Astaxanthin Abstracts 1


Suppressive effect of astaxanthin on retinal injury induced by elevated intraocular pressure
         (Cort et al., 2010) Download
The aim of this study was to clarify the possible protective effect of astaxanthin (ASX) on the retina in rats with elevated intraocular pressure (EIOP). Rats were randomly divided into two groups which received olive oil or 5mg/kg/day ASX for a period of 8 weeks. Elevated intraocular pressure was induced by unilaterally cauterizing three episcleral vessels and the unoperated eye served as control. At the end of the experimental period, neuroprotective effect of ASX was determined via electrophysiological measurements of visual evoked potentials (VEP) and rats were subsequently sacrificed to obtain enucleated globes which were divided into four groups including control, ASX treated, EIOP, EIOP+ASX treated. Retinoprotective properties of ASX were determined by evaluating retinal apoptosis, protein carbonyl levels and nitric oxide synthase-2 (NOS-2) expression. Latencies of all VEP components were significantly prolonged in EIOP and returned to control levels following ASX administration. When compared to controls, EIOP significantly increased retinal protein oxidation which returned to baseline levels in ASX treated EIOP group. NOS-2 expression determined by Western blot analysis and immunohistochemical staining was significantly greater in rats with EIOP compared to ASX and control groups. Retinal TUNEL staining showed apoptosis in all EIOP groups; however ASX treatment significantly decreased the percent of apoptotic cells when compared to non treated ocular hypertensive controls. The presented data confirm the role of oxidative injury in EIOP and highlight the protective effect of ASX in ocular hypertension.

Astaxanthin, a carotenoid with potential in human health and nutrition.
         (Hussein et al., 2006) Download
Astaxanthin (1), a red-orange carotenoid pigment, is a powerful biological antioxidant that occurs naturally in a wide variety of living organisms. The potent antioxidant property of 1 has been implicated in its various biological activities demonstrated in both experimental animals and clinical studies. Compound 1 has considerable potential and promising applications in human health and nutrition. In this review, the recent scientific literature (from 2002 to 2005) is covered on the most significant activities of 1, including its antioxidative and anti-inflammatory properties, its effects on cancer, diabetes, the immune system, and ocular health, and other related aspects. We also discuss the green microalga Haematococcus pluvialis, the richest source of natural 1, and its utilization in the promotion of human health, including the antihypertensive and neuroprotective potentials of 1, emphasizing our experimental data on the effects of dietary astaxanthin on blood pressure, stroke, and vascular dementia in animal models, is described.

Inhibition of choroidal neovascularization with an anti-inflammatory carotenoid astaxanthin
         (Izumi-Nagai et al., 2008) Download
PURPOSE: Astaxanthin (AST) is a carotenoid found in marine animals and vegetables. The purpose of the present study was to investigate the effect of AST on the development of experimental choroidal neovascularization (CNV) with underlying cellular and molecular mechanisms. METHODS: Laser photocoagulation was used to induce CNV in C57BL/6J mice. Mice were pretreated with intraperitoneal injections of AST daily for 3 days before photocoagulation, and treatments were continued daily until the end of the study. CNV response was analyzed by volumetric measurements 1 week after laser injury. Retinal pigment epithelium-choroid levels of IkappaB-alpha, intercellular adhesion molecule (ICAM)-1, monocyte chemotactic protein (MCP)-1, interleukin (IL)-6, vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR)-1, and VEGFR-2 were examined by Western blotting or ELISA. AST was applied to capillary endothelial (b-End3) cells, macrophages, and RPE cells to analyze the activation of NF-kappaB and the expression of inflammatory molecules. RESULTS: The index of CNV volume was significantly suppressed by treatment with AST compared with that in vehicle-treated animals. AST treatment led to significant inhibition of macrophage infiltration into CNV and of the in vivo and in vitro expression of inflammation-related molecules, including VEGF, IL-6, ICAM-1, MCP-1, VEGFR-1, and VEGFR-2. Importantly, AST suppressed the activation of the NF-kappaB pathway, including IkappaB-alpha degradation and p65 nuclear translocation. CONCLUSIONS: AST treatment, together with inflammatory processes including NF-kappaB activation, subsequent upregulation of inflammatory molecules, and macrophage infiltration, led to significant suppression of CNV development. The present study suggests the possibility of AST supplementation as a therapeutic strategy to suppress CNV associated with AMD.

