astaxanthine and Inflammation

Astaxanthin (AST) is a red pigmented carotenoid with significant antioxidant, anti-inflammatory, anti-proliferative, and anti-apoptotic properties. In this study, we summarize the available literature on the anti-inflammatory efficacy of AST in various chronic and acute disorders, such as neurodegenerative, renal-, hepato-, skin- and eye-related diseases, as well as gastrointestinal disorders. In addition, we elaborated on therapeutic efficacy of AST and the role of several pathways, including PI3K/AKT, Nrf2, NF-κB, ERK1/2, JNK, p38 MAPK, and JAK-2/STAT-3 in mediating its effects. However, additional experimental and clinical studies should be performed to corroborate the anti-inflammatory effects and protective effects of AST against inflammatory diseases in humans. Nevertheless, this review suggests that AST with its demonstrated anti-inflammatory property may be a suitable candidate for drug design with novel technology.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Humans; Inflammation; Xanthophylls

Astaxanthin (AST) is a dietary xanthophyll predominantly found in marine organisms and seafood. Due to its unique molecular features, AST has an excellent antioxidant activity with a wide range of applications in the nutraceutical and pharmaceutical industries. In the past decade, mounting evidence has suggested a protective role for AST against a wide range of diseases where oxidative stress and inflammation participate in a self-perpetuating cycle. Here, we review the underlying molecular mechanisms by which AST regulates two relevant redox-sensitive transcription factors, such as nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor κB (NF-κB). Nrf2 is a cellular sensor of electrophilic stress that coordinates the expression of a battery of defensive genes encoding antioxidant proteins and detoxifying enzymes. Likewise, NF-κB acts as a mediator of cellular stress and induces the expression of various pro-inflammatory genes, including those encoding cytokines, chemokines, and adhesion molecules. The effects of AST on the crosstalk between these transcription factors have also been discussed. Besides this, we summarize the current clinical studies elucidating how AST may alleviate the etiopathogenesis of oxidative stress and inflammation.

Topics: Animals; Gene Expression Regulation; Humans; Inflammation; NF-E2-Related Factor 2; NF-kappa B; Oxidative Stress; Signal Transduction; Xanthophylls

Previous in vitro and animal studies showed that astaxanthin improved oxidative stress and inflammation biomarkers. We hypothesized the same effects of astaxanthin in humans and conducted a systematic review and meta-analysis of previous randomized controlled trials to test this hypothesis. The literature search was performed on PubMed, Cochrane Library, and Scopus databases from January 1970 to April 2021. Main eligibility criteria include: intervention using astaxanthin for at least 1 week; inclusion of placebo control; and measuring at least 1 of the common oxidative stress and inflammation biomarkers before and after intervention. Twelve randomized controlled trials including 380 participants were included. Compared with placebo, astaxanthin significantly reduced blood malondialdehyde concentration (standardized mean difference [SMD]: -0.95; 95% CI, -1.67 to -0.23; P = .01). The lowering effect of astaxanthin supplementation on malondialdehyde was particularly significant in type 2 diabetes mellitus (T2DM) patients (SMD: -0.64; 95% CI, -1.26 to -0.01; P < .05). A limited number of trials were available for the effects of astaxanthin on other oxidative stress biomarkers. Astaxanthin supplementation appeared to improve superoxide dismutase activity and reduce serum isoprostane concentration in overweight subjects. Astaxanthin significantly reduced blood interleukin-6 concentration in T2DM patients (weighted mean difference: -0.70 pg/mL; 95% CI, -1.29 to -0.11 pg/mL; P = .02). The effects of astaxanthin on blood C-reactive protein and tumor necrosis factor-α concentrations were not significant. The current work indicated that astaxanthin supplementation may be beneficial for improving oxidative stress and certain inflammation biomarkers, particularly in T2DM patients. Future work should investigate the effects of astaxanthin on T2DM.

Topics: Animals; Biomarkers; Diabetes Mellitus, Type 2; Dietary Supplements; Humans; Inflammation; Oxidative Stress; Randomized Controlled Trials as Topic; Xanthophylls

Most neurodegenerative diseases, such as Alzheimer's and Parkinson's disease, demonstrate preceding or on-going inflammatory processes. Therefore, discovering effective means of counteracting detrimental inflammatory mediators in the brain could help alter aging-related disease onset and progression. Fish oil and marine-derived omega-3, long-chain polyunsaturated fatty acids (LC n-3) have shown promising anti-inflammatory effects both systemically and centrally. More specifically, krill oil (KO), extracted from small Antarctic crustaceans, is an alternative type of LC n-3 with reported health benefits including improvement of spatial memory and learning, memory loss, systemic inflammation and depression symptoms. Similar to the more widely studied fish oil, KO contains the long chain fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) which are essential for basic brain functions. Moreover, the phospholipid bound nature of fatty acids found in KO improves bioavailability and efficiency of absorption, thus supporting the belief that KO may offer a superior method of dietary n-3 delivery. Finally, KO contains astaxanthin, an antioxidant capable of reducing potentially excessive oxidative stress and inflammation within the brain. This review will discuss the potential benefits of KO over other marine-based LC n-3 on brain inflammation and cognitive function in the context of high fat diets and aging.

Topics: Aging; Animals; Anti-Inflammatory Agents; Brain; Cognition; Diet, High-Fat; Docosahexaenoic Acids; Eicosapentaenoic Acid; Euphausiacea; Humans; Inflammation; Xanthophylls

Astaxanthin is a natural lipid-soluble and red-orange carotenoid. Due to its strong antioxidant property, anti-inflammatory, anti-apoptotic, and immune modulation, astaxanthin has gained growing interest as a multi-target pharmacological agent against various diseases. In the current review, the anti-inflammation mechanisms of astaxanthin involved in targeting for inflammatory biomarkers and multiple signaling pathways, including PI3K/AKT, Nrf2, NF-κB, ERK1/2, JNK, p38 MAPK, and JAK-2/STAT-3, have been described. Furthermore, the applications of anti-inflammatory effects of astaxanthin in neurological diseases, diabetes, gastrointestinal diseases, hepatic and renal diseases, eye and skin disorders, are highlighted. In addition to the protective effects of astaxanthin in various chronic and acute diseases, we also summarize recent advances for the inconsistent roles of astaxanthin in infectious diseases, and give our view that the exact function of astaxanthin in response to different pathogen infection and the potential protective effects of astaxanthin in viral infectious diseases should be important research directions in the future.

Topics: Animals; Anti-Inflammatory Agents; Disease; Humans; Inflammation; Xanthophylls

Peroxisome proliferator-activated receptors (PPARs) are part of the nuclear hormone receptors superfamily that plays a pivotal role in functions such as glucose and lipid homeostasis. Astaxanthin (ASX) is a lipid-soluble xanthophyll carotenoid synthesized by many microorganisms and various types of marine life that is known to possess antioxidant, anti-inflammatory, antidiabetic, anti-atherosclerotic, and anticancer activities. As such, it is a promising nutraceutical resource. ASX-mediated modulation of PPARs and its therapeutic implications in various pathophysiological conditions are described in this review. ASX primarily enhances the action of PPARα and suppresses that of PPARβ/δ and PPARγ, but it has also been confirmed that ASX displays the opposite effects on PPARs, depending on the cell context. Anti-inflammatory effects of ASX are mediated by PPARγ activation, which induces the expression of pro-inflammatory cytokines in macrophages and gastric epithelial cells. The PPARγ-agonistic effect of ASX treatment results in the inhibition of cellular growth and apoptosis in tumor cells. Simultaneous and differential regulation of PPARα and PPARγ activity by ASX has demonstrated a hepatoprotective effect, maintaining hepatic lipid homeostasis and preventing related hepatic problems. Considering additional therapeutic benefits of ASX such as anti-gastric, cardioprotective, immuno-modulatory, neuroprotective, retinoprotective, and osteogenic effects, more studies on the association between ASX-mediated PPAR regulation and its therapeutic outcomes in various pathophysiological conditions are needed to further elucidate the role of ASX as a novel nutraceutical PPAR modulator.

Topics: Animals; Cytokines; Glucose; Homeostasis; Humans; Inflammation; Liver; Macrophages; PPAR alpha; PPAR gamma; Transcription Factors; Xanthophylls

Astaxanthin is a xanthophyll carotenoid present in microalgae, fungi, complex plants, seafood, flamingos and quail. It is an antioxidant with anti-inflammatory properties and as such has potential as a therapeutic agent in atherosclerotic cardiovascular disease. Synthetic forms of astaxanthin have been manufactured. The safety, bioavailability and effects of astaxanthin on oxidative stress and inflammation that have relevance to the pathophysiology of atherosclerotic cardiovascular disease, have been assessed in a small number of clinical studies. No adverse events have been reported and there is evidence of a reduction in biomarkers of oxidative stress and inflammation with astaxanthin administration. Experimental studies in several species using an ischaemia-reperfusion myocardial model demonstrated that astaxanthin protects the myocardium when administered both orally or intravenously prior to the induction of the ischaemic event. At this stage we do not know whether astaxanthin is of benefit when administered after a cardiovascular event and no clinical cardiovascular studies in humans have been completed and/or reported. Cardiovascular clinical trials are warranted based on the physicochemical and antioxidant properties, the safety profile and preliminary experimental cardiovascular studies of astaxanthin.

Topics: Animals; Antioxidants; Atherosclerosis; Cardiovascular Diseases; Disease Models, Animal; Humans; Inflammation; Oxidative Stress; Xanthophylls

It is accepted that oxidative stress and inflammation play an integral role in the pathophysiology of many chronic diseases including atherosclerotic cardiovascular disease. The xanthophyll carotenoid dietary supplement astaxanthin has demonstrated potential as an antioxidant and anti-inflammatory therapeutic agent in models of cardiovascular disease. There have been at least eight clinical studies conducted in over 180 humans using astaxanthin to assess its safety, bioavailability and clinical aspects relevant to oxidative stress, inflammation or the cardiovascular system. There have been no adverse outcomes reported. Studies have demonstrated reduced markers of oxidative stress and inflammation and improved blood rheology. A larger number of experimental studies have been performed using astaxanthin. In particular, studies in a variety of animals using a model of myocardial ischemia and reperfusion have demonstrated protective effects from prior administration of astaxanthin both intravenously and orally. Future clinical studies and trials will help determine the efficacy of antioxidants such as astaxanthin on vascular structure, function, oxidative stress and inflammation in a variety of patients at risk of, or with, established cardiovascular disease. These may lead to large intervention trials assessing cardiovascular morbidity and mortality.

Topics: Animals; Antioxidants; Blood Circulation; Cardiovascular Diseases; Carotenoids; Diabetic Nephropathies; Humans; Inflammation; Lipid Peroxidation; Muscle, Skeletal; Myocardium; Oxidative Stress; Xanthophylls

Oxidative stress and inflammation are implicated in several different manifestations of cardiovascular disease (CVD). They are generated, in part, from the overproduction of reactive oxygen species (ROS) and reactive nitrogen species (RNS) that activate transcriptional messengers, such as nuclear factor-kappaB, tangibly contributing to endothelial dysfunction, the initiation and progression of atherosclerosis, irreversible damage after ischemic reperfusion, and even arrhythmia, such as atrial fibrillation. Despite this connection between oxidative stress and CVD, there are currently no recognized therapeutic interventions to address this important unmet need. Antioxidants that provide a broad, "upstream" approach via ROS/RNS quenching or free radical chain breaking seem an appropriate therapeutic option based on epidemiologic, dietary, and in vivo animal model data. However, human clinical trials with several different well-known agents, such as vitamin E and beta-carotene, have been disappointing. Does this mean antioxidants as a class are ineffective, or rather that the "right" compound(s) have yet to be found, their mechanisms of action understood, and their appropriate targeting and dosages determined? A large class of potent naturally-occurring antioxidants exploited by nature-the oxygenated carotenoids (xanthophylls)-have demonstrated utility in their natural form but have eluded development as successful targeted therapeutic agents up to the present time. This article characterizes the mechanism by which this novel group of antioxidants function and reviews their preclinical development. Results from multiple species support the antioxidant/anti-inflammatory properties of the prototype compound, astaxanthin, establishing it as an appropriate candidate for development as a therapeutic agent for cardiovascular oxidative stress and inflammation.

Topics: Animals; Antioxidants; Cardiovascular Diseases; Endothelium, Vascular; Humans; Inflammation; Inflammation Mediators; Oxidative Stress; Reactive Nitrogen Species; Reactive Oxygen Species; Xanthophylls

The carotenoid pigment astaxanthin has important applications in the nutraceutical, cosmetics, food and feed industries. Haematococcus pluvialis is the richest source of natural astaxanthin and is now cultivated at industrial scale. Astaxanthin is a strong coloring agent and a potent antioxidant - its strong antioxidant activity points to its potential to target several health conditions. This article covers the antioxidant, UV-light protection, anti-inflammatory and other properties of astaxanthin and its possible role in many human health problems. The research reviewed supports the assumption that protecting body tissues from oxidative damage with daily ingestion of natural astaxanthin might be a practical and beneficial strategy in health management.

Topics: Adjuvants, Immunologic; Administration, Oral; Antioxidants; Arteriosclerosis; beta Carotene; Biological Availability; Blindness; Chlorophyta; Diet Therapy; Humans; Inflammation; Macular Degeneration; Neoplasms; Neurodegenerative Diseases; Nutritional Physiological Phenomena; Photosensitivity Disorders; Radiation-Sensitizing Agents; Species Specificity; Xanthophylls

Waldman, HS, Bryant, AR, Parten, AL, Grozier, CD, and McAllister, MJ. Astaxanthin supplementation does not affect markers of muscle damage or inflammation after an exercise-induced muscle damage protocol in resistance-trained males. J Strength Cond Res 37(7): e413-e421, 2023-It is well documented that exercise-induced muscle damage (EIMD) decreases exercise performance by elevated inflammation and subjective discomfort. Due to its potent antioxidative properties, astaxanthin (AX) may serve as a potential dietary supplement strategy for mitigating delayed-onset muscle soreness (DOMS) and enhancing recovery and performance. This study aimed to investigate the effects of AX on markers of muscle damage, inflammation, DOMS, and anaerobic performance and substrate metabolism. Thirteen resistance-trained men (mean ± SD , age, 23.4 ± 2.1 years) completed a double-blind, counterbalanced, and crossover design with a 1-week washout period between 2, 4-week supplementation periods at 12 mg·d -1 of AX or placebo. After each supplementation period, subjects completed 2 trials, with trial 1 including a graded exercise test (GXT) and a 30-second Wingate and trial 2 including an EIMD protocol followed by the collection of fasting blood samples (pre-post) to measure creatine kinase, advanced oxidative protein products, C-reactive protein, interleukin-6, insulin, and cortisol. Astaxanthin supplementation had no statistical effects on markers of substrate metabolism during the GXT, Wingate variables, or markers of muscle damage, inflammation, or DOMS when compared with placebo (all p > 0.05). However, 4 weeks of AX supplementation did significantly lower oxygen consumption during the final stage of the GXT (12%, p = 0.02), as well as lowered systolic blood pressure (∼7%, p = 0.04), and significantly lowered baseline insulin values (∼24%, p = 0.05) when compared with placebo. Collectively, these data suggest that 4 weeks of AX supplementation at 12 mg·d -1 did not affect markers of muscle damage, inflammation, or DOMS after an EIMD protocol in a resistance-trained male cohort.

Topics: Dietary Supplements; Double-Blind Method; Humans; Infant; Inflammation; Insulins; Male; Muscle, Skeletal; Muscles; Myalgia; Randomized Controlled Trials as Topic

In a randomized, triple-blind, placebo-controlled clinical trial (RCT) including 50 infertile women with endometriosis candidate for assisted reproductive techniques (ART), we studied the effect of Astaxanthin (AST) on pro-inflammatory cytokines, oxidative stress (OS) markers, and early pregnancy outcomes.. Before and after 12 weeks of AST treatment (6 mg per day), blood serum and follicular fluid (FF) samples were collected from 50 infertile women with endometriosis stage III/IV undergoing ART. Pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and OS markers (malondialdehyde [MDA], superoxide dismutase [SOD], catalase [CAT], and total antioxidant capacity [TAC]) were measured in the serum and FF. ART outcomes were also compared between the groups.. Increased serum levels of TAC (398.661 ± 57.686. AST pretreatment can modulate inflammation and OS in endometriosis-induced infertile patients. ART outcomes also improved after 12 weeks of AST therapy. Our results suggest that AST can be a potential therapeutic target for infertile patients with endometriosis undergoing ART.

