosmetics, medicines, agriculture, bioremediation, bioenergy, nutraceuticals, and biofuels. The goal of this chapter is to go through many types of cyanobacterial photopigments as well as the most important properties for biotechnological applications, with an emphasis
on their bioactivities. Finally, photopigments are briefly articulated in terms of their significance in sustainable development, and their future potential for creating a decent, sustainable world.
... Spirulina phycocyanin buffer extract is utilized in eye shadow, eyeliner, and lipsticks. Because the product is water-insoluble, it does not fade or irritate the skin when exposed to water or sweat [36]. Cyanobacteria manufacture carbohydrates, particularly the compatible solutes glucosyl glycerol, trehalose, and sucrose, under various osmotic conditions. ...
Fish has long been a source of “rich food for poor people” and has played an important role in increasing food security and nutrition in developing countries. Because various chemicals in algae can have confusing effects, the results of experimental research can be difficult to understand. Algae has been associated with strengthening immune systems, lipid metabolism, antiviral and antibacterial action, improved gut function, stress resistance besides providing a source of protein, amino acids, fatty acids, vitamins and minerals, and other biologically active phytochemicals in cattle and aquaculture feeds, even when used in modest amounts. The addition of algae to the fish diet modified the growth performance of the fish, causing it to improve. Its use resulted in a decrease in feed conversion ratio expenses, which plays an important part in determining aquaculture costs, an increase in feed efficiency ratio, and a decrease in feed conversion ratio. In accordance with the findings of chemical composition, various statements were acquired wherein the high proportion of algae significantly affects the protein and fat ratio. The outcomes demonstrated that algae could be a decent option as an additive for fish feed.
... Isolated enzyme and whole-blood assays indicated that C-PC from Spirulina platensis is a selective inhibitor of cyclooxygenase-2 (COX-2), which is upregulated during inflammation. Reduced PC and PCB are poor inhibitors of COX-2 without selectivity, implying that apoprotein plays a key role in the selective inhibition of COX-2 [96]. In cyclophosphamide (CYP)-induced cystitis in mice, C-PC relieved symptoms by inhibiting bladder inflammation through COX-2 and EP4 expression [97]. ...
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.
... Frontiers in Pharmacology | www.frontiersin.org May 2022 | Volume 13 | Article 826649 of prostaglandins, in addition to their chemical structure possessing antioxidant property functioning as a scavenger of free radicals (Reddy et al., 2000). It was also observed that the high dose of S. platensis actually increased nitrite levels, and that despite it being a precursor to nitrosative stress, concomitantly for the same supplementation doses, we also identified a high rate of inhibition of oxidation in the trachea, ratifying the antioxidant power of Spirulina platensis. ...
Spirulina platensis has shown effectiveness in the treatment of allergic rhinitis in rats, but its action in tracheal reactivity or on markers of relaxation and antioxidant profile has not yet been possible to determine. In this paper, the animals were divided into the groups healthy (SG) and supplemented with S. platensis at doses of 50 (SG50), 150 (SG150), and 500 mg/kg (SG500). We also evaluated nitrite levels, lipid peroxidation, and antioxidant activity through biochemical analysis. For contractile reactivity, only SG500 (pEC50 = 5.2 ± 0.06 showed reduction in carbachol contractile potency. Indomethacin caused a higher contractile response to carbachol in SG150 and SG500. For relaxation, curves for SG150 (pEC50 = 5.0 ± 0.05) and SG500 (pEC50 = 7:3 ± 0:02) were shifted to the left, more so in SG500. We observed an increase in nitrite in the trachea only with supplementation of 500 mg/kg (54.0 ± 8.0 µM), also when compared to SG50 (37.0 ± 10.0 µM) and SG150 (38.0 ± 7.0 µM). We observed a decrease in lipid peroxidation in the plasma and an increase in oxidation inhibition for the trachea and lung in SG150 and SG500, suggesting enhanced antioxidant activity. S. platensis (150/500 mg/kg) decreased the contractile response and increased relaxation by increasing antioxidant activity and nitrite levels and modulating the inflammatory response.
... The anti-inflammatory properties of PC could be due to its aptitude to downregulate the expression of IL-1β, IL-2, interferon-γ, and TNF-α and increase IL-4 anti-inflammatory cytokines expression [73]. PC is a COX-2 inhibitor with hepatoprotective and anti-inflammatory activities [74]. Its hepatoprotective property is attributed to its ability to inhibit hepatocyte growth factor and TGF-β1 production, obstructing inflammatory infiltration [75]. ...
This study investigated the dietary effect of Spirulina platensis phycocyanin (SPC) on
growth performance (body weight (BW), body weight gain (BWG), feed intake (FI), feed conversion
ratio (FCR)) at starter, grower, and finisher stages, intestinal histomorphology, serum biochem-
ical parameters, inflammatory and antioxidant indices, and proinflammatory cytokines (tumor
necrosis factor-α and caspase-3) immune expression in broiler chickens. In total, 250 one-day-old
chicks (Ross 308 broiler) were randomly allotted to five experimental groups (5 replicates/group,
10 chicks/replicate) and fed basal diets supplemented with five levels of SPC (0, 0.25, 0.5, 0.75, and
1 g kg–1 diet) for 35 days. Compared with SPC0 treatment, different SPC levels increased the overall
BW and BWG without affecting the total feed consumption. However, the FCR decreased linearly
with an increase in supplementation level. The serum levels of total proteins, albumin, globulins,
and growth hormone increased linearly by increasing levels of SPC supplementation. Further, SPC
supplementation increased the thyroxin hormones without affecting serum glucose and leptin levels.
Serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) values decreased in
broilers fed SPC0.250 and SPC1 diets. Triglycerides (TG) decreased in SPC0.25-, SPC0.75-, and
SPC1-treated groups. Though antioxidant enzyme activities (total antioxidant capacity, catalase, and
superoxide dismutase) increased linearly and quadratically, malondialdehyde (MDA) decreased
linearly by increasing the SPC level. There was no effect on serum proinflammatory cytokines IL1β
levels. Immunolabelling index of caspase-3 and tumor necrosis factor-α (TNF-α) were downregu-
lated by SPC supplementation. The intestinal histomorphology is represented by increased villus
height, the villus height to crypt depth ratio, and numbers of goblet cells in different sections of the
small intestine. In conclusion, SPC supplementation is beneficial in broiler chicken diets due to its
growth-promoting, antioxidant, and anti-inflammatory properties.