Amelioration of ultraviolet-induced photokeratitis in mice treated with astaxanthin eye drops
         (Lennikov et al., 2012) Download
PURPOSE: Ultraviolet (UV) acts as low-dose ionizing radiation. Acute UVB exposure causes photokeratitis and induces apoptosis in corneal cells. Astaxanthin (AST) is a carotenoid, present in seafood, that has potential clinical applications due to its high antioxidant activity. In the present study, we examined whether topical administration of AST has preventive and therapeutic effects on UV-photokeratitis in mice. METHODS: C57BL/6 mice were administered with AST diluted in polyethylene glycol (PEG) in instillation form (15 mul) to the right eye. Left eyes were given vehicle alone as controls. Immediately after the instillation, the mice, under anesthesia, were irradiated with UVB at a dose of 400 mJ/cm(2). Eyeballs were collected 24 h after irradiation and stained with H&E and TUNEL. In an in vitro study, mouse corneal epithelial (TKE2) cells were cultured with AST before UV exposure to quantify the UV-derived cytotoxicity. RESULTS: UVB exposure induced cell death and thinning of the corneal epithelium. However, the epithelium was morphologically well preserved after irradiation in AST-treated corneas. Irradiated corneal epithelium was significantly thicker in eyes treated with AST eye drops, compared to those treated with vehicles (p<0.01), in a doses dependent manner. Significantly fewer apoptotic cells were observed in AST-treated eyes than controls after irradiation (p<0.01). AST also reduced oxidative stress in irradiated corneas. The in vitro study showed less cytotoxicity of TKE2 cells in AST-treated cultures after UVB-irradiation (p<0.01). The cytoprotective effect increased with the dose of AST. CONCLUSIONS: Topical AST administration may be a candidate treatment to limit the damages by UV irradiation with wide clinical applications.

Modulatory effects of an algal extract containing astaxanthin on UVA-irradiated cells in culture
         (Lyons and O'Brien, 2002) Download
UV radiation from sunlight is the most potent environmental risk factor in skin cancer pathogenesis. In the present study the ability of an algal extract to protect against UVA-induced DNA alterations was examined in human skin fibroblasts (1BR-3), human melanocytes (HEMAc) and human intestinal CaCo-2 cells. The protective effects of the proprietary algal extract, which contained a high level of the carotenoid astaxanthin, were compared with synthetic astaxanthin. DNA damage was assessed using the single cell gel electrophoresis or comet assay. In 1BR-3 cells, synthetic astaxanthin prevented UVA-induced DNA damage at all concentrations (10 nM, 100 nM, 10 microM) tested. In addition, the synthetic carotenoid also prevented DNA damage in both the HEMAc and CaCo-2 cells. The algal extract displayed protection against UVA-induced DNA damage when the equivalent of 10 microM astaxanthin was added to all three-cell types, however, at the lower concentrations (10 and 100 nM) no significant protection was evident. There was a 4.6-fold increase in astaxanthin content of CaCo-2 cells exposed to the synthetic compound and a 2.5-fold increase in cells exposed to algal extract. In 1BR-3 cells, exposure to UVA for 2 h resulted in a significant induction of cellular superoxide dismutase (SOD) activity, coupled with a marked decrease in cellular glutathione (GSH) content. However pre-incubation (18 h) with 10 microM of the either the synthetic astaxanthin or the algal extract prevented UVA-induced alterations in SOD activity and GSH content. Similarly, in CaCo-2 cells a significant depletion of GSH was observed following UVA-irradiation which was prevented by simultaneously incubating with 10 microM of either synthetic astaxanthin or the algal extract. SOD activity was unchanged following UVA exposure in the intestinal cell line. This work suggests a role for the algal extract as a potentially beneficial antioxidant.