Topics: Antioxidants; Case-Control Studies; Endometriosis; Female; Fibrinolytic Agents; Follicular Fluid; Humans; Infertility, Female; Inflammation; Interleukin-6; Oxidative Stress; Pregnancy; Pregnancy Outcome; Superoxide Dismutase; Tumor Necrosis Factor-alpha

There is evidence that renal transplant recipients have accelerated atherosclerosis that is manifest by increased cardiovascular morbidity and mortality. The high incidence of atherosclerosis is, in part, related to increased arterial stiffness, vascular dysfunction, elevated oxidative stress, and inflammation associated with immunosuppressive therapy. The carotenoid astaxanthin has shown potent antioxidant and anti-inflammatory properties.. The aim was to investigate the effects of oral astaxanthin on arterial stiffness, oxidative stress, and inflammation in renal transplant recipients.. This trial used a randomized, placebo-controlled, double-blind design in which 61 patients received either 12 mg astaxanthin/d or an identical placebo orally for 1 y. Primary outcomes were 1) arterial stiffness measured by aortic pulse wave velocity (PWV), 2) oxidative stress assessed by total plasma F2-isoprostanes, and 3) inflammation assessed by plasma pentraxin-3. Secondary outcomes included vascular function, carotid artery intima-media thickness, augmentation index, central blood pressure, subendocardial viability ratio, and additional measures of oxidative stress and inflammation. Patients underwent assessments at baseline and at 6 and 12 mo.. Fifty-eight participants completed the study. There were no significant between-group differences in the changes in any of the primary outcome measures (PWV changed by +9.5% and +6.0%, F2-isoprostanes changed by -3.0% and -9.7%, and pentraxin-3 changed by +50.6% and -11.0% in the placebo and astaxanthin groups, respectively). There were no significant between-group differences in secondary outcome measures. Larger-than-expected variability decreased the power of the study and increased the possibility of a type 2 statistical error.. Astaxanthin (12 mg/d for 12 mo) had no effect on arterial stiffness, oxidative stress, or inflammation in renal transplant recipients. This trial was registered at the Australian New Zealand Clinical Trials Registry (http://www.anzctr.org.au/) as ACTRN12608000159358.

Topics: Adult; Anti-Inflammatory Agents; Antioxidants; Atherosclerosis; C-Reactive Protein; Double-Blind Method; F2-Isoprostanes; Female; Humans; Immunosuppression Therapy; Inflammation; Kidney; Kidney Transplantation; Male; Middle Aged; Oxidative Stress; Pulse Wave Analysis; Serum Amyloid P-Component; Vascular Stiffness; Xanthophylls

Young (2.97±0.01 yr; 8.16±0.15 kg BW) and geriatric (10.71±0.01 yr; 9.46±0.18 kg BW) healthy female Beagle dogs (n=14/age group) were fed 0 or 20 mg astaxanthin daily for 16 wk to examine modulation of mitochondrial function. Fasted blood was sampled on wk 0, 8, and 16. Mitochondria membrane permeability, ATP production, cytochrome c oxidase/reductase, and number were assessed in leukocytes whereas astaxanthin uptake, glutathione, superoxide dismutase, nitric oxide, 8-hydroxy-2'-deoxyguanosine, 8-isoprostane, and protein carbonyl were measured in plasma. Aging increased (P<0.05) complex III cytochrome c oxidoreductase but decreased (P<0.05) 8-hydroxy-2'-deoxyguanosine and protein carbonyl. Mitochondrial function improved in both young and geriatric dogs by increasing (P<0.05) ATP production, mitochondria mass, and cytochrome c oxidoreductase activity, especially in geriatric dogs compared with young dogs. Astaxanthin feeding also increased (P<0.05) the reduced glutathione to oxidized glutathione ratio in young dogs and decreased (P<0.05) nitric oxide in both young and geriatric dogs. Dietary astaxanthin improved mitochondrial function in blood leukocytes, most likely by alleviating oxidative damage to cellular DNA and protein.

Topics: Aging; Animal Feed; Animals; Biomarkers; Cell Membrane; Diet; Dog Diseases; Dogs; Female; Inflammation; Leukocytes; Mitochondria; Mitochondrial Diseases; Oxidative Stress; Permeability; Xanthophylls

The chronic active inflammation caused by Helicobacter pylori is dominated by neutrophils, macrophages, lymphocytes and plasma cells. Several interleukins are involved in the inflammatory process. The aim of this study was to investigate the effect of astaxanthin on gastric inflammation in patients with functional dyspepsia. Forty-four consecutive patients were included, and biopsies were examined for IL-4, IL-6, IL-8, IL-10, interferon-gamma, CD4, CD8, CD14, CD19, CD25 and CD30. Patients were randomized: 21 patients were treated with 40 mg of astaxanthin daily, and 23 patients were treated with a placebo. There was a significant decrease in gastric inflammation in H. pylori-positive patients from both groups. There were no significant changes in the density of H. pylori or in any of the interleukins during or after treatment. There was a significant up-regulation of CD4 and down-regulation of CD8 in patients with H. pylori treated with astaxanthin. Astaxanthin had an effect on the inflammation and on the density of H. pylori in mice in a study where the diet could be standardized without antioxidants (Bennedsen et al., 1999). These dietary conditions are impossible in studies involving humans, and may be due to the minor effect when the host have access to antioxidants in their diet.

Topics: Adult; Aged; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antigens, CD; Biomarkers; Biopsy; Colony Count, Microbial; Cytokines; Disease Models, Animal; Dyspepsia; Female; Helicobacter Infections; Humans; Inflammation; Male; Mice; Middle Aged; Stomach; Xanthophylls

Oxidative stress and chronic inflammation play key roles in the pathogenesis of chronic obstructive pulmonary disease (COPD). Astaxanthin (AXT) is a keto-carotenoid with a variety of biological functions, including antioxidant and anti-inflammatory effects This study aimed to explore the protective role and underlying mechanism of AXT in the pathogenesis of COPD. In this study, we found AXT alleviated pulmonary emphysema in a CS-exposed mouse model and regulated the expression of MMP-9/TIMP-1. And, AXT attenuates CSE-induced small airway fibrosis. Meanwhile, AXT inhibited Nrf2-modulated oxidative stress and the p65 NF-κB-regulated inflammatory pathway in both the mouse model and CSE-treated HBE cells. Mechanistically, AXT could directly bind to SIRT1 (the binding energy of the complex was -8.8 kcal/mol) and regulate the deacetylation activity of SIRT1. Finally, by activating SIRT1 deacetylation, AXT deacetylated Nrf2 and contributed to its action of reducing oxidative stress by generating antioxidant enzymes, and inhibiting p65 NF-κB transcriptional activity to suppress the inflammatory response. Our results show that treatment with AXT significantly reverses the oxidative stress and inflammation induced by cigarette smoke both in vivo and in vitro in a sirtuin 1-dependent manner.

Topics: Animals; Antioxidants; Cigarette Smoking; Disease Models, Animal; Inflammation; Mice; NF-E2-Related Factor 2; NF-kappa B; Nicotiana; Oxidative Stress; Pulmonary Disease, Chronic Obstructive; Sirtuin 1

Topics: Acetylcholinesterase; Animals; Anti-Inflammatory Agents; Antioxidants; Catalase; Drosophila melanogaster; Humans; Hydrogen Peroxide; Inflammation; Kelch-Like ECH-Associated Protein 1; Molecular Docking Simulation; NF-E2-Related Factor 2; Oxidative Stress; Sulfhydryl Compounds

The pathophysiology of diabetic retinopathy (DR) is thought to be influenced by oxidative stress. Astaxanthin (ASX) is a natural product with antioxidant effect, but it is not clear whether its mechanism of inhibiting the development of DR is related to anti-oxidation.. Rats were intraperitoneally injected with streptozotocin (60 mg/kg) to create DR rat models followed by ASX (20 mg/kg) for 45 days. Retinal tissue was examined by Hematoxylin and Eosin staining. By using Enzyme-linked immunosorbent assay (ELISA), 2,7-Dichlorodrhydrofluorescein diace (DCFH-DA) probes, immunohistochemistry and western blot, it was feasible to evaluate the contents of inflammation-related factors (tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6 and macrophage inhibitory cytokine-1 (MIC-1)), oxidative stress-related indicators (glutathione (GSH), malonic dialdehyde (MDA), glutathione peroxidase (GPx), reactive oxygen species (ROS) and Total antioxidant capacity (T-AOC)), antioxidant enzymes (hemoxgenase-1(HO-1) and Quinone Oxidoreductase 1 (NQO1)), and apoptosis-related proteins (Bcl-2, Bcl2 Associated X Protein (BAX), and cleaved-caspase-3). Additionally, antioxidant proteins downstream of the nuclear factor E2 related factors (Nrf-2) pathway, expression levels of Nrf2/ Kelch-like ECH-associated protein 1(Keap 1) pathway-associated proteins, and nuclear and cytoplasmic levels of Nrf2 were assessed using immunohistochemistry, western blot, or quantitative real-time polymerase chain reaction (qRT-PCR).. ASX alleviated retinal tissue damage by increasing overall retina thickness and ganglion cell layer (GCL) cell numbers and exerted the anti-inflammatory, anti-oxidative stress, and anti-apoptosis effects in DR rats. Additionally, ASX could inhibit the expression of Keap1, promote the transport of Nrf2 from cytoplasm to nucleus and facilitate the expressions of HO-1, NQO1, γ-glutamylcysteine synthetase, (γ-GCS) and GPx.. ASX exerted antioxidant effects through Nrf2/keap1 pathway, thereby alleviating apoptosis, inflammation, and oxidative stress in retinal tissues of DR rats.

Topics: Animals; Antioxidants; Diabetes Mellitus; Diabetic Retinopathy; Glutathione; Inflammation; Kelch-Like ECH-Associated Protein 1; NF-E2-Related Factor 2; Oxidative Stress; Rats

Astaxanthin (AXT) is a lipophilic antioxidant and anti-inflammatory natural pigment whose cellular uptake and bioavailability could be improved via liposomal encapsulation. Endothelial cells (EC) line the lumen of all blood vessels and are tasked with multiple roles toward maintaining cardiovascular homeostasis. Endothelial dysfunction is linked to the development of many diseases and is closely interconnected with oxidative stress and vascular inflammation. The uptake of free and liposomal AXT into EC was investigated using Raman and fluorescence microscopies. AXT was either encapsulated in neutral or cationic liposomes. Enhanced uptake and anti-inflammatory effects of liposomal AXT were observed. The anti-inflammatory effects of liposomal AXT were especially prominent in reducing EC lipid unsaturation, lowering numbers of lipid droplets (LDs), and decreasing intercellular adhesion molecule 1 (ICAM-1) overexpression, which is considered a well-known marker for endothelial inflammation. These findings highlight the benefits of AXT liposomal encapsulation on EC and the applicability of Raman imaging to investigate such effects.

Topics: Endothelial Cells; Humans; Inflammation; Liposomes; Optical Imaging

Defective degradation and clearance of amyloid-β as well as inflammation per se are crucial players in the pathology of Alzheimer's disease (AD). A defective transport across the blood-brain barrier is causative for amyloid-β (Aβ) accumulation in the brain, provoking amyloid plaque formation. Using primary porcine brain capillary endothelial cells and murine organotypic hippocampal slice cultures as in vitro models of AD, we investigated the effects of the antioxidant astaxanthin (ASX) on Aβ clearance and neuroinflammation. We report that ASX enhanced the clearance of misfolded proteins in primary porcine brain capillary endothelial cells by inducing autophagy and altered the Aβ processing pathway. We observed a reduction in the expression levels of intracellular and secreted amyloid precursor protein/Aβ accompanied by an increase in ABC transporters ABCA1, ABCG1 as well as low density lipoprotein receptor-related protein 1 mRNA levels. Furthermore, ASX treatment increased autophagic flux as evidenced by increased lipidation of LC3B-II as well as reduced protein expression of phosphorylated S6 ribosomal protein and mTOR. In LPS-stimulated brain slices, ASX exerted anti-inflammatory effects by reducing the secretion of inflammatory cytokines while shifting microglia polarization from M1 to M2 phenotype. Our data suggest ASX as potential therapeutic compound ameliorating AD-related blood brain barrier impairment and inflammation.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Animals; Anti-Inflammatory Agents; Autophagy; Blood-Brain Barrier; Disease Models, Animal; Endothelial Cells; Inflammation; Mice; Mice, Transgenic; Swine

Topics: Animals; Carps; Ecosystem; Head Kidney; Homeostasis; Inflammation; Lymphocytes; Microplastics; MicroRNAs; Mitochondria; Necroptosis; Plastics; Polystyrenes

As a fat-soluble carotenoid, astaxanthin has excellent antioxidant and anti-inflammation biological activities, but its poor biocompatibility and low stability limit application of astaxanthin in the food industry. In this study, cauliflower-like carriers (CCs) were constructed based on caseinate, chitosan-triphenylphosphonium (TPP) and sodium alginate through an electrostatic self-assembly method to improve the biocompatibility, stability and targeting transport properties of astaxanthin. The smart CCs showed pH-response release and mitochondrial targeted characteristics. In vitro studies demonstrated that the CCs could improve the internalization of astaxanthin, and significantly inhibited the excessive production of reactive oxygen species and the depolarization of mitochondrial membrane potential caused by oxidative stress. In vivo studies revealed that the astaxanthin-loaded CCs could effectively relieve the colitis induced by dextran sodium sulfate and protect the integrity of the colon tissue structure. The astaxanthin-loaded CCs could significantly inhibit the expression of inflammation factors such as interleukin-1β, interleukin-6, tumor necrosis factor alpha, cyclooxygenase-2, myeloperoxidase, inducible nitric oxide synthase, and nitric oxide. Moreover, the astaxanthin-loaded CCs could maintain the expression of zonula occludens-1, increase the abundance of Firmicutes and Lactobacillaceae in the intestine. In a word, the constructed astaxanthin delivery system provided a potential application for the oral uptake hydrophobic bio-activator in intervention of ulcerative colitis.

Topics: Colitis; Colitis, Ulcerative; Colon; Dextran Sulfate; Humans; Inflammation; Xanthophylls

Ultrasound (US) has been reported to improve the permeability of cell membranes to pharmaceuticals by causing cavitation. Astaxanthin (AX) potently terminates the induction of inflammation, but it has low oral bioavailability, which limits its incorporation in local cells and organs and its therapeutic potential. In this study, we aimed to investigate the contribution of US to AX incorporation to compensate for the limited incorporation of AX, and regulation of the pro-inflammatory factor interleukin-1β (IL-1β) by AX.. Murine bone marrow-derived macrophages were stimulated by lipopolysaccharide (LPS). After 2 h, cells were treated with 10 μM AX and/or pulsed high-intensity US irradiation. The cells were then incubated for another 3 h and harvested. AX incorporation in cells was measured by absorbance, and the expression of IL-1β was measured by qPCR. All values are expressed as means ± standard error of the mean.. The combination of AX and US significantly increased AX incorporation in cells compared to AX alone (p < 0.05). In addition, this combination further suppressed the expression of IL-1β compared to AX alone (p < 0.05).. Pulsed high-intensity US irradiation combined with AX treatment promoted AX incorporation in cells and enhanced the anti-inflammatory effect on macrophages.