... Besides, C-phycocyanin has potent anti-inflammatory influences and exerts its effects through inhibition of the expression of tumor necrosis factor-alpha (tnf-α), cyclooxygenase-2 (cox-2) genes, and also decreases prostaglandin E2 production (Romay et al., 1998). Both C-phycocyanin and phycocyanobilin play a significant role in the selective inhibition of cox-2 production (Reddy et al., 2000). Spirulina can also regulate the expression of several interleukins such as interleukin (il)-1β, il-4, il-6, il-10, and il-2 (Mao et al., 2000). ...
Farmed fish and shrimp are continuously challenged by multiple stressors during their life stages, such as hypoxia, pH fluctuations, different salinities, high nitrite, un-ionized ammonia, injury during handling, inadequate nutrition, or food shortage, which can eventually adversely impact their health, welfare, and growth rates. Besides, these stressors can weaken production and decrease their resistance to diseases. Scientists and researchers have been making concerted efforts to find new, safe, and inexpensive supplements to mitigate the negative influences of stressors and thereby enhance the productivity of farmed aquatic animals. Some micro-algae are microscopic unicellular organisms that were found to be promising feed supplements due to their richness in important nutrients such as minerals and vitamins. Moreover, some microalgae contain several bioactive phytochemicals that exhibit anti-inflammatory, antioxidant, and immunomodulatory properties. Several field-controlled studies provided evidence that using microalgae as feed supplements led to improved growth, physiological functions, immunity, antioxidant capacity, and disease resistance in farmed finfish and shellfish species. This review article emphasizes the beneficial role of the cyanobacterium Arthrospira platensis and seven microalgal species, including Chlorella vulgaris, Parietochloris incisa, Dunaliella salina, Aurantiochytrium sp., Haematococcus pluvialis, Tetraselmis sp., and Nannochloropsis oculata in mitigating stress effects in farmed finfish and shellfish species. The conclusions of this article throw light on the potential benefits of using microorganisms in aquaculture.
Citation: Govindasamy, R.; Gayathiri, E.; Sankar, S.; Venkidasamy, B.; Prakash, P.; Rekha, K.; Savaner, V.; Pari, A.; Thirumalaivasan, N.; Thiruvengadam, M. Emerging Trends of Nanotechnology and Genetic Engineering in Cyanobacteria to Optimize Production for Future Applications. Life 2022, 12, 2013.
Spirulina is a food that is gaining increasing attention in the field of sports and exercise nutrition due to its rich biochemical composition and positive effects on health. The antioxidant, anti-inflammatory and immunomodulatory effects of spirulina have been proven in various studies, but its effects on athletes and people exercising are not clear. The effects of a herbal food with high protein content, such as spirulina, are important in the athlete population, where the use of vegetable protein increases. The purpose of this review is to examine current studies on spirulina supplements and exercise and to provide updated and complementary information on the subject by summarizing the use of spirulina to increase exercise and sports performance and accelerate post-training recovery.
Phycocyanin (PC) and phycoerythrin (PE) stand out among the phycobiliproteins (PCBs) known to date. These bioactive protein complexes found in certain organisms, particularly cyanobacteria, red algae, and some cryptophytes have a wide range of applications from foods, cosmetics, and healthcare to biotechnology. Reviews focusing only on PC and PE are lacking. Therefore, in this review, an overview of PCBs was provided first. To ensure high extraction yields and purity, the optimization of PC and PE production was discussed followed by the extraction of PC and PE highlighting the novel techniques used. Multifarious applications and biofunctional uses, as well as commercialization of the PCBs in various forms, were thereafter described. Available reports show that culture conditions including light quality affect the production of PC and PE. In addition, the pigments have wide applications in the healthcare, food, biotech, and cosmetics industries.
Aphanizomenon flos-aquae (AFA) is a Gram-negative nitrogen-fixing freshwater filamentous cyanobacterium with a rich nutritional profile that is approved for human consumption by both the Food and Drug Administration and the European Food and Safety Authorities. It has a high protein content (60-70%) and contains numerous vitamins, minerals and trace elements together with several high-value compounds with nutraceutical properties, such as C-phycocyanin and β-phenylethylamine. 500-1000 t of AFA dry biomass are currently wild harvested from natural blooms that occur seasonally in Klamath Lake, Oregon, USA, and distributed as a nutritional supplement worldwide. The requirements and unreliability of wild harvesting, owing to the dependence of AFA growth on environmental conditions and potential contamination by microcystin toxins, threaten the availability of biomass supply and restricts commercial expansion. In this review we propose AFA cultivation in open ponds or closed photobioreactors to obtain a reliable production of unialgal biomass to resolve the supply issue and enhance AFA as a feedstock for specific high-value by-products. Furthermore, we explore potential strategies for maximising overall yield and seasonal robustness by using a synergistic combination of cultivation and wild harvesting. Controlled AFA cultivation would also facilitate the use of genetic manipulation to generate bespoke strains with improved commercial applications, such as increasing the cyanobacterium’s nitrogen-fixation rate to enhance its value as a biofertiliser. Ultimately, realising the untapped biotechnological potential of AFA requires a better understanding of its fundamental biology, robust methodologies for laboratory and large-scale cultivation, and the development of AFA-specific genetic engineering techniques.
In aquaculture studies, Spirulina can be used to replace fish meal in aquafeed to lower the cost of producing fish feed while adding therapeutic and health benefits. Proteins, carbohydrates, vitamins, minerals, pigments, and fatty acids from Spirulina could enhance the cellular and humoral immunities of a variety of fish species. This review focuses on the functions of various Spirulina components that play a role in haematopoiesis, haemato-biochemical variables, pro-inflammatory and anti-inflammatory cytokine production, stress prevention, disease resistance, and immune responses in a variety of finfish species. Herein, we also presented the overlooked areas on the functionality of Spirulina on the immune response pathway and connected the missing link with the help of a better knowledge of the mammalian system, albeit these must be proved experimentally. This review will inspire the scientific community to investigate the biological role of Spirulina in fish, which is critical to the commercial viability of Spirulina as fish feed.
Background-Freshwater microalgae called spirulina have been consumed for many years as a dietary supplement. This algae possesses a diversified concentration of nutrients and has been known as a wonder medicine due to its many applications. It promotes immunity and resistance to several illness. Spirulina possesses a high content of proteins, essential amino acid, lipids, polysaccharides, dietary minerals, vitamins, and fatty acids which is responsible for its pharmacological action like antimicrobial effect, anticancer and metaloprotective effect, potent immunostimulant and antioxidant effects. Methodology-The experimental analysis and data reported on the species of spirulina were reviewed since the year 2005 to 2021.Various database were used as article source like Medline and Pubmed and literature review was done by using the key words spirulina, habitat, species, pharmacological action, toxicities and traditional uses. Result-This article provides an outline of this algae's basic biochemical makeup before moving on to its potential uses in medicine. The fundamental description of the illness, the mechanism of harm, the specific Spirulina spp. content for therapy, in vivo and/or in vitro usage, variables related with therapeutic role, challenges encountered, and benefits are presented for each application.
