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Phycocyanin prevents hypertension and low serum adiponectin level in a rat model of metabolic syndrome
Abstract
Endothelial dysfunction is associated with hypertension, atherosclerosis, and metabolic syndrome. Phycocyanin is a pigment found in the blue-green algae, Spirulina, which possesses antihypertensive effect. In this study, we hypothesized that phycocyanin derived from Spirulina exerts antihypertensive actions by improving endothelial dysfunction in metabolic syndrome. Spontaneously hypertensive/NIH-corpulent (SHR/NDmcr-cp) rats were divided into 4 groups then fed a normal diet with or without phycocyanin (2500-, 5000-, or 10 000-mg/kg diet) for 25 weeks. At 34 weeks of age, although systolic blood pressure was not significantly different among groups, phycocyanin-fed groups exhibited a dose-dependent decrease in blood pressure. Serum levels of adiponectin and messenger RNA levels of adiponectin and CCAAT/enhancer-binding protein α in the adipose tissue of rats fed diets containing phycocyanin tended to be higher than those of rats fed a normal diet, but the differences were not statistically significant. Immunohistochemistry analysis showed a significant and positive correlation between aortic endothelial nitric oxide synthase (eNOS) expression levels, a downstream target of the adiponectin receptor, and serum adiponectin levels, although there were no significant differences in eNOS expression among groups. There was also no significant correlation between eNOS expression levels and systolic blood pressure. These results suggest that long-term administration of phycocyanin may ameliorate systemic blood pressure by enhancing eNOS expression in aorta that is stimulated by adiponectin. Phycocyanin may be beneficial for preventing endothelial dysfunction-related diseases in metabolic syndrome.
... C-PC (a 2500-10,000 mg kg −1 diet for 25 weeks) was able to prevent hypertension in a rat model of metabolic syndrome by enhancing the eNOS expression in aorta [106]. Moreover, the antioxidant action of C-PC (100 mg kg −1 per os) was able to reduce the damage on rat endothelium induced by a chronic kidney disease, promoting an antihypertensive effect [107]. ...
... The following supporting information can be downloaded at: https: //www.mdpi.com/article/10.3390/nu16111752/s1, Table S1: Effects of C-PC or PCB-B on different disease models [20,[24][25][26][27][28][29][30][31][32][33][34]36,[38][39][40][41][43][44][45][46][47][48][49][50][51][52][62][63][64][65][66][67][68]71,72,[76][77][78][79][80][81][82][85][86][87][88][90][91][92][93][94][95][96][97][98][99][100][101][102][103][104][105][106][107][108][109][111][112][113][114][115][116][117]. ...
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.
... Research has demonstrated the clinical versatility of spirulina's nutritional composition through a multitude of benefits, including positive effects against hyperlipidemia, malnutrition, obesity, diabetes, and anemia as well as antioxidant and anti-inflammatory activity (Mani et al. 2000;Lee et al. 2008;Selmi et al. 2011;Hosseini et al. 2013;Ichimura et al. 2013;Wu et al. 2016;Hernández-Lepe et al. 2018). Consequently, this has evoked an interest into spirulina and whether it can also perform as a potential ergogenic aid. ...
... Arginine, an essential amino acid, increases nitric oxide bioavailability (Lafarga et al. 2020) which consequently improves endothelium-dependant vasodilation via the intracellular second-messenger cGMP (Bode-Böger et al. 1996). Whilst phycocyanin has been found to increase the expression of endothelial nitric oxide synthase in rats (Ichimura et al. 2013). Although further human trials are needed, the increase in nitric oxide bioavailability could suggest an enhanced oxygen provision to skeletal muscle resulting from the improvements in blood flow (Gurney and Spendiff 2020) achieved via increases in vascular reactivity and decreases in contractile reactivity. ...
Spirulina supplementation has been reported to increase hemoglobin concentration as well as a variety of cardiorespiratory and lactate-based performance parameters during maximal and submaximal states of exercise. This study investigates the efficacy of supplementing a 6 g/day dosage of spirulina for 14-days in recreationally active individuals, analyzing cardiorespiratory parameters during maximal and submaximal cycling as well as the potential mechanistic role of hemoglobin augmentation. 17 recreationally active individuals (Male = 14, Female = 3, Age 23 ± 5 years, V̇O2max 43.3 ± 8.6 ml/min·kg) ingested 6 g/day of spirulina or placebo for 14-days in a double-blinded randomized crossover study, with a 14-day washout period between trials. Participants completed a 20-min submaximal cycle at 40% maximal power output (WRmax), followed by a V̇O2max test. Hemoglobin (g/L), WRmax (watts), time to fatigue (seconds), heart rate (bpm), oxygen uptake (ml/min·kg), RER and blood lactate response (mmol/L) were measured and compared between conditions. Cardiorespiratory variables were recorded at 5-min intervals and lactate was measured at 10-min intervals during the submaximal exercise. There was a significant 3.4% increase in hemoglobin concentration after spirulina supplementation in comparison to placebo (150.4 ± 9.5 g/L Vs 145.6 ± 9.4 g/L, p = 0.047). No significant differences existed between either condition in both testing protocols for V̇O2max, WRmax, time to fatigue, heart rate, oxygen uptake, RER and blood lactate response (p > 0.05). 14-days of spirulina supplementation significantly improved hemoglobin concentration but did not lead to any considerable ergo-genic improvements during maximal or submaximal exercise at a 6 g/day dosage in recreationally active individuals whilst cycling.
... This possible mechanism was proposed due to previous work demonstrating that 5 mmol of nitrate supplementation can elevate circulatory Hb by up to 3% via splenic contraction (Engan et al., 2020(Engan et al., , 2021. Despite the possible nitrate content in Spirulina yet to be confirmed, rodent studies indicate that Spirulina can increase nitric oxide availability in the aorta and plasma (Brito et al., 2018;Ichimura et al., 2013). Extensive clinical reviews into the applicability of microalgae for the aforementioned benefits can also be found elsewhere but are beyond the scope of this chapter (DiNicolantonio et al., 2020;Fallah et al., 2018;Soheili and Khosravi-Darani, 2011). ...
... The 20-min submaximal arm crank was followed by an incremental test to fatigue, and at the time of fatigue oxygen uptake was higher following spirulina supplementation. Speculative mechanisms were the increase in Hb and possibly the phycocyanin constituent found in spirulina, which has previously been reported to increase the expression of endothelial nitric oxide synthase in rats (Ichimura et al., 2013). Localized vasodilation from nitric oxide may have therefore allowed for an increased oxygenated blood flow to the working muscles and the removal of deleterious by-products associated with metabolic acidosis during arm cranking. ...
... Obesity is essentially caused by the imbalance between intake and consumption. Few studies reported the anti-obesity activity of phycocyanin [101,102]. To be specific, phycocyanin was demonstrated to enhance the expression of endothelial nitric oxide synthase (eNOS) in the aorta under the stimulation of adiponectin, improving blood pressure levels and obesity [101]. ...
... Few studies reported the anti-obesity activity of phycocyanin [101,102]. To be specific, phycocyanin was demonstrated to enhance the expression of endothelial nitric oxide synthase (eNOS) in the aorta under the stimulation of adiponectin, improving blood pressure levels and obesity [101]. It was also reported that phycocyanin could attenuate obesity, possibly by reducing adipogenesis in 3T3-L1 cells and HFD-induced obese mice [102]. ...
Large-scale production of microalgae and their bioactive compounds has steadily increased in response to global demand for natural compounds. Spirulina, in particular, has been used due to its high nutritional value, especially its high protein content. Promising biological functions have been associated with Spirulina extracts, mainly related to its high value added blue pigment, phycocyanin. Phycocyanin is used in several industries such as food, cosmetics, and pharmaceuticals, which increases its market value. Due to the worldwide interest and the need to replace synthetic compounds with natural ones, efforts have been made to optimize large-scale production processes and maintain phycocyanin stability, which is a highly unstable protein. The aim of this review is to update the scientific knowledge on phycocyanin applications and to describe the reported production, extraction, and purification methods, including the main physical and chemical parameters that may affect the purity, recovery, and stability of phycocyanin. By implementing different techniques such as complete cell disruption, extraction at temperatures below 45 °C and a pH of 5.5–6.0, purification through ammonium sulfate, and filtration and chromatography, both the purity and stability of phycocyanin have been significantly improved. Moreover, the use of saccharides, crosslinkers, or natural polymers as preservatives has contributed to the increased market value of phycocyanin.
... Phycocyanin attracts an attention of the researchers in different fields due to its nutritional and medicinal properties and the role of colorant in the food and medicinal products [3,12]. Phycocyanin pigment, as a bioactive component of phycobiliprotein complexes, possesses antioxidant [26], anticancer [8,15,31,32], antiplatelet [23,33], antibacterial [25,34], antihypertensive [35], anti-inflamation [36] activities. ...
... The long-term administration of phycocyanin can reduce systemic blood pressure by enhancing eNOS expression in aorta that is stimulated by adiponectin. Therefore, phycocyanin may be beneficial for preventing endothelial the dysfunction-related diseases in metabolic syndrome [35]. ...
c-phycocyanin (phycocyanin) is a pigment-protein complex of the light-harvesting phycobiliprotein family that takes part in the primary phase of photosynthesis in lower plants. The phycocyanin content depends on such factors as the species of microalgae, physical state of biomass, extraction techniques, etc. The main methods for obtaining phycocyanin from biomass include chemical, physical and enzyme treatments with the following purification by such methods as precipitation with ammonium sulfate, ion exchange chromatography, and gel filtration chromatography. The commercial value of phycocyanin is directly related to the methods of its obtaining, purification and purity. The ratio of absorbances A620/A280 indicates the grade of phycocyanin and is the principal index of its purity. If the ratio of A620/A280 is greater than 4, phycocyanin can be used for pharmaceutical and analytical studies; at not less than 0.7, phycocyanin can be used for the food industry and at not less than 3.9 phycocyanin can be used as a reagent. The purified phycocyanin has some absorption maxima at the wavelengths of 610–625 nm, 353 nm and 277 nm. Its molecular mass ranges from 110 to 220 kDa. The search for extraction methods is aimed at obtaining a high yield of phycocyanin of an appropriate purity in industrial scale. This will allow a wider introduction of phycocyanin into the food, cosmetics and pharmaceutical industries as a safe product with many positive biological properties, in particular, antioxidant, antitumor, antiplatelet, antibacterial, hypotensive, anti-inflammatory, etc
... A recent study by Engan et al. (2020) demonstrated that 5 mmol nitrate supplementation can stimulate the contraction of the spleen during apneas, which can consequently elevate circulatory Hb by up to 3%. Although previous investigations into SP and nitrate are sparse, previous studies by Brito et al. (2018) and Ichimura et al. (2013) may support the notion that SP can increase circulatory nitrate/nitrite, whereby it was reported that the phycocyanin constituent found in SP increased nitric oxide availability in the aorta and plasma in rats, and increased the expression of endothelial nitric oxide synthase (eNOS). ...
... These overlapping mechanisms may influence similar pathways. First, SP contains phycocyanin, a pigment-protein complex that has previously been reported to increase the expression of endothelial nitric oxide synthase (eNOS) in rats (Ichimura et al. 2013). Second, SP contains arginine (Lafarga et al. 2020), the amino acid precursor to nitric oxide, which has previously been reported to increase muscle blood volume via its endothelium vasodilatory effects (Álvares et al. 2012). ...
Spirulina supplementation has been reported to improve time to exhaustion and maximal oxygen consumption (V̇O2max). However, there is limited information on its influence over the multiple intensities experienced by cyclists during training and competition. Fifteen trained males (age 40 ± 8 years, V̇O2max 51.14 ± 6.43 mL/min/kg) ingested 6 g/day of spirulina or placebo for 21 days in a double-blinded randomised crossover design, with a 14-day washout period between trials. Participants completed a 1-hour submaximal endurance test at 55% external power output max and a 16.1-km time trial (day 1), followed by a lactate threshold test and repeated sprint performance tests (RSPTs) (day 2). Heart rate (bpm), respiratory exchange ratio, oxygen consumption (mL/min/kg), lactate and glucose (mmol/L), time (seconds), power output (W), and hemoglobin (g/L) were compared across conditions. Following spirulina supplementation, lactate and heart rate were significantly lower (P < 0.05) during submaximal endurance tests (2.05 ± 0.80 mmol/L vs 2.39 ± 0.89 mmol/L and 139 ± 11 bpm vs 144 ± 12 bpm), hemoglobin was significantly higher (152.6 ± 9.0 g/L) than placebo (143.2 ± 8.5 g/L), and peak and average power were significantly higher during RSPTs (968 ± 177 W vs 929 ± 149 W and 770 ± 117 W vs 738 ± 86 W). No differences existed between conditions for all oxygen consumption values, 16.1-km time trial measures, and lactate threshold tests (P > 0.05). Spirulina supplementation reduces homeostatic disturbances during submaximal exercise and augments power output during RSPTs.
Novelty: Spirulina supplementation lowers heart rate and blood lactate during ∼1-hour submaximal cycling.
Spirulina supplementation elicits significant augmentations in hemoglobin and power outputs during RSPTs.
... As espécies de Spirulina têm mostrado grande potencial terapêutico e nutricional, incluindo atividades antibacterianas, antifúngicas, antivirais e antiparasitárias (13)(14) .Também já foi apresentada função antioxidante, imunomoduladora, anti-inflamatória, antidiabética, e melhora do perfil lipídico (15)(16)(17)(18)(19) .Além disso, há alguns anos tem sido reportado o impacto da Spirulina sobre a pressão arterial, mostrando sua atividade anti-hipertensiva por administração via oral em humanos, em roedores e in vitro (20)(21)(22) . ...