Topics: Animals; Humans; Inflammation; Lipopolysaccharides; Macrophages; Mice; Xanthophylls

We first explore whether aircraft noise (AN) induces cognitive deficit via inducing oxidative damage in multiple vital organs including intestines, hearts and hippocampus tissues. Second, we explore whether the AN-induced cognitive deficits and inflammatory and oxidative damage to multiple organs can be alleviated by Astaxanthin (AX) pretreatment.. Cognitive deficits were induced by subjecting the mice to AN 2 h daily for 7 consecutive days. An intragastrical dose of AX emulsifier (at the dose of daily feed intake [6 g] of a mouse three times weekly) was given to mice for consecutive 8 weeks prior to the start of AN. Cognitive functions were evaluated by using passive avoidance apparatus, Y-maze, Morris water maze and novel recognition test. Intestinal permeability was determined by measuring the intestinal clearance of fluorescein-isothiocyante. Evans Blue extravasation assay was used to measure the permeability of blood-brain-barrier. Inflammatory and oxidative damage to multiple organs were determined by measuring several pro-inflammatory cytokines and oxidative stress indicators in intestines; hearts and hippocampus.. Mice treated with AN displayed exacerbated stress reactions, cognitive deficits, gut barrier hyperpermeability, increased upload of lipopolysaccharide translocation, systemic pro-inflammatory cytokines overproduction, blood-brain-barrier hyperpermeability, hippocampal neuroinflammation and increased levels of oxidative stress indicators in intestine, heart and hippocampus. All of the above-mentioned disorders caused by AN were significantly (P < 0.05) reversed by AX.. Our data indicate that AX pretreatment alleviates cognitive deficits in aircraft noised mice by attenuating inflammatory and oxidative damage to intestines, hearts and hippocampal tissues.

Topics: Aircraft; Animals; Cognitive Dysfunction; Heart; Hippocampus; Inflammation; Intestinal Absorption; Intestines; Male; Mice; Mice, Inbred C57BL; Noise, Transportation; Oxidative Stress; Xanthophylls

Astaxanthin has been reported to possess anti-inflammatory effect but the exact mechanism in protecting the retinal pigment epithelial (RPE) cells is not clear. Hence, we hypothesized that astaxanthin could protect RPE by inhibiting ROS-mediated inflammation. The purpose of this study is to understand the retinal protective mechanism of astaxanthin in modulating hyperglycemia (HG) induced inflammation in ARPE-19 cell and diabetic rat retina. ARPE-19 cells were treated with 30 mM glucose to induce hyperglycemia whereas diabetes was induced in rats with streptozotocin followed by astaxanthin treatment. The level of oxidative stress markers, antioxidant enzyme activity, inflammatory markers (NF-κB, TNF-α, ICAM-1), signaling mediators (PI3K, p-Akt) and nuclear translocation of NF-κB were analyzed in ARPE-19 cells and rat retina. HG-mediated ROS generation and lipid peroxidation were declined upon astaxanthin treatment in ARPE-19 cells. Similarly, astaxanthin treatment found to reduce the elevated levels of nitric oxide, protein carbonyl, and lipid peroxides in diabetic group. Astaxanthin restored the activity of superoxide dismutase, catalase, glutathione peroxidase, and glutathione transferase in serum and retina of diabetic rats. NF-κB, TNF-α, and ICAM-1 levels were higher in HG-treated ARPE-19 cells and diabetic retina compared to control group, whereas astaxanthin treatment lowered their expression. PI3K and p-Akt were higher in high glucose treated ARPE-19 cells and diabetic retina. NAC, LY294002 and PDTC treatment resulted in reduced nuclear translocation of NF-κB and decreased expression of inflammatory markers in HG treated ARPE-19 cells. Thus, we conclude that astaxanthin protected the retinal cells from HG-induced inflammation by modulating NF-κB through ROS-PI3K/Akt signaling cascade.

Topics: Animals; Antioxidants; Diabetes Mellitus, Experimental; Glucose; Hyperglycemia; Inflammation; Intercellular Adhesion Molecule-1; NF-kappa B; Oxidative Stress; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Rats; Reactive Oxygen Species; Retina; Tumor Necrosis Factor-alpha; Xanthophylls

Ferroptosis is a form of regulated nonapoptotic cell death associated with iron-dependent lipid peroxidation. Previous studies have shown that ferroptosis is involved in the occurrence and development of acute lung injury (ALI). In this study, a systems pharmacology approach was performed through the overall process of target acquisition, network construction, and further analysis. Then, the effects of astaxanthin on LPS-induced inflammation and ferroptosis were investigated in RAW264.7 cells induced by LPS in vitro and ALI mice induced by LPS in vivo. The enrichment analysis of astaxanthin-target gene is closely related to the occurrence and development mechanism of ferroptosis. GO and KEGG enrichment analysis of astaxanthin acting on ALI found that these intersection genes are associated with ALI inflammatory pathway. In addition, astaxanthin can effectively inhibit LPS-induced production of pro-inflammatory cytokines and ferroptosis in RAW264.7 cells. Consistently, administration of astaxanthin protected mice against LPS-induced ALI and significantly decreased the extent of lung edema, inflammatory cells infiltration, and ferroptosis in vivo, and Keap1-Nrf2/HO-1 pathway is involved in astaxanthin inhibits LPS-induced ALI and ferroptosis. Taken together, these results demonstrate that astaxanthin inhibit inflammation and ferroptosis by regulating Keap1-Nrf2/HO-1 pathway to reduce LPS-induced ALI.

Topics: Acute Lung Injury; Animals; Ferroptosis; Inflammation; Kelch-Like ECH-Associated Protein 1; Lipopolysaccharides; Lung; Mice; NF-E2-Related Factor 2; Signal Transduction

Acute lung injury (ALI) is a systemic inflammatory process. A large number of studies have shown that astaxanthin (ASTA) has strong anti-inflammatory effects and almost non-toxic side effects. The purpose of this study was to explore the effect of ASTA on lipopolysaccharide (LPS)-induced ALI in mice and its underlying mechanism. The result showed that compared with the LPS group, the expression levels of the respiratory resistance (Re), inspiratory resistance (Ri), dynamic lung compliance (Cdyn), wet/dry weight (W/D) ratio, albumin (BA/SA) ratio and myeloperoxidase (MPO) activity in the ASTA pretreatment group were significantly reduced, and total cell, neutrophil and macrophage counts were significantly decreased. HE staining results showed that alveolar interstitial edema, bleeding and erythrocyte exudation were reduced. Compared with the LPS group, the percentage of Th17 cells and the content of interleukin (IL)-17 and tumor necrosis factor-α (TNF-α) in the ASTA pretreatment group were significantly decreased, while the content of the transforming growth factor (TGF)-β and the percentage of Treg cells were significantly increased. Western blot analysis showed that ASTA could up-regulate the expression level of the suppressor of cytokine signaling-3 (SOCS3) and down-regulate the expression levels of phosphorylated Janus kinase 2 (p-JAK2), phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in lung tissue. The results showed that ASTA had a protective effect on LPS-induced acute lung injury in mice, and its protective mechanism was through activating the SOCS3/JAK2/STAT3 signaling pathway, promoting Treg cell differentiation and reducing inflammatory reactions and Th17 cell differentiation, which provided a theoretical basis for the clinical treatment of ALI.

Topics: Acute Lung Injury; Animals; Inflammation; Janus Kinase 2; Lipopolysaccharides; Lung; Mice; Signal Transduction; Suppressor of Cytokine Signaling 3 Protein; Transforming Growth Factor beta

We aimed to compare biochemical and histopathological findings of astaxanthin's potential effects on oxidative stress in ischemia/reperfusion damage (I/R).. Thirty-two rats were randomly divided into four groups: control group; I/R group; I/R + treatment group; drug group. Astaxanthin was orally administered to groups C and D for 14 days. In groups B and C, the femoral artery was clamped for 2 h to form ischemia. The clamp was opened, and reperfusion was performed for 1 h. In all groups, 4 ml of blood sample through intracardiac puncture and gastrocnemius muscle tissue samples were collected. Serum and tissue samples were analyzed by measuring malondialdehyde (MDA), superoxide dismutase (SOD), total antioxidant capacity (TAC), and total oxidative level (TOL). Necrosis, inflammation, and caspase-3 in muscle tissue collected for histopathological examination were evaluated.. Tissue MDA, SOD and TOL values significantly differed between groups. Serum MDA, SOD, TOL and TAC values significantly differed between groups. On necrosis examination, there was a significant difference between groups B and C. Although signs of inflammation significantly differed between groups, there was no significant difference between groups A and C and groups A and D. Although there was a significant difference in caspase-3 results between groups, there was no significant difference between groups A and C.. The use of astaxanthin before and after surgery showed preventive or therapeutic effects against I/R damage.

Topics: Animals; Antioxidants; Caspase 3; Inflammation; Necrosis; Oxidative Stress; Rats; Reperfusion Injury; Superoxide Dismutase; Xanthophylls

Astaxanthin, originating from marine organisms, is a natural bioactive compound with powerful antioxidant activity. Here, we evaluated the antioxidant ability of astaxanthin on dendritic cells (DCs), a key target of immune regulation, for inflammatory control in a sepsis model. Our results showed that astaxanthin suppressed nitric oxide (NO) production, reactive oxygen species (ROS) production, and lipid peroxidation activities in LPS-induced DCs and LPS-challenged mice. Moreover, the reduced glutathione (GSH) levels and the GSH/GSSG ratio were increased, suggesting that astaxanthin elevated the level of cellular reductive status. Meanwhile, the activities of antioxidant enzymes, including glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD), were significantly upregulated. Astaxanthin also inhibited the LPS-induced secretions of IL-1β, IL-17, and TGF-β cytokines. Finally, we found that the expressions of heme oxygenase 1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2) were significantly upregulated by astaxanthin in LPS-induced DCs, suggesting that the HO-1/Nrf2 pathway plays a significant role in the suppression of oxidative stress. These results suggested that astaxanthin possesses strong antioxidant characteristics in DC-related inflammatory responses, which is expected to have potential as a method of sepsis treatment.

Topics: Animals; Antioxidants; Aquatic Organisms; Cytokines; Dendritic Cells; Disease Models, Animal; Inflammation; Lipopolysaccharides; Mice; Mice, Inbred C57BL; Oxidative Stress; Random Allocation; Xanthophylls

Inflammation is an important pathological feature of hyperuricemia, which in turn aggravates hyperuricemia. Astaxanthin is a carotenoid with strong antioxidant capacity and possesses many biological activities. This study was aimed to evaluate the effect of astaxanthin (ASX) on hyperuricemia and kidney inflammation in potassium oxonate (PO) and hypoxanthine (HX)-induced hyperuricemic mice. Male ICR mice were administered intragastrically with PO and HX (250 mg/kg, respectively) for 14 days. ASX was given by gavage one hour after PO and HX administration. ASX treatment significantly reversed PO and HX-induced hyperuricemia and kidney inflammation in mice as evidenced by decreased serum levels of uric acid (UA), creatinine (Cr), blood urea nitrogen (BUN), and inflammatory factors (IL-1β, IL-6, and TNF-α) and increased activities of antioxidant enzymes (CAT, SOD and GSH-Px). Furthermore, ASX administration effectively inhibited the activities of key enzymes related to UA synthesis (xanthine oxidase (XOD) and adenosine deaminase (ADA)) and modulated the protein expressions of NF-κ B p65, p-NF-κ B p65, Iκ Bα, p-Iκ Bα, NLRP3, ASC, Caspase-1, and cleavedCaspase-1 involved in inflammation pathways. Our results suggested that ASX improved hyperuricemia and kidney inflammation induced by PO and HX, probably by reducing UA synthesis and suppressing the NF-κ B and NLRP3 pathways simultaneously.

Topics: Animals; Antioxidants; Hyperuricemia; Hypoxanthine; Inflammation; Kidney; Male; Mice; Mice, Inbred ICR; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Oxonic Acid; Signal Transduction; Transcription Factor RelA; Uric Acid; Xanthine Oxidase; Xanthophylls

Recently, obesity-induced insulin resistance, type 2 diabetes, and cardiovascular disease have become major social problems. We have previously shown that Astaxanthin (AX), which is a natural antioxidant, significantly ameliorates obesity-induced glucose intolerance and insulin resistance. It is well known that AX is a strong lipophilic antioxidant and has been shown to be beneficial for acute inflammation. However, the actual effects of AX on chronic inflammation in adipose tissue (AT) remain unclear. To observe the effects of AX on AT functions in obese mice, we fed six-week-old male C57BL/6J on high-fat-diet (HFD) supplemented with or without 0.02% of AX for 24 weeks. We determined the effect of AX at 10 and 24 weeks of HFD with or without AX on various parameters including insulin sensitivity, glucose tolerance, inflammation, and mitochondrial function in AT. We found that AX significantly reduced oxidative stress and macrophage infiltration into AT, as well as maintaining healthy AT function. Furthermore, AX prevented pathological AT remodeling probably caused by hypoxia in AT. Collectively, AX treatment exerted anti-inflammatory effects via its antioxidant activity in AT, maintained the vascular structure of AT and preserved the stem cells and progenitor's niche, and enhanced anti-inflammatory hypoxia induction factor-2α-dominant hypoxic response. Through these mechanisms of action, it prevented the pathological remodeling of AT and maintained its integrity.

Topics: Adipose Tissue; Animals; Anti-Inflammatory Agents; Antioxidants; Cytokines; Dietary Supplements; Glucose; Inflammation; Inflammation Mediators; Insulin Resistance; Macrophages; Male; Mice, Inbred C57BL; Mitochondria; Oxidative Stress; Xanthophylls

This study aimed to ascertain the effects of astaxanthin on the lungs of rat pups with bronchopulmonary dysplasia (BPD) induced by hyperoxia and lipopolysaccharide (LPS).. Forty-two newborn Wistar rats, born to spontaneous pregnant rats, were divided into three groups: Hyperoxia (95% O2) + lipopolysaccharide (LPS) group, hyperoxia + LPS + astaxhantin group, and control: no treatment group (21% O2). Pups in the hyperoxia + LPS + astaxanthin group were given 100 mg/kg/day oral astaxanthin from the first day to the fifth day. Histopathologic and biochemical evaluations, including glutathione (GSH), total anti-oxidant status (TAS), total oxidant status (TOS), lipid hydroperoxide (LPO), 8-hydroxydeoxyguanosine (8-OHdG), advanced oxidation protein products (AOPP), myeloperoxidase (MPO), total thiol, tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1β), and caspase-3 activities, were performed.. Better survival rates and weight gain were demonstrated in the hyperoxia + LPS + astaxanthin group (p <0.001). In the histopathologic evaluation, the severity of lung damage was significantly reduced in the hyperoxia+LPS+astaxanthin group, as well as decreased apoptosis (ELİSA for caspase-3) (p <0.001). The biochemical analyses of lung tissues showed that TAS, GSH, and Total thiol levels were significantly higher in the astaxanthin treated group compared to the hyperoxia + LPS group (p <0.05) while TOS, AOPP, LPO, 8-OHdG, MPO levels were significantly lower (p <0.001). In addition, unlike the hyperoxia + LPS group, TNF-α and IL-1β levels in lung tissue were significantly lower in the astaxanthin-treated group (p <0.001).. Astaxanthin was shown to reduce lung damage caused by inflammation and hyperoxia with its anti-inflammatory, anti-oxidant, anti-apoptotic properties, and to protect the lung from severe destruction.