Em virtude de várias publicações terem mostrado a alta associação entre a geração de radicais livres e as doenças crônico-degenerativas, tem havido grande interesse por alimentos funcionais antioxidantes. O excesso de espécies reativas no organismo resulta em estresse oxidativo que provoca danos celulares e teciduais. A microalga Spirulina tem sido pesquisada em função de suas propriedades nutricionais e antioxidantes. O objetivo desse trabalho foi de avaliar a atividade antioxidante da microalga Spirulina, utilizando-se a levedura Saccharomyces cerevisiae como modelo biológico. A levedura foi submetida ao estressor 1,1’- dimetil - 4,4’- bipiridilio (paraquat), nas concentrações 0, 10 e 15 mM. O potencial antioxidante foi avaliado pela técnica de sobrevivência celular (plaqueamento) e pelo ensaio de lipoperoxidação (valores de TBA). Observou-se aumento significativo de sobrevivência celular (p ≤ 0,05), quando submetidos aos tratamentos com paraquat e Spirulina, em comparação com o experimento em que foi utilizado somente o paraquat. O agente estressor gerou aumento significativo (p ≤ 0,05) na lipoperoxidação (valores de TBA), o qual foi atenuado pelo tratamento com Spirulina, não diferindo do tratamento controle (p > 0,05). A microalga Spirulina apresentou capacidade antioxidante, que protege as células da levedura contra os danos oxidantes provocados pelo paraquat.
Introduction
The antinociceptive and pharmacological activities of C-Phycocyanin (C-PC) and Phycocyanobilin (PCB) in the context of inflammatory arthritis remain unexplored so far. In the present study, we aimed to assess the protective actions of these compounds in an experimental mice model that replicates key aspects of human rheumatoid arthritis.
Methods
Antigen-induced arthritis (AIA) was established by intradermal injection of methylated bovine serum albumin in C57BL/6 mice, and one hour before the antigen challenge, either C-PC (2, 4, or 8 mg/kg) or PCB (0.1 or 1 mg/kg) were administered intraperitoneally. Proteome profiling was also conducted on glutamate-exposed SH-SY5Y neuronal cells to evaluate the PCB impact on this key signaling pathway associated with nociceptive neuronal sensitization.
Results and discussion
C-PC and PCB notably ameliorated hypernociception, synovial neutrophil infiltration, myeloperoxidase activity, and the periarticular cytokine concentration of IFN-γ, TNF-α, IL-17A, and IL-4 dose-dependently in AIA mice. In addition, 1 mg/kg PCB downregulated the gene expression for T-bet, RORγ, and IFN-γ in the popliteal lymph nodes, accompanied by a significant reduction in the pathological arthritic index of AIA mice. Noteworthy, neuronal proteome analysis revealed that PCB modulated biological processes such as pain, inflammation, and glutamatergic transmission, all of which are involved in arthritic pathology.
Conclusions
These findings demonstrate the remarkable efficacy of PCB in alleviating the nociception and inflammation in the AIA mice model and shed new light on mechanisms underlying the PCB modulation of the neuronal proteome. This research work opens a new avenue to explore the translational potential of PCB in developing a therapeutic strategy for inflammation and pain in rheumatoid arthritis.
Since the banning of antibiotics in animal feeds (2006), there has been an increase in the number of studies looking for alternatives to stimulate the gut immune system. The main objective of our review article is to underline the nutraceutical properties of Curcuma longa and Spirulina platensis in the broiler chicken industry, and the experimental data were obtained by analyzing literature sources. Spirulina platensis is widely recognized as a valuable protein source, containing approximately 55-70% protein, 25% carbohydrates, essential amino acids, and 18% fatty acids. It is also rich in various vitamins like thiamin, riboflavin, pyridoxine, vitamin B12, vitamin C, gamma-linolenic acid, phycocyanins, tocopherols, chlorophyll, beta-carotenes, carotenoids, exhibiting positive effects on growth performance, gut integrity, and immunity. The anti-inflammatory effect of spirulina supplementation at different levels showed a decrease in caspase-3 and the TNF-α immunolabeling index; a reduction in IL-1β, IL-2 and IFN-γ; and an increase in the expression of the anti-inflammatory cytokine IL-4. Spirulina inhibits the synthesis of cytokines IL-1, IL-6, and TNF-gamma in addition to the activities of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) enzymes. Turmeric also positively influences the growth, egg production, and overall health of chickens. Cur-cumin, the most potent component of turmeric, possesses additional pharmacological activities, including hepatoprotective, immunostimulant, and anticancer effects. Its immunomodulatory properties greatly enhance the immune system response, acting as a natural antibiotic against pathogens and decreasing levels of proinflammatory interleukins IL-1β, IL-6, IL-2, IL-18, and TNF-α.
Spirulina platensis is a photosynthetic, blue-green, spiral- or bulb-shaped microalgae. Due to the presence of minerals, vitamins, pigments (carotenes, phycocyanin and chlorophyll) proteins (55%-70%), carbohydrates (15%-25%), and essential fatty acids (5%-8%), it has been used as a nutritional supplement for decades. NASA successfully employed it as a nutritional supplement for astronauts on space missions then its popularity was increased. The chemical composition of Spirulina, which is rich in vitamins, minerals, phenolics, vital fatty acids, amino acids, and pigments, can be beneficial to human health when incorporated into meals. The pharmacological effects include antibacterial, anticancer, metalloprotective, immune-stimulating, and antioxidant. It modulates immunological activities and possesses anti-inflammatory qualities by preventing mast cells from releasing histamine. Due to its high quantity of protein, carbohydrate, lipid, vital amino and fatty acids, dietary minerals and vitamins, Spirulina exerts the abovementioned benefits. In this review, up-to-date and possible biological aspects, patents applied on Spirulina and heights of confirmation are addressed, and the extent of current and future exploration is also explored.
