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Potential health‐promoting effects of astaxanthin: A high‐value carotenoid mostly from microalgae
Abstract
The ketocarotenoid astaxanthin can be found in the microalgae Haematococcus pluvialis, Chlorella zofingiensis, and Chlorococcum sp., and the red yeast Phaffia rhodozyma. The microalga H. pluvialis has the highest capacity to accumulate astaxanthin up to 4-5% of cell dry weight. Astaxanthin has been attributed with extraordinary potential for protecting the organism against a wide range of diseases, and has considerable potential and promising applications in human health. Numerous studies have shown that astaxanthin has potential health-promoting effects in the prevention and treatment of various diseases, such as cancers, chronic inflammatory diseases, metabolic syndrome, diabetes, diabetic nephropathy, cardiovascular diseases, gastrointestinal diseases, liver diseases, neurodegenerative diseases, eye diseases, skin diseases, exercise-induced fatigue, male infertility, and HgCl₂-induced acute renal failure. In this article, the currently available scientific literature regarding the most significant activities of astaxanthin is reviewed.
... Similar rates of astaxanthin accumulation were observed in the study by Wood et al. for a 65 L PBR system using a two-stage process, ranging from 0.30 to 0.36 mg/(g·d) [14]. The final astaxanthin concentration of 4.9 mg/g and the impact of osmotic stress are consistent with findings from various studies [22,48,49], which report astaxanthin concentrations of up to 6 mg/g under common stress factors such as high light intensities, osmotic stress, and nitrogen depletion at smaller scales. The cellular astaxanthin content of the gold standard of astaxanthin production, Haematococcus pluvialis, was reported to accumulate astaxanthin concentrations up to 25.92 mg/g [50] exposed to osmotic salt stress, a factor of 5 higher than that for C. zofingiensis. ...
... Biomass accumulation of C. zofingiensis and nitrate concentration (NO3 − ) during the three different cultivation phases, starting with an initial growth phase (day 0 to 19), a first nutrientdepletion stress phase (day 19-38) and a second stress phase combining nitrogen depletion and osmotic salt stress (day[39][40][41][42][43][44][45][46][47][48][49][50][51]. ...
... Biomass accumulation of C. zofingiensis and nitrate concentration (NO 3 − ) during the three different cultivation phases, starting with an initial growth phase (day 0 to 19), a first nutrientdepletion stress phase (day 19-38) and a second stress phase combining nitrogen depletion and osmotic salt stress (day[39][40][41][42][43][44][45][46][47][48][49][50][51]. ...
Chromochloris zofingiensis is a green alga that serves as a valuable source of lipids, pro-teins, and carotenoids. Compared to well-studied microalgal carotenoid producers, C. zofingiensis offers several advantages, including high biomass, lipid and carotenoid productivity as well as less susceptibility to contaminations. C. zofingiensis can achieve growth rates up to four times higher than those of H. pluvialis under optimal photo-trophic conditions. Although several studies have examined its cultivation and carote-nogenesis under different tropic growth modes at laboratory scale, few have focused on pilot-scale systems. The goal of this study is to investigate the microalga’s physiological adaptation in a 200 L tubular photobioreactor during a three-phase semi-continuous cultivation strategy, particularly focusing on the changes in macromolecular and pig-ment composition. After an initial biomass accumulation phase, a two-phased stress phase was applied combining nutrient depletion (phase 1) and osmotic salt stress con-ditions (phase 2). Following this procedure, the cellular protein content dropped to 44.7 % of its initial level, while the lipid content rose by up to 320 %. Additionally, the astaxanthin concentration increased from 1.1 mg/gDW to 4.9 mg/gDW during the last os-motic stress phases, aligning with results from published laboratory-scale studies..
... Astaxanthin (AST), which is known as "super vitamin E,″ is a potent ketocarotenoid antioxidant that exhibits strong antiinflammatory properties, attracting considerable interest due to its various biological effects, including antioxidation, neuroprotection, anti-hyperplasia, anti-inflammation, anti-apoptosis (Yuan et al., 2011;Galasso et al., 2018), and even anti-ferroptosis properties in several diseases, which are different to those of vitamin E (Kong et al., 2023;Ren et al., 2023). Astaxanthin can activate GPX4 to inhibit ferroptosis and reduce metal-induced biotoxicity (Li et al., 2024). ...
... Previous studies have revealed that several substances can induce ferroptosis by different mechanisms (Liang et al., 2019;Wu et al., 2019). Although the physiological function of ferroptosis remains poorly defined, it has been shown to be involved in various diseases (Yuan et al., 2011;Coursey et al., 2016;Chen et al., 2020;Zuo et al., 2022). High concentrations of NaCl were used as our irritants to induce ferroptosis in HCECs. ...
Dry eye disease (DED) is a common eye disease in clinical practice. The crucial pathogenesis of DED is that hyperosmolarity activates oxidative stress signaling pathways in corneal epithelial and immune cells and, thus, produces inflammatory molecules. The complex pathological changes in the dry eye still need to be elucidated to facilitate treatment. In this study, we found that astaxanthin (AST) can protect against DED through the SLC7A11/GPX4 pathway. After treatment with AST, the SLC7A11/GPX4 pathway was positively activated in DED both in vivo and in vitro, accompanied by enhanced autophagy and decreased ferroptosis. In hyperosmolarity-induced DED corneal epithelial cells, AST increased the expression of ferritin to promote iron storage and reduce Fe²⁺ overload. It increased glutathione (GSH) and GPX4, scavenged reactive oxygen species (ROS) and lipid peroxide, and rescued the mitochondrial structure to prevent ferroptosis. Furthermore, inhibition of ferroptosis by ferrostatin-1 (Fer-1), iron chelator deferoxamine mesylate (DFO), or AST could activate healthy autophagic flux. In addition, in a dry eye mouse model, AST upregulated SLC7A11 and GPX4 and inhibited ferroptosis. To summarize, we found that AST can ameliorate DED by reinforcing the SLC7A11/GPX4 pathway, which mainly affects oxidative stress, autophagy, and ferroptosis processes.
... It has been shown that its antioxidant capacity is approximately 100 fold stronger than vitamin E, which is a well-known potent antioxidant [7]. In addition, it has recently attracted significant attention with its DNA repair, cell regeneration, neuroprotective, anti-inflammatory, anti-diabetic, anticancer, anti-apoptotic and anti-autophagic properties [8][9][10]. Studies indicate that a healthy diet containing high amounts of antioxidants may be effective in increasing semen quality and fertility. ...
... Studies indicate that a healthy diet containing high amounts of antioxidants may be effective in increasing semen quality and fertility. Researchers have demonstrated the positive effects of astaxanthin on sperm quality and fertility by significantly reducing the secretion of reactive oxygen species and inhibin B by Sertoli cell [8]. Reveal of its many positive effects on human health has made astaxanthin a nutritional supplement in the daily diet of individuals [11]. ...
A significant clinical condition known as testicular torsion leads to permanent ischemic damage to the testicular tissue and consequent loss of function in the testicles. In this study, it was aimed to evaluate the protective effects of Astaxanthin (ASTX) on testicular damage in rats with testicular torsion/detorsion in the light of biochemical and histopathological data. Spraque Dawley rats of 21 were randomly divided into three groups; sham, testicular torsion/detorsion (TTD) and astaxanthin + testicular torsion/detorsion (ASTX + TTD). TTD and ASTX + TTD groups underwent testicular torsion for 2 hours and then detorsion for 4 hours. Rats in the ASTX + TTD group were given 1 mg/kg/day astaxanthin by oral gavage for 7 days before torsion. Following the detorsion process, oxidative stress parameters and histopathological changes in testicular tissue were evaluated. Malondialdehyde (MDA) and total oxidant status (TOS) levels were significantly decreased in the ASTX group compared to the TTD group, while superoxide dismutase (SOD), glutathione (GSH) and total antioxidant status (TAS) levels were increased (p < 0.05). Moreover, histopathological changes were significantly reduced in the group given ASTX (p < 0.0001). It was determined that ASTX administration increased Beclin-1 immunoreactivity in ischemic testicular tissue, while decreasing caspase-3 immunoreactivity (p < 0.0001). Our study is the first to investigate the antiautophagic and antiapoptotic properties of astaxanthin after testicular torsion/detorsion based on the close relationship of Beclin-1 and caspase-3 in ischemic tissues. Our results clearly demonstrate the protective effects of ASTX against ischemic damage in testicular tissue. In ischemic testicular tissue, ASTX contributes to the survival of cells by inducing autophagy and inhibiting the apoptosis.
... Astaxanthin (AXT) is a xanthophyll carotenoid with a unique molecular structure. This distinctive structure imparts strong antioxidant properties to AXT, allowing it to function both inside and outside the cell membrane (1). It has been widely studied for its health benefits, including alleviating diabetes mellitus, neurodegenerative and cardiovascular diseases, hepatic disorders, and providing protection against various cancers. ...
Introduction: The beneficial effects on health result from the protective action of astaxanthin (AXT) as a powerful antioxidant capable of scavenging free radicals and protecting cells from oxidative stress. The study aimed to evaluate the protective role of astaxanthin derived from Haematococcus pluvialis in reducing the thermal oxidation of fatty acids in vegetable oils. Material and Methods: Astaxanthin, obtained by extraction from the biomass of Haematococcus pluvialis, at a concentration of 0.26-0.29 mg/mL, was added to olive, sunflower, almond, walnut, sesame, and poppy seed oils. The progression of oxidation was monitored based on the formation of conjugated dienes. The formation of conjugated dienes was monitored spectrophotometrically. Results: Astaxanthin reduced the content of conjugated dienes in sesame, almond, and walnut oils by 30-34%. A strong antioxidant effect of AXT was noted in the case of poppy seed oil, for which the formation of conjugated dienes was decreased by 42% and the oxidation was delayed by 60 min when exposed to high temperatures compared to native oil. For sunflower oil, which exhibited a high degree of thermal oxidation, addition of AXT reduced the formation of conjugated dienes by 22% during the experiment. Conclusions: Astaxanthin from Haematococcus pluvialis significantly reduced the formation of conjugated dienes, indicating it does not act as a prooxidant in various vegetable oils.
... This is an antioxidant that protects damaged cells and improves the immune system (Galasso et al., 2018;Park et al., 2010). Some previous studies reported that the amount of astaxanthin in Sergestid shrimp can help healthy skin (Yuan et al., 2011), prevent cardiovascular disease (Bjorklund et al., 2022), and reduce joint pain (Ambati et al., 2014;Saini et al., 2018). Several other reports have also pointed to a finding on the possibility of treating cancer thanks to this active antioxidant active ingredient (Faraone et al., 2020). ...
One of the important components of Sergestid shrimp is astaxanthin, which brings many health benefits to humans such as antioxidant protection, prevent cancer and immune system enhancement. However, a limited understanding of the effects of packaging and storage conditions on product quality is responsible for the low shelf life of dried Sergestid shrimp products. The objective of this study is to investigate the influence of five types of packaging and temperature conditions (5-45 °C) and the duration of storage 15 days on product quality, including PE bags coated with aluminum film (Al/PE), colored PE bags, paper coated PE bags (Paper/PE), vacuum PE bags (VC) and glass bottle (TT) to select a suitable storage condition. Moisture content, astaxanthin, and total aerobic microbial content were evaluated during storage. The results showed that the Al/PE bags were highly effective in maintaining the moisture content and astaxanthin content. The transparent packaging (VC, TT) has negatively affected astaxanthin in dried Sergestid shrimp due to light exposure. Temperatures between 5 and 15 °C are ideal to protect astaxanthin, stabilize moisture content, and inhibit microbial growth. The results of the study are the basis for choosing packaging and storage conditions that extend the storage time of the dried product.
... This beneficial carotenoid also reduces bacterial infectionsinduced stomach irritation. It has been claimed that astaxanthin generated from microalgae can decrease the generation or expression of inflammatory mediators and cytokines, as well as the expression of cyclooxygenase-2 and inducible nitric oxide synthase that can causes diseases like, atherosclerosis, or inflammatory bowel disease and brain inflammatory disease [125]. ...
Microalgae are promising sources of valuable carotenoids like β-carotene and astaxanthin with numerous health benefits. This review summarizes recent studies on producing these carotenoids in microalgae under different salinity and light-intensity conditions, which are key factors influencing their biosynthesis. The carotenoid biosynthesis pathways in microalgae, involving the methylerythritol phosphate pathway in chloroplasts, are described in detail. The effects of high salinity and light stress on stimulating astaxanthin accumulation in species like Haematococcus pluvialis and Chromochloris zofingiensis and their synergistic impact are discussed. Similarly, the review covers how high light and salinity induce β-carotene production in Dunaliella salina and other microalgae. The diverse health-promoting properties of astaxanthin and β-carotene, such as their antioxidant, antiinflammatory, and anticancer activities, are highlighted. Strategies to improve carotenoid yields in microalgae through environmental stresses, two-stage cultivation, genetic engineering, and metabolic engineering approaches are evaluated. Overall, this review highlights advancements in β-carotene and astaxanthin production reporting the different microalgal capability to produce carotenoids under different stress level like 31.5% increase in β-carotene accumulation in Dunaliella salina and astaxanthin productivity reaching 18.1 mg/L/day in Haematococcus lacustris. It also explores novel biotechnological strategies, including CRISPR–Cas9, for enhancing carotenoid yield.
Graphical Abstract
... Astaxanthin is a natural carotenoid known for its strong antioxidant properties that can help reduce the risk of cardiovascular disease, cancer, arthritis, and improve skin health (Yuan et al., 2011). However, astaxanthin can degrade during storage (Martínez et al., 2017). ...