... O mecanismo de ação sugerido é que a Spirulina possua peptídeos inibidores de enzima conversora de angiotensina (ECA) em sua composição e essa enzima participa do Sistema Renina-Angiotensina, responsável pelo controle da pressão arterial (22)(23) . A ECA atua na conversão de angiotensina I em angiotensina II, um peptídeo vasoconstritor que, em grande concentração no organismo, induz a HAS (24) Além disso, um estudo mostrou que a Spirulina foi capaz de aumentar a expressão de óxido nítrico sintase endotelial (ONSe) no endotélio aórtico de ratos, com suplementação de 2,5g/kg; 5g/kg e 10g/kg por 25 semanas, levando à vasodilatação, sendo este, outro possível mecanismo de proteção endotelial (21) . ...
... In our conditions, SLE was not reported to have any effect on food intake. This could be due to phycocyanin, which has already been reported without any effect on this parameter [48,49]. Concerning drinking water, adding SLE led to an increase in water intake at weeks 1, 2, 6, and 7 in the SP and SPT groups compared to the C and T groups ( Figure 1B). ...
Background: Physical activity, such as running, protects against cardiovascular disease and obesity but can induce oxidative stress. Athletes often consume antioxidants to counteract the overproduction of reactive oxygen and nitrogen species during exercise. Spirulina, particularly its phycocyanin content, activates the Nrf2 pathway, stimulating antioxidant responses. Studies show that phycocyanin enhances antioxidant defenses and reduces inflammation, potentially improving muscle adaptation and recovery. This study evaluates a Spirulina liquid extract (SLE) supplementation during endurance training, hypothesizing that phycocyanin improves oxidant status and performance in soleus and extensor digitorum longus muscles. Methods: Three-week-old male Wistar rats were divided into four groups: a sedentary control group (C), a sedentary group supplemented with SLE (SP), an endurance training group (T), and an endurance training group supplemented with SLE (SPT). After 8 weeks of treadmill training, blood and muscle were collected. Biochemical parameters and gene expression analyses were performed to assess the effects of training and supplementation. Results: The maximal aerobic speed improved significantly in the SPT group. Plasma lipid profiles showed a reduction in triglyceridemia, cholesterolemia, and atherogenic index in the trained groups, especially with SLE supplementation. Muscle malondialdehyde levels decreased in the SPT group compared to T. Gene expression analysis revealed upregulation of Nrf2 and mitochondrial biogenesis genes in both muscles, with differences between groups for genes related to glycogen storage and β-oxidation. Conclusions: This study demonstrated that SLE supplementation enhanced exercise performance and promoted muscle molecular adaptations. These findings suggest SLE as a promising functional food supplement for athletes, optimizing recovery and performance.
... In addition, an APE-induced increase in endothelial nitric oxide synthase (eNOS) expression has been repeatedly reported [59][60][61][62]. The subsequent improvement in endothe- ...
Atherosclerosis is initiated by injury or damage to the vascular endothelial cell monolayer. Therefore, the early repair of the damaged vascular endothelium by a proliferation of neighbouring endothelial cells is important to prevent atherosclerosis and thrombotic events. Arthrospira platensis (AP) has been used as a dietary supplement, mainly due to its high content of vitamins, minerals, amino acids, and pigments such as chlorophylls, carotenoids, and phycocyanin, ingredients with antioxidant, anti-inflammatory, and anti-thrombotic properties. Therefore, in this prospective, placebo-controlled, data-driven, sample-size-estimated in vitro study, we tested whether an aqueous extract of AP at different concentrations (50, 100, and 200 µg/mL) had an effect on the different cellular parameters of human umbilical vein endothelial cells. Therefore, cell impedance measurement and cell proliferation were measured to investigate the monolayer formation. In addition, cell viability, integrity, and metabolism were analysed to evaluate singular cellular functions, especially the antithrombotic state. Furthermore, cell–cell and cell–substrate interactions were observed. The highest proliferation was achieved after the addition of 100 µg/mL. This was consistently confirmed by two independent optical experiments in cell cultures 48 h and 85 h after seeding and additionally by an indirect test. At this concentration, the activation or dysfunction of HUVECs was completely prevented, as confirmed by prostacyclin and interleukin-6 levels. In conclusion, in this study, AP induced a significant increase in HUVEC proliferation without inducing an inflammatory response but altered the hemostasiological balance in favour of prostacyclin over thromboxane, thereby creating an antithrombotic state. Thus, APE could be applied in the future as an accelerator of endothelial cell proliferation after, e.g., stent placement or atherosclerosis.
... In addition, Espinosa et al. [ 47 ] noted the degeneration of renal tissue in zebrafish that had consumed MP particles. Furthermore, raising angiotensin II levels can partially raise blood pressure in people following exposure to diethylhexyl phthalate 98 .It has been determined that an increase in blood pressure places the glomerular walls under mechanical stress that may cause damage 99 . ...
The joint impact of tadalafil (Cilais) as a pharmaceutical residue and microplastics on fish is not well comprehended. The current study examined haematological, biochemical, and antioxidant parameters, along with immunohistochemical and histological indications in tilapia (Oreochromis niloticus) after being exposed to tadalafil, polyethylene microplastics (PE-MPs), and their mixtures for 15 days. The fish were distributed into 1st group control group (The fish was maintained in untreated water without any supplements); 2nd group exposed to 10 mg/L PE-MPs;3rd group exposed to 20 mg/l tadalafil (Cilais); 4th group exposed to 20 mg/l tadalafil (Cilais) + 10 mg/LPE-MPs (in triplicate). The levels of creatinine, uric acid, glucose, AST, ALT, and albumin in fish treated with tadalafil alone or in combination with PE-MPs were significantly higher than those in the control group. Fish exposed to PE-MPs, tadalafil, and tadalafil plus PE-MPs showed significantly lower levels of RBCs, Hb, Ht, neutrophils, and lymphocytes compared to the control group. Serum levels of total antioxidant capacity and reduced glutathione (GSH) were notably lowered in fish groups subjected to PE-MPs, tadalafil, and tadalafil + PE-MPs combinations in comparison to the control group. Malondialdehyde (MDA) serum levels were notably elevated in fish groups subjected to PE-MPs, tadalafil, and tadalafil + PE-MPs combinations compared to the control group. The most severe impact was observed in the tadalafil + PE-MPs combination group. Interleukin-6 (IL-6) levels were significantly increased in liver tissues following exposure to both tadalafil and microplastics compared to tissues exposed to only one substance or the control group. Changes in the gills, liver, and renal tissues were seen following exposure to PE-MPs, tadalafil, and tadalafil + PE-MPs combination in comparison to the control group of fish. Ultimately, the mixture of tadalafil and PE-MPs resulted in the most detrimental outcomes. Tadalafil and PE-MPs exhibited showed greater adverse effects, likely due to tadalafil being absorbed onto PE-MPs.
... Spirulina (Arthrospira sp) is one of the most studied nutraceuticals with antihypertensive action [11]. It has been proposed that c-phycocyanin (CPC), a primary metabolite in the photosynthetic apparatus, is responsible for its nutraceutical antihypertensive actions [12,13]. However, unknown is whether CPC treatment avoids CKD-altered vascular response to Ang II and Ang-(1-7). ...
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.
... They play a crucial role in pharmaceutical applications and human health because of their antioxidant, antiviral, antibacterial, and antifungal actions. Several studies have demonstrated the effectiveness of Spirulina in treating diseases linked to free radicals, inflammation, neurodegenerative disorders [7,8], diabetes [9,10], polycystic ovarian syndrome [11], hypertension HTN [12], and cancers [13]. ...
Objective: A well-known endocrine disruptor, Bisphenol A (BPA) is used as a monomer in the manufacture of polyester,
epoxy resin, and polycarbonate plastics. Previous studies have shown the antioxidant efect of Arthrospira platensis in several
experimental models of oxidative stress. The current study was carried out to evaluate the antioxidant activity of Arthrospira
platensis against BPA-induced nephrotoxicity and oxidative damage in rats.
Methods: The bioactive compounds in the aqueous extract of AP were identifed and confrmed by FTIR and HPLC. Nev-
ertheless, this study pre-assessed the AP in vitro antioxidant activity (DPPH, ABTS, and FRAP).
Female Wistar rats were randomly divided into four groups: group I (C) received 0.5mL corn oil and served as control.
Group II (AP) were treated with Arthrospira platensis (4.75g/Kg of diet)+0.5 mL of corn oil. Rats of group III (BPA) have
received BPA (100mg/kg bw) dissolved in corn oil administered by orally way. Animals of group IV (BPA + AP) were
treated with BPA and AP.
Results: The results reveal a various and rich phytochemical composition of the aqueous extract of Arthrospira platensis. Six
polyphenols that have been linked to bioactivities were found by HPLC analysis: quercetin, chlorogenic acid, rutin, vanillin,
p-coumaric acid, and cafeic acid. Additionally, the FTIR profle detected the cyanobacteria’s functional groups.
The exposure of rats to BPA for 3 weeks provoked renal damage with signifcant increases in hematological parameters,
oxidative stress-related parameters (i.e., malondialdehyde “MDA” protein carbonyl “PC” content, advanced oxidation protein
products “AOPP”, and hydrogen peroxide “H2O2”), creatinine, urea, and uric acid levels in plasma. Conversely, antioxidant
enzyme activities (i.e., glutathione peroxidase “GPx” and superoxide dismutase “SOD”) and levels of reduced glutathione
“GSH”, creatinine, urea, and uric acid decreased. The administration of Arthrospira platensis to BPA-treated rats signifcantly
improved weight, peripheral blood parameters, oxidative stress-related parameters, renal biomarker levels, and antioxidant
enzyme activities. Also, rats treated with BPA and Arthrospira platensis had normal kidney histology. These healing efects
are likely the result of the high phenol content and signifcant antioxidant capacity of A. platensis.
Conclusion: Our data strongly suggest that A. platensis supplementation improves kidney function and plays an important
role in the prevention against BPA-induced nephrotoxicity in rats, and that the efects are associated with the antioxidant
efect of Spirulina.
Keywords: Arthrospira platensis · Bisphenol A · Oxidative stress · Antioxidants · Spirulina
... Torres-Duran et al (20) reported that Spirulina has an antihypertensive effect in humans. In addition, an experimental report revealed that phycocyanins have a protective effect on hypertension or metabolic syndrome (21). ...
Background
Nuts and algae have been shown to improve BP levels, but their effectiveness is controversial.
Aims
This study aims to illustrate the effect of dietary pattern with nuts and algae-less on BP levels in children and adolescents from a cross-sectional study.
Methods
A total of 5645 children from the Chongqing Children’s Health Cohort, aged 9.34 ± 1.74 years with 52.05% males, were analyzed. Stratified analysis was conducted to explore the differences between the two dietary patterns in urban or rural areas, as well as the differences in different gender. Logistic regression was used to analyze the influence factors of increased BP. And a GLM was used to analyze the influence of the two dietary patterns on systolic blood pressure (SBP, mmHg), diastolic blood pressure (DBP, mmHg), and mean arterial pressure (MAP, mmHg).
Results
Children with nuts and algae-less dietary patterns had higher SBP (104.68 ± 10.31 vs 103.81 ± 9.74, P = .006), DBP (64.27 ± 7.53 vs 63.55 ± 7.52, P = .002), and MAP (77.74 ± 7.75 vs 76.97 ± 7.52, P = .001) compared with those children with a balanced diet. After adjusting for covariates, the nuts and algae-less diet was a risk factor for hypertension in children when compared with the balanced diet(OR(95%CI):1.455(1.097,1.930), P = .009). The nuts and algae-less diet has a significant influence on SBP (104.68 ± 10.31 mmHg vs.103.81 ± 9.74 mmHg, P = .006). Stratified analysis by sex showed that nuts and algae-less dietary patterns had a more significant impact on females than males.
Conclusion
Nuts and algae-less dietary pattern correlated with increased BP levels in children, and a greater impact on SBP levels was found in females, suggesting that a balanced diet with appropriate nuts and algae should be proposed for children in China.
... Because of this, C-PC may be beneficial in preventing endothelial dysfunction caused by comorbidity with high blood pressure, atherosclerosis, and development of metabolic syndrome. 37 Preclinical evidence has reported that the administration of C-PC at a dose of 100 mg/kg for 3 weeks, to spontaneously diabetic KKAy mice, significantly reduces body weight and plasma glucose levels and improves insulin sensitivity and excretion by protecting pancreatic INS-1 cells b. These changes are observed as C-PC acts by reducing malondialdehyde (MDA) levels. ...
Spirulina maxima is a cyanobacterium considered a "superfood" due to its metabolites and nutrient content. These include a complex mixture of minerals, vitamins, fatty acids, proteins, and accessory pigments. In recent years, it has positioned itself as a promising source of bioactive molecules for the treatment of several diseases, including metabolic syndrome, coronary diseases, cancer, and the improvement of health modulating oxidative stress. C-Phycocyanin (C-PC) is a photosynthetic pigment from green-blue cyanobacterium and the most abundant phycobiliprotein in the Spirulina genus with various pharmacological properties attributed due to its antioxidant capacity but has no specific cellular target. This has made it a molecule of great interest in biomedical research. This review focuses on the pharmacological effects and the benefits on metabolic syndrome and oxidative stress of C-PC.
... In the α subunit, the PCBs are located at Cys-84, while in the β subunit, the PCB is positioned between Cys-84 and Cys-155 [1][2][3]. Several studies have reported the bioactive properties of CPC, including antioxidant, anti-inflammatory, anticancer, cytoprotective, antihypertensive, and immunomodulatory activities, and potential modulation of intestinal microbiota, promoting gut health [4][5][6][7]. ...
