Anti-inflammatory Effects Of Astaxanthin Research Articles

Astaxanthin Alleviates Chronic Prostatitis via the ERK1/2 Signaling Pathway: Evidence from Network Pharmacology and Experimental Validation.

Astaxanthin (AST) has been widely recognized for its therapeutic potential in chronic inflammatory ailments. This study investigates the therapeutic efficacy and underlying mechanisms of AST in the management of chronic prostatitis (CP). Male Sprague-Dawley (SD) rats were randomly divided into control, complete Freund's adjuvant (CFA), and CFA + AST groups. CFA was used to induce the CP model, and saline was used for the control group. Inflammation of the prostate was detected 28 days after oral administration of AST. qRT-PCR and ELISA were used to detect pro-inflammatory factors in RWPE-1 and WPMY-1 cells. Potential targets of AST for CP were explored by network pharmacology, and related proteins were detected by Western blotting. Oral administration of AST alleviated the increase in prostate stroma and reduced inflammatory cell infiltration in CP rats. The IC50 of AST-treated RWPE-1 and WPMY-1 cells for 48 h were 171 and 212.1 μM, respectively. AST pretreatment reduced IL-6 and IL-8 expression in these cells. PPI network, GO, and KEGG enrichment analyses suggested that the antiinflammatory effect of AST was associated with the ERK1/2 pathway. Western blotting showed that AST inhibited ERK1/2 phosphorylation. In addition, AST and ERK1/2 pathway inhibitors (U0126) synergistically inhibited LPS-induced inflammation in prostate cells. Our study identified the potential of AST in the treatment of CP. However, subsequent randomized controlled trials are needed to validate its clinical efficacy.

Anti-Oxidant and Anti-Inflammatory Effects of Astaxanthin on Gastrointestinal Diseases.

A moderate amount of reactive oxygen species (ROS) is produced under normal conditions, where they play an important role in cell signaling and are involved in many aspects of the immune response to pathogens. On the other hand, the excessive production of ROS destructs macromolecules, cell membranes, and DNA, and activates pro-inflammatory signaling pathways, which may lead to various pathologic conditions. Gastrointestinal (GI) mucosa is constantly exposed to ROS due to the presence of bacteria and other infectious pathogens in food, as well as alcohol consumption, smoking, and the use of non-steroidal anti-inflammatory drugs (NSAID). Prolonged excessive oxidative stress and inflammation are two major risk factors for GI disorders such as ulcers and cancers. Bioactive food compounds with potent anti-oxidant and anti-inflammatory activity have been tested in experimental GI disease models to evaluate their therapeutic potential. Astaxanthin (AST) is a fat-soluble xanthophyll carotenoid that is naturally present in algae, yeast, salmon, shrimp, and krill. It has been shown that AST exhibits protective effects against GI diseases via multiple mechanisms. Residing at the surface and inside of cell membranes, AST directly neutralizes ROS and lipid peroxyl radicals, enhances the activity of anti-oxidant enzymes, and suppresses pro-inflammatory transcription factors and cytokines. In addition, AST has been shown to inhibit cancer cell growth and metastasis via modulating cell proliferation-related pathways, apoptosis, and autophagy. Considering the potential benefits of AST in GI diseases, this review paper aims to summarize recent advances in AST research, focusing on its anti-oxidant and anti-inflammatory effects against gastric and intestinal ulcers and cancers.

Astaxanthin and Coenzyme Q10 are not synergistic against oxidative damage in cerulein-induced acute pancreatitis

Background/Aim: The anti-inflammatory effects of Astaxanthin (ATX) and Coenzyme Q10 (Ubiquinone) are studied in different inflammation models. The study aims to investigate the synergistic effect of astaxanthin and Coenzyme Q10 in a rat model of acute pancreatitis. Methods: Twenty-four female Wistar rats were grouped as control (C), carrier-treated control (AP), astaxanthin-treated (ATX; 40 mg/kg), astaxanthin+coenzyme Q10- treated (ATX+Q10; 40 mg/kg and 1 gr/kg) groups. Cerulein was administered (50 µg/kg) twice, one hour apart. Seven hours after the first cerulein injection, the rats were sacrificed. Pancreatic oxidative damage was evaluated with an increase in the serum activity of lipase and amylase, tissue levels of myeloperoxidase activity (MPO), malondialdehyde (MDA), luminol and lucigenin and decrease of glutathione. Results: In all AP groups, MDA and MPO increased while GSH decreased (P<0.001). ATX and ATX+Q10 both decreased MDA and MPO (P<0.001) and increased GSH (P<0.01). Both therapies significantly increased luminol levels (P<0.001, and P<0.01, respectively). Lucigenin markedly decreased in the ATX+Q10 group (P<0.01). Conclusion: Antioxidant combination therapy does not alleviate oxidative damage in pancreatic tissue better than astaxanthin alone.