Topics: Animals; Animals, Newborn; Disease Models, Animal; Female; Hyperoxia; Inflammation; Lung; Lung Injury; Pregnancy; Rats; Rats, Wistar; Xanthophylls

We previously demonstrated that astaxanthin (ASTX), a xanthophyll carotenoid, repressed ethanol-induced inflammation and oxidative stress in macrophages. We explored the role of sirtuin 1 (SIRT1) and histone deacetylase 4 (HDAC4) in the inhibitory effect of ASTX on inflammation and oxidative stress in macrophages exposed to ethanol. Ethanol decreased mRNA and protein of SIRT1 while increasing those of HDAC4, which was attenuated by ASTX in RAW 264.7 macrophages and mouse bone marrow-derived macrophages (BMDMs). Inhibition of SIRT1 expression or activity augmented ethanol-induced Hdac4 expression, but SIRT1 activation elicited the opposite effect. Consistently, Hdac4 knockdown increased Sirt1 expression with decreases in ethanol-induced inflammatory gene expression, but its overexpression resulted in the opposite effects. Furthermore, BMDMs from mice with macrophage specific-deletion of Hdac4 (Hdac4

Topics: Adenosine Triphosphate; Animals; Antioxidants; Ethanol; Gene Expression Regulation; Glycolysis; Histone Deacetylases; Inflammation; Macrophages; Mice; Mice, Knockout; Mitochondria; Organelle Biogenesis; Oxidative Phosphorylation; Oxidative Stress; Primary Cell Culture; RAW 264.7 Cells; Reactive Oxygen Species; Sirtuin 1; Xanthophylls

Astaxanthin is a natural carotenoid, can readily cross the blood-brain barrier and exerts a powerful neuroprotective effect. In this study, experiments were performed to explore the underlying molecular mechanisms of which Astaxanthin inhibiting the microglia M1 activation.. BV2 cells and mice were pre-treated with Astaxanthin and treated by Lipopolysaccharide (LPS). The expressions of M1-related factors (pro-inflammatory cytokines and M1 markers) were measured by RT-qPCR and western blot. The target association between miR-31-5p and Numb was explored via luciferase activity assay. MiR-31-5p mimic was transfected into BV2 cells, then the cells were treated with Astaxanthin in combination with LPS. The expression of M1-related factors and Notch pathway-related molecules were measured via RT-qPCR, western blot and immunofluorescence assay.. Precondition of BV2 cells with Astaxanthin inhibited the expression of M1-related factors triggered by LPS. In addition, Astaxanthin decreased the number of Iba1-positive microglia and downregulated the levels of M1-related factors in hippocampus in LPS-treated mice. Further investigation revealed that Astaxanthin-mediated suppression of M1-related factors levels was reversed by miR-31-5p mimic in BV2 cells stimulated by LPS. Subsequently, we verified that miR-31-5p repressed Numb expression by binding to the 3'-UTR of Numb mRNA. Also, Astaxanthin suppressed the expression of Notch1, Hes1 and Hes5 and improved the expression of Numb in BV2 cells challenged by LPS, but this alteration can be reversed by miR-31-5p mimic.. Our study demonstrated that down-regulating miR-31-5p by Astaxanthin could be a potential therapeutic approach to suppress neuroinflammation via regulating microglia M1 activation.

Topics: Animals; Brain; Cell Line; Cytokines; Hippocampus; Inflammation; Lipopolysaccharides; Macrophage Activation; Male; Mice; Mice, Inbred C57BL; Microglia; MicroRNAs; NF-kappa B; Signal Transduction; Xanthophylls

Astaxanthin (AST) has been shown to have neuroprotective effects; however, its bioavailability in vivo is low due to its hydrophobic properties. In this study, lactoferrin (LF) was prepared by heat-treatment at different temperatures, and on this basis, a layer-by-layer self-assembly method was used to construct double-layer emulsions with LF as the inner layer and polysaccharide (beet pectin, BP or carboxymethyl chitosan, CMCS) as the outer layer. Then AST was encapsulated in the emulsions and their physiochemical properties and function were investigated. The results indicated that high temperature heated LF (95 °C) showed a more stable structure than the lower temperature one, and the exposed internal nonpolar groups of LF could give the emulsion an enhanced stability. The rheology results showed that compared with CMCS, the double-layer emulsion formed by BP had a higher viscosity. In addition, the 95 °C LF-AST-BP emulsion showed the best stability among all the bilayer emulsions. The best emulsion was then used as a model drug to investigate its effects on lipopolysaccharide (LPS)-induced neuroinflammation and learning-memory loss in C57BL/6J mice. Through animal behavioral experiments, it was found that dietary supplementation with the AST emulsion could effectively improve the brain cognitive and learning memory impairment caused by inflammation. Transmission electron microscopy, mRNA and western blotting results also illustrated that the AST emulsion could alleviate neuroinflammation caused by LPS. This study provides a feasible scheme for exploring an AST loaded system and may be suitable for food and drug applications.

Topics: Animals; Brain; Chemical Phenomena; Emulsions; Inflammation; Lipopolysaccharides; Locomotion; Male; Mice; Mice, Inbred C57BL; Nerve Growth Factors; Particle Size; Pectins; Rheology; Viscosity; Xanthophylls

Astaxanthin (AST), a natural antioxidant carotenoid, has been shown to exert anti-inflammatory effects. However, to our knowledge, no study has specifically addressed the potential protective effects of AST against bovine endometritis. The purpose of this study was to examine whether treatment with AST could protect endometrial epithelial cells against lipopolysaccharide (LPS)-induced inflammatory injury. Treatment of bovine endometrial (BEND) epithelial cell line with AST reduced LPS-induced production of interleukin-6 and tumor necrosis factor-alpha, increased the cellular activity of superoxide dismutase and catalase, decreased the proportion of apoptotic cells, and promoted the production of insulin-like growth factor and epithelial growth factor. The effects of AST were mediated through the downregulation of B-cell lymphoma 2 (Bcl-2) associated X, apoptosis regulator (Bax), and cleaved caspase-3 and through the upregulation of Bcl-2. Moreover, AST significantly increased the expression of the tight junction proteins (TJP) claudin, cadherin-1, and TJP1, which play an essential role in the maintenance of host endometrial defense barrier against pathogen infection. Collectively, these results demonstrated that treatment with AST protected against oxidative stress, prevented cell apoptosis, promoted BEND cells viability, and increased the production of growth factors, in addition to activating the endometrial defense barrier. Therefore, AST is a promising therapeutic agent for the prevention and treatment of endometritis. This finding is of utmost importance in the present times when the excessive use of antibiotics has resulted in the development of antibiotic-resistant bacteria.

Topics: Animals; Apoptosis; Catalase; Cattle; Cell Survival; Endometrium; Epithelial Cells; Female; Inflammation; Interleukin-6; Lipopolysaccharides; Oxidative Stress; Protective Agents; Superoxide Dismutase; Tumor Necrosis Factor-alpha; Xanthophylls

Astaxanthin (ATX), a natural xanthophyll carotenoid, has shown to exert significant protective effects against various diseases via its antioxidant and anti-inflammatory properties. However, its potential role in arthritis is still not reported. Therefore, the aim of the present study was to investigate the potential anti-arthritic properties of ATX against complete Freund's adjuvant (CFA)-induced arthritis rats.. Adjuvant arthritis was induced by single intraplantar injection of complete Freund's adjuvant (CFA) in the left hind paw of adult female Wistar rats. ATX (25, 50 and 100 mg/kg) and indomethacin (5 mg/kg) were given orally from days 14 to 28. The anti-arthritic activity was evaluated through various nociceptive behavioral tests (mechanical allodynia, mechanical hyperalgesia, cold allodynia, and thermal hyperalgesia), paw edema assessment, and arthritis scores. Serum tumor necrosis factor-α (TNF-α), C-reactive protein (CRP) and cyclic citrullinated peptide (CCP) antibody levels were assessed. Moreover, malondialdehyde (MDA), nitrite, glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) levels were also evaluated.. Oral administration of ATX (50 and 100 mg/kg) exhibited significant anti-arthritic activity via enhancing the nociceptive threshold, reducing paw edema and improving arthritis scores. Moreover, ATX treatment also markedly suppressed inflammatory and oxidative mediators in adjuvant-administered rats.. Our findings suggest that ATX possesses potential anti-arthritic activity, which could be attributed to its anti-inflammatory and antioxidant properties.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents; Antioxidants; Antirheumatic Agents; Arthritis, Experimental; Behavior, Animal; Dose-Response Relationship, Drug; Female; Freund's Adjuvant; Indomethacin; Inflammation; Oxidative Stress; Rats; Rats, Wistar; Xanthophylls

Osteoarthritis (OA) is a degenerative joint disease and a leading cause of adult disability. Since there is no cure for OA and no effective treatment to slow its progression, current pharmacologic treatments, such as analgesics and non-steroidal anti-inflammatory drugs (NSAIDs), only alleviate symptoms, such as pain and inflammation, but do not inhibit the disease process. Moreover, chronic intake of these drugs may result in severe adverse effects. For these reasons, patients have turned to the use of various complementary and alternative approaches, including diverse dietary supplements and nutraceuticals, in an effort to improve symptoms and manage or slow disease progression. The present study was conducted to evaluate the anti-osteoarthritic effects of FlexPro MD

Topics: Animals; Cartilage, Articular; Dietary Supplements; Disease Models, Animal; Euphausiacea; Hyaluronic Acid; Inflammation; Iodoacetates; Male; Osteoarthritis; Pain; Phytotherapy; Plant Oils; Rats, Sprague-Dawley; Treatment Outcome; Xanthophylls

As a life-threatening neurological emergency, status epilepticus (SE) is often refractory to available treatment. Current studies have shown a causal role of neuroinflammation in patients with lower seizure thresholds and driving seizures. The ATP-gated purinergic P2X7 receptor (P2X7R) is mainly expressed on the microglia, which function as gatekeepers of inflammation. Although emerging evidence has demonstrated significant anti-inflammatory effects of astaxanthin (AST) in SE, the associated mechanism remains unclear. Therefore, this study aimed to clarify the effects of AST on P2X7R-related inflammation in SE.. SE was induced in rats using lithium-pilocarpine, and AST was administered 1 h after SE induction. Rat microglia were treated with lipopolysaccharide (LPS), AST, ATP, 2,3-O-4-benzoyl-4-benzoyl-ATP (BzATP) and oxidized ATP (oxATP). The Morris water maze, immunohistochemistry, and Nissl staining were performed in rats. Expressions of P2X7R and inflammatory cytokines (such as cycloxygenase-2 (Cox-2), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α)) were detected using real-time polymerase chain reaction (RT-PCR) and Western blot (WB) both in rats and microglia. ATP concentration in the microglia was evaluated using ELISA.. The AST alleviated hippocampal injury and improved cognitive dysfunction induced by SE. AST also effectively inhibited inflammation and downregulated P2X7R expression in both rat brain and microglia. The results also showed that AST reduced the extracellular ATP levels and that P2X7R expression could be increased by extracellular ATP. In addition, BzATP upregulates the expression of P2X7R and inflammatory factors in microglia. Conversely, it downregulates the expression of P2X7R and inflammatory factors.. Our study suggests that AST attenuated ATP-P2X7R mediated inflammation in SE.

Topics: Adenosine Triphosphate; Animals; Anti-Inflammatory Agents, Non-Steroidal; Dose-Response Relationship, Drug; Inflammation; Lipopolysaccharides; Male; Rats; Rats, Wistar; Receptors, Purinergic P2X7; Signal Transduction; Status Epilepticus; Structure-Activity Relationship; Xanthophylls

Gouty arthritis is the one of the most painful arthritis and is caused by an inflammatory reaction. This study investigated whether astaxanthin (AXT), which has documented anti-inflammatory and antioxidant properties, exhibits protective effects against monosodium urate (MSU) crystal-induced inflammation. Cell viability of J774A.1 murine macrophages was assessed by AXT dose-dependent incubation by MTT assays, and expression levels of iNOS and COX-2 proteins as well as secretion of IL-1β were also analyzed under MSU crystals stimulation with or without AXT treatment. The production of inflammatory mediators was found to significantly decrease with AXT treatment, and the formation of the inflammasome complex was also attenuated when cells were co-stimulated with MSU crystals and AXT. Furthermore, we found that expression of the MAPK pathway was downregulated in J774A.1 cells. AXT also inhibited the induction of COX-2 and IL-6 in human chondrocytes and synovial fibroblasts by western blots. Finally, an MSU crystal intra-articular injection rat model for gouty arthritis was utilized in which treatment groups received 5-daily intraperitoneal injections of AXT prior to MSU crystal stimulation, or once intra-articular injections of AXT following MSU crystal stimulation for 6 hours. Results of synovitis score analysis revealed that inflammation was significantly attenuated in the group which received intraperitoneal AXT injection prior to MSU crystal stimulation compared to the group which received MSU only. These results indicate that AXT attenuates the effects of MSU crystal-induced inflammation by suppressing the production of pro-inflammatory cytokines and inflammatory mediators. Our findings that the anti-inflammatory activities of AXT may be beneficial in the treatment of MSU crystal-induced arthritis.

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Gouty; Cells, Cultured; Chondrocytes; Cyclooxygenase 2; Cytokines; Fibroblasts; Humans; Inflammation; Interleukin-1beta; Interleukin-6; Joints; Macrophages; Male; Mice; Rats; Rats, Sprague-Dawley; Synovitis; Uric Acid; Xanthophylls

Cardiac remodeling after acute myocardial infarction (AMI) is an important process. The present study aimed to assess the protective effects of astaxanthin (ASX) on cardiac remodeling after AMI.. The study was conducted between April and September 2018. To create a rat AMI model, rats were anesthetized, and the left anterior descending coronary artery was ligated. The rats in the ASX group received 10 mg·kg·day ASX by gavage for 28 days. On the 1st day after AMI, but before ASX administration, six rats from each group were sacrificed to evaluate changes in the heart function and peripheral blood (PB) levels of inflammatory factors. On the 7th day after AMI, eight rats from each group were sacrificed to evaluate the PB levels of inflammatory factors and the M2 macrophage count using both immunofluorescence (IF) and flow cytometry (FC). The remaining rats were observed for 28 days. Cardiac function was examined using echocardiography. The inflammatory factors, namely, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-10, were assessed using enzyme-linked immunosorbent assay. The heart weight/body weight (BW), and lung weight (LW)/BW ratios were calculated, and myocardial fibrosis in the form of collagen volume fraction was measured using Masson trichrome staining. Hematoxylin and eosin (H&E) staining was used to determine the myocardial infarct size (MIS), and TdT-mediated dUTP nick-end labeling staining was used to analyze the myocardial apoptosis index. The levels of apoptosis-related protein, type I/III collagen, transforming growth factor β1 (TGF-β1), metalloproteinase 9 (MMP9), and caspase 3 were assessed by Western blotting. Unpaired t-test, one-way analysis of variance, and non-parametric Mann-Whitney test were used to analyze the data.. On day 1, cardiac function was worse in the ASX group than in the sham group (left ventricular end-systolic diameter [LVIDs]: 0.72 ± 0.08 vs. 0.22 ± 0.06 cm, t = -11.38; left ventricular end-diastolic diameter [LVIDd]: 0.89 ± 0.09 vs. 0.48 ± 0.05 cm, t = -9.42; end-systolic volume [ESV]: 0.80 [0.62, 0.94] vs. 0.04 [0.03, 0.05] mL, Z = -2.89; end-diastolic volume [EDV]: 1.39 [1.03, 1.49] vs. 0.28 [0.22, 0.32] mL, Z = -2.88; ejection fraction [EF]: 0.40 ± 0.04 vs. 0.86 ± 0.05, t = 10.00; left ventricular fractional shortening [FS] rate: 0.19 [0.18, 0.20] %FS vs. 0.51 [0.44, 0.58] %FS, Z = -2.88, all P < 0.01; n = 6). The levels of inflammatory factors significantly increased (TNF-α: 197.60 [133.89, 237.94] vs. 50.48 [47.21 57.10] pg/mL, Z = -2.88; IL-1β: 175.23 [160.74, 215.09] vs. 17.78 [16.83, 19.56] pg/mL, Z = -2.88; IL-10: 67.64 [58.90, 71.46] vs. 12.33 [11.64, 13.98] pg/mL, Z = -2.88, all P < 0.01; n = 6). On day 7, the levels of TNF-α and IL-1β were markedly lower in the ASX group than in the AMI group (TNF-α: 71.70 [68.60, 76.00] vs. 118.07 [106.92, 169.08] pg/mL, F = 42.64; IL-1β: 59.90 [50.83, 73.78] vs. 151.60 [108.4, 198.36] pg/mL, F = 44.35, all P < 0.01, n = 8). Conversely, IL-10 levels significantly increased (141.84 [118.98, 158.36] vs. 52.96 [42.68, 74.52] pg/mL, F = 126.67, P < 0.01, n = 8). The M2 macrophage count significantly increased (2891.42 ± 211.29 vs. 1583.38 ± 162.22, F = 274.35, P < 0.01 by immunofluorescence test; 0.96 ± 0.18 vs. 0.36 ± 0.05, F = 46.24, P < 0.05 by flowcytometry test). On day 28, cardiac function was better in the ASX group than in the AMI group (LVIDs: 0.50 [0.41, 0.56] vs. 0.64 [0.56, 0.74] cm, Z = -3.60; LVIDd: 0.70 [0.60, 0.76] vs. 0.80 [0.74 0.88] cm, Z = -2.96; ESV: 0.24 [0.18, 0.45] vs. 0.58 [0.44, 0.89] mL, Z = -3.62; EDV: 0.76 [0.44, 1.04] vs. 1.25 [0.82, 1.46] mL, Z = -2.54; EF: 0.60 ± 0.08 vs. 0.50 ± 0.12, F = 160.48; %FS: 0.29 [0.24, 0.31] vs. 0.20 [0.17, 0.21], Z = -4.43, all P < 0.01; n = 16). The MIS and LW/BW ratio were markedly lower in the ASX group than in the AMI group (myocardial infarct size: 32.50 ± 1.37 vs. 50.90 ± 1.73, t = 23.63, P < 0.01, n = 8; LW/BW: 1.81 ± 0.15 vs. 2.17 ± 0.37, t = 3.66, P = 0.01, n = 16). The CVF was significantly lower in the ASX group than in the AMI group: 12.88 ± 2.53 vs. 28.92 ± 3.31, t = 10.89, P < 0.01, n = 8. The expression of caspase 3, TGF-β1, MMP9, and type I/III collagen was lower in the ASX group than in the AMI group (caspase 3: 0.38 ± 0.06 vs. 0.66 ±. ASX treatment after AMI may promote M2 macrophages and effectively attenuate cardiac remodeling by inhibiting inflammation and reducing myocardial fibrosis.