Each food product has distinct characteristics. Selecting appropriate storage conditions for each product is essential to minimize quality degradation and extend its shelf life. This study focused on understanding how different packaging materials and storage temperatures influence the quality, longevity of spiced Sergestid shrimp, and on determining the optimal conditions to inhibit microbial activity, prevent moisture absorption, while still preserving maximum astaxanthin content. Polyethylene bags with an aluminum film (Al/PE), PET bottles (polyethylene terephthalate), paper bags with a polyethylene film (Paper/PE), and glass bottles were used for packaging. Storage was carried out at four different temperatures: 5; 15; 25; 35°C. The moisture content, astaxanthin content, and total aerobic microorganisms were also determined at least once every 3 to 7 days and continuously monitored for 77 days. The findings indicated that PET bottles effectively prevent moisture absorption and protect astaxanthin from degradation over time. However, transparent packaging, such as glass bottles that allow direct exposure of the product to light, negatively affects the stability of astaxanthin. The optimal temperature range for storing this product was identified as being between 5 and 15°C, which helped stabilize moisture content (5.55-6.34%) and inhibit the growth of aerobic microorganisms (2.42-2.58 LogCFU/g). These findings provide crucial insights for the seafood industry, particularly in choosing the right packaging materials and storage conditions to enhance the shelf life and maintain the quality of spiced Sergestid shrimp products. This study contributes to the existing knowledge and aids stakeholders in making informed decisions regarding product packaging and storage strategies.
... Additionally, microalgae possess a variety of bioactive pigments, making them interesting for various applications in pharmaceuticals, cosmetics, and food production [14][15][16]. These pigments include primary and secondary carotenoids with antioxidant properties, such as lutein, β-carotene, astaxanthin, canthaxanthin, and zeaxanthin. ...
... Although the immunostimulatory activity of carotenoids is well known [31,70], there have been a few conflicting reports. For example, Amar et al. [71] observed that CR elevated phagocytic activity and resistance to infectious viruses in rainbow trout. ...
The body color state is an important determinant of the value of golden severum (Heros efasciatus)—a popular ornamental fish. The use of dietary supplements to improve the color development and health of this species is unexplored. Herein, the effects of marigold extract (MG) and carophyll red (CR) are examined on the growth, body color development, antioxidant properties, and innate immunity in golden severum. Fish were maintained under controlled water quality conditions (pH, temperature, and dissolved oxygen) and fed six experimental diets containing either 0% MG and CR, 1% MG, 2% MG, 5% MG, 0.5% CR, or 2% CR for five weeks. Both MG and CR significantly decreased lipid peroxide levels in hepatic tissues. In contrast, only MG enhanced the activities of reactive oxygen species (ROS)-scavenging enzymes (superoxide dismutase and catalase). Although MG and CR decreased the respiratory burst activity of splenic leukocytes, other innate immune parameters remained unchanged. Additionally, MG and CR stimulated body color development patterns in golden severum that reflect their unique coloring principles. The ROS-scavenging abilities of MG and CR appear to be related to their antioxidant activity. Hence, MG and CR at the optimal levels of 1.0% and 0.5%, respectively, can improve the body color of golden severum and protect against oxidative stress.
... Research suggested extracting a lipid extract rich in α-tocopherol, polyunsaturated fatty acids (PUFAs), and astaxanthin (AST) from this waste (Gómez-Guillén et al. 2018;Montero et al. 2016). AST, a carotenoid pigment responsible for the vibrant red color of shrimp, holds promise as a natural food colorant (Montero et al. 2016;Yuan et al. 2011). This compound (3,3′-dihydroxy-β, β-carotene-4,4′-dione) is found in various aquatic organisms, including shrimp, crabs, salmon, and others (Liu et al. 2023;Pitacco et al. 2022). ...
The research aimed to study how different drying methods (spray and freeze drying) affect the release kinetics of microencapsulated astaxanthin in various environmental conditions. Shrimp shell extract containing astaxanthin was encapsulated using different wall components (maltodextrin with different dextrose equivalents and modified starch) via a simplex lattice mixture design. The encapsulated extract was then subjected to storage at different temperatures (25°C ± 2°C and 2°C ± 4°C) and humidity conditions (52% ± 2% and 75% ± 2%), as well as exposure to UV light (four 15 W lamps, 254 nm, for 10 h). The release kinetics of astaxanthin were analyzed using various models (page, Newton Korsmeyer–Peppas model, Modified Henderson and Pabis, Diffusion approach, and Two‐term exponential). The evaluation results of correlation coefficient (R²), root mean square deviation (RMSE), and mean absolute percentage error (MAPE) values of different models showed that the astaxanthin degradation followed a two‐term exponential kinetics in both types of microcapsules. Astaxanthin degradation increased with higher temperatures, humidity, and UV light exposure. However, microcapsules with equal wall compound ratios exhibited better preservation of astaxanthin. The study also emphasized the significance of optimizing storage conditions and wall materials for microencapsulated astaxanthin, as well as the utility of the two‐term exponential model in enhancing stability and shelf life.
... Fakhri et al. highlighted the antioxidant, anti-inflammatory, antiapoptotic, anticancer, antiobesity, antidiabetic, and neuroprotective effects of AST (Fakhri et al. 2018). Strong AST antioxidant activity is 100 to 1000 times higher than other phytochemical compounds (Yuan et al. 2011). Possessing 13 conjugated double polyunsaturated bonds gives AST its distinctive chemical properties and molecular structure toward antioxidant potentials. ...
Acute kidney injury (AKI) is a sudden onset of renal injury that occurs within a few hours or days. Ischemia-reperfusion (IR) is a major cause of AKI. There are multiple dysregulated mechanisms behind the pathogenesis of AKI and IR which urges the need for finding multi-targeting therapies. Natural products are multi-targeting agents with promising sources of anti-inflammation, antioxidant, and antiapoptosis. Among them, astaxanthin (AST) is a keto-carotenoid with a high antioxidant potential. Using solid lipid nanoparticles (SLNs) as a novel formulation of AST helps to increase its efficacy and reduce side effects against AKI. After SLN preparation and loading of AST, the physicochemical properties were evaluated, using scanning electron microscopy (SEM) and dynamic light scattering (DLS) tests. For the in vivo study, 28 rats were divided into four groups, including sham, ischemia/reperfusion (I/R), and groups receiving protective and daily doses of AST-SLN (5 and 10 mg/kg, i.p.) during all 5 days before ischemia. Exactly 24 h after ischemia, kidneys were isolated for histological studies, and also, serum levels of catalase (CAT), glutathione (GSH), nitrite, blood urea, and creatinine were measured. The results indicated that intraperitoneal administration of SLN-AST reduced oxidative stress by decreasing serum nitrite levels, while increasing CAT and GSH. SLN-AST also improved renal function by decreasing serum urea and creatinine and preventing tissue damage. Therefore, SLN-AST could be a hopeful adjuvant candidate to prevent AKI by modulating renal function, preventing tissue damage, and through antioxidant mechanisms.
... Research has focused on extracting a lipid-rich extract containing α-tocopherol, polyunsaturated fatty acids (PUFAs), and astaxanthin (AST) from this waste (Gómez-Guillén et al., 2018; Montero et al., 2016). AST (3,3'-dihydroxy-β,β-carotene-4,4'-dione), a carotenoid pigment responsible for the red color of various aquatic organisms, holds promise as a natural food colorant with potent antioxidant properties (Montero et al., 2016;Yuan et al., 2011). While synthetic production exists, AST derived from biological sources shows superior chemical stability and antioxidant capacity due to its natural esteri cation with fatty acids (Vakarelova et al., 2017;Yang et al., 2023). ...
This study aimed to investigate the effects of free (FAST) and microencapsulated forms (MFAST, and MSAST) of astaxanthin (AST) on the quality, antioxidant and sensory properties of chicken lunch meat (CLM) over a 45-day period at 4°C, and were compared along with synthetic sodium nitrate and a control sample. The results demonstrated that AST levels in CLMs decreased during storage; however, microencapsulation significantly preserved approximately twice as much AST compared to CLMs containing free AST. Samples containing AST showed significantly higher antioxidant activity compared to both the control and sodium nitrate samples. Microencapsulated forms exhibited stronger radical scavenging activity, surpassing the free forms by more than 10 units, particularly in CLMs supplemented with freeze-dried AST (approximately 44% higher). Microbial growth rate increased over time, ranging from 2.82 ± 0.03 log 10 (CFU/g) on the first day to over 5.35 ± 0.04 log 10 (CFU/g) on day 45, while still remaining within acceptable microbial limits. In terms of sensory attributes, the FAST treatment at different concentrations resulted in moderately acceptable levels, however, the MFAST and MSAST treatments at higher concentrations received excellent scores. These findings highlight the potential of microencapsulation as a valuable technique for preserving AST and developing high-quality meat products with extended shelf life and enhanced sensory characteristics.
... The well-known microalgae Haematococcus pluvialis is frequently used to produce astaxanthin. [59] Other Chlorophyceae family microalgae including Chlamydomonas and Muriellopsis are known for producing a variety of secondary carotenoids including lycopene, fucoxanthin, canthaxanthin, echinenone, and dinoxanthin. [60][61][62] Brown algae species are particularly notable for their fucoxanthin content. ...
... There are different types of microalgae like Chlorella spp, Dunaliella spp, Spirulina spp and Haematococcus spp [12]. The most important and high yielding source of Astaxanthin is microalgae specifically Haematococcus pluvialis [13]. It is served as a food source to different marine animals. ...
Astaxanthin, a microalgal carotenoid is basically beneficial because of its multi-beneficiary effect on health. Nowadays, due to environmental pollution, sedentary lifestyle, unhealthy food habits etc are influencing the production of ROS in the body, which are reaching at their peak and harm different organs, resulting in different dreaded and degenerative diseases. Astaxanthin being a powerful antioxidant than other carotenoids act as a safe-guard to different organs that are affected by oxidative stress. In this review, detailed insight of the preventive role of Astaxanthin in various diseases is to be discussed.
... It is a keto carotenoid with π-π conjugation and an ionone ring containing polar hydroxyl and carbonyl groups (Ambati et al., 2014). It has a strong antioxidant capacity and can reduce •OH, thus effectively inhibiting the lipid peroxidation caused by •OH (Yuan et al., 2011) and inhibiting ROS generation by increasing SOD and CAT activities (Lee et al., 2011). For example, Cao et al. (2021) found that astaxanthin could reduce ROS levels caused by GO-COOH and adjust genes related to Parkinson disease symptoms affected by GO-COOH. ...
... The ocean green growth Chlorella zofingiensis and Hematococcus pluvialis, as well as the Phaffia rhodozyma red yeast, contain Astaxanthin (ASX), a xanthophyll color. Astaxanthin has been found to have strong cell reinforcement, hostile to cancer, against diabetic, calming, and cardioprotective exercises in a few studies [108][109][110][111][112][113]. ...
Diabetes is a metabolic condition characterized by high blood glucose levels. Aquatic products like microalgae, bacteria, seagrasses, macroalgae, corals, and sponges have been investigated for potential anti-diabetic properties. We looked at polyphenols, peptides, pigments, and sterols, as well as other bioactive substances found in marine resources, to see if they could help treat or manage diabetes, in addition to describing the several treatment strategies that alter diabetes and its implications, such as inhibition of protein tyrosine phosphatases 1B (PTP1B), α-glucosidase, α-amylase, dipeptidyl peptidase IV (DPP-IV), aldose reductase, lipase, glycogen synthase kinase 3β (GSK-3β), and insulin resistance prevention, promotion of liver antioxidant capacity, natural killer cell stimulant, anti-inflammatory actions, increased AMP-activated protein kinase (AMPK) phosphorylation and sugar and metabolism of the lipid, reducing oxidative stress, and β-pancreatic cell prevention. This study highlights the revolutionary potential of marine bioactive compounds and microorganisms in transforming diabetes care. We believe in a future in which innovative, sustainable, and efficient therapeutic approaches will result in improved quality of life and better outcomes for people with diabetes mellitus by forging a new path for treatment, utilizing the power of the world’s oceans, and capitalizing on the symbiotic relationship between humans and the marine ecosystem. This study area offers optimism and promising opportunities for transforming diabetes care.
Graphical Abstract
... Astaxanthin, a carotenoid similar to carotene and lycopene, is commonly found in nature, particularly in naturally occurring deep red seafood such as salmon, shrimp, and crab [19]. As humans are unable to produce carotenoids, astaxanthin must be acquired through dietary sources [20]. ...
Background
Heart failure is a chronic and progressive disease where the heart muscle is unable to pump enough blood and oxygen to meet the body’s needs. Oxidative stress and inflammation are key elements in the development and progression of heart failure. Astaxanthin, a carotenoid, has strong anti-inflammatory and antioxidant effects that may protect the cardiovascular system. A study will evaluate the effect of astaxanthin supplementation on inflammatory status, oxidative stress, lipid profile, uric acid levels, endothelial function, quality of life, and disease symptoms in people with heart failure.
Methods
The current study is a double-blind controlled randomized clinical trial for 8 weeks, in which people with heart failure were randomly assigned to two groups: intervention (one capsule containing 20 mg of astaxanthin per day, n = 40) and placebo (one capsule containing 20 mg of maltodextrin per day, n = 40) will be divided. At the beginning and end of the intervention, uric acid, lipid profile, oxidative stress indices, inflammatory markers, blood pressure, nitric oxide, and anthropometric factors will be measured, and questionnaires measuring quality of life, fatigue intensity, shortness of breath, and appetite will be completed. SPSS version 22 software will be used for statistical analysis.
Discussion
There is a growing global interest in natural and functional food products. This RCT contributes to the expanding body of research on the potential benefits of astaxanthin in heart failure patients, including its antioxidant, lipid-lowering, and anti-inflammatory effects.
Trial registration
Iranian Registry of Clinical Trials IRCT20200429047235N3. Registered on 26 March 2024.