Astaxanthin, a dietary carotenoid, protects retinal cells against oxidative stress in-vitro and in mice in-vivo
         (Nakajima et al., 2008) Download
We have investigated whether astaxanthin exerted neuroprotective effects in retinal ganglion cells in-vitro and in-vivo. In-vitro, retinal damage was induced by 24-h hydrogen peroxide (H2O2) exposure or serum deprivation, and cell viability was measured using a WST assay. In cultured retinal ganglion cells (RGC-5, a rat ganglion cell-line transformed using E1A virus), astaxanthin inhibited the neurotoxicity induced by H2O2 or serum deprivation, and reduced the intracellular oxidation induced by various reactive oxygen species (ROS). Furthermore, astaxanthin decreased the radical generation induced by serum deprivation in RGC-5. In mice in-vivo, astaxanthin (100 mg kg(-1), p.o., four times) reduced the retinal damage (a decrease in retinal ganglion cells and in thickness of inner plexiform layer) induced by intravitreal N-methyl-D-aspartate (NMDA) injection. Furthermore, astaxanthin reduced the expressions of 4-hydroxy-2-nonenal (4-HNE)-modified protein (indicator of lipid peroxidation) and 8-hydroxy-deoxyguanosine (8-OHdG; indicator of oxidative DNA damage). These findings indicated that astaxanthin had neuroprotective effects against retinal damage in-vitro and in-vivo, and that its protective effects may have been partly mediated via its antioxidant effects.

Carotenoids and antioxidants in age-related maculopathy italian study: multifocal electroretinogram modifications after 1 year
         (Parisi et al., 2008) Download
OBJECTIVE: To evaluate the influence of short-term carotenoid and antioxidant supplementation on retinal function in nonadvanced age-related macular degeneration (AMD). DESIGN: Randomized controlled trial. PARTICIPANTS: Twenty-seven patients with nonadvanced AMD and visual acuity > or =0.2 logarithm of the minimum angle of resolution were enrolled and randomly divided into 2 age-similar groups: 15 patients had oral supplementation of vitamin C (180 mg), vitamin E (30 mg), zinc (22.5 mg), copper (1 mg), lutein (10 mg), zeaxanthin (1 mg), and astaxanthin (4 mg) (AZYR SIFI, Catania, Italy) daily for 12 months (treated AMD [T-AMD] group; mean age, 69.4+/-4.31 years; 15 eyes); 12 patients had no dietary supplementation during the same period (nontreated AMD [NT-AMD] group; mean age, 69.7+/-6.23 years; 12 eyes). At baseline, they were compared with 15 age-similar healthy controls. METHODS: Multifocal electroretinograms in response to 61 M-stimuli presented to the central 20 degrees of the visual field were assessed in pretreatment (baseline) conditions and, in nonadvanced AMD patients, after 6 and 12 months. MAIN OUTCOME MEASURES: Multifocal electroretinogram response amplitude densities (RAD, nanovolt/deg(2)) of the N1-P1 component of first-order binary kernels measured from 5 retinal eccentricity areas between the fovea and midperiphery: 0 degrees to 2.5 degrees (R1), 2.5 degrees to 5 degrees (R2), 5 degrees to 10 degrees (R3), 10 degrees to 15 degrees (R4), and 15 degrees to 20 degrees (R5). RESULTS: At baseline, we observed highly significant reductions of N1-P1 RADs of R1 and R2 in T-AMD and NT-AMD patients when compared with healthy controls (1-way analysis of variance P<0.01). N1-P1 RADs of R3-R5 observed in T-AMD and NT-AMD were not significantly different (P>0.05) from controls. No significant differences (P>0.05) were observed in N1-P1 RADs of R1-R5 between T-AMD and NT-AMD at baseline. After 6 and 12 months of treatment, T-AMD eyes showed highly significant increases in N1-P1 RADs of R1 and R2 (P<0.01), whereas no significant (P>0.05) change was observed in N1-P1 RADs of R3-R5. No significant (P>0.05) changes were found in N1-P1 RADs of R1-R5 in NT-AMD eyes. CONCLUSIONS: In nonadvanced AMD eyes, a selective dysfunction in the central retina (0 degrees -5 degrees ) can be improved by the supplementation with carotenoids and antioxidants. No functional changes are present in the more peripheral (5 degrees -20 degrees ) retinal areas.

