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Marine Drugs
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Astaxanthin: A Potential Therapeutic Agent
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Astaxanthin: A Potential Therapeutic Agent

A special issue of Marine Drugs (ISSN 1660-3397).

Deadline for manuscript submissions: closed (15 June 2020) | Viewed by 83572

Special Issue Editor

Dr. Graciela Pavon-Djavid

E-Mail Website
Guest Editor
Laboratory for Vascular Translational Science, Cardiovascular Bioengineering, Université Sorbonne Paris Nord-INSERM U1148, 99 Av. Jean-Baptiste Clément, 93430 Villetaneuse, France
Interests: nanotechnology; lipid formulations; drug delivery; drug targeting; cellular models; animal models; oxidative stress; antioxidants
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Oxidative stress, inflammation, and apoptosis are some of the mechanisms involved in the pathogenesis of several diseases such as cardiovascular pathologies, neurodegenerative disorders, diabetes, and cancer. Founding new therapeutic molecules capable of maintaining cellular redox homeostasis and blocking oxidative stress are hallenges of crucial importance.

Because of its anti-inflammatory and antioxidant properties, astaxanthin, a xanthophyll carotenoid extracted from marine organisms and microalgae, has been proposed for repairing and protecting cells and tissues or as a nutraceutical/cosmeceutical ingredient to prevent oxidative stress-related diseases. Epidemiological studies suggest that astaxanthin prevents the free radical-dependent oxidation of LDL, cholesterol, proteins, or DNA, by capturing free radicals and by reducing stress induced by ROS.

This Special Issue aims to highlight recent research about astaxanthin’s potential as a therapeutic agent. Despite significant growing evidence suggesting that astaxanthin has a potential health-promoting effect in the prevention and treatment of several pathologies, research advances need to be reported. Original research (in vitro, in vivo, and clinical) and reviews to highlight the therapeutic potential effect of astaxanthin are encouraged to be presented in this Special Issue.

Dr. Graciela Pavon-Djavid
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Marine Drugs is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • astaxanthin
  • therapeutic agent
  • oxidative stress
  • ROS
  • antioxidant
  • clinical trials
  • animal studies
  • in vitro
  • nanotools
  • nutraceutical
  • health-promoting
  • gene expression
  • drug delivery

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Published Papers (16 papers)