Astaxanthin alleviates oxidative damage in acute pancreatitis via direct antioxidant mechanisms.

Astaxanthin (ATX) is a naturally occurring carotenoid and a potent antioxidant. Various anti-inflammatory effects of ATX have been examined. We aimed to investigate the protective effect of ATX and its mechanism in a cerulein-induced acute pancreatitis rat model. The rats were randomized into 2 main groups as control (C) and acute pancreatitis group (AP). AP group was subsequently divided into subgroups as AP+vehicle (AP), AP+ATX, and ATX+peroxisome proliferator-activated receptor-alpha antagonist GW6471 (ATX+GW) groups. To induce AP, the rats were administered cerulein (50 µg/kg, intraperitonally [ip]) at 1 hour intervals, whereas the C group received saline. The AP group was treated with vehicle olive oil, ATX 40 mg/kg/orally, or GW6471 and ATX (GW1 mg/kg/ip; ATX; 40 mg/kg/peroral). Treatments were administered after the 1st cerulein injection. At the 7th hour after the final injection, the rats were killed and the pancreatic tissue was used for the determination of malondialdehyde (MDA), glutathione (GSH), and myeloperoxidase (MPO) activities and luminol-lucigenin chemiluminescence levels. Serum amylase, lipase, and histopathological analyses were performed. Elevated serum lipase and amylase levels in the vehicle-treated AP group (p<0.01) decreased in the ATX and ATX+GW groups (p<0.05). In the AP groups, GSH was reduced and MDA, MPO, luminol, and lucigenin levels were increased (p<0.05-0.001). ATX reversed these changes (p<0.05-0.001). The vehicle-treated group revealed significant severe cytoplasmic degeneration and vacuolization, whereas ATX ameliorated these destructions. GW6471 did not abolish the positive effects of ATX biochemically or histologically. ATX has a potent protective effect on AP via its radical scavenging and antioxidant properties. Therefore, we believe that ATX may have therapeutic potential.

Anti-inflammatory effects of astaxanthin against fungal keratitis.

To characterize effect of astaxanthin (ASX) in Aspergillus fumigatus (A. fumigatus) induced keratitis in mouse model. In vivo, fungal keratitis mouse model was established in C57BL/6 mice using A. fumigatus, followed by ASX or dimethyl sulfoxide (DMSO) treatment. Clinical responses were evaluated by clinical score and myeloperoxidase (MPO) assay. Inflammatory cytokines were assessed by reverse-transcription polymerase chain reaction (RT-PCR), Western blot, immunofluorescence, and enzyme-linked immuno sorbent assay (ELISA). In animal model, ASX improved corneal transparency and clinical response, suppressed the expression of inflammatory cytokine like IL-1β, TNF-α, and HMGB-1. Neutrophil levels have been shown to decrease in ASX-treated cornea by immunofluorescence and MPO. TLR2 and TLR4 levels were lower in ASX-treated group than DMSO-treated. ASX can suppress inflammatory response and reduce inflammatory cytokine production in mice model with A. fumigatus keratitis.