Topics: Animals; Inflammation; Macrophages; Myocardial Infarction; Myocardium; Rats; Ventricular Remodeling; Xanthophylls

Mastitis is a major inflammatory response of the mammary gland due to various pathogenic invasions and is a serious disease that affects the production yield and health status of cows. Astaxanthin (AST), a xanthophyll carotenoid, is a secondary metabolite synthesized by microalgae and yeasts that has been reported to suppress various inflammatory responses. However, the protective effect of AST on lipopolysaccharide (LPS)-induced mammary epithelial cells has not yet been reported. The present study results indicated that AST treatment markedly attenuated the oxidative stress markers and nitric oxide (NO) while improving the anti-oxidant enzymes in LPS exposed cells. On the other hand, LPS-exposed cells showed nuclear translocation of nuclear factor-κB (NF-κB) with the activation of inflammatory cytokines such as monocyte chemoattractant protein-1, tumor necrosis factor-α, interferon-γ, and interleukin-6 (IL-6). In addition, mRNA expression analysis revealed that the histone deacetylase (HDAC) -1, -2, -3, -6, -7 and pentraxin 3 (PTX3) expressions were increased in the LPS group. Furthermore, the activity of HDAC was increased to 2-fold with a significant reduction in the histone acetyltransferase activity in cells exposed to LPS. However, AST was able to inhibit the nuclear translocation of NF-κB with attenuated HDAC activity. Intriguingly, HDAC inhibition studies demonstrated that the cytokines such as IL-4, IL-8, granulocyte-mcrophage colony stimulating factor, C-reactive protein, IL-17A, and IL-22 were significantly suppressed which were upregulated in LPS treatment; while AST was found acting by improving the anti-inflammatory cytokine IL-10, and thioredoxin reductase levels. Collectively, these findings provide novel insights into the role of HDACs in regulating cellular processes involved in the pathogenesis of LPS-induced mastitis as well as the potential use of AST as a therapeutic in treatment for controlling disease progression.

Topics: Animals; Cell Line; Female; Histone Deacetylase Inhibitors; Histone Deacetylases; Inflammation; Lipopolysaccharides; Mammary Glands, Animal; Mice; Oxidative Stress; Xanthophylls

Alcohol induces inflammation and oxidative stress, causing cell damages. We previously demonstrated that astaxanthin (ASTX), a xanthophyll carotenoid, exerts anti-inflammatory and antioxidant properties in macrophages exposed to inflammatory insults. In this study, we investigated whether ASTX can inhibit alcohol-induced inflammation and oxidative stress in macrophages with the elucidation of mechanisms.. RAW 264.7 macrophages and mouse bone marrow-derived macrophages were treated with 80 mM ethanol in the presence or absence of 25 μM of ASTX for 72 h. Subsequently, the expression of genes related to inflammation and oxidative stress, cellular reactive oxygen species accumulation, cellular NAD. Ethanol increased mRNA expression of interleukin (Il)-6, Il-1b and tumor necrosis factor α with a concomitant increase in nuclear translocation of nuclear factor κB, which was abolished by ASTX. Importantly, ethanol significantly decreased SIRT1 activity and cellular NAD. ASTX showed anti-inflammatory and antioxidant properties by inhibiting decreases in SIRT1 expression and cellular NAD

Topics: Alcohol Drinking; Animals; Anti-Inflammatory Agents; Antioxidants; Cells, Cultured; Ethanol; Inflammation; Macrophages; Mice; Mice, Inbred C57BL; Oxidative Stress; RAW 264.7 Cells; Sirtuin 1; Xanthophylls

Astaxanthin is a red lipophilic carotenoid that is often undetectable in human plasma due to the limited supply in typical Western diets. Despite its presence at lower than detectable concentrations, previous clinical feeding studies have reported that astaxanthin exhibits potent antioxidant properties.. We examined astaxanthin accumulation and its effects on gut microbiota, inflammation, and whole-body metabolic homeostasis in wild-type C57BL/6 J (WT) and β-carotene oxygenase 2 (BCO2) knockout (KO) mice.. Six-wk-old male and female BCO2 KO and WT mice were provided with either nonpurified AIN93M (e.g., control diet) or the control diet supplemented with 0.04% astaxanthin (wt/wt) ad libitum for 8 wk. Whole-body energy expenditure was measured by indirect calorimetry. Feces were collected from individual mice for short-chain fatty acid assessment. Hepatic astaxanthin concentrations and liver metabolic markers, cecal gut microbiota profiling, inflammation markers in colonic lamina propria, and plasma samples were assessed. Data were analyzed by 3-way ANOVA followed by Tukey's post hoc analysis.. BCO2 KO but not WT mice fed astaxanthin had ∼10-fold more of this compound in liver than controls (P < 0.05). In terms of the microbiota composition, deletion of BCO2 was associated with a significantly increased abundance of Mucispirillum schaedleri in mice regardless of gender. In addition to more liver astaxanthin in male KO compared with WT mice fed astaxanthin, the abundance of gut Akkermansia muciniphila was 385% greater, plasma glucagon-like peptide 1 was 27% greater, plasma glucagon and IL-1β were 53% and 30% lower, respectively, and colon NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome activation was 23% lower (all P < 0.05) in male KO mice than the WT mice.. Astaxanthin affects the gut microbiota composition in both genders, but the association with reductions in local and systemic inflammation, oxidative stress, and improvement of metabolic homeostasis only occurs in male mice.

Topics: Animal Feed; Animals; Bacteria; Diet; Dietary Supplements; Dioxygenases; Energy Metabolism; Female; Gastrointestinal Microbiome; Homeostasis; Inflammation; Male; Mice; Mice, Knockout; Xanthophylls

Air pollution has become one of the most serious issues for human health and has been shown to be particularly concerning for neural and cognitive health. Recent studies suggest that fine particulate matter of less than 2.5 (PM2.5), common in air pollution, can reach the brain, potentially resulting in the development and acceleration of various neurological disorders including Alzheimer's disease, Parkinson's disease, and other forms of dementia, but the underlying pathological mechanisms are not clear. Astaxanthin is a red-colored phytonutrient carotenoid that has been known for anti-inflammatory and neuroprotective effects. In this study, we demonstrated that exposure to PM2.5 increases the neuroinflammation, the expression of proinflammatory M1, and disease-associated microglia (DAM) signature markers in microglial cells, and that treatment with astaxanthin can prevent the neurotoxic effects of this exposure through anti-inflammatory properties. Diesel particulate matter (Sigma-Aldrich) was used as a fine particulate matter 2.5 in the present study. Cultured rat glial cells and BV-2 microglial cells were treated with various concentrations of PM2.5, and then the expression of various inflammatory mediators and signaling pathways were measured using qRT-PCR and Western blot. Astaxanthin was then added and assayed as above to evaluate its effects on microglial changes, inflammation, and toxicity induced by PM2.5. PM2.5 increased the production of nitric oxide and reactive oxygen species and upregulated the transcription of various proinflammatory markers including Interleukin-1β (IL-1β), Interleukin-6 (IL-6), Tumor necrosis factor α (TNFα), inducible nitric oxide synthase (iNOS), triggering receptor expressed on myeloid cells 2 (TREM2), Toll-like receptor 2/4 (TLR2/4), and cyclooxygenase-2 (COX-2) in BV-2 microglial cells. However, the mRNA expression of IL-10 and arginase-1 decreased following PM2.5 treatment. PM2.5 treatment increased c-Jun N-terminal kinases (JNK) phosphorylation and decreased Akt phosphorylation. Astaxanthin attenuated these PM2.5-induced responses, reducing transcription of the proinflammatory markers iNOS and heme oxygenase-1 (HO-1), which prevented neuronal cell death. Our results indicate that PM2.5 exposure reformulates microglia via proinflammatory M1 and DAM phenotype, leading to neurotoxicity, and the fact that astaxanthin treatment can prevent neurotoxicity by inhibiting transition to the proinflammatory M1 and DAM phenotyp

Topics: Air Pollution; Alzheimer Disease; Animals; Anti-Inflammatory Agents; Cyclooxygenase 2; Gasoline; Gene Expression Regulation; Humans; Inflammation; Interleukin-1beta; Microglia; Neuroprotective Agents; NF-kappa B; Nitric Oxide Synthase Type II; Parkinson Disease; Particulate Matter; Proto-Oncogene Proteins c-akt; Rats; Xanthophylls

High-fat diet (HFD) usually induces oxidative stress and astaxanthin is regarded as an excellent anti-oxidant. An 8-week feeding trial was conducted to investigate the effects of dietary astaxanthin supplementation on growth performance, lipid metabolism, antioxidant ability, and immune response of juvenile largemouth bass (

Topics: Adiposity; Animals; Antioxidants; Bass; Body Fat Distribution; Cytokines; Diet, High-Fat; Dietary Supplements; Growth; Immunity; Inflammation; Lipid Metabolism; Malondialdehyde; Oxidative Stress; Superoxide Dismutase; Xanthophylls

Inflammation plays a key role in the progression of subarachnoid hemorrhage (SAH). Here, we examined the effects of astaxanthin (ATX) on the inflammatory response and secondary damage after SAH and the underlying mechanisms of action. In vivo, a prechiasmatic cistern injection model was established in rats and mice. In addition, neuron-microglia cocultures were exposed to oxyhemoglobin to mimic SAH in vitro. Western blotting revealed that protein expression of TLR4 was markedly increased in microglia at 24 h after SAH, with consequent increases in the downstream molecules myeloid differentiation factor 88 and NF-кB. Treatment with ATX significantly inhibited the TLR4 activation, increased sirtuin 1 expression, and inhibited the subsequent inflammatory response both in vivo and in vitro. ATX also significantly decreased high-mobility group box 1 nuclear translocation and secretion in neurons, an effect that was reversed by the sirtuin 1-specific inhibitor sirtinol. ATX administered 4 h after SAH ameliorated cerebral inflammation, brain edema, and neuronal death and improved neurologic function. ATX reduced neuronal death but did not improve neurologic function in TLR4 knockout mice. These results suggest that ATX reduces the proinflammatory response and secondary brain injury after SAH, primarily by increasing sirtuin 1 levels and inhibiting the TLR4 signaling pathway.-Zhang, X., Lu, Y., Wu, Q., Dai, H., Li, W., Lv, S., Zhou, X., Zhang, X., Hang, C., Wang, J. Astaxanthin mitigates subarachnoid hemorrhage injury primarily by increasing sirtuin 1 and inhibiting the Toll-like receptor 4 signaling pathway.

Topics: Animals; Disease Models, Animal; Female; Inflammation; Male; Mice; Mice, Knockout; Neuroprotective Agents; NF-kappa B; Rats; Rats, Sprague-Dawley; Signal Transduction; Sirtuin 1; Subarachnoid Hemorrhage; Toll-Like Receptor 4; Xanthophylls

The present study was conducted to evaluate the protective effects of astaxanthin against lipopolysaccharide (LPS)-induced inflammatory responses in Channa argus in vivo and ex vivo. Primary hepatocytes were exposed to different concentrations of LPS for 24 h to induce an inflammatory response, and the protective effects of astaxanthin against LPS-induced inflammation were studied ex vivo and in vivo. Hepatocytes exposed to LPS (5-20 μg mL

Topics: Animals; Anti-Inflammatory Agents; Cells, Cultured; Fishes; Hepatocytes; Inflammation; Lipopolysaccharides; MAP Kinase Signaling System; NF-kappa B; Signal Transduction; Xanthophylls

Present study was conducted on 12 Karan Fries (Holstein Friesian X Tharparkar) heifers (10-12 months) to assess the effect of astaxanthin supplementation on heat stress amelioration and inhibition of NF-κB signaling pathway for prevention of heat stress-induced inflammatory changes and apoptosis in the cell during the summer season. The heifers were randomly and equally divided into two groups, i.e., control (fed as per ICAR 2013) and treatment groups (additionally supplemented astaxanthin at a dose rate of 0.25 mg/kg BW/day/animal). Temperature humidity index used to assess the levels of summer stress during the experimental period. Blood samples were collected at the fortnightly interval for quantification of plasma cortisol and IL-12 from both the groups of the heifers and from collected blood samples, RNA was isolated and transcribed into cDNA for real time PCR, for genes expression of NF-κB, IL-2, caspase-3, and Bcl-2. Plasma cortisol, IL-12 levels, and expression pattern of NF-κB, IL-2, and caspase-3 were significantly (P ≤ 0.05) lower in treatment group of Karan Fries heifers than control group, whereas, Bcl-2 was higher (P ≤ 0.05) in astaxanthin supplemented group. The temperature humidity index had a positive correlation (P ≤ 0.05) with plasma cortisol and IL-12 and expression pattern of NF-κB, IL-2, and caspase-3. However, it was negatively correlated with Bcl-2. The supplementation of astaxanthin can ameliorate the impact of summer stress through NF-κB downregulation, might be due to the quenching of free radicals, which regulates the expression of pro-inflammatory mediators and apoptotic genes.

Topics: Animal Feed; Animals; Apoptosis; Cattle; Cattle Diseases; Diet; Dietary Supplements; Female; Heat-Shock Response; India; Inflammation; NF-kappa B; Signal Transduction; Xanthophylls

The incidence of neurodegenerative disorders and cognitive impairment is increasing. Rising prevalence of age-related medical conditions is associated with a dramatic economic burden; therefore, developing strategies to manage these health concerns is of great public health interest. Nutritionally based interventions have shown promise in treatment of these age-associated conditions. Astaxanthin is a carotenoid with reputed neuroprotective properties in the context of disease and injury, while emerging evidence suggests that astaxanthin may also have additional biological activities relating to neurogenesis and synaptic plasticity. Here, we investigate the potential for astaxanthin to modulate cognitive function and neural plasticity in young and aged mice. We show that feeding astaxanthin to aged mice for 1 month improves performance on several hippocampal-dependent cognitive tasks and increases long-term potentiation. However, we did not observe an alteration in neurogenesis, nor did we observe a change in microglial-associated IBA1 immunostaining. This demonstrates the potential for astaxanthin to modulate neural plasticity and cognitive function in aging.