C-phycocyanin (CPC) is an antioxidant protein that, when purified, is photosensitive and can be affected by environmental and gastrointestinal conditions. This can impact its biological activity, requiring an increase in the effective amount to achieve a therapeutic effect. Therefore, the aim of this study was to develop a microencapsulate of a complex matrix, as a strategy to protect and establish a matrix for the controlled release of CPC based on polysaccharides such as agavins (AGV) using ionic gelation. Four matrices were formulated: M1 (alginate: ALG), M2 (ALG and AGV), M3 (ALG, AGV, and κ-carrageenan: CGN), and M4 (ALG, AGV, CGN, and carboxymethylcellulose: CMC) with increasing concentrations of CPC. The retention and diffusion capacities of C-phycocyanin provided by each matrix were evaluated, as well as their stability under simulated gastrointestinal conditions. The results showed that the encapsulation efficiency of the matrix-type encapsulates with complex composites increased as more components were added to the mixtures. CMC increased the retention due to the hydrophobicity that it provides by being in the polysaccharide matrix; CGN enabled the controlled diffusive release; and AGV provided protection of the CPC beads under simulated gastrointestinal conditions. Therefore, matrix M4 exhibited an encapsulation efficiency for CPC of 98% and a bioaccessibility of 10.65 ± 0.65% after the passage of encapsulates through in vitro digestion.
... These deformities of the kidney are more or less similar to other published reports (Espinosa et al., 2017;Hamed et al., 2021;Zhu et al., 2020). Additionally, these alterations might have happened due to immune responses of kidneys due to MP associated chemical toxicity effects and sharp edges of fragments, increased blood pressure exerting mechanical pressure on glomerular walls, which might cause injury (Ichimura et al., 2013;Hamed et al., 2021). The intestine of fish is essential for immunity, endocrine regulating digestion and metabolism, water and electrolyte balance, and feed digestion and absorption (Le et al., 2019;Schirinzi et al., 2020). ...
Fish inhabiting various trophic levels are affected differently as the presence of microplastic (MP) in the water column and their ingestion by fish varies. Walking catfish (Clarias batrachus) inhabits the bottom of the water bodies. To understand the effects of MP, we exposed C. batrachus to two types of MP - polyethylene terephthalate (PET) and low-density polyethylene (LDPE) for 60 days. After exposure, hematological indices, mainly red blood cells and hemoglobin levels decreased, and white blood cells increased significantly compared to the control group (p<0.05). A significant increase in the levels of blood urea and glucose was observed, and serum glutamic pyruvate transaminase and serum glutamyl oxaloacetic transaminase activity remained elevated (p<0.05). Histopathological examination of the liver, kidney, intestine, and gills showed morphological alterations. Moreover, MP exposure caused growth retardation (p<0.05) in C. batrachus. Widespread pollution of water bodies by MP may impose serious ecological risks to bottom-feeding fish in Bangladesh.
... Local NO production by the vascular endothelium improves the flow-mediated dilation (FMD) that affects arterial function by decreasing peripheral vascular resistance, thus impacting general vascular health [44]. Chlorella supplementation increases NO production [45] and the expression of endothelial nitric oxide synthase (eNOS) in men, thereby augmenting blood flow to muscles [46], which could eventually enhance performance. The vasodilatation induced by NO would lead to greater muscle perfusion and O 2 delivery, theoretically speeding up VO 2 kinetics and improving muscle performance and recovery [47]. ...
Chlorella is a marine microalga rich in proteins and containing all the essential amino acids. Chlorella also contains fiber and other polysaccharides, as well as polyunsaturated fatty acids such as linoleic acid and alpha-linolenic acid. The proportion of the different macronutrients in Chlorella can be modulated by altering the conditions in which it is cultured. The bioactivities of these macronutrients make Chlorella a good candidate food to include in regular diets or as the basis of dietary supplements in exercise-related nutrition both for recreational exercisers and professional athletes. This paper reviews current knowledge of the effects of the macronutrients in Chlorella on physical exercise, specifically their impact on performance and recovery. In general, consuming Chlorella improves both anaerobic and aerobic exercise performance as well as physical stamina and reduces fatigue. These effects seem to be related to the antioxidant, anti-inflammatory, and metabolic activity of all its macronutrients, while each component of Chlorella contributes its bioactivity via a specific action. Chlorella is an excellent dietary source of high-quality protein in the context of physical exercise, as dietary proteins increase satiety, activation of the anabolic mTOR (mammalian Target of Rapamycin) pathway in skeletal muscle, and the thermic effects of meals. Chlorella proteins also increase intramuscular free amino acid levels and enhance the ability of the muscles to utilize them during exercise. Fiber from Chlorella increases the diversity of the gut microbiota, which helps control body weight and maintain intestinal barrier integrity, and the production of short-chain fatty acids (SCFAs), which improve physical performance. Polyunsaturated fatty acids (PUFAs) from Chlorella contribute to endothelial protection and modulate the fluidity and rigidity of cell membranes, which may improve performance. Ultimately, in contrast to several other nutritional sources, the use of Chlorella to provide high-quality protein, dietary fiber, and bioactive fatty acids may also significantly contribute to a sustainable world through the fixation of carbon dioxide and a reduction of the amount of land used to produce animal feed.
... In such a case, they may cause blood artery obstruction and loading of red blood cells (RBCs) with plastic particles at a high ratio of 10:50, revealing RBC damage caused by mechanical, osmotic, and oxidative stresses [67]. Furthermore, DEHP elevates blood pressure in humans by raising angiotensin II levels [69]; thus, deducing that an increase in blood pressure causes mechanical stress on the glomerular walls, which can lead to damage, is plausible [70]. In addition, medical research on rats and humans has revealed that polyvinyl chloride [8] and PS [71] MPs smaller than 150 µm may quickly diffuse from the GI cavity to the lymph and circulatory systems [72]. ...
In the last few decades, microplastics (MPs) have been among the emerging environmental pollutants that have received serious attention from scientists and the general population due to their wide range of potentially harmful effects on living organisms. MPs may originate from primary sources (micro-sized plastics manufactured on purpose) and secondary sources (breakdown of large plastic items through physical, chemical, and biological processes). Consequently, serious concerns are escalating because MPs can be easily disseminated and contaminate environments, including terrestrial, air, groundwater, marine, and freshwater systems. Furthermore, an exposure to even low doses of MPs during the early developmental stage may induce long-term health effects, even later in life. Accordingly, this study aims to gather the current evidence regarding the effects of MPs exposure on vital body systems, including the digestive, reproductive, central nervous, immune, and circulatory systems, during the early developmental stage. In addition, this study provides essential information about the possible emergence of various diseases later in life (i.e., adulthood).
... Previous reports have documented MPinduced expansion and congestion of glomerular capillaries, increased glomerular size, glomerular atrophy, vacuolation of glomerular cells, expansion of Bowman's spaces, inflammatory cell infiltration, shrinkage and convolution of tubules, widening of intertubular spaces, and signs of fatty tubules among other pathogenic changes (Espinosa et al. 2017;González-Doncel et al. 2022;Hamed et al. 2022a;Hodkovicova et al. 2021;Meng et al 2022;Zhu et al. 2020). These changes may stem from increased intrarenal pressure associated with MP-induced congestion and concomitant mechanical stress on glomerular, capillary, and tubular walls (Ichimura et al. 2013), from cellular oxidative stress, or from both pathomechanisms. ...
Microplastic particles (MPs) are a common environmental pollutant easily ingested by fish in aquaculture. The current study evaluated the protective efficacies of some antioxidant e.g. lycopene, citric acid, and chlorella against the toxic effects of MPs ingestion by Clarias gariepinus using histopathological biomarkers. Five experimental groups were established, a control group receiving only a standard diet, a group exposed to 500 mg/kg MPs concomitant with the standard diet, and three antioxidant groups exposed to MPs plus either lycopene (500 mg/kg), citric acid (30 g/kg), or chlorella (50 g/kg)in the standard diet. After 15 days, fish were sacrificed for histological and histochemical examinations. Histological analysis of the kidney for group 2( fed 500 mg/kg MPs alone) revealed distributed tissue dissociation, regional glomerular hypertrophy or shrinkage, melanomacrophage accumulation, and expansion of Bowman’s space, while liver tissue exhibited dilation and rupture of the central vein wall, hemorrhage, cytoplasmic vacuolation, and cellular necrosis orapoptosis. Fish exposed to MPs also exhibited connective tissue fiber accumulation around renal blood vessels, renal tubules, the central hepatic vein, hepatic blood sinusoids, and serosal, muscle, and submucosal layers of the intestine. In addition, MPs exposure reduced carbohydrate(mainly glycogen) contents in the brush borders and basement membranes of renal tubules, glomeruli, and intestinal tissues as well as in the cytoplasm of hepatocytes.These signs of renal, hepatic, and intestinal histopathology were fully or partially reversed by dietary lycopene, chlorella, or citric acid. Enhancing dietary antioxidants is an effective strategy for preventing MPs toxicity in Clarias gariepinus in aquaculture.
... Arthrospira platensis (commonly known as spirulina) is a well-known cyanobacterium of increasing interest mainly for its high protein content (up to 70% of the cell mass) (Lupatini, Colla, Canan, & Colla, 2017), polysaturated fatty acids (Ljubic, Safafar, Holdt, & Jacobsen, 2018), chlorophylls and other antioxidant pigments (da Rosa, Moraes, Cardias, & Costa, 2015;Ljubic et al., 2018). Spirulina synthesizes C-phycocyanin (C-pc), a water-soluble blue pigment-protein complex, that has been studied and positively characterized for its antioxidant (Zepka, Jacob-Lopes, & Roca, 2019), anti-inflammatory , hepatoprotective (Ichimura et al., 2013) and anticarcinogenic properties (Pattarayan, Rajarajan, Sivanantham, Palanichamy, & Rajasekaran, 2017;Romay, Gonzalez, Ledon, Remirez, & Rimbau, 2003). However, since C-pc is an intracellular biomolecule an extraction step is necessary to obtain it. ...
The application of high-pressure technology (100–600 MPa, 20 °C for up to 20 min) for cell disruption and consequent extraction of proteins -including C-phycocyanin- from the cyanobacteria Arthrospira platensis (spirulina), was investigated. Wet spirulina biomass was suspended in three different aqueous systems (deionized water, phosphate buffer, 10% sodium chloride solution). During a-24 h post processing storage period at 20 °C, the concentration of total soluble proteins and C-phycocyanin content and purity were measured. Color-spectrum and chroma analyses were also performed. The use of deionized water and phosphate buffer as processing/extraction media favoured the extraction process compared to the NaCl solution. Proteins extraction was significantly assisted by pressure. Equal/higher intensity than 400 MPa led to lower C-phycocyanin extraction yields, probably due to denaturation of proteins. HP conditions at 300 MPa for 10 min -using deionized water or phosphate buffer as medium- were selected as optimum, leading to higher extraction yields and purity extracts within ~2 h after processing.
... This study demonstrated that CPC has a nutraceutical effect on the kidney, preventing renal fibrosis in the remanent kidney, SAH, and cardiovascular complications [12]. Although the antihypertensive effect of CPC was previously reported [5,24], this study proposed that pharmacological nutraceutical mechanisms are associated with the effect of CPC on vascular endothelium. CPC prevented endothelium dysfunction by reducing CKD-caused oxidative stress and NO production disturbance. ...
C-phycocyanin (CPC) is an antihypertensive that is not still wholly pharmacologically described. The aim of this study was to evaluate whether CPC counteracts endothelial dysfunction as an antihypertensive mechanism in rats with 5/6 nephrectomy (NFx) as a chronic kidney disease (CKD) model. Twenty-four male Wistar rats were divided into four groups: sham control, sham-treated with CPC (100 mg/Kg/d), NFx, and NFx treated with CPC. Blood pressure was measured each week, and renal function evaluated at the end of the treatment. Afterward, animals were euthanized, and their thoracic aortas were analyzed for endothelium functional test, oxidative stress, and NO production. 5/6 Nephrectomy caused hypertension increasing lipid peroxidation and ROS production, overexpression of inducible nitric oxide synthase (iNOS), reduction in the first-line antioxidant enzymes activities, and reduced-glutathione (GSH) with a down-expression of eNOS. The vasomotor response reduced endothelium-dependent vasodilation in aorta segments exposed to acetylcholine and sodium nitroprusside. However, the treatment with CPC prevented hypertension by reducing oxidative stress, NO system disturbance, and endothelial dysfunction. The CPC treatment did not prevent CKD-caused disturbance in the antioxidant enzymes activities. Therefore, CPC exhibited an antihypertensive activity while avoiding endothelial dysfunction.
... Phycocyanin contributes to lowering BP by increasing the expression of endothelial nitric oxide synthase [23]. Substances, such as the tripeptide Ile-Gln-Pro (IQP) present in Spirulina, also showed antihypertensive activity by inhibiting angiotensin-converting enzymes [24]. ...
The nutritional and health benefits of Spirulina have been known for thousands of years. Spirulina has been grown and harvested by ancient cultures since written history, and likely before. Much anecdotal evidence has been put forth, and more recently, evidence-based scientific research confirms many of Spriluina's nutritional and health benefits. However, such benefits are far-reaching (and only recently researched). In the commercial exuberance surrounding Spirulina, sparse research regarding any potential toxicity or adverse effects has been undertaken. This review-as a miscellany-highlights notable benefits, potential toxicity, and adverse effects in the human consumption of Spirulina. It is hoped that this review will provide the reader, especially those new to Spirulina, with an introduction and overview regarding the benefits and detriments of Spirulina, which will act as a springboard to more in-depth research regarding Spirulina as a vital nutritional and medicinal source for humans-needed now more than ever.