Nanotechnology has the potential to revolutionize various fields of research and development. Multiple nanoparticles employed in a nanotechnology process are the magic elixir that provides unique features that are not present in the component’s natural form. In the framework of contemporary research, it is inappropriate to synthesize microparticles employing procedures that include noxious elements. For this reason, scientists are investigating safer ways to produce genetically improved Cyanobacteria, which has many novel features and acts as a potential candidate for nanoparticle synthesis. In recent decades, cyanobacteria have garnered significant interest due to their prospective nanotechnological uses. This review will outline the applications of genetically engineered cyanobacteria in the field of nanotechnology and discuss its challenges and future potential. The evolution of cyanobacterial strains by genetic engineering is subsequently outlined. Furthermore, the recombination approaches that may be used to increase the industrial potential of cyanobacteria are discussed. This review provides an overview of the research undertaken to increase the commercial avenues of cyanobacteria and attempts to explain prospective topics for future research.
Spirulina is also known as Arthrospira platensis is algae that belong to cyanobabcteria having lots of bioactivities. Cyanobacteria (blue-green algae) are among the most primordial life forms on the planet. It contains proteins, vitamins, carbohydrates, and lipids. It has been established that Arthrospira platensis has strong antioxidant activity, inhibits the colonisation of wounds by multi-resistant bacteria, and stops viruses from entering target cells. Anti-cancer action was also seen in mouth cancer, melanoma, and UV-induced non-melanoma skin cancer animals. Arthrospira platensis has an immunostimulating impact on humans, animals, chickens, and fish by increasing their resistance to infections, altering hemopoiesis, and stimulating the synthesis of antibodies and cytokines. Here we discussed about some pharmacological activities of Arthrospira platensis.
The fatty acid cyclooxygenase (ec 1.14.99.1) that produces the prostaglandin and thromboxane precursor, 15-hydroperoxy-9 alpha, 11 alpha-peroxidoprosta-5, 13-dienoic acid (PGG2), has been purified from sheep vesicular glands to a specific activity of 46,000 units/mg of protein by combining detergent solubilization, (NH4)SO4 fractionation, chromatography on DEAE-cellulose and Flurbiprofen-Sepharose, isoelectric focusing, and gel filtration. The final enzyme preparation exhibited only one band of 70,000 molecular weight following sodium dodecyl sulfate gel electrophoresis and staining with Coomassie blue. Treatment of the purified oxygenase with [3H] acetylsalicylic acid yielded a radioactive product which co-electrophoresed with the protein of 70,000 molecular weight. Thus, the isolated protein appeared to be the same one which, in crude preparations, selectively binds acetyl groups in association with prostaglandin synthetic activity. Incubation of the purified oxygenase with [1-14C] arachidonic acid in the presence of stannous chloride yielded only 9 alpha, 11 alpha, 15-trihydroxy-prosta-5,13-dienoic acid (PGF2alpha). Without stannous chloride, a mixture of radioactive products was observed which was characteristic of nonenzymic breakdown of PGG2. Thus, the isolated enzyme catalyzed the insertion of both oxygen molecules required for the formation of prostaglandins and thromboxanes from polyunsaturated fatty acid substrates. The aerobic absorption spectrum of the isolated oxygenase showed a faint peak at 412 nm indicative of heme. The iron content indicated that a significant amount of nonheme iron was present. The purified oxygenase was activated by added hemin, which was readily bound to the protein. The subsequently isolated heme-protein complex showed a major absorption peak at 407 nm.
The phytochrome chromophore precursor, 3E-phytochromobilin, and the phycobiliprotein chromophore precursors, 3E-phycocyanobilin and 3E-phycoerythrobilin, are enzymatically converted to novel rubinoid products by purified rat liver biliverdin reductase. Phytochromobilin and phycocyanobilin are particularly good substrates for biliverdin reductase with Km and Vmax values very similar to those of the natural substrate, biliverdin IX alpha. Phycoerythrobilin is the least preferred of the three bilin substrates. 1H NMR spectroscopy of phycocyanorubin, the product of phycocyanobilin catalysis by biliverdin reductase, and comparison of absorption spectra of all three rubinoid products reveal that the C10 methine bridge is selectively reduced by biliverdin reductase without altering the A-ring ethylidene substituent. In vitro phytochrome assembly experiments demonstrate that the phytorubin products do not form photoactive adducts with recombinant apophytochrome. These results suggest that ectopic expression of biliverdin reductase in plants will prevent assembly of the functional photoreceptor and thus will potentially alter light-mediated plant growth and development.
Murine prostaglandin endoperoxide (PGH) synthase-1 and PGH synthase-2 expressed in cos-1 cells were found to be differentially sensitive to inhibition by common nonsteroidal anti-inflammatory drugs (NSAIDs). Aspirin completely inhibited bis-oxygenation of arachidonate by PGH synthase-1; in contrast, aspirin-treated PGH synthase-2 metabolized arachidonate primarily to 15-hydroxyeicosatetraenoic acid (15-HETE) instead of PGH2. ID50 values were determined for a panel of common NSAIDs by measuring instantaneous inhibition of cyclooxygenase activity using an oxygen electrode. Among common NSAIDs tested, indomethacin, sulindac sulfide, and piroxicam preferentially inhibited PGH synthase-1; ibuprofen, flurbiprofen, and meclofenamate inhibited both enzymes with comparable potencies; and 6-methoxy-2-naphthylacetic acid preferentially inhibited PGH synthase-2. These results demonstrate that the two PGH synthases are pharmacologically distinct and indicate that it may be possible to develop isozyme-specific cyclooxygenase inhibitors useful both for anti-inflammatory therapy and for delineating between the biological roles of the PGH synthase isozymes.
Epidemiological and laboratory studies suggest that nonsteroidal antiinflammatory drugs reduce the risk of colon cancer and that the inhibition of colon carcinogenesis is mediated through modulation of prostaglandin production by cyclooxygenase (COX) isozymes (COX-1 and -2). Overexpression of COX-2 has been observed in colon tumors; therefore, specific inhibitors of COX-2 activity could potentially serve as chemopreventive agents. Our recent study indicated that celecoxib (SC-58635), a specific COX-2 inhibitor, suppressed colonic aberrant crypt foci formation induced by azoxymethane in rats and led us to investigate more specifically the chemopreventive potential of this compound using colon tumors as end points. Five-week-old male F344 rats were fed the control diet (modified AIN-76A) or an experimental diet containing 1500 ppm celecoxib. Two weeks later, all animals except those in the saline-treated groups received s.c. injections of azoxymethane (15 mg/kg of body weight) once weekly for 2 weeks. All groups were kept on their regimen until the experiment was terminated, 50 weeks after carcinogen treatment. Colon tumors were evaluated histopathologically. Remarkably, dietary administration of celecoxib inhibited both incidence and multiplicity of colon tumors by about 93 and 97%, respectively. It also suppressed the overall colon tumor burden by more than 87%. The degree of tumor inhibition was more pronounced with celecoxib than it was with previously evaluated nonsteroidal anti-inflammatory drugs. The results of this study provide evidence, for the first time, that a specific COX-2 inhibitor, celecoxib, possesses strong chemopreventive activity against colon carcinogenesis.