虾青素在烟曲霉菌诱导的真菌性角膜炎中的抗炎作用

虾青素在烟曲霉菌诱导的真菌性角膜炎中的抗炎作用

Astaxanthin Inhibits Alcohol-induced Inflammation and Oxidative Stress in Macrophages (P02-014-19)

ObjectivesMacrophages play crucial roles in the development of alcohol-induced inflammation. We previously demonstrated the inhibitory effects of astaxanthin (ASTX), a xanthophyll carotenoid, on the expression of pro-inflammatory and antioxidant genes as well as cellular accumulation of reactive oxygen species (ROS) in macrophages stimulated with lipopolysaccharides. The objective of this study was to determine whether ASTX can prevent alcohol-induced inflammation and oxidative stress in macrophages with the elucidation of the underlying mechanisms. MethodsRAW 264.7 macrophages, a murine macrophage cell line, and mouse bone marrow-derived macrophages (BMDM) were treated with 80 mM ethanol in the absence or presence of 25 mM of ASTX for 72 h with daily media change. The expression levels of pro-inflammatory and antioxidant genes and proteins were measured by quantitative real-time PCR and Western blot, respectively. Cellular ROS accumulation was also determined in both macrophage cell types. ResultsASTX significantly decreased ethanol-induced mRNA expression of interleukin (IL)-6, IL-1β, and tumor necrosis factor α (TNFα) as well as TNFα secretion in RAW 264.7 macrophages. Elevated levels of cellular ROS levels by ethanol were also attenuated by ASTX with a concomitant decrease in the expression of NADPH oxidase 2, a ROS-producing enzyme, in RAW 264.7 macrophages. The similar inhibitory effects of ASTX on inflammatory gene expression and cellular ROS accumulation were observed with BMDM. Furthermore, ethanol significantly decreased in sirtuin1 (SIRT1) mRNA and protein levels, which were markedly attenuated by ASTX in RAW 264.7 macrophages. ConclusionsASTX inhibited the expression and production of pro-inflammatory mediators and ROS accumulation in both RAW 264.7 macrophages and BMDM when the cells were exposed to ethanol. The anti-inflammatory effect of ASTX in ethanol-treated macrophages may be mediated, at least in part, by the activation of the SIRT1 pathway. Thus, ASTX may be used for the prevention of inflammatory and oxidative conditions triggered by excessive alcohol consumption. Funding SourcesThis study was supported by USDA Multistate Hatch.

Astaxanthin as a Peroxisome Proliferator-Activated Receptor (PPAR) Modulator: Its Therapeutic Implications.

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.

Astaxanthin suppresses cigarette smoke and lipopolysaccharide-induced airway inflammation through induction of heme oxygenase-1

The present study was carried out to evolve an effective treatment strategy for chronic obstructive pulmonary disease (COPD). Astaxanthin (AS) is abundantly present in red pigments of crustaceans, and has also been proven to have considerable biological activities. The anti-inflammatory effect of AS was evaluated in lipopolysaccharide (LPS)-exposed RAW264.7 macrophages. It was found that AS markedly inhibited elevation of NO and pro-inflammatory mediators. Moreover, it downregulated iNOS in LPS-stimulated RAW264.7 cells, suppressed the release of pro-inflammatory cytokines, and decreased ROS levels in mice exposed to cigarette smoke (CS) and LPS. These results imply that AS has therapeutic and prophylactic potential in the airway inflammatory response associated with COPD.

Astaxanthin exerts anti-inflammatory and antioxidant effects in macrophages in NRF2-dependent and independent manners

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.

Investigation of anti-inflammatory effects of astaxanthin in rat liver tissue in LPS-induced sepsis

Investigation of anti-inflammatory effects of astaxanthin in rat liver tissue in LPS-induced sepsis

Investigation of the effect of astaxanthin on alveolar bone loss in experimental periodontitis.