... There is also growing evidence that both spirulina and chlorella can induce vasodilatory effects. Spirulina may augment circulatory nitrate/nitrite whereby the phycocyanin constituent reportedly increases nitric oxide (NO) availability in the aorta and plasma in rats, including the increase in the expression of endothelial nitric oxide synthase (eNOS) (38,39). Reviewing the ergogenic effects of nitrate on exercise performance are beyond the scope of this study but can be found elsewhere (40). ...
Nutritional clinical trials have reported algae such as spirulina and chlorella to have the capability to improve cardiovascular risk factors, anemia, immune function, and arterial stiffness. With positive results being reported in clinical trials, researchers are investigating the potential for algae as an ergogenic aid for athletes. Initial studies found spirulina and chlorella supplementation to increase peak oxygen uptake and time to exhaustion, with the mechanistic focus on the antioxidant capabilities of both algae. However, a number of oxidative stress biomarkers reported in these studies are now considered to lack robustness and have consequently provided equivocal results. Considering the nutrient complexity and density of these commonly found edible algae, there is a need for research to widen the scope of investigation. Most recently algae supplementation has demonstrated ergogenic potential during submaximal and repeated sprint cycling, yet a confirmed primary mechanism behind these improvements is still unclear. In this paper we discuss current algae supplementation studies and purported effects on performance, critically examine the antioxidant and ergogenic differing perspectives, and outline future directions.
... Ichimura et al. indicated that long-term administration of phycocyanin would improve systemic blood pressure by boosting aortic eNOS expression stimulated by adiponectin. Phycocyanin is beneficial in the prevention of metabolic syndrome-related endothelial dysfunction diseases [30]. ...
Oxy+ is a natural source of arthrospira found in nature, used as a dietary supplement and manufactured in Aruba for lifefactors. Arthrospira contains good quality of proteins, sulfated polysaccharides, γ-linoleic acid, along with an array of carotene and phytopigments, vitamins, and minerals which are reported to be antioxidant, immunomodulator, antihyperglycemic, antidyslipidemic, cardioprotective, hepatoprotective, antiviral, anticancerous, antihypertensive, anti-inflammatory, analgesic, neuroprotective and renoprotective activities. Several studies have shown arthrospira, and active ingredients of it revealed various pharmacological activities. It can be used for the management of various ailments such as diabetes, dyslipidemia, obesity, hypertension, cancer, arthritis, osteoarthritis, autoimmune disorders, etc. This review attempts to explore the hidden benefits of Oxy+ (arthrospira).
... Under specific pathogen-free conditions, 6-week-old male TSNO and TSOD mice (Institute for Animal Reproduction) were fed iHFC diet #5, which is high in fat, cholesterol, and cholate (Hayashi Kasei, Osaka, Japan), or a normal (NM) diet (MF, Oriental Yeast, Tokyo, Japan). The MF diet is formulated to promote adequate growth of rats, according to the manufacturer's information and proximate analyses described previously (Ichimura et al. 2013). All mice had free access to food and water throughout the study. ...
Nonalcoholic steatohepatitis (NASH) progresses to liver fibrosis and cirrhosis. Existing mouse models of NASH rarely develop diet-induced severe fibrosis. We aimed to establish a dietary model of NASH with rapid progression to fibrosis. Six-week-old male Tsumura-Suzuki obese diabetes (TSOD) mice (a model of spontaneous metabolic syndrome) and corresponding control Tsumura-Suzuki nonobese (TSNO) mice were fed a novel diet high in fat, cholesterol, and cholate (iHFC). Histologic steatohepatitis, including steatosis, inflammation, and fibrosis, were observed in both TSNO and TSOD iHFC diet–fed mice at 20 weeks of age. As compared with TSOD mice, TSNO mice developed much more severe fibrosis and reached stage 3 of bridging fibrosis within 14 weeks under the iHFC diet feeding. Perivenular/perisinusoidal pattern of fibrosis in TSNO mice resembled human NASH. Our model of NASH with advanced fibrosis by simple diet offers many advantages useful in studying the mechanism of liver fibrosis and preclinical drug testing.
... Moreover, in humans, it has been reported that diethylhexyl phthalate (DEHP) can increase blood pressure partially by increasing angiotensin II levels (Mariana et al., 2016). It is reasonable to conclude that an increase in blood pressure exerts mechanical stress on glomerular walls, which may result in injury (Ichimura et al., 2013). ...
Although microplastics (MPs) have received increasing focus and currently have become an emerging area of research, there is limited knowledge about their effect on whole body histology of fish. In this study, tilapia (Oreochromis niloticus) early juveniles were exposed to 1, 10, or 100 mg/L of MPs for 15 days and 15 days post-exposure, after which whole body histological examinations were performed. Histological analysis of kidney revealed congestion of blood capillaries, inflammatory cells, loss of basophilic cytoplasm in several tubules, vacuolated tubules, shrinking of convoluted tubules, widening of intertubular space, complete deformation, glomerular atrophy, vacuolated glomerular cells, and signs of fatty tubules. The liver tissue exhibited vacuoles, hydropic degeneration, necrotic area, severe deformation of hepatocytes, pyknotic nuclei, and dilation and congestion of blood sinusoids. The pancreatic tissue revealed shrunken and degenerated acini with pyknotic nuclei, hemorrhage, necrotic area, inflammatory cells, fatty cells, and congested blood capillaries. In the muscle tissue, fiber core dissociation, edema, necrosis, segmented fibers, and inflammatory cells were detected. The gill tissue demonstrated dilation and congestion of blood vessels, complete lamellar fusions, lifting of epithelium, shortening and degeneration of secondary lamellae, hyperplasia, and deposition of MPs between primary lamellae. In the spinal cord and notochord, the effects were degeneration and protrusion of meninges, deformation and deviation of notochord from its central axis, edema, degeneration of notochord (disappearance of vacuolar cells), deviation of spinal cord from the central axis, and loss of vacuolar cells in notochord. The intestinal tissue exhibited degeneration of basement membrane, inflammatory cells, goblet cells, atrophy of submucosa, pyknotic nuclei, hemorrhage, and vacuolization of mucosal cells. The histopathological changes in different organs were noticed even post-exposure in fish exposed to MPs compared to those in control fish and these changes were concentration dependent. In conclusion, these data together with our previous data suggest that MPs can cause different changes, ranging from biochemical alterations in single cells to lesions in the entire tissue, which can affect the vitality and life of fish.
... Phycocyanin is also a powerful agent for the immune system in human and animals, and provides protection from a number of diseases [58]. Phycocyanin has proven for strong antioxidant, immunomodulatory, antidiabetic, anticancer, neuroprotective, hepatoprotective, hypolipidemic, antiobesity, antianemic, antibacterial, antiinflammatory, antifungal activities, antihypertensive, etc. [59,60]. ...
Oxy+ is a natural source of arthrospira found in nature, used as a dietary supplement and manufactured in Aruba for lifefactors. Arthrospira contains good quality of proteins, sulfated polysaccharides, γ-linoleic acid, along with an array of carotene and phytopigments, vitamins, and minerals which are reported to be antioxidant, immunomodulator, antihyperglycemic, antidyslipidemic, cardioprotective, hepatoprotective, antiviral, anticancerous, antihypertensive, anti-inflammatory, analgesic, neuroprotective and renoprotective activities. Several studies have shown arthrospira, and active ingredients of it revealed various pharmacological activities. It can be used for the management of various ailments such as diabetes, dyslipidemia, obesity, hypertension, cancer, arthritis, osteoarthritis, autoimmune disorders, etc. This review attempts to explore the hidden benefits of Oxy+ (arthrospira).
... The use of SP has been found to reduce high serum lipids 5 and decrease high blood pressure. 5,6 Moreover, it demonstrated neuroprotective and reactive oxygen species (ROS) scavenging actions observed in various experimental studies. 7,8 A biliprotein, C-phycocyanin, extracted from SP, had anti-inflammatory activity. ...
Introduction
Diabetic neuropathy is a common consequence of diabetes. Hyperalgesia is one of the main symptoms of diabetic neuropathy. In response to noxious stimuli, streptozotocin (STZ)-induced diabetic rats show exaggerated hyperalgesic behavior, while Spirulina platensis has anti-inflammatory, antioxidant, and insulin-like effects. To assess the antinociceptive effect of oral Spirulina platensis (SP) powder on formalin-induced nociceptive responses in STZ-induced diabetic rats.
Methods
Sixty mature male albino rats were randomly allocated into six equal groups (10 in each group). Group 1 (control non-diabetic group) received 0.9% saline; group 2 was given oral pure SP powder-treated as a non-diabetic control group, group 3 was sodium salicylate-treated rats and used as a positive non-diabetic control group, group 4 managed as vehicle-treated diabetic rats, group 5 considered as SP-treated-diabetic group, and sodium salicylate-treated-diabetic rats used as a diabetic positive control group (group 6). STZ-diabetic rats were orally given SP in a dose of 500 mg kg/day for 1 month. The formalin test was implemented in two phases: the early phase in the first 10-min post-formalin injection, and the late phase was considered in the 15–60 min post-formalin injection time interval.
Results
Pain scores were increased in the diabetic groups during both phases of the experiment. Blood glucose was significantly reduced in diabetic rats that received oral SP, P < 0.01. Besides, SP-treated rats had lower pain scores during both phases of the experiment than untreated diabetic ones. However, in the sodium salicylate group, the pain score was reduced only during the second phase. An exaggerated nociceptive response occurred in diabetic rats after the formalin test. A significant antinociceptive effect appeared in SP-treated control and diabetic rats.
Discussion
The findings suggest that oral Spirulina platensis could have a potential therapeutic role for managing induced painful diabetic neuropathy in rats.
... Arginine is an essential amino acid associated with augmenting the bioavailability of Nitric Oxide (NO), a well-established signaling molecule associated with endothelium vasodilation (Hishkawa et al. 1992). Similarly, the phycocyanin constituent of SP has previously been reported to increase the expression of Endothelial Nitric Oxide Synthase (eNOS) in rats (Ichimura et al. 2013). This localized vasodilation from NO increases blood flow which may improve peripheral oxygen offload to working muscles and efflux of deleterious byproducts. ...
Purpose:
Spirulina has previously been reported to improve high-intensity exercise performance and hemoglobin. However, spirulina's effect on arm cycling exercise has yet to be investigated. The purpose of this study was to investigate the responses of spirulina supplementation on hemoglobin and on oxygen uptake, RER and HR during seated arm cycling exercise.
Methods:
In a double-blinded randomized crossover design, eleven males untrained in arm cycling ingested 6 g/day of spirulina or placebo for seven days. Seated on the Arm Crank Ergometer, each participant performed a baseline V̇O2max test, and then after supplementation, 2 × 30-min submaximal exercise bouts corresponding to 55% of their V̇O2max, followed by an incremental test to fatigue. A seven-day wash-out period was required between conditions. Oxygen uptake, RER and HR were measured continuously during exercise and hemoglobin measured prior to exercise after both conditions.
Results:
Spirulina significantly (p < 0.05) increased Hb in comparison to Placebo (144.1 g/l ± 10.5 Vs 154.5 g/l ± 6.9). After spirulina supplementation, during the 30-min exercise bouts, oxygen uptake and HR were significantly lower (2170 ml/min ± 173 Vs 2311 ml/min ± 189 and 154 bpm ± 14 Vs 149 bpm ± 17), RER was not significantly different. In comparison to placebo, Spirulina significantly increased oxygen uptake at time of fatigue (34.10 ml/min/kg ± 6.03 Vs 37.37 ml/min/kg ± 5.98). Time taken to fatigue was not different.
Conclusion:
Spirulina supplementation significantly reduces oxygen uptake and HR during arm cycling submaximal exercise, allowing for an increased oxygen uptake during an incremental test to fatigue.
... However, phycobiliproteins are more than just a coloured molecule and have been associated with several potential positive health outcomes including antihypertensive effects. Ichimura et al. (2013) suggested that long-term administration of phycocyanin may ameliorate systemic blood pressure by enhancing nitric oxide synthase expression levels in aorta that is simulated by adiponectin and also prevent endothelial dysfunction-related diseases. That study was conducted using spontaneously hypertensive rats that were fed a normal diet with phycocyanin at a dosage of 2500, 5000, or 10,000 mg/kg diet for 26 weeks. ...
Humans are no strangers to the consumption of Spirulina as already in the sixteenth century Spirulina was harvested from Lake Texcoco and consumed in markets in Tenochtitlan (today Mexico City). Nowadays, microalgae are being incorporated into many food formulations. Most of these use microalgae as a marketing strategy or as a colouring agent. However, Spirulina (and compounds derived thereof) show potential for being used as ingredients in the development of novel foods, which are one of the top trends in the food industry. Several human intervention studies demonstrated the potential of Spirulina for being used in the prevention or treatment of disorders related to metabolic syndrome. The aim of the current paper was to review current and potential applications of this microalga in the food and functional food industries. Health benefits associated with consuming Spirulina and/or some of the most important compounds derived from Spirulina were also discussed.
... In addition, these data reinforced the importance of the endothelium in the effects observed with S. platensis and showed that these responses in smooth muscle were modulated by an increase in the bioavailability of NO. In view of these results, we can hypothesize that the constituents present in S. platensis, such as phycocyanin, can chronically increase the expression of endothelial nitric oxide synthase and consequently promote greater bioavailability of nitric oxide [47]. ...