... Its bioactivity surpasses that of lutein and zeaxanthin, with promising improvements in inflammation and oxidative markers in preclinical studies (249). Given its foundational role in chronic disease mechanisms, astaxanthin's research trajectory is directed toward its efficacy as an anti-aging agent (250). ...
Considering a growing, aging population, the need for interventions to improve the healthspan in aging are tantamount. Diet and nutrition are important determinants of the aging trajectory. Plant-based diets that provide bioactive phytonutrients may contribute to offsetting hallmarks of aging and reducing the risk of chronic disease. Researchers now advocate moving toward a positive model of aging which focuses on the preservation of functional abilities, rather than an emphasis on the absence of disease. This narrative review discusses the modulatory effect of nutrition on aging, with an emphasis on promising phytonutrients, and their potential to influence cellular, organ and functional parameters in aging. The literature is discussed against the backdrop of a recent conceptual framework which describes vitality, intrinsic capacity and expressed capacities in aging. This aims to better elucidate the role of phytonutrients on vitality and intrinsic capacity in aging adults. Such a review contributes to this new scientific perspective—namely—how nutrition might help to preserve functional abilities in aging, rather than purely offsetting the risk of chronic disease.
... Furthermore, this pigment can neutralize superoxide radicals (O 2− ) and inhibit the activation of the transcription factor NF-κB, thereby reducing the production of proinflammatory cytokines. It also blocks cytokine production by modulating the expression of protein tyrosine phosphatase-1, which helps reduce inflammation and protect against oxidative stress [72][73][74][75]. It has been suggested that astaxanthin, due to its antioxidant properties, is, therefore, a neuroprotective agent [76]. ...
The marine kingdom is an important source of a huge variety of scaffolds inspiring the design of new drugs. The complex molecules found in the oceans present a great challenge to organic and medicinal chemists. However, the wide variety of biological activities they can display is worth the effort. In this article, we present an overview of different seaweeds as potential sources of bioactive pigments with activity against neurodegenerative diseases, especially due to their neuroprotective effects. Along with a broad introduction to seaweed as a source of bioactive pigments, this review is especially focused on astaxanthin and fucoxanthin as potential neuroprotective and/or anti-neurodegenerative agents. PubMed and SciFinder were used as the main sources to search and select the most relevant scientific articles within the field.
... Vitamin E protects the cell membranes from peroxidation reaction caused by free radicals, i.e., reactive oxygen species (Sandmann 1994;Seyrek et al. 2004). Specifically, astaxanthin (a strong carotenoid) could protect cells, lipids and membrane lipoproteins from oxidative damage (Naguib 2000;Yuan et al. 2011). In Murrah buffaloes, astaxanthin supplementation lowered the levels of antioxidant enzymes and pro-inflammatory cytokines (IL-2) and higher levels of anti-inflammatory cytokines (IL-10) (Somagond et al. 2021), besides improving milk performance during heat stress (Somagond et al. 2019). ...
Climate change is currently an undisputable reality and an increased environmental temperature in recent times is one of the indicators for the changing climatic scenario. “Heat stress” detrimentally affects ruminant production, causing adverse economic consequences to the producers. Therefore, mitigating the adverse impact of heat stress on ruminants may be highly beneficial in terms of improving/sustaining productive performance and thereby the livelihood security for the farming community. The strategies to sustain livestock production in the changing climate scenario must invariably follow two different approaches short-term (e.g., housing management, nutrition, etc.) and long-term (e.g., genetics and health management) strategies. There are several nutritional approaches exist to reverse the adverse impacts of heat stress. Specifically, altered ratio of roughage (forage)-to-concentrate, additional feeding of fats, probiotics, antioxidants, electrolytes, and mineral mixture may prove beneficial to relieve the heat stress in ruminant. In this regard, the objective of this chapter is to project to the readers the various strategies that are available to ameliorate heat stress effect in ruminants with a special emphasis on nutritional interventions. Given the huge economic loss attributed to thermal stress in ruminant operations worldwide, the dietary fortification strategies discussed in this chapter would help relieve stress on one hand and sustain productivity of ruminants as well as farm sustainability on the other.
... Animal studies can provide insights into the effects of microalgae-derived antioxidants on liver function and hepatic health. Research on animals may reveal the impact of microalgae-derived antioxidants on immune function and overall immune system support [27,78]. ...
In recent times, there has been a revolutionary surge in antioxidant research, with a focus on harnessing microalgae to enhance wellness and extend human longevity. Microalgae, a diverse group of unicellular photosynthetic organisms, have emerged as promising sources of natural antioxidants due to their ability to synthesize various bioactive compounds, including carotenoids, polyphenols, and tocopherols. These antioxidants play a pivotal role in scavenging free radicals and reducing oxidative stress, known contributors to aging and chronic diseases. This review provides an over-view of recent advancements in understanding microalgae’s antioxidant potential, covering their biochemical composition, extraction techniques, and purification methods. Moreover, it delves into compelling in vitro and in vivo studies showcasing microalgae-derived antioxidants’ protective effects against oxidative damage, inflammation, cardiovascular diseases, and neurodegenerative disorders. The sustainable cultivation of microalgae in controlled environments further supports the potential for large-scale production and commercialization of their antioxidant compounds. As microalgae continue to revolutionize antioxidant research, they hold immense promise in developing novel preventive and therapeutic strategies to promote human health and wellbeing.
Humans encounter ionizing radiation (IR) through various ways, such as medical applications, agricultural industry,
and potential exposure from radioactive materials or acts of radiological terrorism. Hematopoietic stem
cells (HSCs) and hematopoietic progenitor cells (HPCs) are crucial for maintaining the balance of blood cell lineages.
The hematopoietic system, recognized as the most sensitive human tissue, is severely affected by IR, which
can result in bone marrow (BM) failure, increased susceptibility to infections, hemorrhagic events, or anemia in
affected individuals. Therefore, it is essential to develop radioprotective compounds to protect HSCs/HPCs. This
review highlights several radioprotective agents that protect the hematopoietic system from IR-related damage
to HSCs and HPCs and provides an overview of the mechanisms involved in damage and protection.
Chronic obstructive pulmonary disease (COPD) is frequently accompanied by skeletal muscle dysfunction, a critical and severe extrapulmonary complication. This dysfunction contributes to reduced exercise capacity, increased frequency of acute exacerbations, and elevated mortality, serving as an independent risk factor for poor prognosis in COPD patients. Owing to the unique physicochemical conditions of the marine environment, marine-derived bioactive compounds exhibit potent anti-inflammatory and antioxidant properties, demonstrating therapeutic potential for ameliorating COPD skeletal muscle dysfunction. This review summarizes marine-derived bioactive compounds with promising efficacy against skeletal muscle dysfunction in COPD, including polysaccharides, lipids, polyphenols, peptides, and carotenoids. The discussed compounds have shown bioactivities in promoting skeletal muscle health and suppressing muscle atrophy, thereby providing potential strategies for the prevention and treatment of COPD skeletal muscle dysfunction. These findings may expand the therapeutic strategies for managing COPD skeletal muscle dysfunction.
Astaxanthin (ASTX), red-colored xanthophyll, also known as the “king of carotenoids” exhibits a strong antioxidant property that can be naturally found in green algae Haematococcus pluvialis, red yeast Phaffia rhodozyma, and various aquatic species including salmon, krill, trout, and fish eggs. Due to their strong antioxidant qualities, ASTX nanoparticles may be crucial in fighting against phytotoxicity caused by heavy metal ions. Similarly, it may also reduce the uptake of heavy metal, i.e. cadmium, and translocation by improving the morpho-physiological profiles of plants. Furthermore, it can also have the ability to scavenge free radicals, therefore, it can protect plants from reactive oxygen species (ROS). Implementing ASTX nanoparticles on crops can also help to achieve higher food production while minimizing toxic effects. Additionally, it can also possess several therapeutic activities including anti-cancerous, anti-diabetic, antioxidant, anti-aging, anti-inflammation, hepatoprotective, and cardiovascular, etc. that can be beneficial to treat various types of diseases in humans and animals. Recently, it has gained more interest in food, agriculture, aquaculture, neutraceuticals, and pharmaceutical industries due to its wide range of applications including food-coloring agents, food supplements, and strong antioxidant property that helps in skin protection, and boosts immune function. However, ASTX possesses poor water solubility and chemical stability so the implementation of ASTX on human health is facing various issues. Therefore, nanoencapsulation of ASTX is very crucial to improve its chemical stability and solubility, ultimately leading to its bioavailability and bioaccessibility. Recently, ASTX has been commercially available with specific dosages in the market mainly in the form of tablets, gels, powders, creams, syrups, etc. The current review mainly highlights the present state of ASTX nanoparticle applications in various fields explaining its natural and synthetic sources, extraction methods, chemical structure, stability, nanoformulations, nano encapsulation, and various commercial aspects.
Carotenoids are lipophilic terpenoid pigments with biotechnological applications. They are ubiquitous in photosynthetic species and are also produced by many non-photosynthetic bacteria, yeasts, and filamentous fungi, which are amenable to genetic manipulations and can be easily cultured in large fermenters. The biotechnological interest of carotenoids derives from their healthy properties due to their antioxidant activity or to physiological functions. Some carotenoids can be used as a source of vitamin A, chromophore of visual opsins and the origin of the retinoid metabolism associated with gene regulation functions in chordates, and others are related to the maintenance of the macula in the eye. In general, consumption of carotenoids is associated with a decrease in the possibilities of suffering from numerous diseases, from cancer to alterations in the immune system. Fungal carotenoid biosynthetic pathways are relatively simpler than those found in photosynthetic organisms, especially in plants, and not many carotenoids are usually found in these organisms. These include carotenes, such as lycopene and β-carotene, and xanthophylls, such as astaxanthin, neurosporaxanthin, or torularhodin. Some of these carotenoids are produced industrially, but it is to be hoped that their applied use will be extended to others. This chapter reviews the biotechnological and production possibilities of the best-known fungal carotenoids. The scientific literature on this subject is very extensive, especially in the areas of the biological effects of carotenoids on humans and the improvement of production for biotechnological purposes. In this review, we select significant contributions, recent or historical, that serve to make a comprehensive review of fungal carotenoids, focusing on their actual or potential production and their possible applications.
Astaxanthin is a ketocarotenoid compound with powerful antioxidant properties and is extracted from a varied group of microorganisms, including microalgae, a diverse multifaceted photosynthetic organism. This pigment possesses great valuable properties like immune-modulating, anticancer, and anti-inflammatory, which enhance its demand in the field medicines, nutraceuticals, and therapies in recent days. Moreover, their utilization in the cosmetic industries, aquaculture, food, and additives make them one of the potent candidates in every sector of applied biology and biotechnology too. A good number of microalgal members, viz. Haematococcus pluvialis, Chlorococcum spp., Chlorella zofingiensis, have already been reported and gained considerable attention among the researchers for their high-valued astaxanthin (ASX). This chapter therefore provides a comprehensive insight into the extraction of ASX from microalgae, its roles in different applied sectors as an innovative green biotechnological tool to enhance its value in the field of bioprospection looking ahead for a secure, wealthy, and sustainable future of mankind.
Algae’s potential for medicinal use is dependent on their biochemical diversity, which is influenced by a variety of elements such as climate, temperature, light intensity, the density of biomass, salinity levels, water velocity, and the accessibility of nutrients. Bioactive chemicals found in algae are numerous and possess significant potential for application as medicines. Numerous bioactive compounds produced by microalgae are beneficial to the health of humans as well as animals. The primary classes of chemicals that exhibit pharmacological action in algae have been emphasised regardless of their diversity. These include polyunsaturated fatty acids, polysaccharides, polyphenols, pigments, alkaloids, and terpenoids. The market for medicines based on naturally occurring chemicals is expanding globally, and there is now considerable interest in the use of various algae components in the treatment of illnesses prevalent in society. Pharmaceutical companies and medical researchers currently focus primarily on three substances for use in drug development: a potential treatment for AIDS, tumours, and lung cancer from a species of Byopsis, antifouling agents derived from Delisea pulchra and antiviral agents in the form of sulphur-based polysaccharides. Thus, the prospective uses of compounds obtained from algae in medicine, research, and pharmaceuticals are discussed.
Astaxanthin (ASX), “king of carotenoids”, is a xanthophyll carotenoid that is characterized by a distinct reddish-orange hue, procured from diverse sources including plants, microalgae, fungi, yeast, and lichens. It exhibits potent antioxidant and anti-ageing properties and has been demonstrated to mitigate ultraviolet-induced cellular and DNA damage, enhance immune system function, and improve cardiovascular diseases. Despite its broad utilization across nutraceutical, cosmetic, aquaculture, and pharmaceutical sectors, the large-scale production and application of ASX are constrained by the limited availability of natural sources, low production yields and stringent production requirements. This review provides a comprehensive analysis of ASX applications, emphasizing its dual roles in cosmetic and nutraceutical fields. It integrates insights into the qualitative differences of ASX from various natural sources and assesses biosynthetic pathways across organisms. Advanced biotechnological strategies for industrial-scale production are explored alongside innovative delivery systems, such as emulsions, films, microcapsules, nanoliposomes, and nanoparticles, designed to enhance ASX’s bioavailability and functional efficacy. By unifying perspectives on its nutraceutical and cosmetic applications, this review highlights the challenges and advancements in formulation and commercialization. Prospective research directions for optimizing ASX’s production and applications are also discussed, providing a roadmap for its future development.
Purpose
Multi-walled carbon nanotubes (MWCNTs) were used as carriers for silver nanoparticles (AgNPs). In this process, MWCNTs were coated with mesoporous silica (MWCNT-Silica) for uniform and regular loading of AgNPs on the MWCNTs. In addition, astaxanthin (AST) extract was used as a reducing agent for silver ions to enhance the antioxidant, antibiofilm, and anticancer activities of AgNPs. In this process, AST was extracted from Haematococcus pluvialis (H. pluvialis) and processed by hot melt extrusion (HME) to enhance the AST content of H. pluvialis. AST has strong antioxidative properties, which leads to anticancer activity. In addition, AgNPs are well known for their strong antibacterial properties. The antibiofilm and anticancer effects were studied comprehensively by loading the AST AgNPs onto MWCNT-Silica.