Topics: Aging; Animals; Behavior, Animal; Cognition; Cognitive Dysfunction; Dietary Supplements; Hippocampus; Inflammation; Long-Term Potentiation; Male; Mice; Mice, Inbred C57BL; Microglia; Neurodegenerative Diseases; Neurogenesis; Neuronal Plasticity; Neuroprotective Agents; Xanthophylls

Astaxanthin (AXT), a xanthophyll carotenoid compound, has potent antioxidant, anti-inflammatory and neuroprotective properties. Neuroinflammation and oxidative stress are significant in the pathogenesis and development of Alzheimer's disease (AD). Here, we studied whether AXT could alleviate neuroinflammation, oxidative stress and memory loss in lipopolysaccharide (LPS) administered mice model. Additionally, we investigated the anti-oxidant activity and the anti-neuroinflammatory response of AXT in LPS-treated BV-2 microglial cells. The AXT administration ameliorated LPS-induced memory loss. This effect was associated with the reduction of LPS-induced expression of inflammatory proteins, as well as the production of reactive oxygen species (ROS), nitric oxide (NO), cytokines and chemokines both in vivo and in vitro. AXT also reduced LPS-induced β-secretase and Aβ

Topics: Amyloid beta-Protein Precursor; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Avoidance Learning; Cell Line; Inflammation; Lipopolysaccharides; Maze Learning; Memory Disorders; Mental Recall; Mice; Mice, Inbred ICR; Microglia; Oxidative Stress; Signal Transduction; STAT3 Transcription Factor; Xanthophylls

Chemobrain refers to a common sequelae experienced by 15-80% of cancer patients exposed to chemotherapeutics. The antineoplastic agent doxorubicin (DOX) has been implicated in a strenuous neurotoxicity manifested as decline in cognitive functions, most probably via cytokine-induced oxidative and nitrosative damage to brain tissues. Astaxanthin (AST), a naturally occurring carotenoid, is reputable for its outstanding antioxidant, anti-inflammatory, and antiapoptotic activities. Therefore, the aim of the current study was to investigate the potential neuroprotective and memory-enhancing effects of AST against DOX-induced behavioral and neurobiological abnormalities. Briefly, AST treatment (25 mg/kg) significantly protected against DOX-induced memory impairment. Furthermore, AST restored hippocampal histopathological architecture, halted DOX-induced oxidative and inflammatory insults, mitigated the increase in acetylcholinesterase activity, and consistently downregulated the overactive apoptotic machineries. In conclusion, these findings suggest that AST offers neuroprotection against DOX-induced cognitive impairment which could be explained at least partly by its antioxidant, anti-inflammatory, and antiapoptotic effects.

Topics: Acetylcholinesterase; Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Behavior, Animal; Biomarkers; Cognitive Dysfunction; Disease Models, Animal; Doxorubicin; Glial Fibrillary Acidic Protein; Hippocampus; Inflammation; Male; Models, Biological; Motor Activity; Nerve Degeneration; Neuroprotective Agents; Oxidative Stress; Rats; Xanthophylls

Despite considerable advances in understanding mechanisms involved in chronic pain, effective treatment remains limited. Astaxanthin, a marine natural drug, having potent anti-oxidant and anti-inflammatory activities is known to possess neuroprotective effects. However, effects of astaxanthin against nerve injury induce chronic pain remains unknown. Overactivity of glutamatergic NMDARs results in excitotoxicity which may participate in astrocytic and microglial activation during pathology which further contribute to the development of neuropathic pain. In this study, we investigate the effects of astaxanthin on oxido-inflammatory and NMDA receptor down-regulation pathway by using in-silico, in-vitro and in-vivo models of neuropathic pain. In-silico molecular docking study ascertained the binding affinity of astaxanthin to NMDA receptors and showed antagonistic effects. Data from in-vitro studies suggest that astaxanthin significantly reduces the oxidative stress induced by the lipopolysaccharides in C6 glial cells. In male Sprague dawley rats, a significant attenuation of neuropathic pain behavior was observed in Hargreaves test and von Frey hair test after astaxanthin treatment. Findings from the current study suggest that astaxanthin can be used as potential alternative in the treatment of chronic neuropathic pain. However, more detailed investigations are required to further probe the in-depth mechanism of action of astaxanthin.

Topics: Analgesics; Animals; Antioxidants; Behavior, Animal; Cell Survival; Cells, Cultured; Disease Models, Animal; Hyperalgesia; Inflammation; Lipopolysaccharides; Male; Molecular Docking Simulation; Neuralgia; Oxidative Stress; Pain Threshold; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; Xanthophylls

Astaxanthin (AXT) is classified as a xanthophyll carotenoid compound which have broader functions including potent antioxidant, anti-inflammatory and neuroprotective properties. Considerable researches have demonstrated that AXT shows preventive and therapeutic properties against for Diabetes, Osteoarthritis and Rheumatoid Arthritis. However, the protective effect of AXT on liver disease has not yet been reported. In this study, we investigated effects of AXT on ethanol-induced liver injury in chronic plus binge alcohol feeding model. The hepatic steatosis and inflammation induced by ethanol administration were alleviated by AXT. Serum levels of aspartate transaminase and alanine transaminase were decreased in the livers of AXT administrated group. The ethanol-induced expression of cytochrome P450 2E1 (CYP2E1), pro-inflammatory proteins, cytokines, chemokines and reactive oxygen species (ROS) levels were also reduced in the livers of AXT administrated group. Moreover, ethanol-induced infiltration of neutrophils was decreased in the livers of AXT administrated group. Docking model and pull-down assay showed that AXT directly binds to the DNA binding site of STAT3. Moreover, AXT decreased STAT3 phosphorylation in the liver of AXT administration group. Therefore, these results suggest that AXT could prevent ethanol-induced hepatic injury via inhibition of oxidant and inflammatory responses via blocking of STAT3 activity.

Topics: Animals; Antioxidants; Aspartate Aminotransferases; Chemical and Drug Induced Liver Injury; Cytokines; Disease Models, Animal; Ethanol; Inflammation; Liver; Male; Mice; Oxidative Stress; Phosphorylation; Reactive Oxygen Species; Signal Transduction; STAT3 Transcription Factor; Xanthophylls

Spinal cord injury (SCI) is a debilitating condition in which inflammatory responses in the secondary phase of injury leads to long lasting sensory-motor dysfunction. The medicinal therapy of SCI complications is still a clinical challenge. Understanding the molecular pathways underlying the progress of damage will help to find new therapeutic candidates. Astaxanthin (AST) is a ketocarotenoid which has shown anti-inflammatory effects in models of traumatic brain injury. In the present study, we examined its potential in the elimination of SCI damage through glutamatergic-phospo p38 mitogen-activated protein kinase (p-p38MAPK) signaling pathway. Inflammatory response, histopathological changes and sensory-motor function were also investigated in a severe compression model of SCI in male rats. The results of acetone drop and inclined plane tests indicated the promising role of AST in improving sensory and motor function of SCI rats. AST decreased the expression of n-methyl-d-aspartate receptor subunit 2B (NR2B) and p-p38MAPK as inflammatory signaling mediators as well as tumor necrosis factor-α (TNF-α) as an inflammatory cytokine, following compression SCI. The histopathological study culminated in preserved white mater and motor neurons beyond the injury level in rostral and caudal parts. The results show the potential of AST to inhibit glutamate-initiated signaling pathway and inflammatory reactions in the secondary phase of SCI, and suggest it as a promising candidate to enhance functional recovery after SCI.

Topics: Animals; Cytokines; Disease Models, Animal; Glutamic Acid; Inflammation; Male; Motor Disorders; Neuralgia; Neuroimmunomodulation; p38 Mitogen-Activated Protein Kinases; Rats; Rats, Wistar; Recovery of Function; Signal Transduction; Spinal Cord; Spinal Cord Injuries; Xanthophylls

Although anti-inflammatory effects of astaxanthin (ASTX) have been suggested, the underlying mechanisms have not been fully understood. Particularly, the modulatory action of ASTX in the interplay between nuclear factor E2-related factor 2 (NRF2) and nuclear factor κB (NFκB) to exert its anti-inflammatory effect in macrophages is unknown. The effect of ASTX on mRNA and protein expression of pro-inflammatory and antioxidant genes and/or cellular reactive oxygen species (ROS) accumulation were determined in RAW 264.7 macrophages, bone marrow-derived macrophages (BMDM) from wild-type (WT) and Nrf2-deficient mice, and/or splenocytes and peritoneal macrophages of obese mice fed ASTX. The effect of ASTX on M1 and M2 macrophage polarization was evaluated in BMDM. ASTX significantly decreased LPS-induced mRNA expression of interleukin 6 (Il-6) and Il-1β by inhibiting nuclear translocation of NFκB p65; and attenuated LPS-induced ROS with an increase in NRF2 nuclear translocation, concomitantly decreasing NADPH oxidase 2 expression in RAW 264.7 macrophages. In BMDM of WT and Nrf2-deficient mice, ASTX decreased basal and LPS-induced ROS accumulation. The induction of Il-6 mRNA by LPS was repressed by ASTX in both types of BMDM while Il-1β mRNA was decreased only in WT BMDM. Furthermore, ASTX consumption lowered LPS sensitivity of splenocytes in obese mice. ASTX decreased M1 polarization of BMDM while increasing M2 polarization. ASTX exerts its anti-inflammatory effect by inhibiting nuclear translocation of NFκB p65 and by preventing ROS accumulation in NRF2-dependent and -independent mechanisms. Thus, ASTX is an agent with anti-inflammatory and antioxidant properties that may be used for the prevention of inflammatory conditions.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Gene Expression Regulation; Inflammation; Lipopolysaccharides; Macrophages, Peritoneal; Mice; Mice, Inbred C57BL; NF-E2-Related Factor 2; NF-kappa B; RAW 264.7 Cells; Reactive Oxygen Species; Spleen; Xanthophylls

The purpose of the present study was to assess the effect of astaxanthin (ASX) treatment on the acute lung injury (ALI) induced by cecal ligation and puncture (CLP) in mice. Mice were randomly allocated into the following groups: (1) the saline control group, in which mice were given saline before sham operation; (2) the ASX control group, in which mice received ASX before sham operation; (3) the ALI group, in which mice were given saline before CLP operation; and (4) the ALI+ASX group, in which mice received ASX before CLP operation. ASX was dissolved in olive oil and administrated by oral gavage for 14days consecutively before the CLP or sham operation. In experiment 1, Kaplan-Meier survival analysis was conducted for 72h after CLP. In experiment 2, blood, bronchoalveolar lavage fluid (BALF) and lung tissues were collected at 24h after the CLP or sham operation to determine the severity of lung injury. The results showed that ASX treatment could significantly decrease the CLP-induced mortality rate in mice. Meanwhile, ASX treatment significantly attenuated CLP-induced lung histopathological injury, inflammatory infiltration, total protein and albumin concentration, and total cell and neutrophil counts in the BALF. Furthermore, ASX treatment alleviated oxidative/nitrative stress, inflammation levels and pulmonary apoptosis in lung tissues. In addition, ASX treatment markedly down-regulated the expression of inducible nitric oxide synthase (i-NOS), nitrotyrosine (NT) and nuclear factor-kappa B (NF-Κb) P65 in the lung tissues compared with that in the ALI group. Astaxanthin treatment had markedly protective effect against ALI in mice, and the potential mechanism is associated with its ability to inhibit the inflammatory response, oxidative/nitrative stress, and pulmonary apoptosis, as well as down-regulate NF-κB P65 expression.

Topics: Acute Lung Injury; Animals; Apoptosis; Bronchoalveolar Lavage Fluid; Cecum; Cytokines; Down-Regulation; Inflammation; Ligation; Lung; Malondialdehyde; Mice, Inbred C57BL; Nitrosative Stress; Organ Size; Oxidative Stress; Peroxidase; Punctures; Reactive Oxygen Species; Transcription Factor RelA; Xanthophylls

The critical factor considered in a depression induced by diabetes is the inflammation eliciting hippocampal, amygdala and thalamic neuronal injury. Therefore, inhibiting inflammatory reactions in the brain and reducing neuronal injury can alleviate depression in rodents suffering from diabetes mellitus. The oral administration of astaxanthin has been employed in emotional disorders and diabetic complications due to its anti-depressant, anti-inflammatory and anti-apoptotic functions. However, it has not been reported whether astaxanthin can improve diabetes-related depression-like behavior, and its potential mechanisms have not been elucidated. The objective of the present study is to elucidate the effect of astaxanthin on depression in diabetic mice and to understand the underlying molecular mechanisms. In this study, experimental diabetic mice were given a single intraperitoneal injection of streptozotocin (STZ, 150mg/kg, dissolved in citrate buffer) after fasting for 12h. The diabetic model was assessed 72h after STZ injection, and mice with a fasting blood glucose level more than or equal to 16.7mmol/L were used in this study, and oral astaxanthin (25mg/kg) was provided uninterrupted for ten weeks. Depression-like behavior was evaluated by the tail suspension test (TST) and forced swimming test (FST). The glial fibrillary acidic protein (GFAP) and cleaved caspase-3-positive cells were measured by immunohistochemistry, and the western blotting was used to test the protein levels of interleukin-6 (IL-6), interleukin-1β (IL-1β) and cyclooxygenase (COX-2). The results showed that astaxanthin had an anti-depressant effect on diabetic mice. Furthermore, we observed that astaxanthin significantly reduced the number of GFAP-positive cells in the hippocampus and hypothalamus, and also the expression of cleaved caspase-3 in the hippocampus, amygdala and hypothalamus was decreased as well. Moreover, astaxanthin could down-regulate the expression of IL-6, IL-1β and COX-2 in the hippocampus. These findings suggest that the mechanism of astaxanthin in preventing depression in diabetic mice involves the inhibition of inflammation/inflammation inhibition, thereby protecting neurons in hippocampus, amygdala and hypothalamus against hyperglycemic damage.

Topics: Amygdala; Animals; Anti-Inflammatory Agents; Antidepressive Agents; Caspase 3; Cyclooxygenase 2; Depression; Diabetes Mellitus, Experimental; Drug Evaluation, Preclinical; Glial Fibrillary Acidic Protein; Hippocampus; Hypothalamus; Inflammation; Interleukin-1beta; Interleukin-6; Male; Mice, Inbred ICR; Random Allocation; Xanthophylls

Burn-wound progression can occur in the initial or peri-burn area after a deep burn injury. The stasis zone has a higher risk of deterioration mediated by multiple factors but is also considered salvageable. Astaxanthin (ATX), which is extracted from some marine organisms, is a natural compound with a strong antioxidant effect that has been reported to attenuate organ injuries caused by traumatic injuries. Hence, we investigated the potential effects of ATX on preventing early burn-wound progression. A classic "comb" burn rat model was established in this study for histological and biological assessments, which revealed that ATX, particularly higher doses, alleviated histological deterioration in the stasis zone. Additionally, we observed dose-dependent improvements in oxidative stress and the release of inflammatory mediators after ATX treatment. Furthermore, ATX dose-dependently attenuated burn-induced apoptosis in the wound areas, and this effect was accompanied by increases in Akt and Bad phosphorylation and a downregulation of cytochrome C and caspase expression. In addition, the administration of Ly 294002 further verified the effect of ATX. In summary, we demonstrated that ATX protected against early burn-wound progression in a rat deep-burn model. This protection might be mediated by the attenuation of oxidative stress-induced inflammation and mitochondria-related apoptosis.

Topics: Animals; Apoptosis; bcl-Associated Death Protein; Burns; Chromones; Disease Progression; Inflammation; Inflammation Mediators; Male; Mitochondria; Models, Biological; Morpholines; Oxidative Stress; Phosphorylation; Protective Agents; Proto-Oncogene Proteins c-akt; Rats, Sprague-Dawley; Up-Regulation; Xanthophylls

Astaxanthin (Ax) is a ketocarotenoid of the xanthophyll family with activities such as antioxidation, preservation of the integrity of cell membranes and protection of the redox state and functional integrity of mitochondria. The aim of this study was to investigate potential gender-related differences in the effect of Ax on the aging rat brain.. In females, interleukin 1 beta (IL1β) was significantly lower in treated rats in both cerebral areas, and in the cerebellum, treated animals also had significantly higher IL10. In males, no differences were found in the cerebellum, but in the hippocampus, IL1β and IL10 were significantly higher in treated rats.. These are the first results to show gender-related differences in the effect of Ax on the aging brain, emphasizing the necessity to carefully analyze female and male peculiarities when the anti-aging potentialities of this ketocarotenoid are evaluated. The observations lead to the hypothesis that Ax exerts different anti-inflammatory effects in female and male brains.