Astaxanthin is a keto-carotenoid that has a strong antioxidant effect. The purpose of this study was to evaluate the effects of astaxanthin on alveolar bone loss and histopathological changes in ligature-induced periodontitis in rats. Wistar rats were divided into four experimental groups: non-ligated (C, n=6); ligature only (L, n=6); ligature and astaxanthin (1mg/kg/day astaxanthin, AS1 group, n=8); ligature and astaxanthin (5mg/kg/day astaxanthin, AS5 group, n=8). Silk ligatures were placed at the gingival margin of lower first molars of the mandibular quadrant. The study duration was 11days and the animals were killed at the end of this period. Changes in alveolar bone levels were clinically measured and tissues were immunohistochemically examined, osteocalcin, bone morphogenic protein-2, inducible nitric oxide synthase, Bax and bcl-2 levels in alveolar bone and tartrate-resistant acid phosphatase-positive osteoclast cells, osteoblast and inflammatory cell counts were determined. Alveolar bone loss was highest in the L group and the differences among the L, AS1 and AS5 groups were also significant (P<.05). Both doses of astaxanthin decreased tartrate-resistant acid phosphatase-positive+ osteoclast cell and increased osteoblast cell counts (P<.05). The inflammation in the L group was also higher than those of the C and AS1 groups were (P<.05) indicating the anti-inflammatory effect of astaxanthin. Although inducible nitric oxide synthase, osteocalcin, bone morphogenic protein-2 and bax staining percentages were all highest in the AS5 group and bcl-2 staining percentage was highest in the AS1 group, values were close to each other (P>.05). Within the limits of this study, it can be suggested that astaxanthin administration may reduce alveolar bone loss by increasing osteoblastic activity and decrease osteoclastic activity in experimental periodontitis model.

Astaxanthin and β-carotene in Helicobacter pylori-induced Gastric Inflammation: A Mini-review on Action Mechanisms.

Helicobacter pylori is a dominant bacterium living in the human gastric tissues. In H. pylori-infected tissues, the infiltrated inflammatory cells produce reactive oxygen species (ROS), leading to gastric inflammation with production of various mediators. According to numerous epidemiological studies, dietary carotenoids may prevent gastric inflammation due to their antioxidant properties. Recent studies showed that antioxidant and anti-inflammatory effects of astaxanthin and β-carotene may contribute to inhibition of H. pylori-induced gastric inflammation. Astaxanthin changes H. pylori-induced activation of T helper cell type 1 response towards T helper cell type 2 response in the infected tissues. Astaxanthin inhibits the growth of H. pylori. Even though astaxanthin reduces H. pylori-induced gastric inflammation, it does not reduce cytokine levels in the infected tissues. β-Carotene suppresses ROS-mediated inflammatory signaling, including mitogen-activated protein kinases and redox-sensitive transcription factors, and reduces expression of inflammatory mediators, including interleukin-8, inducible nitric oxide synthase, and cyclooxygenase-2 in the infected tissues. Therefore, consumption of astaxanthin- and β-carotene-rich foods may be beneficial to prevent H. pylori-induced gastric inflammation. This review will summarize anti-inflammatory mechanisms of astaxanthin and β-carotene in H. pylori-mediated gastric inflammation.

Anti-inflammatory Effect of Astaxanthin on the Sickness Behavior Induced by Diabetes Mellitus.

Chronic inflammation appears to play a critical role in sickness behavior caused by diabetes mellitus. Astaxanthin has been used in treating diabetes mellitus and diabetic complications because of its neuroprotective and anti-inflammatory actions. However, whether astaxanthin can improve sickness behavior induced by diabetes and its potential mechanisms are still unknown. The aim of this study was to investigate the effects of astaxanthin on diabetes-elicited abnormal behavior in mice and its corresponding mechanisms. An experimental diabetic model was induced by streptozotocin (150mg/kg) and astaxanthin (25mg/kg/day) was provided orally for 10weeks. Body weight and water consumption were measured, and the sickness behavior was evaluated by the open field test (OFT) and closed field test (CFT). The expression of glial fibrillary acidic protein (GFAP) was measured, and the frontal cortical cleaved caspase-3 positive cells, interleukin-6 (IL-6), and interleukin-1β (IL-1β) expression levels were also investigated. Furthermore, cystathionine β-synthase (CBS) in the frontal cortex was detected to determine whether the protective effect of astaxanthin on sickness behavior in diabetic mice is closely related to CBS. As expected, we observed that astaxanthin improved general symptoms and significantly increase horizontal distance and the number of crossings in the OFT and CFT. Furthermore, data showed that astaxanthin could decrease GFAP-positive cells in the brain and down-regulate the cleaved caspase-3, IL-6, and IL-1β, and up-regulate CBS in the frontal cortex. These results suggest that astaxanthin provides neuroprotection against diabetes-induced sickness behavior through inhibiting inflammation, and the protective effects may involve CBS expression in the brain.