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.
Cyclooxygenase (COX), first purified in 1976 and cloned in 1988, is the key enzyme in the synthesis of prostaglandins (PGs) from arachidonic acid. In 1991, several laboratories identified a product from a second gene with COX activity and called it COX-2. However, COX-2 was inducible, and the inducing stimuli included pro-inflammatory cytokines and growth factors, implying a role for COX-2 in both inflammation and control of cell growth. The two isoforms of COX are almost identical in structure but have important differences in substrate and inhibitor selectivity and in their intracellular locations. Protective PGs, which preserve the integrity of the stomach lining and maintain normal renal function in a compromised kidney, are synthesized by COX-1. In addition to the induction of COX-2 in inflammatory lesions, it is present constitutively in the brain and spinal cord, where it may be involved in nerve transmission, particularly that for pain and fever. PGs made by COX-2 are also important in ovulation and in the birth process. The discovery of COX-2 has made possible the design of drugs that reduce inflammation without removing the protective PGs in the stomach and kidney made by COX-1. These highly selective COX-2 inhibitors may not only be anti-inflammatory but may also be active in colon cancer and Alzheimer's disease.
We determined whether resveratrol, a phenolic antioxidant found in grapes and other food products, inhibited phorbol ester
(PMA)-mediated induction of COX-2 in human mammary and oral epithelial cells. Treatment of cells with PMA induces COX-2 and
causes a marked increase in the production of prostaglandin E2. These effects were inhibited by resveratrol. Resveratrol suppressed PMA-mediated increases in COX-2 mRNA and protein. Nuclear
run-offs revealed increased rates of COX-2transcription after treatment with PMA, an effect that was inhibited by resveratrol. PMA caused about a 6-fold increase in
COX-2promoter activity, which was suppressed by resveratrol. Transient transfections utilizing COX-2 promoter deletion constructs and COX-2 promoter constructs, in which specific enhancer elements were mutagenized, indicated that the effects of PMA and resveratrol
were mediated via a cyclic AMP response element. Resveratrol inhibited PMA-mediated activation of protein kinase C. Overexpressing
protein kinase C-α, ERK1, and c-Jun led to 4.7-, 5.1-, and 4-fold increases in COX-2 promoter activity, respectively. These effects also were inhibited by resveratrol. Resveratrol blocked PMA-dependent activation
of AP-1-mediated gene expression. In addition to the above effects on gene expression, we found that resveratrol also directly
inhibited the activity of COX-2. These data are likely to be important for understanding the anti-cancer and anti-inflammatory
properties of resveratrol.
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.
A protein determination method which involves the binding of Coomassie Brilliant Blue G-250 to protein is described. The binding of the dye to protein causes a shift in the absorption maximum of the dye from 465 to 595 nm, and it is the increase in absorption at 595 nm which is monitored. This assay is very reproducible and rapid with the dye binding process virtually complete in approximately 2 min with good color stability for 1 hr. There is little or no interference from cations such as sodium or potassium nor from carbohydrates such as sucrose. A small amount of color is developed in the presence of strongly alkaline buffering agents, but the assay may be run accurately by the use of proper buffer controls. The only components found to give excessive interfering color in the assay are relatively large amounts of detergents such as sodium dodecyl sulfate, Triton X-100, and commercial glassware detergents. Interference by small amounts of detergent may be eliminated by the use of proper controls.
Although diet therapy for arthritis has received considerable publicity, there is little objective information about its efficacy. We undertook a 10-week, controlled, double-blind, randomized trial of patients with active rheumatoid arthritis (RA). Twenty-six patients completed the study; 11 were on an experimental diet (a specific popular diet free of additives, preservatives, fruit, red meat, herbs, and dairy products) and 15 were on a ‘placebo’ diet. Of 183 variables analyzed, there were no clinically important differences among rheumatologic, laboratory, immunologic, radiologic, or nutritional findings between patients on experimental and placebo diets. Six RA patients on the placebo and 5 on the experimental diet improved by objective criteria. Improvement averaged 29% for patients on placebo and 32% for patients on experimental diets. Two patients on the experimental diet improved notably, elected to remain on the experimental diet following the study period, have continued to improve, and noted exacerbations of disease upon consuming nonexperimental diet foods. Our study failed to provide evidence of objective overaii clinical benefit of this diet as followed by a group of patients with longstanding, progressive, active RA. However, our data are not inconsistent with the possibility that individualized dietary manipulations might be beneficial for selected patients with rheumatic disease.
Two main biliproteins c-phycocyanin and allophycocyanin were identified and characterized in the blue-green alga Spirulina platensis. The specific absorbance, fluorescence maxima, sub-unit make-up and amino acid composition of the biliproteins in Spirulina platensis resemble those reported for other blue-green algae. However, the minimum molecular weights (44,000 for c-phycocyanin and 38,000 for the allophycocyanin) and the specific extinction coefficients (73, and 58 for c-phycocyanin and allophycocyanin respectively) of these biliproteins were different from these values in other blue-green algae.
Cyclooxygenase-2 (COX-2), an enzyme responsible for catalyzing the committed step in prostanoid biosynthesis, is the product of an immediate early gene capable of being upregulated by diverse stimuli. Based on the experimental evidence that oxidative stress is associated with the upregulation of COX-2, we evaluated the effect of the oxidized fatty acid metabolites on COX-2 induction in rat liver epithelial RL34 cells. Among the compounds tested, only 4-hydroxy-2-nonenal (HNE), a highly mutagenic and genotoxic aldehyde generated during oxidative stress, dramatically induced COX-2. Enhanced gene expression of COX-2 by treatment with HNE was evident as a drastic elevation of the mRNA level. We also found that intracellular glutathione status was strictly related to HNE-induced COX-2 expression. These findings suggest the presence of a signaling pathway in the cellular response mediated by locally produced lipid peroxidation products under oxidative stress.