Topics: Aging; Animals; Brain; Brain Chemistry; Cerebellum; Female; Hippocampus; Inflammation; Interleukin-10; Interleukin-1beta; Male; Rats; Rats, Wistar; Sex Characteristics; Xanthophylls

We have previously reported that astaxanthin (AX), a dietary carotenoid, directly interacts with peroxisome proliferator-activated receptors PPARα and PPARγ, activating PPARα while inhibiting PPARγ, and thus reduces lipid accumulation in hepatocytes in vitro. To investigate the effects of AX in vivo, high-fat diet (HFD)-fed C57BL/6J mice were orally administered AX (6 or 30mg/kg body weight) or vehicle for 8weeks. AX significantly reduced the levels of triglyceride both in plasma and in liver compared with the control HFD mice. AX significantly improved liver histology and thus reduced both steatosis and inflammation scores of livers with hematoxylin and eosin staining. The number of inflammatory macrophages and Kupffer cells were reduced in livers by AX administration assessed with F4/80 staining. Hepatic PPARα-responsive genes involved in fatty acid uptake and β-oxidation were upregulated, whereas inflammatory genes were downregulated by AX administration. In vitro radiolabeled assays revealed that hepatic fatty acid oxidation was induced by AX administration, whereas fatty acid synthesis was not changed in hepatocytes. In mechanism studies, AX inhibited Akt activity and thus decreased SREBP1 phosphorylation and induced Insig-2a expression, both of which delayed nuclear translocation of SREBP1 and subsequent hepatic lipogenesis. Additionally, inhibition of the Akt-mTORC1 signaling axis by AX stimulated hepatic autophagy that could promote degradation of lipid droplets. These suggest that AX lowers hepatic lipid accumulation in HFD-fed mice via multiple mechanisms. In addition to the previously reported differential regulation of PPARα and PPARγ, inhibition of Akt activity and activation of hepatic autophagy reduced hepatic steatosis in mouse livers.

Topics: Animals; Diet, High-Fat; Down-Regulation; Hep G2 Cells; Humans; Inflammation; Lipid Metabolism; Liver; Male; Mice; Mice, Inbred C57BL; PPAR alpha; PPAR gamma; Proto-Oncogene Proteins c-akt; Xanthophylls

Glycemic fluctuations may play a critical role in the pathogenesis of diabetic complications, such as cardiovascular disease. We investigated whether the oxycarotenoid astaxanthin can reduce the detrimental effects of fluctuating glucose on vascular endothelial cells. Human umbilical venous endothelial cells were incubated for 3 days in media containing 5.5mM glucose, 22 mM glucose, or 5.5mM glucose alternating with 22 mM glucose in the absence or presence of astaxanthin or N-acetyl-L-cysteine (NAC). Constant high glucose increased reactive oxygen species (ROS) generation, but such an effect was more pronounced in fluctuating glucose. This was associated with up-regulated p22(phox) expression and down-regulated peroxisome proliferator activated receptor-γ coactivator (PGC-1α) expression. Astaxanthin inhibited ROS generation, p22(phox) up-regulation, and PGC-1α down-regulation by the stimuli of glucose fluctuation. Fluctuating glucose, but not constant high glucose, significantly decreased the endothelial nitric oxide synthase (eNOS) phosphorylation level at Ser-1177 without affecting total eNOS expression, which was prevented by astaxanthin as well as by the anti-oxidant NAC. Transferase-mediated dUTP nick end labeling (TUNEL) showed increased cell apoptosis in fluctuating glucose. Glucose fluctuation also resulted in up-regulating gene expression of pro-inflammatory mediators, interleukin-6 and intercellular adhesion molecule-1. These adverse changes were subdued by astaxanthin. The phosphorylation levels of c-Jun N-terminal kinase (JNK) and p38 were significantly increased by glucose fluctuations, and astaxanthin significantly inhibited the increase in JNK and p38 phosphorylation. Taken together, our results suggest that astaxanthin can protect vascular endothelial cells against glucose fluctuation by reducing ROS generation.

Topics: Acetylcysteine; Antioxidants; Apoptosis; Glucose; Human Umbilical Vein Endothelial Cells; Humans; Inflammation; Mitogen-Activated Protein Kinases; NADPH Oxidases; Nitric Oxide Synthase Type III; Oxidative Stress; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Reactive Oxygen Species; Transcription Factors; Xanthophylls

Carrageenan produces both inflammation and pain when injected in mouse paws via enhancement of reactive oxygen species formation. We have investigated an effect of astaxanthin extracted from Litopenaeus vannamei in carrageenan-induced mice paw edema and pain. The current study demonstrates interesting effects from astaxanthin treatment in mice: an inhibition of paw edema induced in hind paw, an increase in mechanical paw withdrawal threshold and thermal paw withdrawal latency, and a reduction in the amount of myeloperoxidase enzyme and lipid peroxidation products in the paw. Furthermore the effect was comparable to indomethacin, a standard treatment for inflammation symptoms. Due to adverse effects of indomethacin on cardiovascular and gastrointestinal systems, our study suggests promising prospect of astaxanthin extract as an anti-inflammatory alternative against carrageenan-induced paw edema and pain behavior.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Edema; Hindlimb; Inflammation; Mice; Pain; Penaeidae; Xanthophylls

To investigate the antioxidative effect of astaxanthin on Nω-nitro-L-arginine methyl ester (L-NAME)-induced preeclamptic rats. Cell survival, the level of reactive oxygen species (ROS) and the changes in mitochondrial membrane potential (MMP) were examined in astaxanthin and H2O2-treated human umbilical vein endothelial cells (HUVECs). The preeclamptic Sprague-Dawley (SD) rat model was established by injection of L‑NAME and treatment with astaxanthin. The activities of malondialdehyde (MDA), superoxide dismutase (SOD) and nitric oxide synthase (NOS) in serum were analyzed. Pathological changes were examined by hematoxylin and eosin (H&E) staining. The expression of nuclear factor (NF)‑κB, Rho‑associated protein kinase II (ROCK II), heme oxygenase‑1 (HO‑1) and caspase 3 in preeclamptic placentas were examined by immunohistochemistry. Astaxanthin significantly reduced H2O2‑induced HUVEC cell death, decreased ROS and increased MMP. Astaxanthin significantly reduced blood pressure and the content of MDA, but significantly increased the activity of SOD in preeclamptic rats. The urinary protein and the level of NO and NOS were also decreased. H&E staining revealed that the thickness of the basilar membrane was increased, while the content of trophoblast cells and spiral arteries were reduced following astaxanthin treatment. Immunohistochemistry results showed that the expression of NF‑κB, ROCK II and caspase 3 in preeclamptic placentas was significantly decreased after astaxanthin treatment, while HO‑1 expression was increased. In conclusion, astaxanthin inhibited H2O2‑induced oxidative stress in HUVECs. Astaxanthin treatment significantly improved L‑NAME‑induced preeclamptic symptoms and reduced the oxidative stress and inflammatory damages in preeclamptic placentas. Astaxanthin treatment may effectively prevent and treat preeclampsia.

Topics: Animals; Antioxidants; Biomarkers; Blood Pressure; Cell Line; Cell Survival; Disease Progression; Female; Gene Expression; Human Umbilical Vein Endothelial Cells; Humans; Hydrogen Peroxide; Inflammation; Male; Malondialdehyde; Matrix Metalloproteinases; Oxidative Stress; Placenta; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Proteinuria; Rats; Reactive Oxygen Species; Superoxide Dismutase; Xanthophylls

FlexPro MD

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Cyclooxygenase 2; Cytokines; Dietary Supplements; Euphausiacea; Gene Expression; Hyaluronic Acid; Inflammation; Lipopolysaccharides; Macrophages; Male; Matrix Metalloproteinase 1; Matrix Metalloproteinase 2; Mice; Mice, Inbred C57BL; NF-kappa B; Nitric Oxide Synthase Type II; Oils; Pain; RAW 264.7 Cells; RNA, Messenger; Xanthophylls

This study was conducted to compare the protective effects of astaxanthin (ASX) with Corni Fructus (CF) against diabetes-induced pathologies such as oxidative stress-induced inflammation and advanced glycation end product (AGE) formation in the liver of type 1 diabetic rats. ASX (50 mg/kg body weight/day) or CF (200 mg/kg body weight/day) was orally administered every day for 18 days to streptozotocin (STZ)-induced diabetic rats, and their effects were compared with nondiabetic and diabetic control rats. The administration of CF, but not ASX, decreased both the elevated serum and hepatic glucose concentration in diabetic rats. In diabetic rats, increased levels of AGE, reactive oxygen species, and lipid peroxidation were significantly decreased by treatment with both ASX and CF in the liver of diabetic rats. STZ treatment markedly augmented the protein expressions of AGE, and both ASX and CF efficiently attenuated these increases in hepatic protein expressions. In addition, oxidative stress and proinflammatory protein expressions were upregulated in the diabetic rats. On the contrary, these upregulations of protein expressions were decreased by the administration of ASX or CF. These results suggest that the inhibitory effect of ASX on diabetes-induced hepatic dysfunction could be derived from the blocking of AGE formation and further anti-inflammation and that CF exhibited beneficial effects through the attenuation of hyperglycemia, and thus the inhibition of AGE formation and the inflammatory responses. Therefore, ASX as well as CF may help prevent ongoing diabetes-induced hepatic injury.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Cornus; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Fruit; Glycation End Products, Advanced; Hyperglycemia; Inflammation; Lipid Peroxidation; Liver; Male; Oxidative Stress; Phytotherapy; Plant Extracts; Rats, Wistar; Xanthophylls

Astaxanthin (ATX) is a powerful antioxidant that occurs naturally in a wide variety of living organisms. Previous studies have shown that ATX has effects of eliminating oxygen free radicals and can protect organs from ischemia/reperfusion (IR) induced injury. The present study was designed to further investigate the protective effects of ATX on oxidative stress induced toxicity in tubular epithelial cells and on IR induced renal injury in mice. ATX, at a concentration of 250 nM, attenuated 100 μM H2O2-inudced viability decrease of tubular epithelial cells. In vivo, ATX preserved renal function 12 h or 24 h post IR. Pretreatment of ATX via oral gavage for 14 consecutive days prior to IR dramatically prevented IR induced histological damage 24 h post IR. Histological results showed that the pathohistological score, number of apoptotic cells, and the expression of α-smooth muscle actin were significantly decreased by pretreatment of ATX. In addition, oxidative stress and inflammation in kidney samples were significantly reduced by ATX 24 h post IR. Taken together, the current study suggests that pretreatment of ATX is effective in preserving renal function and histology via antioxidant activity.

Topics: Actins; Animals; Antioxidants; Apoptosis; Cell Survival; Cells, Cultured; Enzyme-Linked Immunosorbent Assay; Free Radicals; Humans; Hydrogen Peroxide; Inflammation; Kidney; Kidney Tubules; Male; Malondialdehyde; Mice; Mice, Inbred ICR; Muscle, Smooth; Oxidative Stress; Reperfusion Injury; Superoxide Dismutase; Xanthophylls

Diabetes-induced cognitive deficit (DICD) is a prevalent disease with substantial morbidity and mortality and as a global health problem with serious economic burdens. Astaxanthin (AST) has a good prospect in production of nutritional, medical, and particularly functional health drug. The present study was aimed to study the effect of AST on DICD in diabetes mellitus (DM) rat through suppression of oxidative stress, nitric oxide synthase (NOS) pathway, inflammatory reaction and upregulation of PI3K/Akt. In the study, Morris water maze teat was used to detect the cognitive function of DM rat. Afterwards, we measured the body weight and blood glucose levels of DM rats. Then, oxidative stress, the activities of eNOS and iNOS, and inflammatory factors were analyzed using a commercial kit in cerebral cortex and hippocampus. Finally, the caspase-3/9 and phosphoinositide 3-kinase (PI3K)/Akt expressions were also checkout with Real Time PCR and immunoblotting, respectively. In this experiment, AST could availably enhance the body weight and reduce blood glucose levels of DM rats. Moreover, AST could observably perfect cognitive function of DM rat. Next, the activities of oxidative stress, nitric oxide synthase and inflammation were distinctly diminution in DM rat, after the treatment of AST. Furthermore, our present results demonstrated that AST had the protective effect on the brain cell of DM rat, decreased the caspase-3/9 expression and promoted the expression of PI3K/Akt in cerebral cortex and hippocampus.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Blood Glucose; Body Weight; Brain; Caspase 3; Caspase 9; Cognition; Cognition Disorders; Diabetes Mellitus, Experimental; Inflammation; Inflammation Mediators; Male; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Oxidative Stress; Phosphatidylinositol 3-Kinase; Proto-Oncogene Proteins c-akt; Rats, Wistar; Signal Transduction; Time Factors; Xanthophylls

Neurons in the hippocampal and cortical functional regions are more susceptible to damage induced by hyperglycemia, which can result in severe spatial learning and memory impairment. Neuroprotection ameliorates cognitive impairment induced by hyperglycemia in diabetic encephalopathy (DE). Astaxanthin has been widely studied in diabetes mellitus and diabetic complications due to its hypoglycemic, antioxidant and anti-apoptotic effects. However, whether astaxanthin can alleviate cognition deficits induced by DE and its precise mechanisms remain undetermined. In this study, DE was induced by streptozotocin (STZ, 150 mg/kg) in ICR mice. We observed the effect of astaxanthin on cognition and investigated its potential mechanisms in DE mice. Results showed that astaxanthin treatment significantly decreased the latency and enhanced the distance and time spent in the target quadrant in the Morris water maze test. Furthermore, neuronal survival was significantly increased in the hippocampal CA3 region and the frontal cortex following treatment with astaxanthin. Meanwhile, immunoblotting was used to observe the nuclear translocation of nuclear factor-kappaB (NF-κB) p65 and the expression of tumor necrosis factor-α (TNF-α) in the hippocampus and frontal cortex. The results indicated that astaxanthin could inhibit NF-κB nuclear translocation and downregulate TNF-α expression in the hippocampus and frontal cortex. Overall, the present study implied that astaxanthin could improve cognition by protecting neurons against inflammation injury potentially through inhibiting the nuclear translocation of NF-κB and down-regulating TNF-α.

Topics: Analysis of Variance; Animals; Blood Glucose; Cognition Disorders; Diabetes Mellitus, Experimental; Disease Models, Animal; Frontal Lobe; Hippocampus; Inflammation; Locomotion; Male; Maze Learning; Mice; Mice, Inbred ICR; NF-kappa B; Reaction Time; Tumor Necrosis Factor-alpha; Xanthophylls

Mangiferin has antioxidant, antiviral, apoptosis regulating, anti‑inflammatory, antitumor and antidiabetic effects, which can also inhibit osteoclast formation and bone resorption. However, whether mangiferin ameliorates the neurological pain of spinal cord injury (SCI) in ratS remains to be elucidated. The present study investigated the therapeutic effects of mangiferin on neurological function, the water content of spinal cord, oxidative stress, the expression of inflammatory cytokines and the protein expression of Bcl‑2/Bax in a SCI rat model. In the present study, the Basso, Beattie and Bresnahan scores, and the water content of the spinal cord were used to analyze the therapeutic effects of mangiferin on neurological pain in the SCI rat. The concentrations of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and the serum levels of glutathione peroxidase (GSH‑PX), nuclear factor‑κB p65 unit, tumor necrosis factor‑α, interleukin (IL)‑1β, IL‑6 and caspase‑3/9 were detected using commercial kits. The expression levels of Bcl‑2 and Bax were measured using western blot analysis. The results demonstrated that administrating mangiferin began to ameliorate neurological function and the water content of the spinal cord in the SCI rat. The mangiferin‑treated group were found to have lower oxidative stress activity and lower expression levels of inflammatory cytokines, compared with the SCI rat. In addition, mangiferin significantly reduced the protein expression of Bax and promoted the protein expression of Bcl-2 in the SCI rat model. Finally, mangiferin markedly suppressed the expression of caspase‑3/9, indicating that the protective action of mangiferin may be associated with anti‑apoptosis activation. In conclusion, mangiferin attenuated contusive SCI in the rats through regulating oxidative stress, inflammation and the Bcl‑2 and Bax pathway.