Methods
AgNPs-loaded MWCNT-silica (MWCNT-Ag) was prepared through the binding reaction of TSD and silanol groups and the aggregation interaction of Ag and TSD. To enhance the antioxidant, antibiofilm, and anticancer activities of AgNPs, HME-treated H. pluvialis extract (HME-AST) was used as a reducing solution of silver ions. The increased AST content of HME-AST was confirmed by high-performance liquid chromatography (HPLC) analysis, and the total phenol and flavonoid content analysis confirmed that HME enhanced the active components of H. pluvialis. The antibiofilm activity of MWCNT-AST was investigated by biofilm inhibition and destruction test, SEM, and CLSM analysis, and the anticancer activity was investigated by WST assay, fluorescent staining analysis, and flow cytometry analysis.
Results
MWCNT-AST showed higher antioxidant activity and antibiofilm activity than MWCNT-Ag against E. coli, S. aureus, and methicillin-resistant S. aureus (MRSA). MWCNT-AST showed higher anticancer activity against breast cancer cells (MDA-MB-231) than MWCNT-Ag, and lower toxicity in normal cells HaCaT and NIH3T3.
Conclusion
MWCNT-AST exhibits higher antioxidant, antibiofilm, and anticancer activities than MWCNT-Ag, and exhibits lower toxicity to normal cells.
Carotenoids, lipid-soluble pigments, are widely distributed in plants, microalgae, bacteria, and fungi, showcasing a diverse range of colors. Integral to the human diet, some carotenoids can be converted into retinoids, exhibiting essential vitamin A activity. Beyond serving as sources of vitamin A, carotenoids play versatile biological roles with therapeutic effects, including anticancer, immunomodulatory, anti-inflammatory, antibacterial, antidiabetic, and neuroprotective properties. Additionally, they contribute as natural pigments, antioxidants, and health-promoting compounds in foods. Recently, they have gained interest in nutricosmetics for their cosmetic benefits when ingested appropriately. This comprehensive review delves into carotenoid research in foods and feeds, covering aspects such as analysis, sources, databases, effects of processing and storage, trends in extraction, daily intakes, human and feed additive use. The review also highlights classical and recent patents on obtaining and formulating carotenoids for various purposes. The chapter emphasizes emerging research lines and identifies research needs. Furthermore, there is a growing interest in using carotenoids as feed ingredients due to their bioactive and health-promoting properties. Carotenoid-rich products are available as food and feed additives, supplements, and natural colorants. Dietary supplementation with carotenoids enhances the production performance and health of poultry, improving the quality of eggs and meat. Studies suggest that plant-derived carotenoids offer various health-promoting activities in poultry, reducing oxidative stress through mechanisms such as free radical quenching, activation of antioxidant enzymes, and inhibition of signaling pathways. The incorporation of carotenoids in poultry feed contributes to bird health and enhances product quality. This chapter aims to compile recent information on the bioactive properties of carotenoids, emphasizing their pharmaceutical and health-promoting effects in the context of foods and feeds.
Food security is one of the critical issues in facing the world food crisis. Utilizing food processing residue waste to make nutritious and healthy functional foods should follow a double-merit approach in facing the world food crisis. Oncom, an overlooked traditional fermented product based on local wisdom, might be an example of potential sustainable food to overcome hunger and support the circular economy programme. This review attempts to portray the existence and role of oncom based on a systematic study of hundreds of reports from different angles, mainly focusing on its processing, the microbes involved, its sensory characteristics, nutritional benefits, and promising bioactivities. Oncom can be produced by various raw materials such as tofu dreg (okara), peanut press cake, and tapioca solid waste, involving various microbes, mainly Neurospora sp. or Rhizopus sp., and various processing steps. The products show promising nutritional values. In terms of sensory characteristics, oncom is sensory-friendly due to its umami dominance. Many bioactivity capacities have been reported, including antioxidants, lowering cholesterol effect, and cardiovascular disease prevention, although some findings are still only preliminary. Undoubtedly, oncom has the potential to be developed as a future functional food with standardized quality and reliable bioefficacy. This kind of solid fermented product, based on agricultural residue wastes, is worthy of further development worldwide with full scientific support to create more reliable functional foods with a modern touch to achieve zero hunger.
The zero-waste microalgal biorefinery presents a viable solution to the challenges of sustainable energy production and environmental impact. By emphasizing waste reduction and comprehensive utilization of microalgae biomass, this approach aligns with the urgent need for economic and sustainable biorefinery models. The capability of microalgae as a versatile source material for renewable biofuel and value-added co-products is significant, but economic viability remains a critical concern. The adoption of waste management principles, coupled with ongoing research into advanced conversion processes, waste mitigation strategies, and economic assessments, offers a pathway toward realizing a truly sustainable and efficient microalgal biorefinery. The ongoing pursuit of these advancements is essential for a successful transition toward carbon-neutral renewable energy and a more environmentally conscious biorefinery industry. Consequently, the multitude of extravagant additional value energy sources made from microalgae such as biodiesel, biogas, bioethanol, etc., is introduced in this chapter together with their complexities and futuristic perspectives.
Astaxanthin (ASTX), a fat-soluble red pigment, belongs to a group of carotenoids with various compounds that are responsible for biological activities. This research investigated the ASTX production of gamma-mutated yeast strain Rhodosporidium toruloides G17 using potato hydrolysate and urea as replacement medium components. Under optimal conditions, the gamma-mutated yeast G17 was cultivated in 29.39 g/L total sugar from potato hydrolysate, 1.02 g/L urea as a nitrogen source, 4.09 g/L MgSO 4 , and 10.05% yeast, resulting in the highest ASTX yield of 2,181.14 μg/mL. For the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, at an IC 50 = 9.98 μg/mL, the ASTX crude extract showed greater antioxidant activity than α-tocopherol (IC 50 = 119.66 μg/mL). This research suggests that ASTX from R. toruloides G17 is a promising antioxidant agent for nutraceutical and pharmaceutical applications and that potato hydrolysate is an efficient carbon source for yeast culturing in batch mode to obtain ASTX.
Simple Summary
This review explores how certain types of microalgae, which thrive in extreme environments, can be used in various industries to promote sustainability. These microalgae, known for their ability to survive harsh conditions, produce valuable substances such as pigments, oils, and proteins. The study highlights the potential of these microorganisms to boost production efficiency, reduce contamination, and create eco-friendly products. For example, they can be used to make nutritional supplements, natural cosmetics, medicines, and biofuels. By understanding and utilizing these hardy microalgae, we can develop innovative solutions to meet the growing demand for sustainable and efficient resources, ultimately benefiting both the economy and the environment. The review concludes that investing in research on extremophilic microalgae can lead to significant advancements in biotechnology, offering new ways to address global challenges in food, energy, and healthcare.
Abstract
Exploring extremotolerant and extremophilic microalgae opens new frontiers in sustainable biotechnological applications. These microorganisms thrive in extreme environments and exhibit specialized metabolic pathways, making them valuable for various industries. The study focuses on the ecological adaptation and biotechnological potential of these microalgae, highlighting their ability to produce bioactive compounds under stress conditions. The literature reveals that extremophilic microalgae can significantly enhance biomass production, reduce contamination risks in large-scale systems, and produce valuable biomolecules such as carotenoids, lipids, and proteins. These insights suggest that extremophilic microalgae have promising applications in food, pharmaceutical, cosmetic, and biofuel industries, offering sustainable and efficient alternatives to traditional resources. The review concludes that further exploration and utilization of these unique microorganisms can lead to innovative and environmentally friendly solutions in biotechnology.
Obesity and overweight are becoming increasingly common conditions throughout the world. It is a medical condition caused by size increase and the amount of fat cells in the body. Many factors contribute to obesity and overweight. Several bioactive molecules such as ginsenosides, oxysterols, resveratrol, carotenoids, especially xanthophylls and their derivatives, fucoxanthinol, and so on have shown potential anti-adipogenic and antiobesity effects.
This chapter highlights the side effects caused by the usage of anti-obese drugs and complications caused by weight loss surgeries. An extensive literature survey is done on the importance of bioactive constituents from natural plant products like polyphenols, flavonoids, terpenoids, alkaloids, and saponins in the treatment of obesity and the mechanism by which these bioactive constituents display anti-obese action are being understood. This chapter also emphasizes on antiobesity properties of various carotenes, β-cryptoxanthin, fucoxanthin, and astaxanthin which are extensively studied for the suppression of obesity in several model systems.
ABSTRAKTujuan penelitian ini adalah membuktikan efek pemberian krim astaxanthin 0,02% mencegah peningkatan jumlah melanin kulit marmut (Cavia porcellus) yang dipapar sinar UVB dengan efektivitas yang sama dengan krim hidrokuinon 4%. ini merupakan penelitian eksperimental dengan metode post test only control group design. Tiga puluh ekor marmut (Cavia Porcellus) jantan dibagi menjadi 3 kelompok dengan jumlah sampel 10 ekor tiap kelompok. Kelompok 1 yaitu kelompok kontrol, diberi paparan sinar UVB dan diolesi krim dasar. Kelompok 2 diberi paparan sinar UVB dan krim hidrokuinon 4%. Kelompok 3 diberi paparan sinar UVB dan krim astaxanthin 0,02%. Dosis total UVB yaitu 390 mJ/cm2 yang diberikan selama 2 minggu. Pemeriksaan histopatologis jaringan kulit dengan pewarnaan Masson-Fontana. Jumlah melanin dihitung dengan persentase pixel luas area melanin dibandingkan dengan pixel seluruh jaringan epidermis. Hasil penelitian menunjukkan jumlah melanin paling tinggi terdapat pada kelompok 1 sebesar 27,55 ±3,63%. Jumlah melanin paling rendah terdapat pada kelompok 2 sebesar 0,90±0,26%, sedangkan jumlah melanin pada kelompok 3 sebesar 1,09±0,40%. Terdapat perbedaan bermakna antara kelompok 1 dengan kelompok 2 dan 3 (p<0,05). Perbandingan antara kelompok 2 dan 3 tidak berbeda bermakna dalam mencegah peningkatan jumlah melanin (p>0,05). Simpulan: krim astaxanthin 0,02% dapat mencegah peningkatan jumlah melanin kulit marmut yang dipapar sinar UVB dengan efektivitas yang sama dengan krim hidrokuinon 4%.Kata kunci: krim astaxanthin, melanin, ultraviolet B, marmut.ABSTRACTThe purpose of this research was to prove the effect of administration of 0.02% astaxanthin cream prevented the increase of skin melanin in guinea pig (Cavia porcellus) exposed to UVB as effective as 4% hydroquinone cream. This study was an experimental research using randomized post test only group design. A total of thirty guinea pigs (Cavia Porcelus) used in this study were divided into 3 groups consisted of 10 male guinea pigs in each group. Group 1 as a control group was treated by UVB exposure and basic cream. Group 2 was treated by UVB and 4% hydroquinone cream. Group 3 was treated by UVB and 0.02% astaxanthin cream. Total 390 mJ/cm2 ultraviolet B dosage was given for 2 weeks. The amount of melanin was examined by histopatological method with Masson-Fontana staining, counting the melanin area by black color. The amount of melanin was calculated by the percentage of the pixels area of melanin and was compared with the pixels of all the epidermal tissues. The results showed that the highest number of melanin was in the group 1 (27.55 ±3.63%).The lowest number of melanin was in group 2 (0.90±0.26%). The amount of melanin in group 3 was 1.09±0.40 % .There was significant difference within group1 compared with group 2 and 3 (p<0.05). There was no significant difference within group 2 compared with group 3 (p>0.05). Conclusion: The administration of 0.02% astaxanthin cream prevented the increase of melanin in guinea pig (Cavia porcellus) exposed to UVB with the same effectiveness with 4% hydroquinone cream.Keywords: astaxanthin cream, melanin, ultraviolet B, guinea pigs.
Polycystic ovarian syndrome (PCOS) is related to pro‐apoptotic and pro‐inflammatory conditions generated by Endoplasmic reticulum (ER) stress. This study aimed to determine the effect of Astaxanthin (ASX), as carotenoid with potent antioxidant and anti‐inflammatory properties, on serum inflammatory markers, apoptotic factors and ER stress‐apoptotic genes in peripheral blood mononuclear cells (PBMCs) of women with PCOS. This randomized, double‐blind clinical trial included 56 PCOS patients aged 18–40. For 8 weeks, subjects were randomly assigned to one of two groups: either 12 mg ASX (n = 28) or placebo (n = 28). Real‐time PCR was used to quantify gene expression associated with ER stress‐apoptosis in PCOS women's PBMCs. The levels of TNF‐α, IL18, IL6 and CRP were determined by obtaining blood samples from all patients before and after the intervention using Enzyme‐linked immunosorbent assay (ELISA). Also, the levels of active caspase‐3 and caspase‐8 were detected in the PBMC by ELISA kit. Furthermore, we evaluated the efficacy of ASX on disease symptoms. Following the 8‐week intervention, ASX supplementation was able to reduce the expression of GRP78 (p = 0.051), CHOP (p = 0.008), XBP1 (p = 0.002), ATF4 (0.038), ATF6 (0.157) and DR5 (0.016) when compared to the placebo. However, this decrease was not statistically significant for ATF6 (p = 0.067) and marginally significant for GRP78 (p = 0.051). The levels of TNF‐α (p = 0.009), IL‐18 (p = 0.003), IL‐6 (p = 0.013) and active caspase‐3 (p = 0.012) were also statistically significant lower in the therapy group. However, there was no significant difference in CRP (p = 0.177) and caspase‐8 (p = 0.491) levels between the treatment and control groups. In our study, ASX had no significant positive effect on BMI, hirsutism, hair loss and regularity of the menstrual cycle. It appears that ASX may benefit PCOS by changing the ER stress‐apoptotic pathway and reducing serum inflammatory markers; however, additional research is required to determine this compound's potential relevance.