The possible mechanism is involved in the effects of Spirulina platensis on vascular reactivity. Animals were divided into sedentary group (SG) and sedentary groups supplemented with S. platensis at doses of 50 (SG50), 150 (SG150), and 500 mg/kg (SG500). To evaluate reactivity, cumulative concentration-response curves were constructed for phenylephrine and acetylcholine. To evaluate the involvement of the nitric oxide (NO) pathway, aorta tissue was preincubated with L-NAME and a new curve was then obtained for phenylephrine. Biochemical analyses were performed to evaluate nitrite levels, lipid peroxidation, and antioxidant activity. To contractile reactivity, only SG500 ( pD2=5.6±0.04 vs. 6.1±0.06 , 6.2±0.02 , and 6.2±0.04 ) showed reduction in phenylephrine contractile potency. L-NAME caused a higher contractile response to phenylephrine in SG150 and SG500. To relaxation, curves for SG150 ( pD2=7.0±0.08 vs. 6.4±0.06 ) and SG500 ( pD2=7.3±0.02 vs. 6.4±0.06 ) were shifted to the left, more so in SG500. Nitrite was increased in SG150 and SG500. Lipid peroxidation was reduced, and oxidation inhibition was increased in all supplemented groups, indicating enhanced antioxidant activity. Chronic supplementation with S. platensis (150/500 mg/kg) caused a decrease in contractile response and increase in relaxation and nitrite levels, indicating greater NO production, due to decreased oxidative stress and increased antioxidant activity.
... In addition, it was suggested that long-term administration of phycocyanin may ameliorate the systemic blood pressure by enhancing eNOS expression in the aorta that is stimulated by adiponectin. Phycocyanin may be beneficial for preventing endothelial dysfunction-related diseases in metabolic syndrome [32]. ...
Background
Atherosclerosis (AS) is the main pathogeny of coronary heart disease, cerebral infarction and peripheral vascular disease. Endothelial dysfunction is one of the important pathogenesis of AS. As an important endothelium-derived relaxation factor, nitric oxide (NO) plays a role in cardiovascular protection and anti-AS function; but in the pathological state, endothelial nitric oxide synthase (eNOS) disorder causes an abnormal production of NO, which may damage endothelial function and trigger AS. This review summarized the research progresses in the treatment strategies for AS based on correcting the disordered eNOS/ NO signaling pathway.
Main body
According to the topic, select the search terms ‘atherosclerosis,’ ‘nitric oxide,’ ‘eNOS,’ ‘treatment,’ ‘management,’ ‘medication,’ ‘maintenance,’ ‘remission’. Using these terms, a structured literature search via multiple electronic databases was performed for the most recent trial evidence in recent years. We read and analyze these literatures carefully, classified these literatures according to their content, and then summarized and outlined the common main points in these classified literatures. Finally, literature data were organized to discuss these main points logically. We found that both aberrant expression and dysfunction of eNOS are closely related to AS development, and some new treatment strategies aimed at eNOS have been proposed, including upregulation of eNOS expression and inhibition of eNOS uncoupling. The former one is mainly related to inflammatory inhibition and protection of the PKB-eNOS signaling pathway; whereas the latter one is associated with the addition of the L-arginine substrate of eNOS, arginase inhibition, and the supplement of tetrahydrobiopterin, which can elevate no level.
Conclusions
eNOS can be an important target for prevention and treatment of AS, and eNOS drugs may be another potent class of effective therapeutic treatment for AS following traditional lipid-lowering, anti-platelet, vasodilator drugs. But applying these experimental results to clinic treatment still requires further studies and development of biotechnology.
... The anti-hypertensive effect of SM in the present study would be explained by its content of C-phycocyanin and by the formation of anti-hypertensive peptides. Phycocyanin is a pigment that induces decreases in blood pressure values through increasing the expression of endothelial nitric oxide synthase [33]. The anti-hypertensive activity substances such as the tripeptide Ile-Gln-Pro (IQP), with the capacity to inhibit the angiotensin-converting enzyme, has been reported [34,35]. ...
(1) Background: Spirulina (Arthrospira) maxima has shown beneficial effects such as being anti-dyslipidemic, antiviral, antioxidant and antihypertensive. However, there are few and limited clinical studies. (2) Methods: a prospective, randomized, parallel pilot study of 4.5 g administration of Spirulina maxima or placebo for 12 weeks in 16 patients with systemic arterial hypertension (SAH) undergoing treatment with angiotensin-converting enzyme (ACE) inhibitors was performed to assess the effects on endothelial damage and oxidative stress indicators. The blood levels of sICAM-1, sVCAM-1, endothelin-1, and sE-selectin were quantified; the activities of catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase and concentrations of reduced glutathione, oxidized glutathione, and thiobarbituric acid reactive substances, were also quantified before and after the treatment period. (3) Results: There were statistically significant (p < 0.05) decreases in systolic blood pressure, sVCAM-1, sE-selectin and endothelin-1 levels, and increases in glutathione peroxidase activity and oxidized glutathione levels. (4) Conclusion: The effects found in the present study agree with antihypertensive and antioxidant effects previously reported for Spirulina maxima. However, this is the first report about the effects on indicators of endothelial damage. More research in this field is necessary to gain an insight into the effects of Spirulina on these indicators.
... The anti-hypertensive effect of SM in the present study would be explained by its content of C-phycocyanin and by the formation of anti-hypertensive peptides. Phycocyanin is a pigment that induces decreases in blood pressure values through increasing the expression of endothelial nitric oxide synthase [33]. The anti-hypertensive activity substances such as the tripeptide Ile-Gln-Pro (IQP), with the capacity to inhibit the angiotensin-converting enzyme, has been reported [34,35]. ...
1) Background: Spirulina (Arthrospira) maxima has shown beneficial effects such anti-dyslipidemic, antiviral, antioxidant and antihypertensive. However, there are few and limited clinical studies. 2) Methods: a prospective, randomized, parallel pilot study of 4.5 g administration of Spirulina maxima or placebo for 12 weeks in 16 patients with systemic arterial hypertension undergoing treatment with ACE inhibitors was performed to assess the effects on endothelial damage and oxidative stress indicators. The blood levels of sICAM-1, sVCAM-1, endothelin-1, and sE-selectin were quantified; the activities of catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase and concentrations of reduced glutathione, oxidized glutathione, and thiobarbituric acid reactive susbtances, were also quantified before and after the treatment period. 3) Results: There were statistically significant (p < 0.05) decreases in systolic blood pressure, sVCAM-1, sE-selectin and endothelin-1 levels, and increases in glutathione peroxidase activity and oxidized glutathione levels. 4) Conclusion: The effects found in the present study agree with antihypertensive and antioxidant effects previously reported for Spirulina maxima. However, this is the first report about the effects on indicators of endothelial damage. More research in this field is necessary to gain an insight into the effects of Spirulina on these indicators.
... The constituents present in S. platensis, such as phycocyanin, can chronically increase the expression of endothelial NOS and consequently promote a greater bioavailability of NO (Ichimura et al., 2013). In previous studies consisted of strength training protocols, two confirmed that the improvement in relaxing effect occurred by mechanisms dependent on endothelium via increased production of NO, a relaxant factor derived from endothelium (Figard et al., 2006) and the increased of Hsp90 expression, a regulator of eNOS activity and binding (Harris et al., 2010). ...
Studies have shown that supplementation with Spirulina platensis improves vascular reactivity. However, it is unclear whether in association with strength training this effect can be enhanced. Thus, this study aimed to determine the effects of strength training and S. platensis on the reactivity of the aorta from Wistar rat and the possible mechanisms involved. The animals were supplemented with S. platensis and divided into sedentary (SG, SG50, SG150, and SG500) and trained groups (TG, TG50, TG150, and TG500). Nitrite, malondialdehyde (MDA) and antioxidant activity were determined by biochemical assays. To evaluate vascular response, cumulative concentration—response curves to phenylephrine (PHE) and acetylcholine (ACh) were constructed. L-NAME was used to assess the participation of nitric oxide (NO). It was observed that the PHE contractile potency was reduced in TG50, TG150, and TG500 groups compared to SG50, SG150, and SG500 groups, respectively. However, the presence of L-NAME increased the contractile response in all groups. Strength training potentiated the increase in relaxing activity induced by S. platensis, where the pCE50 values of ACh increased in TG150 and TG500. These responses were accompanied by increased nitrite production, MDA reduction and increased antioxidant activity in the aorta of both TG150 and TG500 groups. Thus, the present study demonstrated that combined with strength training, S. platensis potentiates vascular improvement through the participation of NO and reduction of oxidative stress.
... Consistent with this prediction, adipocyte-specific overexpression of HO-1, systemic induction HO-1, and oral administration of phycocyanin or whole spirulina have all been shown to promote proper adipocyte function and mitigate induction of metabolic syndrome in rodents fed high-fat or fructose-rich diets. [70][71][72][73][74][75] Additionally, treatment with the broad-spectrum NADPH oxidase inhibitor apocynin attenuated development of metabolic syndrome in KKAy diabetes-prone mice. Oral administration of phycocyanin has a similar impact in these mice. ...
Arthrospira platensis, also known as spirulina, is currently one of the most well-known algae supplements, mainly due to its high content of bioactive compounds that may promote human health. Some authors have hypothesized that spirulina consumption could protect subjects from exercise-induced oxidative stress, accelerate recovery by reducing muscle damage, and stimulate the immune system. Based on this, the main goal of this review was to critically analyze the effects of spirulina on oxidative stress, immune system, inflammation and performance in athletes and people undergoing exercise interventions. Of the 981 articles found, 428 studies were considered eligible and 13 met the established criteria and were included in this systematic review. Most recently spirulina supplementation has demonstrated ergogenic potential during submaximal exercise, increasing oxygen uptake and improving exercise tolerance. Nevertheless, spirulina supplementation does not seem to enhance physical performance in power athletes. Considering that data supporting benefits to the immune system from spirulina supplementation is still lacking, overall evidence regarding the benefit of spirulina supplementation in healthy people engaged in physical exercise is scarce and not consistent. Currently, spirulina supplementation might be considered in athletes who do not meet the recommended dietary intake of antioxidants. Further high-quality research is needed to evaluate the effects of spirulina consumption on performance, the immune system and recovery in athletes and active people.
Systematic review registration
[https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=262896], identifier [CRD42021262896].
The cyanobacterium Arthrospira platensis (AP) is a natural source of considerable amounts of ingredients that are relevant for nutra- and pharmaceutical uses. Beyond its nutritionally valuable components, such as carbohydrates, minerals, and proteins, bioactive ingredients extracted from AP have been studied for their therapeutical values.
Phycobiliproteins, fucoxanthin, and krill oil are natural marine products with excellent activities. In the study, we prepared the complex of phycobiliproteins, fucoxanthin, and krill oil (PFK) and assessed the anti-obesity, lipid-lowering, and antioxidant activities in high-fat diet rats. The results showed that the rats significantly and safely reduced body weight gain and regulated serum biochemical parameters at 50 mg/kg phycobiliproteins, 10 mg/kg fucoxanthin, and 100 mg/kg krill oil. Furthermore, the molecular mechanism study suggested that the complex of PFK confined the enzyme activities of lipid synthesis and enhanced antioxidant activity to improve obesity indirectly. The conclusions demonstrated that the complex of PFK has potent anti-obesity and hypolipidemic effects which have potential use as a natural and healthy food and medicine for anti-obesity and lowering blood lipids in the future.
Arthrospira platensis (AP) and some of its derived products have well-established biological activities as antioxidants or as agents to reduce cardiovascular disease risk factors. Furthermore, AP products have gained increasing importance as potential anti-cancer agents. However, the ingredients of the available products vary greatly with the origin, the type of production and processing, which could have significant consequences for their biological effects. Therefore, the composition and biological influence of five distinct AP powders, which were acquired commercially or produced at a public biotechnology institute, were investigated in regard to their endothelialization capacity using a cell impedance- (CI) based measurement method. The study revealed that the AP composition and especially the influence on HUVEC proliferation differed significantly between the five AP powders up to 109%. Thus, it could be shown that the method used allows the reliable detection of quantitative differences in biological effects of different AP preparations.
Although well documented drug therapies are available for the management of ventricular hypertrophy (VH) and heart failure (HF), most patients nonetheless experience a downhill course, and further therapeutic measures are needed. Nutraceutical, dietary, and lifestyle measures may have particular merit in this regard, as they are currently available, relatively safe and inexpensive, and can lend themselves to primary prevention as well. A consideration of the pathogenic mechanisms underlying the VH/HF syndrome suggests that measures which control oxidative and endoplasmic reticulum (ER) stress, that support effective nitric oxide and hydrogen sulfide bioactivity, that prevent a reduction in cardiomyocyte pH, and that boost the production of protective hormones, such as fibroblast growth factor 21 (FGF21), while suppressing fibroblast growth factor 23 (FGF23) and marinobufagenin, may have utility for preventing and controlling this syndrome. Agents considered in this essay include phycocyanobilin, N-acetylcysteine, lipoic acid, ferulic acid, zinc, selenium, ubiquinol, astaxanthin, melatonin, tauroursodeoxycholic acid, berberine, citrulline, high-dose folate, cocoa flavanols, hawthorn extract, dietary nitrate, high-dose biotin, soy isoflavones, taurine, carnitine, magnesium orotate, EPA-rich fish oil, glycine, and copper. The potential advantages of whole-food plant-based diets, moderation in salt intake, avoidance of phosphate additives, and regular exercise training and sauna sessions are also discussed. There should be considerable scope for the development of functional foods and supplements which make it more convenient and affordable for patients to consume complementary combinations of the agents discussed here. Research Strategy: Key word searching of PubMed was employed to locate the research papers whose findings are cited in this essay.