Topics: Animals; Antioxidants; bcl-2-Associated X Protein; Caspase 3; Caspase 9; Catalase; Cytokines; Disease Models, Animal; Glutathione Peroxidase; Inflammation; Male; Malondialdehyde; Neuroprotective Agents; Oxidative Stress; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Sprague-Dawley; Spinal Cord Injuries; Superoxide Dismutase; Xanthones; Xanthophylls

Health authorities worldwide have consistently recommended the regular consumption of marine fishes and seafood to preserve memory, sustain cognitive functions, and prevent neurodegenerative processes in humans. Shrimp, crabs, lobster, and salmon are of particular interest in the human diet due to their substantial provision of omega-3 fatty acids (n-3/PUFAs) and the antioxidant carotenoid astaxanthin (ASTA). However, the optimal ratio between these nutraceuticals in natural sources is apparently the key factor for maximum protection against most neuro-motor disorders. Therefore, we aimed here to investigate the effects of a long-term supplementation with (n-3)/PUFAs-rich fish oil, ASTA-rich algal biomass, the combination of them, or krill oil (a natural combination of both nutrients) on baseline redox balance and neuro-inflammation indexes in cerebellum and motor cortex of Wistar rats. Significant changes in redox metabolism were only observed upon ASTA supplementation, which reinforce its antioxidant properties with a putative mitochondrial-centered action in rat brain. Krill oil imposed mild astrocyte activation in motor cortex of Wistar rats, although no redox or inflammatory index was concomitantly altered. In summary, there is no experimental evidence that krill oil, fish oil, oralgal biomass (minor variation), drastically change the baseline oxidative conditions or the neuro-inflammatory scenario in neuromotor-associated rat brain regions.

Topics: Animals; Antioxidants; Biomass; Cerebellum; Dietary Supplements; Euphausiacea; Fatty Acids, Omega-3; Fish Oils; Inflammation; Male; Motor Cortex; Oxidation-Reduction; Rats; Rats, Wistar; Xanthophylls

We recently showed that astaxanthin (ASX), a xanthophyll carotenoid, activates phosphatidylinositol 3-kinase pathway of insulin signaling and improves glucose metabolism in liver of high fructose-fat diet (HFFD)-fed mice. The aim of this study is to investigate whether ASX influences phosphorylation of c-Jun-N-terminal kinase 1 (JNK1), reactive oxygen species (ROS) production, endoplasmic reticulum (ER) stress, and inflammation in liver of HFFD-fed mice. Adult male Mus musculus mice were fed either with control diet or HFFD for 15 days. After this period, mice in each group were divided into two and administered ASX (2 mg/kg/day, p.o) in 0.3 ml olive oil or 0.3 ml olive oil alone for the next 45 days. At the end of 60 days, liver tissue was excised and examined for lipid accumulation (Oil red O staining), intracellular ROS production, ER stress, and inflammatory markers. Elevated ROS production, lipid accumulation, and increased hepatic expression of ER stress markers such as Ig-binding protein, PKR-like ER kinase, phosphorylated eukaryotic initiation factor 2α, X-box binding protein 1, activating transcription factor 6, and the apoptotic marker caspase 12 were observed in the liver of the HFFD group. ASX significantly reversed these changes. This reduction was accompanied by reduced activation of JNK1 and I kappa B kinase β phosphorylation and nuclear factor-kappa B p65 nuclear translocation in ASX-treated HFFD mice. These findings suggest that alleviation of inflammation and ER stress by ASX could be a mechanism responsible for its beneficial effect in this model. ASX could be a promising treatment strategy for insulin resistant patients.

Topics: Animals; Azo Compounds; Biomarkers; Cell Nucleus; Diet, High-Fat; Endoplasmic Reticulum Stress; Frozen Sections; Fructose; I-kappa B Kinase; Inflammation; Intracellular Space; JNK Mitogen-Activated Protein Kinases; Liver; Male; Mice; NF-kappa B; Phosphorylation; Reactive Oxygen Species; Staining and Labeling; Xanthophylls

It has been suggested that oxidative stress activates various intracellular signaling pathways leading to secretion of a variety of pro-inflammatory cytokines and chemokines. SHP-1 is a protein tyrosine phosphatase (PTP) which acts as a negative regulator of immune cytokine signaling. However, intracellular hydrogen peroxide (H(2)O(2)), generated endogenously upon stimulation and exogenously from environmental oxidants, has been known to be involved in the process of intracellular signaling through inhibiting various PTPs, including SHP-1. In this study, we investigated the potential role of astaxanthin, an antioxidant marine carotenoid, in re-establishing SHP-1 negative regulation on pro-inflammatory cytokines secretion in U-937 cell line stimulated with oxidative stimulus. ELISA measurement suggested that ASTA treatment (10 µM) reduced pro-inflammatory cytokines secretion (IL-1β, IL-6 and TNF-α) induced through H(2)O(2), (100 µM). Furthermore, this property is elicited by restoration of basal SHP-1 protein expression level and reduced NF-κB (p65) nuclear expression, as showed by western blotting experiments.

Topics: Antioxidants; Carotenoids; Cell Survival; Cells, Cultured; Cytokines; Humans; Hydrogen Peroxide; Inflammation; Interleukin-1beta; Interleukin-6; NF-kappa B; Oxidative Stress; Protein Tyrosine Phosphatase, Non-Receptor Type 6; Protein Tyrosine Phosphatases; Signal Transduction; Tumor Necrosis Factor-alpha; U937 Cells; Xanthophylls

Astaxanthin is a carotenoid known to have antioxidant and antiinflammatory properties. This study examined if shrimp astaxanthin modulates the production of superoxide (O(-)(2)), nitric oxide (NO), and tumor necrosis factor-α (TNF-α) in rat alveolar macrophages. The oxidative effect was induced by phorbol myristate acetate and lipopolysacharide. The treatment was compared with superoxide dismutase, butylated hydroxytoluene, commercial astaxanthin, N-nitric-L-arginine methyl ester and L- canavanine, all administered as a 43.5-μg/mL dose in the presence of 1% EtOH/0.5% DMSO. All treatments maintained cell viability, as observed in the MTT assay, and shrimp extract increased the viable alveolar macrophages to 168%. Shrimp extract and commercial astaxanthin showed a suppressive effect on the generation of both free radicals O(-)(2) and NO, while purified shrimp astaxanthin was specific to NO. TNF-α secretion was correlated with NO production. However, in this correlation, the shrimp extract completely inhibited TNF-α. In the light of these findings, the antioxidant action demonstrated in this study suggests that the shrimp extract could be considered as a promising source of bioactive substances with antioxidant and anti-inflammatory activity.. The hydrolysis process of shrimp waste generates bioactive products that add economic value to shrimp processing, mainly because they may have applications in nutraceutical and animal feed industry.

Topics: Animals; Anti-Inflammatory Agents; Arginine; Butylated Hydroxytoluene; Canavanine; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Ethanol; Female; Free Radicals; Inflammation; Macrophages, Alveolar; Male; Nitric Oxide; Oxidative Stress; Penaeidae; Rats; Rats, Wistar; Superoxide Dismutase; Superoxides; Tumor Necrosis Factor-alpha; Waste Products; Xanthophylls

Colon cancer is the third most malignant neoplasm in the world and it remains an important cause of mortality in Asian and Western countries. Astaxanthin (AST), a major component of carotenoids possesses attractive remedial features. The purpose of this study is to investigate the possible mechanism of action of astaxanthin against 1, 2 dimethyl hydrazine (DMH)-induced rat colon carcinogenesis. Wistar male rats were randomized into five groups, group 1 were control rats, group 2 were rats that received AST (15 mg/kg body wt p.o. everyday), rats in group 3 were induced with DMH (40 mg/kg body wt, s.c.), DMH-induced rats in groups 4 and 5 were either pre or post initiated with AST, respectively as in group 2. DMH-induced rats exhibited elevated expressions of Nuclear factor kappa B-p65 (NF-κB-p65), Cyclooxygenase-2 (COX-2), Matrixmetallo proteinases (MMP) 2/9, Proliferating cell nuclear antigen (PCNA), and Extracellular signal-regulated kinase-2 (ERK-2) as confirmed by immunofluorescence. Further, Westernblot analysis of MMPs-2/9, ERK-2 and Protein kinase B (Akt) revealed increased expressions of these proteins in DMH-induced groups of rats. AST-treatment decreased the expressions of all these vital proteins, involved in colon carcinogenesis. The ability of AST to induce apoptosis in the colon of DMH-induced rats was confirmed by Annexin-V/PI staining in a confocal microscopy, DNA fragmentation analysis and expression of caspase-3 by Western blotting. In conclusion, astaxanthin exhibits anti-inflammatory and anti-cancer effects by inducing apoptosis in DMH-induced rat colon carcinogenesis by modulating the expressions of NFkB, COX-2, MMPs-2/9, Akt and ERK-2.

Topics: 1,2-Dimethylhydrazine; Animals; Apoptosis; Cell Count; Colonic Neoplasms; Cyclooxygenase 2; DNA Fragmentation; Drug Screening Assays, Antitumor; Extracellular Matrix; Inflammation; Male; Mast Cells; Matrix Metalloproteinases; Mitogen-Activated Protein Kinase 1; Models, Biological; Neoplasm Invasiveness; NF-kappa B; Proliferating Cell Nuclear Antigen; Proto-Oncogene Proteins c-akt; Rats; Rats, Wistar; Xanthophylls

No information is available on the possible role of astaxanthin on immune response in domestic canine. Female Beagle dogs (9-10 mo old; 8.2 ± 0.2 kg body weight) were fed 0, 10, 20 or 40 mg astaxanthin daily and blood sampled on wk 0, 6, 12, and 16 for assessing the following: lymphoproliferation, leukocyte subpopulations, natural killer (NK) cell cytotoxicity, and concentrations of blood astaxanthin, IgG, IgM and acute phase proteins. Delayed-type hypersensitivity (DTH) response was assessed on wk 0, 12 and 16. Plasma astaxanthin increased dose-dependently and reached maximum concentrations on wk 6. Dietary astaxanthin enhanced DTH response to vaccine, concanavalin A-induced lymphocyte proliferation (with the 20mg dose at wk 12) and NK cell cytotoxic activity. In addition, dietary astaxanthin increased concentrations of IgG and IgM, and B cell population. Plasma concentrations of C reactive protein were lower in astaxanthin-fed dogs. Therefore, dietary astaxanthin heightened cell-mediated and humoral immune response and reduced DNA damage and inflammation in dogs.

Topics: Acute-Phase Proteins; Adjuvants, Immunologic; Animals; C-Reactive Protein; Cytotoxicity, Immunologic; Diet; DNA Damage; Dogs; Female; Hypersensitivity, Delayed; Immunoglobulin G; Immunoglobulin M; Inflammation; Killer Cells, Natural; Leukocytes; Lymphocyte Activation; Xanthophylls

Effect of dietary supplementation of astaxanthin (Ax) from Phaffia rhodozyma on lipopolysaccharide-induced inflammatory responses was investigated in male broiler chickens fed a corn-based diet. Birds (1 week of age) were fed a corn-enriched diet containing either 0 or 100 ppm Ax for 2 weeks and were intraperitoneally injected with lipopolysaccharide (LPS, 1 mg/kg body weight). Inflammatory responses were evaluated by determining changes in expression of messenger RNA (mRNA) in cytokines and mediators related to inflammatory responses (interleukin (IL)-1 beta and -6, inducible nitrite synthase (iNOS), interferon (IFN)- γ and cyclooxygenase (Cox)-2 in the liver and spleen after 2 h of LPS injection and plasma ceruloplasmin concentration as an acute phase protein. Birds fed Ax showed significantly higher iNOS mRNA expression in the liver and spleen compared to that of control birds. Ax-fed birds also showed greater increase in mRNA expression in the liver of IL-1, IL-6 and IFN-γ compared to that of control birds. The enhancing effect of Ax was further progressed when LPS was injected. No difference was found in plasma ceruloplasmin concentration between the Ax-fed group and control group. The results suggest that feeding supplementation of Ax (100 ppm) to a corn-enriched diet possibly does not have anti-inflammatory effect in male broiler chickens.

Topics: Animal Feed; Animals; Basidiomycota; Chickens; Cytokines; Diet; Dietary Supplements; Inflammation; Inflammation Mediators; Lipopolysaccharides; Male; Nitric Oxide Synthase Type II; Poultry Diseases; RNA, Messenger; Xanthophylls; Zea mays

Astaxanthin is a carotenoid with powerful antioxidant properties that exists naturally in various plants, algae, and seafood. The purpose of the present study is to examine the protective action of astaxanthin against high-glucose-induced oxidative stress, inflammation, and apoptosis in proximal tubular epithelial cells (PTECs). To assess the efficacy of astaxanthin, several key markers and activities were measured, including lipid peroxidation, total reactive species (RS), superoxide (*O(2)), nitric oxide (NO*), and peroxynitrite (ONOO(-)), as well as expressions of inflammatory proteins, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), nuclear factor-kappa B (NF-kappaB) nuclear translocation, and levels of Bcl2/Bax protein. Results showed that astaxanthin effectively suppressed lipid peroxidation, total RS, *O(2), NO*, ONOO(-), iNOS and COX-2 protein levels, NF-kappaB nuclear translocation, and pro-apototic Bax, whereas it increased anti-apoptotic Bcl2 protein levels. On the basis of these findings, it was concluded that in PTECs, astaxanthin has a protective efficacy against several deleterious effects caused by high glucose exposure and proposed that astaxanthin should be explored further as a potential antidiabetic remedy for the treatment of diabetic nephropathy.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Biomarkers; Cell Line; Epithelial Cells; Free Radical Scavengers; Glucose; Inflammation; Kidney Diseases; Kidney Tubules, Proximal; Oxidative Stress; Swine; Xanthophylls

Disodium disuccinate astaxanthin ('rac'-dAST; Cardax) is a water-dispersible C40 carotenoid derivative under development for oral and parenteral administration for cardioprotection of the at-risk ischemic cardiovascular patient. In experimental infarction models in animals (rats, rabbits, and dogs), significant myocardial salvage has been obtained, up to 100% at the appropriate dose in dogs. The documented mechanism of action in vitro includes direct scavenging of biologically produced superoxide anion; in vivo in rabbits, modulation of the complement activity of serum has also been shown. A direct correlation between administration of the test compound in animals and reductions of multiple, independent markers of oxidative stress in serum was recently obtained in a rat experimental infarction model. For the current study, it was hypothesized that oral Cardax administration would inhibit oxidative damage of multiple relevant biological targets in a representative, well-characterized murine peritoneal inflammation model. A previously developed mass spectrometry-based (LC/ESI/MS/MS) approach was used to interrogate multiple distinct pathways of oxidation in a black mouse (C57/BL6) model system. In vivo markers of oxidant stress from peritoneal lavage samples (supernatants) were evaluated in mice on day eight (8) after treatment with either Cardax or vehicle (lipophilic emulsion without drug) orally by gavage at 500 mg/kg once per day for seven (7) days at five (5) time points: (1) baseline prior to treatment (t=0); (2) 16 h following intraperitoneal (i.p.) injection with thioglycollate to elicit a neutrophilic infiltrate; (3) 4 h following i.p. injection of yeast cell wall (zymosan; t=16 h/4 h thioglycollate+zymosan); (4) 72 h following i.p. injection with thioglycollate to elicit monocyte/macrophage infiltration; and (5) 72 h/4 h thioglycollate+zymosan. A statistically significant sparing effect on the arachidonic acid (AA) and linoleic acid (LA) substrates was observed at time points two and five. When normalized to the concentration of the oxidative substrates, statistically significant reductions of 8-isoprostane-F(2alpha) (8-iso-F(2alpha)) at time point three (maximal neutrophil recruitment/activation), and 5-HETE, 5-oxo-EET, 11-HETE, 9-HODE, and PGF(2alpha) at time point five (maximal monocyte/macrophage recruitment/activation) were observed. Subsequently, the direct interaction of the optically inactive stereoisomer of Cardax (meso-dAST) with human 5

Topics: Animals; Arachidonate 5-Lipoxygenase; Biomarkers; Chromatography, High Pressure Liquid; Circular Dichroism; Crystallography, X-Ray; Inflammation; Mice; Mice, Inbred C57BL; Models, Molecular; Neutrophil Infiltration; Oxidative Stress; Peritonitis; Pharmaceutical Vehicles; Succinates; Xanthophylls; Zymosan