The bile-pigment chromophores of C-phycoerythrin (phycoerythrobilin) and C-phycocyanin (phycocyanobilin) were cleaved from their respective proteins with boiling methanol or butan-1-ol. They were purified as dicarboxylic acids by preparative reverse-phase liquid chromatography. Each pigment existed in two principal forms, which were characterized by using 20 pmol samples by proton-transfer chemical-ionization mass spectroscopy. These two principal forms were isomeric species, and all had protonated parent molecular ions with m/e 587, corresponding to a molecular weight of 586.
The syndrome of hypercalcemia in patients with renal cell carcinoma without metastasis to bone, in association with elevated levels of immunoreactive prostaglandin E and normal parathyroid hormone levels, prompted the investigation of an etiologic relationship of increased prostaglandin in this syndrome. Ethyl acetate extracts of tissue culture effluents, primary and metastatic renal cell carcinoma, and plasma were chromatographed on silicic acid columns and assayed by double antibody immunoprecipitative methods for immunoprecipitative methods for immunoreactive prostaglandins A and E. Increased levels of immunoreactive prostaglandins A and E were found 1) to be generated in parallel with cell growth during a period of time by renal cell carcinoma in monolayer growth, 2) in extracts of primary and metastatic renal cell carcinoma tissue and 3) in the venous effluent of a kidney bearing a renal cell carcinoma. These findings support the hypothesis that renal cell carcinoma can produce prostaglandins. Furthermore, reported syndromes of patients with renal cell carcinoma associated with elevated prostaglandin levels may result from the autonomous production of prostaglandins in vivo by the tumor.
A protein determination method which involves the binding of Coomassie Brilliant Blue G-250 to protein is described. The binding of the dye to protein causes a shift in the absorption maximum of the dye from 465 to 595 nm, and it is the increase in absorption at 595 nm which is monitored. This assay is very reproducible and rapid with the dye binding process virtually complete in approximately 2 min with good color stability for 1 hr. There is little or no interference from cations such as sodium or potassium nor from carbohydrates such as sucrose. A small amount of color is developed in the presence of strongly alkaline buffering agents, but the assay may be run accurately by the use of proper buffer controls. The only components found to give excessive interfering color in the assay are relatively large amounts of detergents such as sodium dodecyl sulfate, Triton X-100, and commercial glassware detergents. Interference by small amounts of detergent may be eliminated by the use of proper controls.
The syndrome of hypercalcemia in patients with renal cell carcinoma without metastasis to bone, in association with elevated levels of immunoreactive prostaglandin E and normal parathyroid hormone levels, prompted the investigation of an etiologic relationship of increased prostaglandin in this syndrome.
As shown by circular dichroism spectroscopy, biliverdin preferentially adopts an M-helicity conformation on human serum albumin in aqueous buffer, pH 7.5, whereas biliverdin exhibits only a weak preference for the P-helicity conformation on bovine serum albumin at the same pH. Upon rapid reduction of the complexes with sodium borohydride, P-helicity bilirubin-IX alpha is obtained on the human albumin complex, and M-helicity bilirubin-IX alpha is obtained on the bovine serum albumin complex. Thus, biliverdin in effect undergoes an inversion of chirality upon reduction. Since the reduction did not afford a rubin with the same helicity as that of the verdin, the observations point to a hitherto undetected conformational mobility of albumin-bound bilirubin.
Rous sarcoma virus was shown to induce in chicken embryo fibroblasts (CEF) a 4.1-kilobase mRNA (designated CEF-147) encoding a 603-amino acid protein. Analysis of the protein sequence showed that it shared 59% amino acid identity with sheep prostaglandin G/H synthase, the enzyme that catalyzes the rate-limiting steps in the production of prostaglandins. Significant differences, at both the protein and mRNA levels, existed between the src oncogene product-inducible prostaglandin synthase and the protein isolated and cloned from sheep seminal vesicle, suggesting that the src-inducible prostaglandin synthase may be a new form of the enzyme. A distinguishing feature of src-inducible prostaglandin synthase mRNA is its low abundance in nonproliferating chicken embryo fibroblasts and its relatively high abundance in src-transformed cells. Additionally, the majority of the src-inducible prostaglandin synthase RNA present in nonproliferating cells was found to be nonfunctional because of the presence of an unspliced intron that separated the signal peptide from the remainder of the protein. Upon mitogenic stimulation, this intron was removed, resulting in the induction of fully-spliced CEF-147 mRNA.
A single dose of CCl4 when administered to a rat produces centrilobular necrosis and fatty degeneration of the liver. These hepatotoxic effects of CCl4 are dependent upon its metabolic activation in the liver endoplasmic reticulum to reactive intermediates, including the trichloromethyl free radical. Positive identification of the formation of this free radical in vivo, in isolated liver cells and in microsomal suspensions in vitro has been achieved by e.s.r. spin-trapping techniques. The trichloromethyl radical has been found to be relatively unreactive in comparison with the secondarily derived peroxy radical CCl3O2., although each free radical species contributes significantly to the biological disturbances that occur. Major early perturbations produced to liver endoplasmic reticulum by exposure in vivo or in vitro to CCl4 include covalent binding and lipid peroxidation; studies of these processes occurring during CCl4 intoxication have uncovered a number of concepts of general relevance to free-radical mediated tissue injury. Lipid peroxidation produces a variety of substances that have high biological activities, including effects on cell division; many liver tumours have a much reduced rate of lipid peroxidation compared with normal liver. A discussion of this rather general feature of liver tumours is given in relation to the liver cell division that follows partial hepatectomy.
Experiments with guinea-pig lung suggest that some of the therapeutic effects of sodium salicylate and aspirin-like drugs are due to inhibition of the synthesis of prostaglandins.
Selective inhibition of the inducible isoform of prostaglandin G/H synthase (cyclooxygenase-2; COX2; EC 1.14.99.1) can be achieved with compounds of the general form of aryl methyl sulfonyls and aryl methyl sulfonamides. DuP 697 and NS-398 are representative examples of these compounds. Both inhibit the constitute (COX1) and inducible (COX2) isoforms of the enzyme with equal potency shortly after mixing, but their potencies increase with time for COX2 selectively. This time-dependent inhibition follows first-order kinetics, and the rate constant for inactivation of COX2 is dose dependent for both compounds. Kinetic analysis allows us to determine KI and kinact (the maximal rate of inactivation) for each inhibitor. The potency of both compounds is substrate concentration dependent, as expected for time-dependent competitive inhibitors. COX2 that has been incubated with these inhibitors, and then extensively dialyzed against buffer, shows no recovery of enzyme activity, while complete recovery of activity is seen for COX1. Thus, these inhibitors irreversibly inactivate COX2 with time, while showing minimal reversible inhibition of COX1. We isolated these inhibitors after long incubation with excess enzyme and subsequent denaturation of the enzyme. Both inhibitors showed no loss of potency resulting from interactions with COX2, suggesting that inhibition is not mediated by covalent modification of the enzyme. These data suggest that binding of these inhibitors to COX2 induces a slow structural transition of the enzyme that results in its selective inactivation.