The majority of neurodegenerative eye disorders occur with aging and significantly impair quality of life. Age-related macular degeneration (AMD) is the third most common cause of visual impairment and blindness worldwide. One of the most important elements in the pathophys-iology of neurodegenerative eye disease is certainly oxidative stress, with neuroinflammation and ocular ischemia which may also be significant factors. Antioxidants, either by food or oral supple-mentation, may be able to mitigate the deleterious effects of reactive oxygen species that build as a result of oxidative stress, ischemia, and inflammation. Over the past few decades, a number of research works examining the potential adjuvant impact of antioxidants in AMD have been published. In fact, there is not only more and more interest in already known molecules but also in new molecules that can help clinicians in the management of this complex multifactorial disease, such as astaxanthin and melatonin. However, while some studies showed encouraging outcomes, others were conflicting. In addition, more and more attention is also being paid to nutrition, considered a pivotal key point, especially to prevent AMD. For this reason, the purpose of this review is to analyze the main antioxidant molecules currently used as oral supplements for AMD treatment, as well as the role of diet and food intake in this ocular disease, to better understand how all these factors can improve the clinical management of AMD patients.
Astaxanthin is a potent lipid-soluble carotenoid produced by several different freshwater and marine microorganisms, including microalgae, bacteria, fungi, and yeast. The proven therapeutic effects of astaxanthin against different diseases have made this carotenoid popular in the nutraceutical market and among consumers. Recently, astaxanthin is also receiving attention for its effects in the co-adjuvant treatment or prevention of neurological pathologies. In this systematic review, studies evaluating the efficacy of astaxanthin against different neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, cerebrovascular diseases, and spinal cord injury are analyzed. Based on the current literature, astaxanthin shows potential biological activity in both in vitro and in vivo models. In addition, its preventive and therapeutic activities against the above-mentioned diseases have been emphasized in studies with different experimental designs. In contrast, none of the 59 studies reviewed reported any safety concerns or adverse health effects as a result of astaxanthin supplementation. The preventive or therapeutic role of astaxanthin may vary depending on the dosage and route of administration. Although there is a consensus in the literature regarding its effectiveness against the specified diseases, it is important to determine the safe intake levels of synthetic and natural forms and to determine the most effective forms for oral intake.
The green alga Haematococcus lacustris (formerly Haematococcus pluvialis) is a primary source of astaxanthin, a ketocarotenoid with high antioxidant activity and several industrial applications. Here, the Haematococcus lacustris highly repetitive genome was reconstructed by exploiting next-generation sequencing integrated with Hi-C scaffolding, obtaining a 151 Mb genome assembly in 32 scaffolds at a near-chromosome level with high continuity. Surprisingly, the distribution of the single-nucleotide-polymorphisms identified demonstrates a diploid configuration for the Haematococcus genome, further validated by Sanger sequencing of heterozygous regions. Functional annotation and RNA-seq data enabled the identification of 13,946 nuclear genes, with >5000 genes not previously identified in this species, providing insights into the molecular basis for metabolic rearrangement in stressing conditions such as high light and/or nitrogen starvation, where astaxanthin biosynthesis is triggered. These data constitute a rich genetic resource for biotechnological manipulation of Haematococcus lacustris highlighting potential targets to improve astaxanthin and carotenoid productivity.
The microalga Haematococcus pluvialis has diversified uses including formulation of fish foods. This microalga containing fish feed produces pigment in the flesh and enhances the growth and survival rate of the aquaculture organisms. The mass culture of H. pluvialis using commercial inorganic medium is expensive; therefore, in the present study, an alternate low-cost vegetable waste-based medium, the supernatant of the digested rotten wax gourd (Benincasa hispida), was used to culture the microalga. To assess the growth performance, H. pluvialis was cultured in 25% (T1), 50% (T2), and 75% (T3) of the digested rotten wax gourd supernatant (DRWGS) and in commercial Kosaric Medium (KM) (T4). The proximate composition of the rotten wax gourd, the physicochemical characteristics of the DRWGS, and the measured physicochemical parameters of the cultured media prepared using the DRWGS revealed the suitability of the rotten wax gourd for the growth of H. pluvialis. The growth of H. pluvialis in terms of cell density, mean daily division rate, optical density, dry cell weight, and chlorophyll-a was found highest in T4, followed by T3, T2, and T1, respectively. Importantly, the growth parameters and the protein and lipid content of the microalga H. pluvialis exhibited no significant (p > 0.05) difference between T4 (KM) and T3 (75% DRWGS). The findings of the present study revealed that the digested rotten wax gourd supernatant can be utilized for the mass culture of the microalga H. pluvialis, and the higher concentration up to a certain level of the supernatant is good for the culture. The cost of production of a certain amount of the commercial medium KM is about two times higher than the production of the same amount of the 75% DRWGS medium. This low-cost DRWGS can be used in mass production of the microalga H. pluvialis which has a high potential in rearing zooplankton and fish larvae in hatcheries. Fish larvae grown on live feeds (microalgae and zooplankton) normally have high growth and survival rate. Adequate supply of high-quality fish larvae to the farmers in due time is the prerequisite for sustainable enhanced aquaculture.
Oxidative stress induced by hyperglycemia possibly causes the dysfunction of pancreatic β-cells and various forms of tissue damage in patients with diabetes mellitus. Astaxanthin, a carotenoid of marine microalgae, is reported as a strong anti-oxidant inhibiting lipid peroxidation and scavenging reactive oxygen species. The aim of the present study was to examine whether astaxanthin can elicit beneficial effects on the progressive destruction of pancreatic β-cells in db/db mice - a well-known obese model of type 2 diabetes. We used diabetic C57BL/KsJ-db/db mice and db/m for the control. Astaxanthin treatment was started at 6 weeks of age and its effects were evaluated at 10, 14, and 18 weeks of age by non-fasting blood glucose levels, intraperitoneal glucose tolerance test including insulin secretion, and β-cell histology. The non-fasting blood glucose level in db/db mice was significantly higher than that of db/m mice, and the higher level of blood glucose in db/db mice was significantly decreased after treatment with astaxanthin. The ability of islet cells to secrete insulin, as determined by the intraperitoneal glucose tolerance test, was preserved in the astaxanthin-treated group. Histology of the pancreas revealed no significant differences in the β-cell mass between astaxanthin-treated and -untreated db/db mice. In conclusion, these results indicate that astaxanthin can exert beneficial effects in diabetes, with preservation of β-cell function. This finding suggests that anti-oxidants may be potentially useful for reducing glucose toxicity.
A number of naturally occurring compounds and several related synthetic agents were confirmed to exert chemopreventive properties against carcinogenesis in the digestive organs. Phenolic compounds, widely distributed as plant constituents, possess chemopreventive activities in tongue, liver, and large bowel of rodents. Of them, a simple phenolic protocatechuic acid seems to be a promising compound. Organosulfur compounds contained in the cruciferous vegetables and known to activate detoxifying enzymes are regarded as a candidate group for cancer preventive agents. We proved a strong protective effect of S-methylmethanethiosulfonate, a constituent in these vegetables, on azoxymethane (AOM)-induced large bowel carcinogenesis. Some oxygenated carotenoids (xanthophylls) are reported to have antitumor effects. Naturally occurring xanthophylls astaxanthin and canthaxanthin have considerable preventive activities on 4-nitroquinoline-1-oxide (4-NQO)-induced tongue carcinogenesis and AOM-induced large bowel carcinogenesis. A novel synthesized retinoidal butenolide, KYN-54, which suppresses large bowel as well as tongue carcinogenesis, could be a useful agent for prevention of digestive organ cancers. Some trace elements are known to have anticarcinogenic effects. Magnesium hydroxide, a protective agent in colorectal carcinogenesis, inhibits c-myc expression and ornithine decarboxylase activity in the mucosal epithelium of the intestine. Our results show that many agents with preventive effects in tongue, liver, and large bowel control carcinogen-induced hyperproliferation of cells in these organs. Carcinogens used to induce large bowel cancers also induce apoptosis in the target sites. Telomerase activity is increased in the tissues of preneoplastic as well as neoplastic lesions in experimental models such as dimethylbenz[a]anthracene-induced oral carcinogenesis in hamsters. These could be useful biomarkers in studies for cancer chemoprevention. J. Cell. Biochem. Suppl. 27:35–41. Published 1998 Wiley-Liss, Inc.
The role of carotenoids in human nutrition has gained increased interest, especially due to their associated health-beneficial effects for a number of chronic diseases, including certain types of cancer and cardiovascular disease. Whereas data is available on the intake and presence of carotenoids in foods, limited information exists on factors influencing their bioavailability, especially for the non-provitamin A carotenoids. However, carotenoid absorption strongly depends on a number of factors which are not entirely understood. These include mainly the release of carotenoids from the food matrix, their incorporation into mixed bile micelles, the transfer of carotenoids from micelles to the mucosa for passive or facilitated absorption (via SR-BI proteins), and the sequestration into chylomicrons. Thus, dietary compounds influencing carotenoid micelle incorporation, e.g. the amount fat present in an ingested meal or components competing for uptake, such as phytosterols and other carotenoids, can have a considerable impact on carotenoid bioavailability. However, the effect of many dietary factors, including dietary fiber, type of fat, or minerals on carotenoid absorption is not well understood. In addition, bioavailability also depends on the carotenoid structure; in general, polar carotenoids are preferably incorporated into mixed micelles and tend to be of higher bioavailability, as may be the case for free vs. esterified xanthophylls, and cis-isomers vs. their trans-form, due to apparent shorter chain-lengths. Whereas their importance as part of a healthy diet warrants an improved understanding of carotenoids, their dietary fate following ingestion, including their stability, efficiency of micelle-incorporation, and pathway of absorption are still marginally understood.
The effects of the carotenoids β-carotene and astaxanthin on the peroxidation of liposomes induced by ADP and Fe2+ were examined. Both compounds inhibited production of lipid peroxides, astaxanthin being about 2-fold more effective than β-carotene. The difference in the modes of destruction of the conjugated polyene chain between β-carotene and astaxanthin suggested that the conjugated polyene moiety and terminal ring moieties of the more potent astaxanthin trapped radicals in the membrane and both at the membrane surface and in the membrane, respectively, whereas only the conjugated polyene chain of β-carotene was responsible for radical trapping near the membrane surface and in the interior of the membrane. The efficient antioxidant activity of astaxanthin is suggested to be due to the unique structure of the terminal ring moiety.
The goal of this study was to investigate the effects of beta-carotene and astaxanthin (ASX) - carotenoid without provitamin A activity on the proliferation and differentiation of rat oval cells (OC) in vitro. Oval cells were isolated from two groups of animals: I - partial hepatectomised (PH) and II- diethylnitrosamine (DEN) treated rats. At various time points cell lysates were separated by PAGE. For immunodetection primary antibodies against CD-34, Ck19 and albumin were used. Medium concentration of fibrinogen and haptoglobin was measured. Mitochondrial competence of cells was expressed as the proliferation index. In comparison to HP- and DEN-obtained oval cells cultured without carotenoids, the addition of beta-carotene and ASX increased albumin expression during the experimental period. The same condition didn't reveal CK19 expression. CD34 expressed by oval cells was detected up to the 5(th) week of beta-carotene and ASX absence in the medium. beta-carotene addition resulted in a decrease of the proliferative activity of OC, with significant changes in 48 h, the 5(th) and 15(th) week of incubation. ASX (p < or = 0.05) inhibited the proliferation, especially in 24h and 5(th) week of cell culture. In respect to haptoglobin concentration, its maximum value after the 10(th) week was observed. The fibrinogen level obtained from DEN-oval cells incubated with beta-carotene elevated from 480+/-6.87 microg/ml after 24h to 5520+/-34,56 microg/ml after the 15(th) week. In a condition without carotenoids fibrinogen concentration did not exceed 2280+/-31.5 microg/ml after the 15(th) week of cell culture.
Astaxanthine (ASTx) is a novel carotenoid nutraceutical occurring in many crustaceans and red yeasts. It has potent antioxidant, photoprotective, hepatodetoxicant, and anti-inflammatory activities. Documented effect of ASTx on treatment of neurodegenerative disease is still lacking. We used the beta-amyloid peptide (Abeta) 25-35-treated PC12 model to investigate the neuron-protective effect of ASTx. The parameters examined included cell viability, caspase activation, and various apoptotic biomarkers that play their critical roles in the transduction pathways independently or synergistically. Results indicated that Abeta25-35 at 30 microM suppressed cell viability by 55%, whereas ASTx was totally nontoxic below a dose of 5.00 microM. ASTx at 0.1 microM protected PC12 cells from damaging effects of Abeta25-35 in several ways: (1) by securing the cell viability; (2) by partially down-regulating the activation of caspase 3; (3) by inhibiting the expression of Bax; (4) by completely eliminating the elevation of interleukin-1beta and tumor necrosis factor-alpha; (5) by inhibiting the nuclear translocation of nuclear factor kappaB; (6) by completely suppressing the phosphorylation of p38 mitogen-activated protein kinase; (7) by completely abolishing the calcium ion influx to effectively maintain calcium homeostasis; and (8) by suppressing the majority (about 75%) of reactive oxygen species production. Conclusively, ASTx may have merit to be used as a very potential neuron protectant and an anti-early-stage Alzheimer's disease adjuvant therapy.
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.
The aim of the present study was to evaluate the in vitro effect of carotenoid astaxanthin (ASTA) on the phagocytic and microbicidal capacities, cytokine release, and reactive oxygen species production in human neutrophils.