Within the last years a comprehensive number of scientific studies demonstrated beneficial effect of Arthropira platensis (AP) as dietary supplement due to a high content of proteins, minerals and vitamins. Positive effects like promoting the immune system, reducing inflammation and an anti-oxidant capacity are reported. In this study, the effect of an aqueous AP extract on primary human venous endothelial cells (HUVEC) was investigated. In addition, the effect of AP on HUVEC treated with a bacterial toxin (lipopolysaccharide, LPA), inducing an activation of HUVEC and cellular detachment, was analyzed. Depending on the concentration of AP extract a significantly accelerated formation of an endothelial cell monolayer was observed. Furthermore, the detachment of HUVEC after LPA addition was dramatically reduced by AP. In conclusion, the data are promising and indicatory for an application of Arthrospira platensis in the clinical field.
A pigment-protein highly dominant in Spirulina is known as C-Phycocyanin. Earlier, in vitro studies has shown that C-phycocyanin is having many biological activities like antioxidant and anti-inflammatory activities, antiplatelet, hepatoprotective, and cholesterol-lowering properties. Interestingly, there are scanty in vivo experimental findings on the immunomodulatory and antioxidant effects of C-phycocyanin. This work is aimed at in vivo evaluation of the effects of C-phycocyanin on immunomodulation and antioxidant potential in Balb/c mice. Our results of in vivo toxicity, immunomodulatory and antioxidant effects of C-Phycocyanin suggests that C-phycocyanin is very safe for consumption and having substantial antioxidant potential and also possess immunomodulatory activities in Balb/c mice in a dosage dependent manner. C-phycocyanin doesn’t cause acute and subacute toxicity in the animal model (Balb/c mice) studied. We have reported that C-phycocyanin exhibited in vivo immunomodulation performance in animal model.
El cáncer es una enfermedad compleja, heterogénea y dinámica, caracterizada por una mitosis descontrolada. Históricamente, se ha tratado con cirugía, radioterapia y quimioterapia, y en años más recientes mediante la inmunoterapia. Para ello, se han investigado distintas proteínas para la modulación de la respuesta inmune. Un grupo de estas son las C-ficocianinas, biliproteinas proveniente de microalgas verde azuladas como Spirulina platensis. El ambiente antiinflamatorio en personas sanas es una medida profiláctica para disminuir el riesgo de desarrollar un determinado tipo de cáncer. Su ingesta ha mostrado ese comportamiento, al suprimir la liberación de sustancias proinflamatorias. También se ha apreciado un efecto inmunomodulador al aumentar o disminuir la expresión de CD59, así como al ocasionar la proliferación de macrófagos y la liberación de sustancias inflamatorias. Esto último es un indicativo de que no se cuenta con información suficiente para corroborar su uso como opción profiláctica o terapéutica contra el cáncer. Por ello, es trascendental la información sobre sustancias naturales como esta, porque aunque se ven más atractivas para tratar esta enfermedad, no existen efectos terapéuticos totalmente comprobados.
C-phycocyanin (C-PC) is a kind of photosynthetically assisted pigment, which is ubiquitous in cyanobacteria cells. We investigated the effect of C-PC on non-alcoholic fatty liver disease (NAFLD) and its mechanism. Through oil red O staining, TC/TG detection, liver SOD/MDA detection and liver H&E staining, we found that C-PC could significantly reduce the lipid accumulation in the steatosis L02 cells and the liver of non-alcoholic steatohepatitis (NASH) mice, and improve the antioxidant capacity of liver. The results of Western Blotting showed that C-PC upregulated the expression of AMPK phosphorylation and downregulated SREBP-1c and its target genes ACC and FAS expression levels. Furthermore, C-PC also upregulated the expression of transcription factor PPARα, which was regulated by AMPK, and its target genes CPT1 level. In addition, C-PC could promote AMPK phosphorylation in hepatocytes while increasing the phosphorylation level of ACC in vivo and in vitro. Besides, C-PC could also improve the liver inflammatory infiltration by upregulated the expression of PPARγ and downregulated the expression of CD36, IL6 and TNFα. These results indicate that C-PC may improve hepatic lipid accumulation and inflammation in the non-alcoholic fatty liver mice by activating AMPK pathway of hepatocytes. The finding provides important help for the research and development of C-PC in the nutraceuticals and therapeutics of NAFLD.
The mechanisms underlying cancer cachexia - the proximate cause of at least 20% of cancer-related deaths - have until recently remained rather obscure. New research, however, clarifies that cancers evoking cachexia release microvesicles rich in heat shock proteins 70 and 90, and that these extracellular heat shock proteins induce cachexia by serving as agonists for toll-like receptor 4 (TLR4) in skeletal muscle, macrophages, and adipocytes. Hence, safe nutraceutical measures which can down-regulate TLR4 signaling can be expected to aid prevention and control of cancer cachexia. There is reason to suspect that phycocyanobilin, ferulic acid, glycine, long-chain omega-3s, green tea catechins, β-hydroxy-β-methylbutyrate, carnitine, and high-dose biotin may have some utility in this regard.
Aims:
Considering phycobiliproteins of Spirulina maxima has shown a wide margin of security in pregnant and non-pregnant animals as well as antioxidant properties, present study aimed to investigate if the cardiovascular and metabolic effects of an experimental model of preeclampsia can be prevented by the administration of this compound.
Main methods:
Subrenal aortic coarctation (SRAC) practiced to female Wistar rats of 8 weeks of age. Animals were divided randomly to conform non-pregnant and pregnant groups and pregnant with SRAC showed fetoplacental ischemia and were considered preeclamptic (PE). Groups were treated with saline solution (control group) or phycobiliproteins solution (100 mg/kg/day ig) for the last 7, 14 or 20 days of pregnancy.
Key findings:
PE animals showed increased systolic blood pressure, weight gain, glucose and GTT as well as vascular contractility. Also, PE animals showed decreased SOD, GPx activities while MDA was increased. Phycobiliproteins oral treatment for 3 weeks significantly decreased systolic blood pressure and reestablished glucose, weight gain and vascular contractility as well as enzyme activities of PE rats to those of normal pregnant animals.
Significance:
Our results show that phycobiliproteins can prevent the damage produced by fetoplacental ischemia and provides evidence of free radical species contribution to the physiopathology of the disease. Also, we conclude phycobiliproteins can be an alternative to reduce preeclampsia manifestations, however, more studies are recommended.
Metabolic syndrome (MetS) represents a combination of cardiometabolic risk factors, including visceral obesity, glucose intolerance or type 2 diabetes, elevated triglycerides, reduced HDL cholesterol, and hypertension. MetS is rapidly increasing in prevalence worldwide as a consequence of the "epidemic" obesity, with a considerable impact on the global incidence of cardiovascular disease and type 2 diabetes. At present, there is a growing interest on the role of visceral fat accumulation in the occurrence of MetS. In this review, the effects of adipocytokines and other proinflammatory factors produced by fat accumulation on the occurrence of the MetS have been also emphasized. Accordingly, the "hypoadiponectinemia" has been proposed as the most interesting new hypothesis to explain the pathophysiology of MetS.
Irbesartan, an angiotensin-receptor blocker, is a known agonist of peroxisome proliferator-activated receptor (PPAR) γ. In this study, thirteen-week-old spontaneously hypertensive (SHR)/NDmcr-cp rats, representing a genetic model of metabolic syndrome, were treated daily with placebo, irbesartan (30 mg/kg), valsartan (10 mg/kg), or pioglitazone (10 mg/kg) for 4 weeks. Significant reductions in systolic blood pressure were seen in the irbesartan- and valsartan-treated groups, but not in the pioglitazone-treated group. Compared with the placebo group, plasma insulin, homeostasis model assessment of insulin resistance index, and plasma triglyceride levels were significantly lower while plasma adiponectin levels were significantly higher in the pioglitazone- and irbesartan-treated groups, but not in the valsartan-treated group. Significant increases in the gene expression of adiponectin and GLUT4 within adipose tissue were also observed in the pioglitazone- and irbesartan-treated groups, but not in the valsartan-treated group. These findings suggest that through PPARγ stimulation along with angiotensin II inhibition, irbesartan may be an optimal treatment option in the prevention of metabolic syndrome as well as hypertension.
We have previously reported that peroxynitrite is involved in dysfunction of nitric oxide (NO)-mediated vasorelaxation in SHR/NDmcr-cp rats (SHR-cp), which display typical symptoms of metabolic syndrome. This study investigated whether peroxynitrite is actually generated in the vascular wall with angiotensin II-induced NADPH-oxidase activation, thus contributing to the dysfunction. In isolated mesenteric arteries of male 18-week-old SHR-cp, relaxations in response to acetylcholine and sodium nitroprusside were impaired compared with that in Wistar-Kyoto rats. This impaired relaxation was not restored by treatment with apocynin, an NADPH-oxidase inhibitor. Protein expression of endothelial NO synthase increased while that of soluble guanylyl cyclase (sGC) decreased in the artery. We observed increased production of superoxide anions and peroxynitrite from the artery and their inhibition by apocynin, and also increased contents of nitrotyrosine, a biomarker of peroxynitrite, in mesenteric arteries and angiotensin II in aortas. Long-term (8 weeks) administration of telmisartan, an angiotensin II type 1-receptor antagonist, prevented the impaired vasorelaxation, decreased sGC expression and increased nitrotyrosine content in mesenteric arteries. These findings suggest that in the vascular wall of SHR-cp, peroxynitrite is continually produced by the reaction of NO with NADPH oxidase-derived superoxide via angiotensin II and gradually denatures sGC protein, leading to vasorelaxation dysfunction.
Mice fed a Spirulina platensis diet showed increased numbers of splenic antibody-producing cells in the primary immune response to sheep red blood cells (SRBC). However, immunoglobulin G (IgG)-antibody production in the secondary immune response was hardly affected. The percentage of phagocytic cells in peritoneal macrophages from the mice fed S. platensis diet, as well as the proliferation of spleen cells by either concanavalin A (Con A) or phytohemagglutinin (PHA) was significantly increased. Addition of a hot-water extract of S. platensis (SHW) to an in vitro culture of spleen cells markedly increased proliferation of these cells, whereas culture of thymus cells was scarcely affected. The Spirulina extract also significantly enhanced interleukin-1 (IL-1) production from peritoneal macrophages. Addition to the in vitro spleen cell culture of SHW as well as the supernatant of macrophages stimulated with SHW resulted in enhancement of antibody production, that is, an increase of the number of PFC. These results suggest that Spirulina enhances the immune response, particularly the primary response, by stimulating macrophage functions, phagocytosis, and IL-1 production.
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.
This study was designed to clarify the mechanisms of the hypocholesterolemic action of Spirulina platensis concentrate (SPC) and identify the novel hypocholesterolemic protein derived from SPC. We investigated the effects of casein or SPC on the solubility of cholesterol, taurocholate binding capacity in vitro, cholesterol absorption in Caco-2 cells, and cholesterol metabolism in rats for 10 d. We also evaluated the effects of SPC, C-phycocyanin (PHY), and PHY residue on cholesterol metabolism in rats fed a high-cholesterol diet for 5 d, and SPC or SPC-acetone extract for 10 d. SPC had a significantly greater bile acid-binding capacity than casein in vitro. Micellar cholesterol solubility and cholesterol uptake by Caco-2 cells was significantly lower in the presence of SPC compared with casein. Fecal excretion of cholesterol and bile acids was significantly greater in rats fed the SPC-supplemented diet than in those fed the casein control diet. Serum and liver cholesterol concentrations were significantly lower in rats fed SPC than in those fed casein. Thus, the hypocholesterolemic action of SPC may involve the inhibition of both jejunal cholesterol absorption and ileal bile acid reabsorption. Although no studies to date have found a hypocholesterolemic protein among the algal proteins, we report here the discovery of a hypocholesterolemic effect in the novel protein C-phycocyanin. This study provides the first direct evidence that PHY, a novel hypocholesterolemic protein derived from Spirulina platensis, can powerfully influence serum cholesterol concentrations and impart a stronger hypocholesterolemic activity than SPC in animals.
The present study has been undertaken to unravel the critical factors involved in the progression of diabetic nephropathy (DN).
A unique type 2 diabetic rat model with a wide range of metabolic derangements and hypertension has been utilized, the spontaneously hypertensive/NIH-corpulent rat SHR/NDmcr-cp(cp/cp). It develops histologically evident glomerular injury and tubulointerstitial damage, including mesangial activation, podocyte injury, and inflammatory cell infiltration in the tubulointerstitium.
A low calorie diet for 22 weeks significantly improves obesity, proteinuria and renal morphological alterations. The correction of renal injury is independent of blood pressure control. Obesity correction, although partial, normalizes the renal content of pentosidine taken as a marker of oxidative stress and advanced glycation end products (AGEs). This occurs despite the fact that, in this model, improvement of glucose control and hyperlipidaemia is limited. Proteinuria and body weight are highly correlated with renal pentosidine content, while proteinuria and body weight are also correlated with each other. Diabetic renal injury is thus inhibited by a low calorie diet with an attendant reduction of oxidative stress and AGE formation, despite sustained hypertension.
The present findings suggest a direct role of obesity in the generation of a localized oxidative stress and AGE formation, directly responsible for DN.