The aim of our study was to characterize a model of human prostaglandin endoperoxide synthase-2 (PGHS-2) expression allowing the assessment of pharmacological inhibition in vitro and ex vivo. Heparinized human whole blood samples were incubated with lipopolysaccharide (LPS, 0.1-50 micrograms/ml) for 0 to 24 hr at 37 degrees C. The contribution of platelet PGHS-1 was suppressed by either pretreating the subjects with aspirin (300 mg 48 hr before sampling) or adding aspirin (10 micrograms/ml) in vitro at time 0. PGE2 was measured by radioimmunoassay. LPS induced expression of cyclooxygenase activity in a time- and concentration-dependent fashion. After 24 hr at 10 micrograms/ml LPS, PGE2 production averaged 12.1 +/- 6.2 ng/ml (mean +/- S.D., n = 7). Cyclooxygenase activity increased in parallel with the mass of a monocyte protein doublet analyzed by Western blot using antibodies directed against the carboxyl-terminal portion of human PGHS-2. Dexamethasone (2 microM) inhibited LPS-induced PGE2 production by 96 +/- 4% (mean +/- S.D., n = 3). Four different inhibitors were tested in vitro on the cyclooxygenase activity of LPS-induced monocyte PGH-2 and thrombin-stimulated platelet PGHS-1. IC50 values (microM) for inhibition of PGHS-1 and PGHS-2 were: indomethacin, 0.70 +/- 0.20 vs 0.36 +/- 0.10 (P < .05); S-indobufen, 0.64 +/- 0.22 vs. 14.9 +/- 8 (P < .05), R-indobufen, 38 +/- 18 vs. 230 +/- 68 (P < .01), 6-methoxy-2-naphthyl acetic acid (the active metabolite of nabumetone), 278 +/- 96 vs. 187 +/- 96.(ABSTRACT TRUNCATED AT 250 WORDS)
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.
The first crystal structure of human cyclooxygenase-2, in the presence of a selective inhibitor, is similar to that of cyclooxygenase-1. The structure of the NSAID binding site is also well conserved, although there are differences in its overall size and shape which may be exploited for the further development of selective COX-2 inhibitors. A second COX-2 structure with a different bound inhibitor displays a new, open conformation at the bottom of the NSAID binding site, without significant changes in other regions of the COX-2 structure. These two COX-2 structures provide evidence for the flexible nature of cyclooxygenase, revealing details about how substrate and inhibitor may gain access to the cyclooxygenase active site from within the membrane.
In this study, PGE2 levels in lipopolysaccharide (LPS)-challenged human whole blood and TxB2 levels following blood coagulation were measured as biochemical index for cyclooxygenase (Cox)-2 and Cox-1 activity respectively. Incubation of human mononuclear cells isolated from whole blood with LPS (100 mu g/mL) induced a time-dependent increase in the expression of Cox-2 protein (>100 fold at 24 hr). This is associated with increases in PGE2 production and free arachidonate release in the plasma. Cox-1 protein was detected in the human mononuclear cells at time zero but was not induced by either LPS or PBS. Most non-steroidal anti-inflammatory drugs (NSAIDs) are more potent at inhibiting Cox-1 than Cox-2. Five experimental compounds CGP-28238, Dup-697, NS-398, SC-58125 and L-745,337, have a greater selectivity for Cox-2. Indomethacin at a single oral dose (25 mg) inhibited approximately 90% the whole blood Cox-2 and Cox-1 activities ex vivo in healthy subjects. These results support the use of this assay to assess the biochemical efficacy of selective Cox-2 inhibitors in clinical trials.
An expanding body of evidence indicates that downregulation of the cyclooxygenases (Cox-1 and Cox-2) will be an important strategy for preventing cancer because cyclooxygenases catalyze the formation of prostaglandins (PGs), and PGs have multiple effects that favor tumorigenesis. PGs also are more abundant in cancers than in the normal tissues from which cancers arise. Overexpression of Cox-2 in epithelial cells inhibits apoptosis and increases the invasiveness of tumor cells; inhibitors of Cox (e.g., NSAIDS) are chemopreventive; and tumorigenesis is inhibited in Cox-2 knockout mice. We focus in this review on strategies to selectively inhibit and downregulate the Cox-2 isoform. This is important because simultaneous inhibition of Cox-1 (constitutively expressed) and Cox-2 (inducible isoform), which is achieved with classical NSAIDs, interferes with the housekeeping functions of Cox-1 and thereby causes serious side effects, such as peptic ulcer disease. Simultaneous inhibition of Cox-1 and Cox-2 hence is not a realistic approach for chemoprevention in individuals at low to moderate risk for cancer. On the other hand, it appears possible to avoid many NSAID-dependent side effects by selective inhibition of Cox-2, which is also the isoform that is upregulated in benign and malignant tumors. Through understanding the biochemistry of these enzymes and the regulation of Cox-1 and Cox-2 gene expression, we review how Cox-2 can be regulated selectively as a target for chemopreventive therapy. We also discuss the potential importance and advantages of a multifaceted approach to diminishing the function of Cox-2 (i.e., combining inhibitors of enzyme function with inhibitors of gene expression).
Effect of C-phycocyanin (from Spirulina platensis) pretreatment on carbontetrachloride and R-(+)-pulegone-induced hepatotoxicity in rats was studied. Intraperitoneal (i.p.) administration (200 mg/kg) of a single dose of phycocyanin to rats, one or three hours prior to R-(+)-pulegone (250 mg/kg) or carbontetrachloride (0.6 ml/kg) challenge, significantly reduced the hepatotoxicity caused by these chemicals. For instance, serum glutamate pyruvate transaminase (SGPT) activity was almost equal to control values. The losses of microsomal cytochrome P450, glucose-6-phosphatase and aminopyrine-N-demethylase were significantly reduced, suggesting that phycocyanin provides protection to liver enzymes. It was noticed that the level of menthofuran, the proximate toxin of R-(+)-pulegone was nearly 70% more in the urine samples collected from rats treated with R-(+)-pulegone alone than rats treated with the combination of phycocyanin and R-(+)-pulegone. The possible mechanism involved in the hepatoprotection is discussed.