Anti-inflammatory effects of astaxanthin in the human gingival keratinocyte line NDUSD-1.

Oral lichen planus is a chronic inflammatory disease that affects the mucous membrane of the oral cavity and can contribute to the development of other diseases. Inflammation in oral lichen planus is a T-cell-mediated autoimmune disease that acts through cytotoxic CD8+ T cells to trigger apoptosis of keratinocytes. However, the specific cause of oral lichen planus remains unknown and no effective medical treatment has yet been established. Astaxanthin is a carotenoid pigment with capacity for anti-inflammatory and anti-oxidant activities. In this study, we evaluated whether astaxanthin could be used to improve the pathology of oral lichen planus by reducing inflammation. In particular, the anti-inflammatory effects of astaxanthin on the chronic inflammation caused by lipopolysaccharide derived from Escherichia coli O55 in human gingival keratinocytes (NDUSD-1) were evaluated. Following astaxanthin treatment, localization of nuclear factor κB/p65 and the level of inflammatory cytokines (interleukin-6, tumor necrosis factor-α) tended to decrease, and cell proliferation significantly increased in vitro. These results suggest that astaxanthin could be useful for improving chronic inflammation such as that associated with oral lichen planus.

Anti-oxidative and anti-inflammatory effects of astaxanthin on H2O2-induced oxidative stress in human submandibular gland cells

Anti-oxidative and anti-inflammatory effects of astaxanthin on H₂O₂-induced oxidative stress in human submandibular gland cells

Anticoagulatory and Antiinflammatory Effects of Astaxanthin in Diabetic Rats

Astaxanthin at 0.01 or 0.05% of the diet was supplied to diabetic rats for 12 wk. Astaxanthin intake significantly increased its deposit in plasma, and retained glutathione content, reduced the production of reactive oxygen species, interleukin-6, tumor necrosis factor-α, and monocyte chemoattractant protein-1 in blood and kidney of diabetic rats (P < 0.05). Astaxanthin treatments also significantly decreased plasma levels of C-reactive protein and von Willebrand factor in diabetic rats (P < 0.05). Astaxanthin intake at 0.05% significantly diminished plasminogen activator inhibitor-1 and factor VII activities, enhanced antithrombin-III and protein C activities in circulation (P < 0.05). These results support that astaxanthin could attenuate diabetes associated coagulatory, oxidative, and inflammatory stress.

Antioxidative and Anti‐Inflammatory Neuroprotective Effects of Astaxanthin and Canthaxanthin in Nerve Growth Factor Differentiated PC12 Cells

Nerve growth factor differentiated PC12 cells were used to examine the antioxidative and anti-inflammatory effects of astaxanthin (AX) and canthaxanthin (CX). PC12 cells were pretreated with AX or CX at 10 or 20 muM, and followed by exposure of hydrogen peroxide (H(2)O(2)) or 1-methyl-4-phenylpyridinium ion (MPP(+)) to induce cell injury. H(2)O(2) or MPP(+) treatment significantly decreased cell viability, increased lactate dehydrogenase (LDH) release, enhanced DNA fragmentation, and lowered mitochondrial membrane potential (MMP) (P < 0.05). The pretreatments from AX or CX concentration-dependently alleviated H(2)O(2) or MPP(+)-induced cell death, LDH release, DNA fragmentation, and MMP reduction (P < 0.05). Either H(2)O(2) or MPP(+) treatment significantly increased malonyldialdehyde (MDA) and reactive oxygen species (ROS) formations, decreased glutathione content, and lowered glutathione peroxidase (GPX) and catalase activities (P < 0.05). The pretreatments from AX or CX significantly retained GPX and catalase activities, and decreased MDA and ROS formations (P < 0.05). H(2)O(2) or MPP(+) treatment significantly decreased Na(+)-K(+)-ATPase activity, elevated caspase-3 activity and levels of interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-alpha (P < 0.05); and the pretreatments from these agents significantly restored Na(+)-K(+)-ATPase activity, suppressed caspase-3 activity and release of IL-1, IL-6, and TNF-alpha (P < 0.05). Based on the observed antioxidative and anti-inflammatory protection from AX and CX, these 2 compounds were potent agents against neurodegenerative disorder.