The following parameters were evaluated: cytotoxic effect of ASTA on human neutrophils viability, phagocytic and microbicidal capacities of neutrophils by using Candida albicans assay, intracellular calcium mobilization (Fura 2-AM fluorescent probe), superoxide anion (lucigenin and DHE probes), hydrogen peroxide (H₂O₂, phenol red), and nitric oxide (NO·) (Griess reagent) production, activities of antioxidant enzymes (total/Mn-SOD, CAT, GPx, and GR), oxidative damages in biomolecules (TBARS assay and carbonyl groups), and cytokine (IL-6 and TNF-alpha) release.
Astaxanthin significantly improves neutrophil phagocytic and microbicidal capacity, and increases the intracellular calcium concentration and NO· production. Both functional parameters were accompanied by a decrease in superoxide anion and hydrogen peroxide and IL-6 and TNF-α production. Oxidative damages in lipids and proteins were significantly decreased after ASTA-treatment.
Taken together our results are supportive to a beneficial effect of astaxanthin-treatment on human neutrophils function as demonstrated by increased phagocytic and fungicide capacity as well as by the reduced superoxide anion and hydrogen peroxide production, however, without affecting neutrophils capacity to kill C. albicans. This process appears to be mediated by calcium released from intracellular storages as well as nitric oxide production.
Upon mitogen sensitization, lymphocytes undergo proliferation by oxyradical-based mechanisms. Through continuous resting–restimulation cycles, lymphocytes accumulate auto-induced oxidative lesions which lead to cell dysfunction and limit their viability. Astaxanthin (ASTA) is a nutritional carotenoid that shows notable antioxidant properties. This study aims to evaluate whether the in vitro ASTA treatment can limit oxyradical production and auto-oxidative injury in human lymphocytes. Activated lymphocytes treated with 5 µM ASTA showed immediate lower rates of O
2•−/H2O2 production whilst NO• and intracellular Ca2+ levels were concomitantly enhanced (≤4 h). In long-term treatments (>24 h), the cytotoxicity test for ASTA showed a sigmoidal dose–response curve (LC50 = 11.67 ± 0.42 µM), whereas higher activities of superoxide dismutase and catalase in 5 µM ASTA-treated lymphocytes were associated to significant lower indexes of oxidative injury. On the other hand, lower proliferative scores of ASTA lymphocytes might be a result of diminished intracellular levels of pivotal redox signaling molecules, such as H2O2. Further studies are necessary to establish the ASTA-dose compensation point between minimizing oxidative damages and allowing efficient redox-mediated immune functions, such as proliferation, adhesion, and oxidative burst.
Astaxanthin modulates immune response, inhibits cancer cell growth, reduces bacterial load and gastric inflammation, and protects against UVA-induced oxidative stress in in vitro and rodent models. Similar clinical studies in humans are unavailable. Our objective is to study the action of dietary astaxanthin in modulating immune response, oxidative status and inflammation in young healthy adult female human subjects.
Participants (averaged 21.5 yr) received 0, 2, or 8 mg astaxanthin (n = 14/diet) daily for 8 wk in a randomized double-blind, placebo-controlled study. Immune response was assessed on wk 0, 4 and 8, and tuberculin test performed on wk 8.
Plasma astaxanthin increased (P < 0.01) dose-dependently after 4 or 8 wk of supplementation. Astaxanthin decreased a DNA damage biomarker after 4 wk but did not affect lipid peroxidation. Plasma C-reactive protein concentration was lower (P < 0.05) on wk 8 in subjects given 2 mg astaxanthin. Dietary astaxanthin stimulated mitogen-induced lymphoproliferation, increased natural killer cell cytotoxic activity, and increased total T and B cell subpopulations, but did not influence populations of Thelper, Tcytotoxic or natural killer cells. A higher percentage of leukocytes expressed the LFA-1 marker in subjects given 2 mg astaxanthin on wk 8. Subjects fed 2 mg astaxanthin had a higher tuberculin response than unsupplemented subjects. There was no difference in TNF and IL-2 concentrations, but plasma IFN-gamma and IL-6 increased on wk 8 in subjects given 8 mg astaxanthin.
Therefore, dietary astaxanthin decreases a DNA damage biomarker and acute phase protein, and enhances immune response in young healthy females.
In the present study, neuroprotective effects of astaxanthin on H2O2-mediated apoptotic cell death using cultured mouse neural progenitor cells (mNPCs) were investigated. To cause apoptotic cell death, mNPCs were pretreated with astaxanthin for 8 h and followed by treatment of 0.3 mM H2O2. Pretreatment of mNPCs with astaxanthin significantly inhibited H2O2-mediated apoptosis and induced cell growth in a dose-dependent manner. In Western blot analysis, astaxanthin-pretreated cells showed the activation of p-Akt, p-MEK, p-ERK, and Bcl-2, and the reduction of p-P38, p-SAPK/JNK, Bax, p-GSK3beta, cytochrome c, caspase-3, and PARP. Because H2O2 triggers caspases activation, this study examined whether astaxanthin can inhibit caspases activation in H2O2-treated mNPCs. After H2O2 treatment, caspases activities were prominently increased but astaxanthin pretreatment significantly inhibited H2O2-mediated caspases activation. Astaxanthin pretreatment also significantly recovered ATP production ability of H2O2-treated cells. These findings indicate that astaxanthin inhibits H2O2-mediated apoptotic features in mNPCs. Inhibition assays with SB203580 (10 microM, a specific inhibitor of p38) and PD98059 (10 microM, a specific inhibitor of MEK) clearly showed that astaxanthin can inhibit H2O2-mediated apoptotic death via modulation of p38 and MEK signaling pathways.
We evaluated the effect of astaxanthin on visual function in 49 eyes of 49 healthy volunteers. They were over 40 years of age. They were divided into 4 groups matched for age and gender. Each group was given peroral astaxanthin once a day. The dosage was 0 mg, 2 mg, 4 mg, or 12 mg for each group. After ingestion of astaxanthin for consecutive 28 days, the uncorrected far visual acuity significantly improved in groups receiving 4 mg or 12 mg. The accommodation time significantly shortened in groups receiving 4 mg or 12 mg. There was no change in refraction, flicker fusion frequency, or pupillary reflex.
Early studies demonstrating the ability of dietary carotenes to prevent infections have left open the possibility that the action of these carotenoids may be through their prior conversion to vitamin A. Subsequent studies to demonstrate the specific action of dietary carotenoids have used carotenoids without provitamin A activity such as lutein, canthaxanthin, lycopene and astaxanthin. In fact, these nonprovitamin A carotenoids were as active, and at times more active, than beta-carotene in enhancing cell-mediated and humoral immune response in animals and humans. Another approach to study the possible specific role of dietary carotenoids has used animals that are inefficient converters of carotenoids to vitamin A, for example the domestic cat. Results have similarly shown immuno-enhancement by nonprovitamin A carotenoids, based either on the relative activity or on the type of immune response affected compared to beta-carotene. Certain carotenoids, acting as antioxidants, can potentially reduce the toxic effects of reactive oxygen species (ROS). These ROS, and therefore carotenoids, have been implicated in the etiology of diseases such as cancer, cardiovascular and neurodegenerative diseases and aging. Recent studies on the role of carotenoids in gene regulation, apoptosis and angiogenesis have advanced our knowledge on the possible mechanism by which carotenoids regulate immune function and cancer.
Nonsteroidal anti-inflammatory drugs such as indomethacin induce severe gastric mucosal damage in humans and rodents. In the present study, the in vivo protective effect of astaxanthin on indomethacin-induced gastric lesions in rats was investigated. The test groups were injected with indomethacin (25 mg/kg) after the oral administration of astaxanthin (25 mg/kg) for 1, 2, and 3 days, while the control group was treated only with indomethacin. Thiobarbituric acid reactive substances in the gastric mucosa, as an index of lipid peroxidation, increased significantly after indomethacin administration and this increase was inhibited by oral administration of astaxanthin. In addition, pretreatment with astaxanthin resulted in a significant increase of the activities of superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH-px). Histologic examination clearly revealed acute gastric mucosal lesions induced by indomethacin in the stomach of the control group, but were not observed in that of the test group. These results indicate that astaxanthin activates SOD, catalase, and GSH-px, and removes the lipid peroxides and free radicals induced by indomethacin. It is evident that astaxanthin acts as a free radical quencher and antioxidant, and is an effective molecule in the remedy of gastric mucosal lesion.
AIM: To elucidate the effect of antioxidants, resveratrol (RVT) and astaxanthin (AXN), on hepatitis C virus (HCV) replication.
METHODS: We investigated the effect of recent popular antioxidant supplements on replication of the HCV replicon system OR6. RVT is a strong antioxidant and a kind of polyphenol that inhibits replication of various viruses. AXN is also a strong antioxidant. The replication of HCV RNA was assessed by the luciferase reporter assay. An additive effect of antioxidants on antiviral effects of interferon (IFN) and ribavirin (RBV) was investigated.
RESULTS: This is the first report to investigate the effect of RVT and AXN on HCV replication. In contrast to other reported viruses, RVT significantly enhanced HCV RNA replication. Vitamin E also enhanced HCV RNA replication as reported previously, although AXN didnot affect replication. IFN and RBV significantly reduced HCV RNA replication, but these effects were dose-dependently hampered and attenuated by the addition of RVT. AXN didnot affect antiviral effects of IFN or RBV.
CONCLUSION: These results suggested that RVT is not suitable as an antioxidant therapy for chronic hepatitis C.
Hepatocyte protection by astaxanthin (100 mg/kg feed for 4 wk with rats) was tested with CCl4 (0.2 mL/100 g weight). The liver catalase and the lipid peroxide contents of the control, CCl4 treated, and CCl4 + astaxanthin treated rats were 17.1, 30.1, and 26.1 mmol/mg protein/min and 1.23, 1.74, and 1.51 μmol/g liver, respectively. These data indicated that astaxanthin attenuated the adverse effect of CCl4. The effect of astaxanthin [300 mg/kg in normal feed for 44 weeks and high-fat feed (10% lard oil, w/w) for the next 26 weeks] on the weight gain was investigated. With the feed of chemically synthesized astaxanthin, the weight increase was significantly slow in the male mice, but not in the females. Chemical astaxanthin decreased the levels of blood glucose, cholesterol, and triglyceride in mice by 4–21%, suggesting astaxanthin can be used to protect hepatocytes and cardiovascular system, and to limit weight gain caused by a high lipid consumption.
We have previously found that in Chlorella emersonii, grown under synergistic conditions of high irradiance and low nitrogen, chlorophyll and primary carotenoids were degraded, whereas secondary carotenoids were produced. In this study Chlorella zofingiensis was cultivated under similar conditions. Maximal growth was achieved in a culture growing under light irradiance of 150 μmol quanta m-2 s-1 and a nitrogen concentration of 0.5 mg/mL of KNO3. Higher nitrogen concentrations or higher irradiance inhibited cell division. The secondary carotenoids produced were identified as canthaxanthin (about 30 %) and astaxanthin (about 70 %) in the form of mono- and diesters. Maximal accumulation occurred in cells starved of nitrogen and grown at a light irradiance of 300 μLmol m-2 s-1. Exposure of a thin layer of algal cells to sunlight resulted in de-esterification of the astaxanthin esters. It is suggested that secondary carotenoids have a photo-protective role, that is, under high light conditions they protect chlorophyll and other photosynthetic pigments against damage.
The isomerization of cis-astaxanthins in organic solvents, a reverse reaction of the isomerization of trans-astaxanthin, was investigated. HPLC analysis revealed that cis-astaxanthins could be also isomerized to produce trans-astaxanthin and the other cis-astaxanthin. The results showed that the isomerization of trans-astaxanthin to cis-astaxanthin was a reversible reaction and followed first-order reversible reaction kinetics. The effect of temperature on the isomerization reaction of trans-astaxanthin, dissolved in dimethyl sulfoxide at 20–70°C or in a mixture of dichloromethane and methanol (25:75) at 10°C, respectively, was also studied. The results indicated that increasing temperature could markedly increase the reaction rate of trans-astaxanthin isomerization. Temperature-dependence of the isomerization rate constants of trans-astaxanthins could be described by the Arrhenius equation with activation energy (Ea) of 105.8±4.2 kJ/mol.
The carotenoid composition in cells of a ketocarotenoid-producing alga, Chlorococcum, was investigated by high-performance liquid chromatgraphy (HPLC). Astaxanthin (free and esters), adonixanthin (free and esters), canthaxanthin, β-carotene, lutein, and some cis-isomers of ketocarotenoids were found. The alga Chlorococcum cells could produce a large amount of ketocarotenoid esters, like the alga Haematococcus pluvialis. The esters of astaxanthin and adonixanthin, and free canthaxanthin were the major carotenoids in the alga Chlorococcum cells, while astaxanthin alone was the major carotenoid in the alga Haematococcus pluvialis. The alga Chlorococcum cells might synthesize astaxanthin from β-carotene via canthaxanthin and adonixanthin in parallel, respectively, which was controlled by the culture conditions.
The ability of astaxanthin to favorably influence the renin-angiotensin system (RAS), blood pressure (BP), and metabolic parameters in Zucker Fatty Rats (ZFR) was examined. In separate experiments, 96 ZFR were equally divided into four groups: control, captopril (30mg/kg), low astaxanthin (5mg/kg) and high astaxanthin (25mg/kg). RAS and insulin systems were examined following recovery from heat stress. RAS was lower in test groups; however, there was no evidence of enhanced insulin sensitivity. Test groups decreased SBP (systolic blood pressure) significantly compared to the control. The tests carried out suggested that RAS was involved in the ability of astaxanthin to lower BP. Astaxanthin at high dosage influenced circulating TNF-α and MCP-1 and lessened fat oxidation in liver and kidneys. Thus, astaxanthin may be considered as a good stress reducer with regards to heat stress. Astaxanthin’s effects on RAS indicate it might overcome perturbations associated with increased activity, especially those related to the cardiovascular system.