This report investigates the plasma and/or urinary levels of 8-iso-PGF2alpha, a nonenzymatic, and 15-keto-dihydro-PGF2alpha, a cyclooxygenase catalyzed oxidation product of arachidonic acid in experimental hepatotoxicity in rats. The study was undertaken to evaluate oxidative injury-induced inflammation as a consequence of cyclooxygenase induction. A significant and immediate increase of 8-iso-PGF2alpha in both plasma and urine after CCl4 administration indicates an oxidative injury during acute hepatotoxicity in rats. The inflammatory response index was determined by measuring 15-keto-dihydro-PGF2alpha levels in plasma which increased significantly 9-fold at 4 h after the administration of CCl4. The oxidative injury index, 8-iso-PGF2alpha, in both plasma and urine increased 17- and 53-fold, respectively. Six hours later the levels of 15-keto-dihydro-PGF2alpha in plasma remained high (5-fold increase) when 8-iso-PGF2alpha levels in plasma and urine elevated to 7- and 87-fold, respectively. Thus, cyclooxygenase and free radical-catalyzed oxidation of arachidonic acid are well involved during CCl4-induced hepatotoxicity. Cyclooxygenase-dependent inflammatory response through PGF2alpha formation in CCl4-induced hepatotoxicity may possibly be a secondary effect to oxidative injury and a conceivable link between inflammatory response and oxidative injury.
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.
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 gbefore 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 increase din the control colitis group. Also, 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.
Several different agents including free radicals, oxidizing compounds and proteases are believed to play a role in the onset of arthritis. The evidence and underlying chemistry presently available for each destructive agent are presented.
The recent marketing of two selective cyclooxygenase 2 (COX-2) inhibitors climaxes the first phase of an exciting and fast-paced effort to exploit a novel molecular target for nonsteroidal anti-inflammatory drugs (NSAIDs). Much has been written in the lay and scientific press about the potential of COX-2 inhibitors as anti-inflammatory and analgesic agents that lack the gastrointestinal side-effects of traditional NSAIDs. Although research on COX-2 inhibitors has focussed mainly on inflammation and pain, experimental and epidemiological data suggest that COX-2 inhibitors could be used in the treatment or prevention of a broader range of diseases. In this review, some key points and unresolved issues related to the discovery of COX-2 inhibitors, the kinetic and structural basis for their selectivity, and possible complications in their development and use will be discussed.
Evidence derived from several lines of investigation suggest that prostaglandins, metabolites of arachidonic acid, play an important role in colon cancer development. Elevated prostaglandin levels are found in colon cancers and their precursor lesions, adenomatous polyps. Agents such as aspirin and NSAIDs, which inhibit the generation of these arachidonic acid metabolites, are associated with a decreased risk of developing or dying from colon cancer. Both the amount of the agent used and the duration of exposure seem to be important variables. In animals, NSAIDs are among the most potent agents discovered for the reduction of tumors in both genetic and carcinogen-induced models. Data from human trials also suggests that NSAIDs such as sulindac can reduce the size and number of polyps in individuals with familial adenomatous polyposis (FAP). In parallel with the above findings, it is now understood that at least two forms of the enzyme responsible for the metabolism of arachidonic acid exist. One of these forms, COX-1, is generally considered a constitutive form that is responsible for maintaining normal physiologic function. Inhibition of COX-1 leads to many of the clinically undesirable side effects associated with NSAID use. The other known form of the enzyme, COX-2, is an inducible form that is found in increased levels in inflammatory states and in many cancers and their associated pre-malignant lesions. Levels of COX-2 are increased by exposure to mitogens and growth factors. Agents that specifically inhibit COX-2 are now in clinical development and appear to be well-tolerated and effective for the treatment of osteoarthritis and rheumatoid arthritis. The potential for use of COX-2 specific NSAIDs in the prevention of colon cancer is suggested from the distribution of COX-2 in adenomatous polyps and colon cancer and the effectiveness of these agents in genetic and carcinogen-induced animal models of colon cancer. The development of these agents for the prevention of colon cancer will be discussed.
C-Phycocyanin (from Spirulina platensis) effectively inhibited CCl(4)-induced lipid peroxidation in rat liver in vivo. Both native and reduced phycocyanin significantly inhibited peroxyl radical-induced lipid peroxidation in rat liver microsomes and the inhibition was concentration dependent with an IC(50) of 11.35 and 12.7 microM, respectively. The radical scavenging property of phycocyanin was established by studying its reactivity with peroxyl and hydroxyl radicals and also by competition kinetics of crocin bleaching. These studies have demonstrated that phycocyanin is a potent peroxyl radical scavenger with an IC(50) of 5.0 microM and the rate constant ratios obtained for phycocyanin and uric acid (a known peroxyl radical scavenger) were 1.54 and 3.5, respectively. These studies clearly suggest that the covalently linked chromophore, phycocyanobilin, is involved in the antioxidant and radical scavenging activity of phycocyanin.
- P Patrignani
- M R Panara
- A Greco
- O Fusco
- C Natoli
- S Iacobelli
- F Cipollone
- A Ganci
- C Creminon
- J Maclouf
- C Patrono
Patrignani, P., Panara, M. R., Greco, A., Fusco, O., Natoli, C.,
Iacobelli, S., Cipollone, F., Ganci, A., Creminon, C., Maclouf, J.,
and Patrono, C. (1994) J. Pharmacol Exp. Ther. 271, 1705-1712.
- B B Vadiraja
- N W Gaikwad
- K M Madyastha
Vadiraja, B. B., Gaikwad, N. W., and Madyastha, K. M. (1998)
Biochem. Biophys. Res. Commun. 249, 428 -431.
- R Miesel
- M Zuber
Miesel, R., and Zuber, M. (1993) Inflammation 17, 551–561.
Rheumatoid arthritis
- R S Katz
Katz, R. S. (1994) Rheumatoid arthritis. In Conn's Therapeutics,
pp. 1027–1033, Interamericana McGraw-Hill.
- W L Smith
- R M Garavito
Smith, W. L., Garavito, R. M., and DeWitt, D. L. (1996) J. Biol.
Chem. 271, 33157–33160.
- T Kumagai
- Y Kawamoto
- Y Nakamura
- I Hatayama
- K Satoh
- T Osawa
- K Uchida
Kumagai, T., Kawamoto, Y., Nakamura, Y., Hatayama, I., Satoh, K., Osawa, T., and Uchida, K. (2000) Biochem. Biophys. Res.
Commun. 273, 437-441.
- D B Fournier
Fournier, D. B., and Gordon, G. B (2000) J. Cell. Biochem. Suppl.
34, 97–102.