Carotenoids in Age-related Maculopathy Italian Study (CARMIS): two-year results of a randomized study
         (Piermarocchi et al., 2012) Download
PURPOSE: The high concentration of carotenoids in the macula, plus evidence linking oxidative stress to age-related macular degeneration (AMD) and carotenoids to antioxidation, generated the hypothesis that higher antioxidant intakes can prevent AMD. The aim of this study was to determine whether nutritional supplementation with a targeted nutritional supplement improves visual acuity and visual function in AMD. METHODS: In this multicenter, prospective open-label randomized study, 145 patients were randomly assigned to 2 different treatment groups. Interventions were lutein (10 mg), zeaxanthin (1 mg), astaxanthin (4 mg; AZYR SIFI, Catania, Italy), and antioxidants/vitamins supplementation formula or no dietary supplementation for 2 years. Primary outcome was mean changes in visual acuity (VA) at 12 and 24 months. Other measures included contrast sensitivity (CS) and National Eye Institute visual function questionnaire (NEI VFQ-25) scores at 12 and 24 months. RESULTS: Patients in the treated group showed stabilization of VA with significantly (p=0.003) better VA scores (81.4 +/- 7.2) compared to the nontreated group (76.8 +/- 8.9) at 24-month follow-up. An improvement in CS (p=0.001) and final mean NEI VFQ-25 composite scores at 12 and 24 months higher in treated group compared to nontreated group were also shown (p<0.001). CONCLUSIONS: Patients treated with lutein/zeaxanthin and astaxanthin together with other nutrients were more likely to report clinically meaningful stabilization/improvements in VA, CS, and visual function through 24 months compared with nontreated subjects. Further studies are needed with more patients and for longer periods of time.

Nitric oxide synthase uncoupling: a therapeutic target in cardiovascular diseases
         (Roe and Ren, 2012) Download
Nitric oxide synthase enzyme (NOS) possesses the unique ability to be "uncoupled" to produce superoxide anion (O(2)(-)) instead of nitric oxide (NO). Reduced NO bioavailability as a result of NOS uncoupling has been speculated to play an essential role in cardiovascular pathologies including dilated cardiomyopathy, ischemia reperfusion injury, endothelial dysfunction, atherosclerosis, hypertension and diabetes mellitus. NO serves many important roles in the heart including stimulation of adenylate cyclase (AC) at low levels or guanalyl cyclase (sGC) at higher levels, or by s-nitrosylation of intracellular Ca(2+) regulatory proteins thus altering excitation-contraction coupling. Not surprisingly, NOS uncoupling is an emerging therapeutic target in cardiovascular diseases. Restoring proper NOS activity by increasing intracellular levels of its cofactor tetrahydrobiopterin (BH4) is effective in the management of hypertensive diastolic dysfunction, ischemia-reperfusion injury, myocardial infarction and endothelial dysfunction. New evidence is constantly emerging highlighting the importance of NOS uncoupling in cardiovascular pathologies thus the purpose of this mini-review is to showcase the new advances and promising treatments for NOS uncoupling in CV disease.

Astaxanthin attenuates the UVB-induced secretion of prostaglandin E2 and interleukin-8 in human keratinocytes by interrupting MSK1 phosphorylation in a ROS depletion-independent manner
         (Terazawa et al., 2012) Download
To elucidate the effects of redox balance regulation on cutaneous inflammation, we used the potent antioxidant astaxanthin (AX) to assess its effect on the UVB-induced secretion of PGE(2) and IL-8 in human keratinocytes and analysed its biological mechanism of action. The addition of AX (at 8 mum) to human keratinocytes even after UVB irradiation significantly down-regulated the increased secretion of PGE(2) or IL-8. Those suppressive effects were accompanied by significantly decreased expression of genes encoding COX-2 or IL-8 as well as COX-2 protein. Analysis using a specific NF-kappaB tanslocation inhibitor demonstrated that the UVB-stimulated secretion of PGE(2) and IL-8 was significantly abolished by its treatment prior to UVB irradiation. Western blotting of phosphorylated signalling molecules revealed that UVB irradiation (80 mJ/cm(2) ) significantly stimulated the phosphorylation of p38, ERK and JNK, which was not suppressed by treatment with AX after irradiation. In contrast, AX significantly inhibited the UVB-increased phosphorylation of mitogen- and stress-activated protein kinase (MSK)-1, NF-kBp65 or CREB even when treated postirradiation. Further, the MSK1 inhibitor H89 significantly down-regulated the increased secretion of PGE(2) and IL-8 in UVB-exposed human keratinocytes, following post-irradiation treatment. These findings suggests that AX attenuates the auto-phosphorylation of MSK1 required for its activation, which results in the decreased phosphorylation of NF-kBp65, which in turn probably leads to a deficiency of NF-kB DNA binding activity. This may be associated with the significant suppression of PGE(2) /IL-8 secretion via the down-regulated expression of COX-2 and IL-8 at the gene and/or protein levels.