Adiponectin is a recently described adipokine that has been recognized as a key regulator of insulin sensitivity and tissue inflammation. It is produced by adipose tissue (white and brown) and circulates in the blood at very high concentrations. It has direct actions in liver, skeletal muscle and the vasculature, with prominent roles to improve hepatic insulin sensitivity, increase fuel oxidation [via up-regulation of adenosine monophosphate-activated protein kinase (AMPK) activity] and decrease vascular inflammation. Adiponectin exists in the circulation as varying molecular weight forms, produced by multimerization. Recent data indicate that the high-molecular weight (HMW) complexes have the predominant action in the liver. In contrast to other adipokines, adiponectin secretion and circulating levels are inversely proportional to body fat content. Levels are further reduced in subjects with diabetes and coronary artery disease. Adiponectin antagonizes many effects of tumour necrosis factor-alpha(TNF-alpha) and this, in turn, suppresses adiponectin production. Furthermore, adiponectin secretion from adipocytes is enhanced by thiazolidinediones (which also act to antagonize TNF-alpha effects). Thus, adiponectin may be the common mechanism by which TNF-alpha promotes, and the thiazolidinediones suppress, insulin resistance and inflammation. Two adiponectin receptors, termed AdipoR1 and AdipoR2, have been identified and these are ubiquitously expressed. AdipoR1 is most highly expressed in skeletal muscle and has a prominent action to activate AMPK, and hence promote lipid oxidation. AdipoR2 is most highly expressed in liver, where it enhances insulin sensitivity and reduces steatosis via activation of AMPK and increased peroxisome-proliferator-activated receptor alpha ligand activity. T-cadherin, which is expressed in endothelium and smooth muscle, has been identified as an adiponectin-binding protein with preference for HMW adiponectin multimers. Given the low levels of adiponectin in subjects with the metabolic syndrome, and the beneficial effect of the adipokine in animal studies, there is exciting potential for adiponectin replacement therapy in insulin resistance and related disorders.
Adiponectin is an adipokine that is specifically and abundantly expressed in adipose tissue and directly sensitizes the body to insulin. Hypoadiponectinemia, caused by interactions of genetic factors such as SNPs in the Adiponectin gene and environmental factors causing obesity, appears to play an important causal role in insulin resistance, type 2 diabetes, and the metabolic syndrome, which are linked to obesity. The adiponectin receptors, AdipoR1 and AdipoR2, which mediate the antidiabetic metabolic actions of adiponectin, have been cloned and are downregulated in obesity-linked insulin resistance. Upregulation of adiponectin is a partial cause of the insulin-sensitizing and antidiabetic actions of thiazolidinediones. Therefore, adiponectin and adiponectin receptors represent potential versatile therapeutic targets to combat obesity-linked diseases characterized by insulin resistance. This Review describes the pathophysiology of adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome.
Spirulina maxima is a filamentous cyanobacterium used as food supplement because of its high nutrient contents. It has been experimentally proven, in vivo and in vitro that posses several pharmacological properties. The purpose of this study was to evaluate the effects of Spirulina maxima orally supplied (4.5 g/day, for 6 weeks) to a sample of 36 subjects (16 men and 20 women, with ages between 18-65 years) on serum lipids, glucose, aminotransferases and on blood pressure. The volunteers did not modify their dietary habits or lifestyle during the whole experimental period. From each subject, a sample of blood was drawn in fasting state of 12 hours to determi the plasma concentrations of glucose, triacylglycerols (TAG), total cholesterol (TC), cholesterol associated to high density lipoprotein (HDL-C) and aspartate aminotransferase (AST). Anthropometric measurements including systolic (SYST-P) and diastolic (DIAST-P) blood pressure, height, weight and Body Mass Index (BMI) were also recorded.
Comparing initial and final data, the results showed that there were no significant changes in the values of glucose and AST, but significant differences in TAG, TC, and HDL-C, were observed: TAG 233.7 +/- 177.8 vs. 167.7 +/- 100.7 mg/dL (p < 0.001), TC 181.7 +/- 37.5 vs. 163.5 +/- 34.4 mg/dL (p < 0.001), C-HDL 43.5 +/- 14.4 vs. 50 +/- 18.8 mg/dL (p < 0.01). The univariated analysis showed that the changes in the HDL-C and TC concentrations were dependent on TAG concentration (p = 0.247 and p = 0.108, respectively); nevertheless the calculated values for cholesterol associated to low density lipoprotein (LDL-C) were significantly reduced by the Spirulina maxima treatment but independently of the TAG changes. In addition, significant differences were found comparing initial and final SYST-P and DIAST-P blood pressure in both male and female: SYST-P male 121 +/- 9 vs. 111 +/- 8 mm Hg (p < 0.01), DIAST-P male 85 +/- 6.5 vs. 77 +/- 9 mm Hg (p < 0.01); SYST-P female 120 +/- 9.5 vs. 109 +/- 11 mm Hg (p < 0.002), DIAST-P female 85 +/- 11 vs. 79 +/- 7.5 mm Hg (p < 0.03).
The Spirulina maxima showed a hypolipemic effect, especially on the TAG and the LDL-C concentrations but indirectly on TC and HDL-C values. It also reduces systolic and diastolic blood pressure.
High blood pressure is an important constituent of the metabolic syndrome. However, the underlying mechanisms for development of hypertension in the metabolic syndrome are very complicated and remain still obscure. Visceral/central obesity, insulin resistance, sympathetic overactivity, oxidative stress, endothelial dysfunction, activated renin-angiotensin system, increased inflammatory mediators, and obstructive sleep apnea have been suggested to be possible factors to develop hypertension in the metabolic syndrome. Here, we will discuss how these factors influence on development of hypertension in the metabolic syndrome.
C-phycocyanin (C-PC) is a blue pigment in cyanobacteria, rhodophytes and cryptophytes with fluorescent and antioxidative properties. C-PC is presently extracted from open pond cultures of the cyanobacterium Arthrospira platensis although these cultures are not very productive and open for contaminating organisms. C-PC is considered a healthy ingredient in cyanobacterial-based foods and health foods while its colouring, fluorescent or antioxidant properties are utilised only to a minor extent. However, recent research and developments in C-PC synthesis and functionality have expanded the potential applications of C-PC in biotechnology, diagnostics, foods and medicine: The productivity of C-PC has been increased in heterotrophic, high cell density cultures of the rhodophyte Galdieria sulphuraria that are grown under well-controlled and axenic conditions. C-PC purification protocols based on various chromatographic principles or novel two-phase aqueous extraction methods have expanded in numbers and improved in performance. The functionality of C-PC as a fluorescent dye has been improved by chemical stabilisation of C-PC complexes, while protein engineering has also introduced increased stability and novel biospecific binding sites into C-PC fusion proteins. Finally, our understanding of the physiological functions of C-PC in humans has been improved by a mechanistic hypothesis that links the chemical properties of the phycocyanobilin chromophores of C-PC to the natural antioxidant, bilirubin, and may explain the observed health benefits of C-PC intake. This review outlines how C-PC is produced and utilised and discusses the novel C-PC synthesis procedures and applications.
The antioxidative activity of phycocyanobilin fromSpirulina platensis was evaluated againstoxidation of methyl linoleate in a hydrophobic systemor with phosphatidylcholine liposomes. Phycocyanobilin as well as phytochemicals including-tocopherol, caffeic acid and zeaxanthin,effectively inhibited the peroxidation of methyllinoleate and produced a prolonged induction period.Oxidation of phosphatidylcholine liposomes was alsocontrolled markedly by adding phycocyanobilin or-tocopherol. Phycocyanobilin was distributedoutside in the liposomes to scavenge radicals fromAAPH and to prevent initiation of radical chainreactions. When the concentrations of phycocyanin andphycocyanobilin in the reaction mixture were adjustedequally on a phycocyanobilin basis, the activity ofphycocyanobilin was almost the same as that ofphycocyanin in the AAPH-containing reaction mixture.The antioxidizing action of phycocyanin prepared fromspray-dried Spirulina almost agreed with thatfrom fresh Spirulina in the AAPH-containingreaction mixture. These results suggest thatphycocyanobilin is responsible for the majority of theantioxidative activity of phycocyanin and may act asan effective antioxidant in a living human body.
Nutritional approaches are sought to overcome the limits of pioglitazone in metabolic syndrome and non-alcoholic fatty liver disease. Spirulina, a filamentous unicellular alga, reduces serum lipids and blood pressure while exerting antioxidant effects.
To determine whether Spirulina may impact macrophages infiltrating the visceral fat in obesity characterizing our metabolic syndrome mouse model induced by the subcutaneous injection treatment of monosodium glutamate.
Mice were randomized to receive standard food added with 5% Spirulina, 0.02% pioglitazone, or neither. We tested multiple biochemistry and histology (both liver and visceral fat) readouts at 24 weeks of age.
Data demonstrate that both the Spirulina and the pioglitazone groups had significantly lower serum cholesterol and triglyceride levels and liver non-esterified fatty acid compared to untreated mice. Spirulina and pioglitazone were associated with significantly lower leptin and higher levels, respectively, compared to the control group. At liver histology, non-alcoholic fatty liver disease activity score and lipid peroxide were significantly lower in mice treated with Spirulina.
Spirulina reduces dyslipidaemia in our metabolic syndrome model while ameliorating visceral adipose tissue macrophages. Human studies are needed to determine whether this safe supplement could prove beneficial in patients with metabolic syndrome.
Obesity is commonly associated with hypertension. Increased sympathetic tonus in obese subjects contributes to the underlying mechanism. However, the precise mechanisms whereby obesity induces this sympathetic activation remain unclear. Hepatic peroxisome proliferator-activated receptor (PPAR)-γ2 expression, which is reportedly upregulated during obesity development, affects sympathetic activation via hepatic vagal afferents. Herein, we report involvement of this neuronal relay in obesity-related hypertension.
Peroxisome proliferator-activated receptor-γ and a direct PPARγ target, fat-specific protein 27 (Fsp27), were adenovirally overexpressed or knocked down in the liver, in combination with surgical dissection or pharmacological deafferentation of the hepatic vagus. Adenoviral PPARγ2 expression in the liver raised blood pressure (BP) in wild-type but not in β1/β2/β3 adrenergic receptor-deficient mice. In addition, knockdown of endogenous PPARγ in the liver lowered BP in murine obesity models. Either surgical dissection or pharmacological deafferentation of the hepatic vagus markedly blunted BP elevation in mice with diet-induced and genetically-induced obesity. In contrast, BP was not elevated in other models of hepatic steatosis, DGAT1 and DGAT2 overexpressions, in which PPARγ is not upregulated in the liver. Thus, hepatic PPARγ upregulation associated with obesity is involved in BP elevation during obesity development. Furthermore, hepatic expression of Fsp27 raised BP and the effect was blocked by hepatic vagotomy. Hepatic Fsp27 is actually upregulated in murine obesity models and its knockdown reversed BP elevation.
The hepatic PPARγ-Fsp27 pathway plays important roles in the development of obesity-related hypertension via afferent vagal signals from the liver.
This study focused on the hepatoprotective activity of C-phycocyanin (C-PC) against carbon tetrachloride-induced hepatocyte damage in vitro and in vivo. In in vitro study, human hepatocyte cell line L02 was used. C-PC showed its capability to reverse CCl(4)-induced L02 cells viability loss, alanine transaminase (ALT) leakage and morphological changes. C-PC also showed the following positive effects: prevent the CCl(4)-induced overproduction of intracellular reactive oxygen species (ROS) and malondialdehyde (MDA); prevent changes in superoxide dismutase (SOD) activity; and reduce glutathione (GSH) level. In vivo, C-PC showed its capability to decrease serum ALT and aspartate transaminase (AST) levels in CCl(4)-induced liver damage in mice. The histological observations supported the results obtained from serum enzymes assays. C-PC also showed the following effects in mice liver: prevent the CCl(4)-induced MDA formation and GSH depletion; prevent SOD and glutathione peroxidase (GSH-Px) activity; and prevent the elevation of transforming growth factor-beta1 (TGF-beta1) and hepatocyte growth factor (HGF) mRNAs. Both the in vitro and in vivo results suggested that C-PC was useful in protecting against CCl(4)-induced hepatocyte damage. One of the mechanisms is believed to be through C-PCs scavenging ability to protect the hepatocytes from free radicals damage induced by CCl(4). In addition, C-PC may be able to block inflammatory infiltration through its anti-inflammatory activities by inhibiting TGF-beta1 and HGF expression.
Metabolic syndrome (MetS) represents a combination of cardio-metabolic risk determinants, including central obesity, insulin resistance, glucose intolerance, dyslipidemia, hypertension, hyperinsulinemia, and microalbuminuria. The prevalence of MetS is rapidly increasing worldwide, largely as a consequence of the ongoing obesity epidemic. Environmental factors during periods early in development have been shown to influence the susceptibility to develop disease in later life. In particular, there is a wealth of evidence from both epidemiological and animal studies for greater incidence of features of MetS as a result of unbalanced maternal nutrition. The mechanisms by which nutritional insults during a period of developmental plasticity result in a MetS phenotype are now beginning to receive considerable scientific interest. This review focuses on recent data regarding these mechanisms, in particular the epigenetic and transcriptional regulation of key metabolic genes in response to nutritional stimuli that mediate persistent changes and an adult MetS phenotype. A continued and greater understanding of these mechanisms will eventually allow specific interventions, with a favorable impact on the global incidence of cardiovascular disease and type 2 diabetes in the future.
Oxidative stress may play an important role in the pathogenesis of non-alcoholic steatohepatitis (NASH). Oleuropein, the active constituent of olive leaf, possesses anti-oxidant, hypoglycaemic, and hypolipidaemic activities. We aimed to investigate the preventive effects of olive leaf extract on hepatic fat accumulation in a rat model of NASH.
Spontaneously hypertensive/NIH-corpulent rats were fed a diet of AIN-93G with or without olive leaf extract (500, 1000, 2000 mg/kg diet, and control; 5 rats each) for 23 weeks. Serological and histopathological findings, anti-oxidative activity, and the alteration of fatty acid synthesis in the liver were evaluated.
Histopathologically, a diet of AIN-93G containing more than 1000 mg/kg olive leaf extract had a preventive effect for the occurrence of NASH. Thioredoxin-1 expression in the liver was more evident in rats fed this diet, and 4-hydroxynonenal expression in the liver was less evident in these rats. There were no significant differences in the activities of hepatic carnitine palmitoyltransferase, fatty acid synthase, malic enzyme, and phosphatidic acid phosphohydrolase among the groups.