Astaxanthin (3,3′-dihydroxy-β,β-carotene-4,4′-dione) is the principal carotenoid pigment of salmonids and gives attractive pigmentation in the eggs, flesh, and skin. Currently, chemically synthesized astaxanthin and canthaxanthin (β,β-carotene-4,4′-dione) are added to salmonid feeds as pigmenters, but there is considerable interest within the aquaculture industry in using natural sources of astaxanthin. The principal biological sources being considered are crustacea and crustacean extracts, the green microalga Haematococcus, and the yeast Phaffia rhodozyma. Each natural pigment source has its limitations and they currently cannot compete economically with the synthetic additive. The yeast P. rhodozyma has desirable properties as a biological source of pigment, including rapid heterotrophic metabolism and production of high cell densities in fermentors. Mutants have been isolated that produce >3000 μg total carotenoid per gram of yeast (>0.30%) in shake flasks after 5 d growth, and measurement of carotenoid fluorescence in individual cells indicates that levels of 10,000 to 15,000 μg/g can be obtained. High-producers, however, are often unstable and further strain development is required. In this article, biological sources of astaxanthin are critically evaluated and compared with the synthetic compound presently being used in animal feeds.
A gradient reversed-phase HPLC method was developed for the separation of astaxanthin esters and the isomers of astaxanthin from the unsaponified and saponified pigment extracts of the microalga Haematococcus pluvialis. Four kinds of isomers of astaxanthin and astaxanthin esters, (3S,3‘S)-trans-astaxanthin, (3S,3‘S)-9-cis-astaxanthin, (3S,3‘S)-13-cis-astaxanthin, (3R,3‘R)-trans-astaxanthin, and their esters, were separated and identified. A small amount of (3S,3‘S)-15-cis-astaxanthin was also detected from the saponified extract. In addition, a chromatographic purification method was established for the preparation of natural trans-astaxanthin from the saponified extract of H. pluvialis. With this method, 3.7 mg of astaxanthin was isolated from 1 g of dry biomass of H. pluvialis. The purified astaxanthin contained approximately 97.7% trans-astaxanthin, 1.1% cis-astaxanthin, and 1.2% impurity. Keywords: Astaxanthin; astaxanthin esters; purification; carotenoids; Haematococcus pluvialis; HPLC
Carotenoids can be effective singlet oxygen quenchers and inhibit free-radical induced lipid peroxidation. A remarkable property of β-carotene (1a) is the change from an antioxidant to a prooxidant depending on oxygen pressure and concentration. In the present study a considerable number of carotenoids (1a, 2c, 2d, 2e, 3a, 4a, 5a, 6a, 7a, 8a, 8h, 8i, 8j, 9f, 10a, 11a, 12g) was investigated using two independent approaches: 1. Comparison of their effects on inhibition of the free-radical oxidation of methyl linoleate, and 2. The direct study of the effect of oxygen partial pressure upon their rates of oxidation. It is shown that some carotenoids (7a, 8a) are even more effective than the well-known compounds β-carotene (1a) and astaxanthin (5a) and are powerful antioxidants without any prooxidative property. Different carotenoids display different behaviour depending on chain length and end groups. The influence of these functional groups on the antioxidative reactivity is discussed.
The unicellular green alga Haematococcus pluvialis Flotow has recently aroused considerable interest due to its capacity to amass large amounts of the ketocarotenoid astaxanthin (3,3′-dihydroxy-β,β-carotene-4,4′-dione), widely used commercially to color flesh of salmon. Astaxanthin accumulation in Haematococcus is induced by a variety of environmental stresses which limit cell growth in the presence of light. This is accompanied by a remarkable morphological and biochemical ‘transformation’ from green motile cells into inert red cysts. In recent years we have studied this transformation process from several aspects: defining conditions governing pigment accumulation, working out the biosynthetic pathway of astaxanthin accumulation and questioning the possible function of this secondary ketocarotenoid in protecting Haematococcus cells against oxidative damage. Our results suggest that astaxanthin synthesis proceeds via cantaxanthin and that this exceptional stress response is mediated by reactive oxygen species (ROS) through a mechanism which is not yet understood. The results do not support in vivo chemical quenching of ROS by the pigment, although in vitro it was shown to quench radicals very efficiently. The finding that most of the pigment produced is esterified and deposited in lipid globules outside the chloroplast further supports this assumption. We have suggested that astaxanthin is the by-product of a defense mechanism rather than the defending substance itself, although at this stage one cannot rule out other protective mechanisms. Further work is required for complete understanding of this transformation process. It is suggested that Haematococcus may serve as a simple model system to study response to oxidative stress and mechanisms evolved to cope with this harmful situation.
The chlorophyte Haematococcus pluvialis accumulates large quantities of astaxanthin under stress conditions. Under either nitrogen starvation or high light, the production of each picogram of astaxanthin was accompanied by that of 5 or 3–4 pg of fatty acids, respectively. In both cases, the newly formed fatty acids, consisting mostly of oleic (up to 34% of fatty acids in comparison with 13% in the control), palmitic, and linoleic acids, were deposited mostly in triacylglycerols. Furthermore, the enhanced accumulation of oleic acid was linearily correlated with that of astaxanthin. Astaxanthin, which is mostly monoesterified, is deposited in globules made of triacylglycerols. We suggest that the production of oleic acid-rich triacylglycerols on the one hand and the esterification of astaxanthin on the other hand enable the oil globules to maintain the high content of astaxanthin esters.
An HPLC method was developed for the separation and identification of the isomers of astaxanthin from the saponification products of the individual astaxanthin ester fractions and the total pigment extract from Haematococcus lacus-tris. Six astaxanthin ester fractions were initially separated and collected by HPLC. These astaxanthin ester fractions and the total pigment extract were subsequently respectively hydrolysed. Four isomers of astaxanthin in the saponified mixtures were separated and identified respectively as (3S, 3S)- trans-astaxanthin (478.8 nm), (3S, 3S)-9-cis-astaxanthin (470.4 nm), (3S, 3S)-13- cis-astaxanthin (371.8 and 468.0 nm) and (3R, 3R)- trans-astaxanthin (477.6 nm) according to their absorbance spectra and absorption maxima by photodiode array detection. The relative contents of these isomers were determined to be 72.8, 9.7, 8.9 and 8.6%, respectively, in Haematococcus lacustris.
Haematococcus green culture starved for either nitrogen or phosphate accumulated astaxanthin up to 4% cell dry wt (2.6gl–1). While under nitrogen starvation astaxanthin accumulation was faster (maximum achieved after 8days in comparison to 14 days in the phosphate-starved culture) and accompanied by a drop in the chlorophyll content per cell down to 50% of its original value (30pgcell–1); in the phosphate-starved culture this parameter did not change. HPLC profiles of carotenoids monitored along the starvation process revealed that astaxanthin esters accounted for more than 99% of total carotenoids at the end of the exposure period at both starvations.
Helicobacter pylori is a Gram-negative bacterium affecting about half of the world population, causing chronic gastritis type B dominated by activated phagocytes. In some patients the disease evolves into gastric ulcer, duodenal ulcer, gastric cancer or MALT lymphoma. The pathogenesis is in part caused by the immunological response. In mouse models and in human disease, the mucosal immune response is characterized by activated phagocytes. Mucosal T-lymphocytes are producing IFN-γ thus increasing mucosal inflammation and mucosal damage. A low dietary intake of antioxidants such as carotenoids and vitamin C may be an important factor for acquisition of H. pylori by humans. Dietary antioxidants may also affect both acquisition of the infection and the bacterial load of H. pylori infected mice. Antioxidants, including carotenoids, have anti-inflammatory effects. The aim of the present study was to investigate whether dietary antoxidant induced modulation of H. pylori in mice affected the cytokines produced by H. pylori specific T-cells. We found that treatment of H. pylori infected mice with an algal cell extract containing the antioxidant astaxanthin reduces bacterial load and gastric inflammation. These changes are associated with a shift of the T-lymphocyte response from a predominant Th1-response dominated by IFN-γ to a Th1/Th2-response with IFN-γ and IL-4. To our knowledge, a switch from a Th1-response to a mixed Th1/Th2-response during an ongoing infection has not been reported previously.
The study evaluated the effects of astaxanthin (ASX) in mice rendered obese by feeding an unbalanced diet. Adult male mice of body weight 25–35 g were fed either normal chow or a high fat-high fructose diet (HFFD). Fifteen days later, mice in each group were divided in to two and treated with either ASX (6 mg/kg b.w.) in olive oil or olive oil alone. The mice were killed at the end of 60 days. Insulin sensitivity, markers of liver injury, inflammation and nitro-oxidative stress, antioxidants and cytochrome P 4502E1 (CYP2E1) activity were assayed. Liver structural integrity was also assessed by histology with hemotoxylin and eosin and Masson's trichrome stains. HFFD-fed mice registered significant increase in body weight and liver weight and displayed hyperglycemia, hyperinsulinemia and insulin resistance and elevated plasma aminotransferases. Lipid deposition, oxidative damage, defective antioxidant system and upregulated transforming growth factor-β (TGF-β1) expression were observed in HFFD-fed mice. ASX supplementation promoted insulin sensitivity and prevented liver injury by decreasing CYP2E1, myeloperoxidase, and nitro-oxidative stress and by improving the antioxidant status in them. Lipid deposition and increased TGF-β1 expression induced by HFFD were also abolished by ASX. This study provides new data showing the beneficial effects of ASX in obese mice.
Diabetes mellitus is a syndrome of impaired insulin secretion/sensitivity and frequently diagnosed by hyperglycemia, lipid abnormalities, and vascular complications. The diabetic ‘glucolipotoxicity’ also induces immunodepression in patients by redox impairment of immune cells. Astaxanthin (ASTA) is a pinkish-orange carotenoid found in many marine foods (e.g. shrimp, crabs, salmon), which has powerful antioxidant, photoprotective, antitumor, and cardioprotective properties. Aiming for an antioxidant therapy against diabetic immunodepression, we here tested the ability of prophylactic ASTA supplementation (30 days, 20 mg ASTA/kg BW) to oppose the redox impairment observed in isolated lymphocytes from alloxan-induced diabetic Wistar rats. The redox status of lymphocytes were thoroughly screened by measuring: (i) production of superoxide (O2−), nitric oxide (NO), and hydrogen peroxide (H2O2); (ii) cytosolic Ca2+; (iii) indexes of oxidative injury; and (iv) activities of major antioxidant enzymes. Hypolipidemic and antioxidant effects of ASTA in plasma of ASTA-fed/diabetic rats were apparently reflected in the circulating lymphocytes, since lower activities of catalase, restored ratio between glutathione peroxidase and glutathione reductase activities and lower scores of lipid oxidation were concomitantly measured in those immune cells. Noteworthy, lower production of NO and O2− (precursors of peroxynitrite), and lower cytosolic Ca2+ indicate a hypothetical antiapoptotic effect of ASTA in diabetic lymphocytes. However, questions are still open regarding the proper ASTA supplementation dose needed to balance efficient antioxidant protection and essential NO/H2O2-mediated proliferative capacities of diabetic lymphocytes.
The purification method including extraction, saponification, and separation was established for preparing free trans-astaxanthin from a high-yielding astaxanthin ester-producing strain of the microalga Haematococcus pluvialis which contained 3.67% trans-astaxanthins and 1.35% cis-astaxanthins of the dry cells. Low temperature (5°C) was chosen to minimize the degradation of astaxanthins during saponification, and 94.4% free trans-astaxanthin was obtained from trans-astaxanthin esters after 12 h of saponification. With this method, 32.2 mg trans-astaxanthin was obtained from 1 g dry algal cells. In addition, a new gradient reversed-phase HPLC method, suited for the quick analysis of free astaxanthins and astaxanthin esters in the unsaponified and saponified pigment extracts from the high-yielding astaxanthin ester-producing strain of the microalga Haematococcus pluvialis, was developed and applied to the determination of astaxanthin contents during the processes of extraction, saponification, and purification.
Astaxanthin is an antioxidant with immunomodulatory, anti-inflammatory and anticancer properties. This study evaluated the use of dietary astaxanthin to decrease oxidative stress and improve cardiac function, thereby providing a potential cardioprotective supplement. Female BALB/c mice (8 weeks of age) were fed a semi-synthetic diet containing 0, 0.02 or 0.08% astaxanthin for 8 weeks. Cardiac function was assessed by echocardiography bi-weekly, and blood and tissue samples were collected at 8 weeks. Plasma astaxanthin concentrations increased (p<0.05) dose-dependently to 0.5 and 4 mumol/l in the astaxanthin-supplemented mice. Blood glutathione concentrations and lymphocyte mitochondrial membrane potential were not significantly affected by astaxanthin treatment. However, mice fed 0.08% astaxanthin had higher (p<0.05) heart mitochondrial membrane potential and contractility index compared to the control group. These results support the possible use of dietary astaxanthin for cardiac protection.
Of the total carotenoids in respective algal samples, beta-carotene in Spirulina platensis was 69.5%, astaxanthin and its esters in Haematococcus pluvialis was 81.38%, and lutein in Botryococcus braunii was 74.6%. The carotenoids were characterized by mass spectrometry. A time-course study of carotenoids in rats after administration of microalgal biomass showed peak levels in plasma, liver, and eyes at 2, 4, and 6 h, respectively. Beta-carotene accumulation in Spirulina-fed rats was maximum in eye tissues at 6 h. Similarly, levels of astaxanthin and lutein in Haematococcus- and Botryococcus-fed rats were also maximal in eye tissues. Astaxanthin from H. pluvialis showed better bioavailability than beta-carotene and lutein. The antioxidant enzymes, catalase, superoxide dismutase, peroxidase, and TBARS were significantly high in plasma at 2 h and in liver at 4 h, evidently offering protection from free radicals. This study implies that microalgae can be a good source of carotenoids of high bioavailability and nutraceutical value.