Cosmetic benefits of astaxanthin on humans subjects
         (Tominaga et al., 2012) Download
Two human clinical studies were performed. One was an open-label non-controlled study involving 30 healthy female subjects for 8 weeks. Significant improvements were observed by combining 6 mg per day oral supplementation and 2 ml (78.9 muM solution) per day topical application of astaxanthin. Astaxanthin derived from the microalgae, Haematococcus pluvialis showed improvements in skin wrinkle (crow's feet at week-8), age spot size (cheek at week-8), elasticity (crow's feet at week-8), skin texture (cheek at week-4), moisture content of corneocyte layer (cheek in 10 dry skin subjects at week-8) and corneocyte condition (cheek at week-8). It may suggest that astaxanthin derived from H. pluvialis can improve skin condition in all layers such as corneocyte layer, epidermis, basal layer and dermis by combining oral supplementation and topical treatment. Another was a randomized double-blind placebo controlled study involving 36 healthy male subjects for 6 weeks. Crow's feet wrinkle and elasticity; and transepidermal water loss (TEWL) were improved after 6 mg of astaxanthin (the same as former study) daily supplementation. Moisture content and sebum oil level at the cheek zone showed strong tendencies for improvement. These results suggest that astaxanthin derived from Haematococcus pluvialis may improve the skin condition in not only in women but also in men.


Cort, A., et al. (2010), ‘Suppressive effect of astaxanthin on retinal injury induced by elevated intraocular pressure’, Regul Toxicol Pharmacol, 58 (1), 121-30. PubMedID: 20457203
Hussein, G, et al. (2006), ‘Astaxanthin, a carotenoid with potential in human health and nutrition.’, J Nat Prod, 69 (3), 443-49. PubMedID: 16562856
Izumi-Nagai, K., et al. (2008), ‘Inhibition of choroidal neovascularization with an anti-inflammatory carotenoid astaxanthin’, Invest Ophthalmol Vis Sci, 49 (4), 1679-85. PubMedID: 18385091
Lennikov, A., et al. (2012), ‘Amelioration of ultraviolet-induced photokeratitis in mice treated with astaxanthin eye drops’, Mol Vis, 18 455-64. PubMedID: 22393271
Lyons, N. M. and N. M. O’Brien (2002), ‘Modulatory effects of an algal extract containing astaxanthin on UVA-irradiated cells in culture’, J Dermatol Sci, 30 (1), 73-84. PubMedID: 12354422
Nakajima, Y., et al. (2008), ‘Astaxanthin, a dietary carotenoid, protects retinal cells against oxidative stress in-vitro and in mice in-vivo’, J Pharm Pharmacol, 60 (10), 1365-74. PubMedID: 18812030
Parisi, V., et al. (2008), ‘Carotenoids and antioxidants in age-related maculopathy italian study: multifocal electroretinogram modifications after 1 year’, Ophthalmology, 115 (2), 324-333 e2. PubMedID: 17716735
Piermarocchi, S., et al. (2012), ‘Carotenoids in Age-related Maculopathy Italian Study (CARMIS): two-year results of a randomized study’, Eur J Ophthalmol, 22 (2), 216-25. PubMedID: 22009916
Roe, N. D. and J. Ren (2012), ‘Nitric oxide synthase uncoupling: a therapeutic target in cardiovascular diseases’, Vascul Pharmacol, 57 (5-6), 168-72. PubMedID: 22361333
Terazawa, S., et al. (2012), ‘Astaxanthin attenuates the UVB-induced secretion of prostaglandin E2 and interleukin-8 in human keratinocytes by interrupting MSK1 phosphorylation in a ROS depletion-independent manner’, Exp Dermatol, 21 Suppl 1 11-17. PubMedID: 22626465
Tominaga, K., et al. (2012), ‘Cosmetic benefits of astaxanthin on humans subjects’, Acta Biochim Pol, 59 (1), 43-47. PubMedID: 22428137