Our data suggest that olive leaf extract may help prevent NASH, presumably through its anti-oxidative activity.
The endothelium is a crucial regulator of vascular physiology, producing in healthy conditions several substances with a potent antiatherosclerotic properties. Accordingly, the presence of endothelial dysfunction is associated with subclinical atherosclerosis and with an increased future risk of cardiovascular events. A large body of evidence supports the fundamental role of nitric oxide (NO) as the main endothelium‐derived relaxing factor. However, in the presence of pathological conditions, such as hypertension, endothelial cells, in response to a number of agents and physical stimuli, become also a source of endothelium‐derived contracting factors (EDCFs), including endothelins and angiotensin II and particularly cyclooxygenase‐derived prostanoids and superoxide anions. These latter were at first identified as responsible for impaired endothelium‐dependent vasodilation in patients with essential hypertension. However, cyclooxygenase‐dependent EDCFs production is characteristic of the aging process, and essential hypertension seems to only anticipate the phenomenon. It is worth noting that both in aging and hypertension EDCF production is associated with a parallel decrease in NO availability, suggesting that this substance could be oxygen free radicals themselves. Accordingly, in hypertension both indomethacin, a cyclooxygenase inhibitor, and vitamin C, an antioxidant, increase the vasodilation to acetylcholine by restoring NO availability. In conclusion, hypertension is characterized by a decline in endothelial function, associated with a progressive decrease in NO bioavailability and increase in the production of EDCF. The mechanisms that regulate the balance between NO and EDCF, and the processes transforming the endothelium from a protective organ to a source of vasoconstrictor, proaggregatory and promitogenic mediators remain to be determined.
British Journal of Pharmacology (2009) 157, 527–536; doi:10.1111/j.1476‐5381.2009.00240.x
This article is part of a themed section on Endothelium in Pharmacology. For a list of all articles in this section see the end of this paper, or visit: http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009
The classical perception of adipose tissue as a storage place of fatty acids has been replaced over the last years by the notion that adipose tissue has a central role in lipid and glucose metabolism and produces a large number of hormones and cytokines, e.g. tumour necrosis factor-α, interleukin-6, adiponectin, leptin, and plasminogen activator inhibitor-1.
The increased prevalence of excessive visceral obesity and obesity-related cardiovascular risk factors is closely associated with the rising incidence of cardiovascular diseases and type 2 diabetes mellitus. This clustering of vascular risk factors in (visceral) obesity is often referred to as metabolic syndrome. The close relationship between an increased quantity of visceral fat, metabolic disturbances, including low-grade inflammation, and cardiovascular diseases and the unique anatomical relation to the hepatic portal circulation has led to an intense endeavour to unravel the specific endocrine functions of this visceral fat depot. The objective of this paper is to describe adipose tissue dysfunction, delineate the relation between adipose tissue dysfunction and obesity and to describe how adipose tissue dysfunction is involved in the development of diabetes mellitus type 2 and atherosclerotic vascular diseases. First, normal physiology of adipocytes and adipose tissue will be described.
The activity and protein expression of endothelial nitric oxide synthase (eNOS) and inducible NOS (iNOS) were investigated during the development of hypertension in spontaneously hypertensive rats (SHR). SHR and Wistar-Kyoto rats (WKY) were studied at three different ages: 4, 14 to 17, and 63 weeks of age. After treatment with saline or lipopolysaccharide (LPS, 10 mg/kg IV) for 3 hours, the aortas were removed for measurement of NOS activity and protein expression assay by [3H]-L-citrulline formation method and Western blot analysis, respectively. Plasma levels of nitrite/nitrate (NO2-/NO3-) and tumor necrosis factor-α (TNF-α) were also determined. At 14 to 17 weeks and 63 weeks, the basal activity and protein expression of eNOS in the aortas were significantly lower in SHR than in WKY. In addition, the aged WKY exhibited lower eNOS activity than that of adult WKY, but this change was not seen in SHR. By comparison, the basal activity and protein expression of iNOS were only observed in SHR of the 14-to-17-week group and in the 63-week group; SHR still exhibited higher activities, and these differences were further exaggerated by treatment with LPS. The basal and LPS-induced NO2- /NO3- and TNF-α levels in the plasma were also higher in the SHR except the 4-week group. After treatment with quinapril, the basal and LPS-induced expressions of iNOS in SHR were significantly attenuated. Our results demonstrated that alterations of activity and protein expression of eNOS and iNOS occurred in SHR. In addition, aging may reduce the activity of eNOS in WKY but not in SHR. The decline of eNOS activity and/or expression may contribute to the development of hypertension, whereas the increase of iNOS expression may be a consequence of the pathological state of vessels associated with hypertension in SHR. However, the augmented expression of iNOS in SHR was attenuated by antihypertensive therapy, suggesting that the abnormal expression of iNOS is associated with hypertension.
The main etiology for mortality and a great percent of morbidity in patients with diabetes mellitus is atherosclerosis. A hypothesis for the initial lesion of atherosclerosis is endothelial dysfunction, defined pragmatically as changes in the concentration of the chemical messengers produced by the endothelial cell and/or by blunting of the nitric oxide-dependent vasodilatory response to acetylcholine or hyperemia. Endothelial dysfunction has been documented in patients with diabetes and in individuals with insulin resistance or at high risk for developing type 2 diabetes. Factors associated with endothelial dysfunction in diabetes include activation of protein kinase C, overexpression of growth factors and/or cytokines, and oxidative stress. Several therapeutic interventions have been tested in clinical trials aimed at improving endothelial function in patients with diabetes. Insulin sensitizers may have a beneficial effect in the short term, but the virtual absence of trials with cardiovascular end-points preclude any definitive conclusion. Two trials offer optimism that treatment with ACE inhibitors may have a positive impact on the progression of atherosclerosis. Although widely used, the effect of hypolipidemic agents on endothelial function in diabetes is not clear. The role of antioxidant therapy is controversial. No data have been published regarding the effects of hormonal replacement therapy on endothelial dysfunction in postmenopausal women with type 2 diabetes.
Vascular integrity in the healthy endothelium is maintained through the release of a variety of paracrine factors such as NO (nitric oxide). Endothelial dysfunction, characterized by reduced NO bioavailability, is associated with obesity, insulin resistance and Type II diabetes. Insulin has been demonstrated to have direct effects on the endothelium to increase NO bioavailability. Therefore altered insulin signalling in the endothelium represents a candidate mechanism underlying the association between insulin resistance and endothelial dysfunction. In recent years, it has become apparent that insulin sensitivity is regulated by the adipocytokines, a group of bioactive proteins secreted by adipose tissue. Secretion of adipocytokines is altered in obese individuals and there is increasing evidence that the adipocytokines have direct effects on the vascular endothelium. A number of current antidiabetic strategies have been demonstrated to have beneficial effects on endothelial function and to alter adipocytokine concentrations in addition to their effects on glucose homoeostasis. In this review we will explore the notion that the association between insulin resistance and endothelial dysfunction is accounted for by adipocytokine action on the endothelium. In addition, we examine the effects of weight loss, exercise and antidiabetic drugs on adipocytokine availability and endothelial function.
This study provided the opportunity to assess the relationship between endothelial vasomotor function and incidence of hypertension in a cohort of postmenopausal women.
Both menopause and hypertension are associated with endothelial dysfunction and are well-known risk factors for atherosclerotic-related disease.
We conducted a prospective cohort study that began in 1996 on 952 apparently healthy postmenopausal women, age 53 +/- 5 years (range 44 to 60 years), with initially normal levels of blood pressure and no history of hypertension. All participants were followed up for a mean period of 3.6 +/- 0.7 years (range 0.5 to 6.9 years). Endothelial function was measured as flow-mediated dilation of the brachial artery using high-resolution ultrasound.
During follow-up 112 women developed hypertension. The adjusted relative risk for women with flow-mediated dilation of 3.5 or less (lowest quartile) was 5.77 (95% confidence interval 4.34 to 8.10) versus women with flow-mediated dilation of 5.5 or greater (highest quartile, referent). Each one-unit decrease of flow-mediated dilation was associated with a significant 16% (95% confidence interval 12% to 33%) increase in the multiple-adjusted relative risk of incident hypertension.
These prospective data indicate a significant increase in the relative risk of hypertension with each unit decrease of flow-mediated dilation that is independent of age and baseline systolic and diastolic pressure values. This could suggest that an impaired endothelial vasomotor function precedes and predicts the future development of hypertension in postmenopausal women.
Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis in the absence of a history of significant alcohol use or other known liver disease. Nonalcoholic steatohepatitis (NASH) is the progressive form of NAFLD. The Pathology Committee of the NASH Clinical Research Network designed and validated a histological feature scoring system that addresses the full spectrum of lesions of NAFLD and proposed a NAFLD activity score (NAS) for use in clinical trials. The scoring system comprised 14 histological features, 4 of which were evaluated semi-quantitatively: steatosis (0-3), lobular inflammation (0-2), hepatocellular ballooning (0-2), and fibrosis (0-4). Another nine features were recorded as present or absent. An anonymized study set of 50 cases (32 from adult hepatology services, 18 from pediatric hepatology services) was assembled, coded, and circulated. For the validation study, agreement on scoring and a diagnostic categorization ("NASH," "borderline," or "not NASH") were evaluated by using weighted kappa statistics. Inter-rater agreement on adult cases was: 0.84 for fibrosis, 0.79 for steatosis, 0.56 for injury, and 0.45 for lobular inflammation. Agreement on diagnostic category was 0.61. Using multiple logistic regression, five features were independently associated with the diagnosis of NASH in adult biopsies: steatosis (P = .009), hepatocellular ballooning (P = .0001), lobular inflammation (P = .0001), fibrosis (P = .0001), and the absence of lipogranulomas (P = .001). The proposed NAS is the unweighted sum of steatosis, lobular inflammation, and hepatocellular ballooning scores. In conclusion, we present a strong scoring system and NAS for NAFLD and NASH with reasonable inter-rater reproducibility that should be useful for studies of both adults and children with any degree of NAFLD. NAS of > or =5 correlated with a diagnosis of NASH, and biopsies with scores of less than 3 were diagnosed as "not NASH."
C-phycocyanin (cpc), a biliprotein isolated from Spirulina platensis, has been reported to exert many therapeutic and nutritional values. In the present study, we examined whether cpc has an antiplatelet activity in vitro and further investigated the possible anti-aggregatory mechanisms involved. Our results showed that preincubation of cpc (1-50 microg/ml) with rabbit washed platelets dose-dependently inhibited the platelet aggregation induced by collagen (10 microg/ml) or arachidonic acid (100 microm), with an IC50 of about 10 microg/ml. Furthermore, the thromboxane B2 formation caused by collagen or arachidonic acid was significantly inhibited by cpc due to suppression of cyclooxygenase and thromboxane synthase activity. Similarly, the rise of platelet intracellular calcium level stimulated by arachidonic acid and collagen-induced platelet membrane surface glycoprotein IIb/IIIa expression were also attenuated by cpc. In addition, cpc itself significantly increased the platelet membrane fluidity and the cyclic AMP level through inhibiting cyclic AMP phosphodiesterase activity. These findings strongly demonstrate that cpc is an inhibitor of platelet aggregation, which may be associated with mechanisms including inhibition of thromboxane A2 formation, intracellular calcium mobilization and platelet surface glycoprotein IIb/IIIa expression accompanied by increasing cyclic AMP formation and platelet membrane fluidity.
Metabolic syndrome is a cluster of metabolic diseases that in essence greatly promotes progression of atherosclerosis. We used a genetic model of the metabolic syndrome, the SHR/NDmcr-cp (SHR/cp) rat, from 6 to 40 weeks of age to investigate whether systemic oxidative stress, a major cause of atherosclerosis, increases in this syndrome. Nine-week-old male rats already showed manifestations of metabolic syndrome, including heavier body weight, higher blood pressure and higher levels of serum glucose, insulin and various lipids compared to the age-matched Wistar Kyoto (WKY) rats used as a genetic control. These metabolic parameters gradually progressed with age. Likewise, the serum levels of oxidative stress markers, including lipid peroxides, which oxidatively modify low-density lipoprotein (LDL) and 8-hydroxydeoxyguanosine (8-OHdG), gradually increased in SHR/cp rats. The serum levels of 3-nitrotyrosine and 3-chlorotyrosine also persistently increased, indicating the involvement of peroxynitrite or myeloperoxidase-catalyzed oxidation. In addition, high-sensitivity C-reactive protein (hsCRP), an early marker of inflammation, temporarily increased in SHR/cp rats compared to WKY rats. These findings suggest that oxidative stress, as well as nitrative stress and inflammation, increases in the metabolic syndrome, which may contribute to the development of atherosclerosis.
Omagari received support from a grant from the DIC Lifetec Co
- Nagasaki
- Grant
- Dic Lifetec Co
- M Ltd
- S Ichimura
- Kato
- K Ltd
- S Tsuneyama
- M Matsutake
- Kamogawa
- A Hirao
- S Miyata
- N Mori
- Yamaguchi
Nagasaki and a research grant from DIC Lifetec Co, Ltd. M. Ichimura, S. Kato, and K. Omagari received support from a grant from the DIC Lifetec Co., Ltd. K. Tsuneyama, S. Matsutake, M. Kamogawa, E Hirao, A. Miyata, S. Mori, N. Yamaguchi, and K. Suruga have no conflict of interest to declare.
Flow-mediated vasodilation and the risk of developing
- Rossi R E Chiurlia
- A Nuzzo
- E Cioni
- G Origliani
- Modena
- Mg
Rossi R, Chiurlia E, Nuzzo A, Cioni E, Origliani G, Modena MG. Flow-mediated vasodilation and the risk of developing Cardiol 2004;44:1636–40.