Time-resolved pulse radiolysis investigations reported herein show that the carotenoids β-carotene, lycopene, zeaxanthin and astaxanthin (the last two are xanthophylls--oxygen containing carotenoids) are capable of both reducing oxidized guanosine as well as minimizing its formation. The reaction of the carotenoid with the oxidized guanosine produces the radical cation of the carotenoid. This behavior contrasts with the reactions between the amino acids and dietary carotenoids where the carotenoid radical cations oxidized the amino acids (tryptophan, cysteine and tyrosine) at physiological pH.
The effects of astaxanthin on tumor growth, cardiac function and immune response in mice were studied. Female BALB/c mice were fed a control diet (diet C) for 8 weeks, 0.005% astaxathin for 8 weeks (diet A), or diet C for weeks 1-5 followed by diet A thereafter (diet CA). Mice were injected with a mammary tumor cell line on day 7 and tumor growth was measured daily. Mice fed diet A had extended tumor latency and lower tumor volume (p<0.05). Interestingly, those fed diet CA showed the fastest tumor growth. Astaxanthin feeding elevated plasma astaxanthin concentrations; there was no difference in plasma astaxanthin between mice fed CA and those fed A. Mice fed diet A, but not CA, had a higher (p<0.05) natural killer cell subpopulation and plasma interferon-gamma concentration compared to those fed diet C. Astaxanthin delayed tumor growth and modulated immune response, but only when astaxanthin was given before tumor initiation. This suggests that an adequate blood astaxanthin status is needed to protect against tumor initiation; conversely, astaxanthin supplementation after tumor initiation may be contraindicated.
In this study, combinations of Ginkgo biloba leaf extract (EGb761) plus the carotenoid antioxidant astaxanthin (ASX) and vitamin C were evaluated for a summative dose effect in the inhibition of asthma-associated inflammation in asthmatic guinea-pigs. Ovalbumin-sensitized Hartley guinea-pigs challenged with ovalbumin aerosol to induce asthma, were administered EGb761, ASX, vitamin C or ibuprofen. Following killing, bronchoalveolar lavage (BAL) fluid was evaluated for inflammatory cell infiltrates and lung tissue cyclic nucleotide content. Each parameter measured was significantly altered to a greater degree by drug combinations, than by each component acting independently. An optimal combination was identified that included astaxanthin (10 mg/kg), vitamin C (200 mg/kg) and EGb761 (10 mg/kg), resulting in counts of eosinophils and neutrophils each 1.6-fold lower; macrophages 1.8-fold lower, cAMP 1.4-fold higher; and cGMP 2.04-fold higher than levels in untreated, asthmatic animals (p < 0.05). In conclusion, EGb761, ASX and vitamin C are shown here to interact summatively to suppress inflammation with efficacy equal to or better than ibuprofen, a widely used non-steroidal antiinflammatory drug (NSAID). Such combinations of non-toxic phytochemicals constitute powerful tools for the prevention of onset of acute and chronic inflammatory disease if consumed regularly by healthy individuals; and may also augment the effectiveness of therapy for those with established illness.
The purpose of this study was to examine the effect and mechanism of astaxanthin, a natural carotenoid, on endogenous glutamate release in nerve terminals of rat cerebral cortex (synaptosomes). Results showed that astaxanthin exhibited a dose-dependent inhibition of 4-aminopyridine (4-AP)-evoked release of glutamate. The effect of astaxanthin on the evoked glutamate release was prevented by chelating the intrasynaptosomal Ca(2+) ions and by the vesicular transporter inhibitor, but was insensitive to the glutamate transporter inhibitor. Astaxanthin decreased depolarization-induced increase in [Ca(2+)](C), whereas it did not alter the resting synaptosomal membrane potential or 4-AP-mediated depolarization. The effect of astaxanthin on evoked glutamate release was abolished by the N-, P- and Q-type Ca(2+) channel blockers, but not by the ryanodine receptor blocker or the mitochondrial Na(+)/Ca(2+) exchanger blocker. In addition, the inhibitory effect of astaxanthin on evoked glutamate release was prevented by the mitogen-activated protein kinase (MAPK) inhibitors PD98059 and U0126. Western blot analyses showed that astaxanthin significantly decreased the 4-AP-induced phosphorylation of MAPK, and this effect was blocked by PD98059. On the basis of these results, it was concluded that astaxanthin inhibits glutamate release from rat cortical synaptosomes through the suppression of presynaptic voltage-dependent Ca(2+) entry and MAPK signaling cascade.
To evaluate the effect of astaxanthin on antioxidant parameters of dental pulp from diabetic rats. The hypothesis tested was that supplementation of diabetic rats with astaxanthin might eliminate, or at least attenuate, the defect in their antioxidative status.
Wistar rats (n=32) were divided into four groups: untreated control, treated control, untreated diabetic and treated diabetic rats. A prophylactic dose of astaxanthin (20 mg kg(-1) body weight) was administered daily by gavage for 30 days. On day 23, diabetes was induced by injection of alloxan (60 mg kg(-1) body weight). After 7 days of diabetes induction, the rats were killed, and pulp tissue from incisor teeth removed. Superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and reductase activities were determined. Data were compared by anova and the Newman-Keuls test (P<0.05).
Diabetes caused a reduction in SOD, GPx and reductase activity in dental pulp tissue. Astaxanthin had no effect on SOD and catalase activities; however, it stimulated GPx in control and diabetic rats.
Diabetes altered the antioxidant system in dental pulp tissue; astaxanthin partially improved the diabetic complications.
To evaluate the effect of astaxanthin on antioxidant parameters of salivary gland from diabetic rats. The hypothesis of the study was whether the supplementation of diabetic rats with astaxanthin might antagonize, or at least prevent, the defect in their antioxidative status.
Wistar rats (n=32) were divided in 4 groups: untreated control, treated control, untreated diabetic and treated diabetic rats. Astaxanthin (20mg/kg body weight) was administered daily by gavage for 30 days. On day 23, diabetes was induced by injection of alloxan (60 mg/kg body weight). After 7 days of diabetes induction, the rats were killed and submandibular and parotid removed. Superoxide dismutase (SOD), catalase, glutathione peroxidase and reductase activities and the content of thiol groups were determined. Data were compared by ANOVA and the Tukey test (p<0.05).
Diabetes caused a reduction of SOD, and thiol content and increase of catalase and glutathione peroxidase activities of submandibular gland whilst in the parotid gland diabetes caused an increase of thiol content and no effect in the antioxidant system. The astaxanthin restores the enzymatic activities in the salivary gland, however does not prevent its oxidative damage.
The submandibular gland presented more susceptibility to oxidative alterations induced by diabetes. Astaxanthin presented a positive effect on the oxidative protection of the salivary gland from diabetic rats.
In the present study, the effect of astaxanthin on improvement of the proliferative capacity as well as the osteogenic and adipogenic differentiation potential in neural stem cells (NSCs) was evaluated. Treatment of astaxanthin-induced actives cell growth in a dose-dependent and time-dependent manner. Results from a clonogenic assay clearly indicated that astaxanthin can actively stimulate proliferation of NSCs. Astaxanthin-induced improvement in the proliferative capacity of NSCs resulted in overexpression of several proliferation-related proteins. Astaxanthin-induced activation of PI3K and its downstream mediators, p-MEK, p-ERK, and p-Stat3 in NSCs resulted in subsequent induction of expression of proliferation-related transcription factors (Rex1, CDK1, and CDK2) and stemness genes (OCT4, SOX2, Nanog, and KLF4). Astaxanthin also improved the osteogenic and adipogenic differentiation potential of NSCs. Astaxanthin-treated NSCs showed prominent calcium deposits and fat formation. These results were consistent with overexpression of osteogenesis-related genes (osteonectin, RXR, and osteopontin) and adipogenesis-related genes (AP and PPAR-gamma) after astaxanthin treatment. These findings clearly demonstrated that astaxanthin acts synergistically on the regulatory circuitry that controls proliferation and differentiation of NSCs.
Repetitive exposure of the skin to UVA radiation elicits sagging more frequently than wrinkling, which is mainly attributed to its biochemical mechanism to up-regulate the expression of matrix-metalloproteinase (MMP)-1 and skin fibroblast elastase (SFE)/neutral endopeptidase (NEP), respectively.
In this study, we examined the effects of a potent antioxidant, astaxanthin (AX), on the induction of MMP-1 and SFE by UVA treatment of cultured human dermal fibroblasts.
Those effects were assessed by real-time RT-PCR, Western blotting and enzymic activity assays.
UVA radiation elicited a significant increase in the gene expression of MMP-1 as well as SFE/NEP (to a lesser extent) which was followed by distinct increases in their protein and enzymatic activity levels. The addition of AX at concentrations of 4-8 microM immediately after UVA exposure significantly attenuated the induction of MMP-1 and SFE/NEP expression elicited by UVA at the gene, protein and activity levels although both the UVA stimulation and the subsequent AX inhibition were greater for MMP-1 than for SFE/NEP. Analysis of the UVA-induced release of cytokines revealed that UVA significantly stimulated only the secretion of IL-6 among the cytokines tested and that AX significantly diminished only the IL-6 secretion.
These findings indicate that, based on different effective concentrations of AX, a major mode of action leading to the inhibition elicited by AX depends on inhibition of UVA effects of the reactive oxygen species-directed signaling cascade, but not on interruption of the IL-6-mediated signaling cascade. We hypothesize that AX would have a significant benefit on protecting against UVA-induced skin photo-aging such as sagging and wrinkles.
To elucidate the effect of antioxidants, resveratrol (RVT) and astaxanthin (AXN), on hepatitis C virus (HCV) replication.
We investigated the effect of recent popular antioxidant supplements on replication of the HCV replicon system OR6. RVT is a strong antioxidant and a kind of polyphenol that inhibits replication of various viruses. AXN is also a strong antioxidant. The replication of HCV RNA was assessed by the luciferase reporter assay. An additive effect of antioxidants on antiviral effects of interferon (IFN) and ribavirin (RBV) was investigated.
This is the first report to investigate the effect of RVT and AXN on HCV replication. In contrast to other reported viruses, RVT significantly enhanced HCV RNA replication. Vitamin E also enhanced HCV RNA replication as reported previously, although AXN did not affect replication. IFN and RBV significantly reduced HCV RNA replication, but these effects were dose-dependently hampered and attenuated by the addition of RVT. AXN did not affect antiviral effects of IFN or RBV.
These results suggested that RVT is not suitable as an antioxidant therapy for chronic hepatitis C.
Cyclophosphamide, an alkylating agent, disturbs the oxidant and antioxidant balance that is associated with several unwanted toxic effects and induction of secondary cancers. Astaxanthin is a powerful antioxidant and possess several beneficial effects against various human diseases and physiological disorders. The present study was aimed to investigate the effects of astaxanthin against cyclophosphamide-induced oxidative stress, DNA damage, cell death and induction of GST-P foci in rat liver. Further attempt has been made to study the influence of astaxanthin on antioxidant response element (ARE) and the transcription factor Nrf2 (nuclear factor E(2)-related factor 2) in the induction of phase-II enzymes NAD(P)H: quinine oxidoreductase-1(NQO-1) and Hemoxygenase-1 (HO-1). Both pre- and post-treatment with astaxanthin (25mg/kg) decreased cyclophosphamide-induced oxidative stress and DNA damage in the liver as evident from the restoration in malondialdehyde and glutathione level as well as modified comet assay parameters. Significant decrease in the number as well as area of GST-P foci in rat hepatocytes was observed with astaxanthin post-treatment. Treatment with astaxanthin significantly decreased the expression of p53 and p38 as compared to cyclophosphamide treated group. It was further observed that the level of Nrf2 and phase-II enzymes, i.e. NQO-1 and HO-1 were increased with astaxanthin treatment. The present study confirms that astaxanthin is a potent antioxidant and attenuates oxidative stress, DNA damage, cell death as well as induction of early hepatocarcinogenesis in rat induced by cyclophosphamide. Our results provide the evidence that one of the mechanism of chemoprotection offered by astaxanthin is mediated through Nrf2-ARE pathway.
This study investigated the effect of astaxanthin (ASX; 3,3-dihydroxybeta, beta-carotene-4,4-dione), a water-dispersible synthetic carotenoid, on liver ischemia-reperfusion (IR) injury. Astaxanthin (5 mg/kg/day) or olive oil was administered to rats via intragastric intubation for 14 consecutive days before the induction of hepatic IR. On the 15th day, blood vessels supplying the median and left lateral hepatic lobes were occluded with an arterial clamp for 60 min, followed by 60 min reperfusion. At the end of the experimental period, blood samples were obtained from the right ventricule to determine plasma alanine aminotransferase (ALT) and xanthine oxidase (XO) activities and animals were sacrificed to obtain samples of nonischemic and postischemic liver tissue. The effects of ASX on IR injury were evaluated by assessing hepatic ultrastructure via transmission electron microscopy and by histopathological scoring. Hepatic conversion of xanthine dehygrogenase (XDH) to XO, total GSH and protein carbonyl levels were also measured as markers of oxidative stress. Expression of NOS2 was determined by immunohistochemistry and Western blot analysis while nitrate/nitrite levels were measured via spectral analysis. Total histopathological scoring of cellular damage was significantly decreased in hepatic IR injury following ASX treatment. Electron microscopy of postischemic tissue demonstrated parenchymal cell damage, swelling of mitochondria, disarrangement of rough endoplasmatic reticulum which was also partially reduced by ASX treatment. Astaxanthine treatment significantly decreased hepatic conversion of XDH to XO and tissue protein carbonyl levels following IR injury. The current results suggest that the mechanisms of action by which ASX reduces IR damage may include antioxidant protection against oxidative injury.