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Research

Jump to: Review

11 pages, 1320 KiB  
Article
Enhanced Biomass and Astaxanthin Production of Haematococcus pluvialis by a Cell Transformation Strategy with Optimized Initial Biomass Density
by Feng Li, Minggang Cai, Mingwei Lin, Xianghu Huang, Jun Wang, Hongwei Ke, Chunhui Wang, Xuehong Zheng, Ding Chen and Shihui Yang
Mar. Drugs 2020, 18(7), 341; https://doi.org/10.3390/md18070341 - 29 Jun 2020
Cited by 16 | Viewed by 4128
Abstract
Astaxanthin from H. pluvialis is an antioxidant and presents a promising application in medicine for human health. The two-stage strategy has been widely adopted to produce astaxanthin by the Haematococcus industry and research community. However, cell death and low astaxanthin productivity have seriously [...] Read more.
Astaxanthin from H. pluvialis is an antioxidant and presents a promising application in medicine for human health. The two-stage strategy has been widely adopted to produce astaxanthin by the Haematococcus industry and research community. However, cell death and low astaxanthin productivity have seriously affected the stability of astaxanthin production. This study aims to test the effect of cell transformation strategies on the production of astaxanthin from H. pluvialis and determine the optimal initial biomass density (IBD) in the red stage. The experimental design is divided into two parts, one is the vegetative growth experiment and the other is the stress experiment. The results indicated that: (1) the cell transformation strategy of H. pluvialis can effectively reduce cell death occurred in the red stage and significantly increase the biomass and astaxanthin production. (2) Compared with the control group, the cell mortality rate of the red stage in the treatment group was reduced by up to 81.6%, and the biomass and astaxanthin production was increased by 1.63 times and 2.1 times, respectively. (3) The optimal IBD was determined to be 0.5, and the highest astaxanthin content can reach 38.02 ± 2.40 mg·g−1. Thus, this work sought to give useful information that will lead to an improved understanding of the cost-effective method of cultivation of H. pluvialis for natural astaxanthin. This will be profitable for algal and medicine industry players. Full article
(This article belongs to the Special Issue Astaxanthin: A Potential Therapeutic Agent)
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15 pages, 1323 KiB  
Article
Astaxanthin Counteracts Excitotoxicity and Reduces the Ensuing Increases in Calcium Levels and Mitochondrial Reactive Oxygen Species Generation
by Francisca García, Pedro Lobos, Alejandra Ponce, Karla Cataldo, Daniela Meza, Patricio Farías, Carolina Estay, Felipe Oyarzun-Ampuero, Rodrigo Herrera-Molina, Andrea Paula-Lima, Álvaro O. Ardiles, Cecilia Hidalgo, Tatiana Adasme and Pablo Muñoz
Mar. Drugs 2020, 18(6), 335; https://doi.org/10.3390/md18060335 - 26 Jun 2020
Cited by 16 | Viewed by 3326
Abstract
Astaxanthin (ASX) is a carotenoid pigment with strong antioxidant properties. We have reported previously that ASX protects neurons from the noxious effects of amyloid-β peptide oligomers, which promote excessive mitochondrial reactive oxygen species (mROS) production and induce a sustained increase in cytoplasmic Ca [...] Read more.
Astaxanthin (ASX) is a carotenoid pigment with strong antioxidant properties. We have reported previously that ASX protects neurons from the noxious effects of amyloid-β peptide oligomers, which promote excessive mitochondrial reactive oxygen species (mROS) production and induce a sustained increase in cytoplasmic Ca2+ concentration. These properties make ASX a promising therapeutic agent against pathological conditions that entail oxidative and Ca2+ dysregulation. Here, we studied whether ASX protects neurons from N-methyl-D-aspartate (NMDA)-induced excitotoxicity, a noxious process which decreases cellular viability, alters gene expression and promotes excessive mROS production. Incubation of the neuronal cell line SH-SY5Y with NMDA decreased cellular viability and increased mitochondrial superoxide production; pre-incubation with ASX prevented these effects. Additionally, incubation of SH-SY5Y cells with ASX effectively reduced the basal mROS production and prevented hydrogen peroxide-induced cell death. In primary hippocampal neurons, transfected with a genetically encoded cytoplasmic Ca2+ sensor, ASX also prevented the increase in intracellular Ca2+ concentration induced by NMDA. We suggest that, by preventing the noxious mROS and Ca2+ increases that occur under excitotoxic conditions, ASX could be useful as a therapeutic agent in neurodegenerative pathologies that involve alterations in Ca2+ homeostasis and ROS generation. Full article
(This article belongs to the Special Issue Astaxanthin: A Potential Therapeutic Agent)
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16 pages, 1925 KiB  
Article
Astaxanthin Attenuates Fish Oil-Related Hepatotoxicity and Oxidative Insult in Juvenile Pacific White Shrimp (Litopenaeus vannamei)
by Yingying Yu, Yang Liu, Peng Yin, Weiwen Zhou, Lixia Tian, Yongjian Liu, Donghui Xu and Jin Niu
Mar. Drugs 2020, 18(4), 218; https://doi.org/10.3390/md18040218 - 17 Apr 2020
Cited by 11 | Viewed by 3356
Abstract
The present study investigated the effect of dietary astaxanthin (AX) on the growth performance, antioxidant parameters, and repair of hepatopancreas damage in Pacific white shrimp (Litopenaeus vannamei). To evaluate the hepatopancreas protective function of AX in shrimps, we compared the effect [...] Read more.
The present study investigated the effect of dietary astaxanthin (AX) on the growth performance, antioxidant parameters, and repair of hepatopancreas damage in Pacific white shrimp (Litopenaeus vannamei). To evaluate the hepatopancreas protective function of AX in shrimps, we compared the effect of five isonitrogenous and isoenergetic diets under oxidized fish oil conditions with varying AX levels during the 50-day experimental period. The formulated diets were as follows: (i) OFO (oxidized fish oil); (ii) OFO/AX150 (oxidized fish oil + AX150 mg/kg); (iii) OFO/AX250 (oxidized fish oil + AX250 mg/kg); (iv) OFO/AX450 (oxidized fish oil + AX450 mg/kg); and, (v) control group (fresh fish oil). Results showed that the oxidized fish oil with 275.2 meq/kg peroxide value (POV) resulted in a substantial decrease in the final body weight of L. vannamei (P > 0.05) and induced some visible histopathological alterations in the hepatopancreas. Growth performance was significantly higher in shrimps fed with the OFO/AX450 diet than those fed with the OFO diet (p < 0.05). However, no significant difference was observed when the OFO/AX450 diet was compared to the control diet containing fresh fish oil (p > 0.05). Moreover, shrimps under the OFO/AX450 diet displayed a significant improvement in hepatopancreatic health and showed a reduction of malondialdehyde (MDA) compared to those under the OFO diet (p < 0.05). Dietary AX improved the antioxidant capacity of L. vannamei by increasing the catalase (CAT) activity in the hemolymph. Acute salinity change test showed a higher shrimp survival rate under OFO/AX450 diet than the OFO diet (p < 0.05), suggesting that AX can contribute to enhanced stress tolerance. In conclusion, our data suggest that AX confers dose-dependent protection against OFO-induced oxidative insults and hepatopancreatic damage in shrimp. Full article
(This article belongs to the Special Issue Astaxanthin: A Potential Therapeutic Agent)
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12 pages, 2833 KiB  
Article
Haematococcus pluvialis-Derived Astaxanthin Is a Potential Neuroprotective Agent against Optic Nerve Ischemia
by Wei-Ning Lin, Kishan Kapupara, Yao-Tseng Wen, Yi-Hsun Chen, I-Hong Pan and Rong-Kung Tsai
Mar. Drugs 2020, 18(2), 85; https://doi.org/10.3390/md18020085 - 28 Jan 2020
Cited by 25 | Viewed by 3672
Abstract
Astaxanthin, a xanthophyll belonging to the family of carotenoids, is a potent antioxidant. However, much less is known about its protective effects on the oxidative stress of ischemic optic nerve. We hypothesized that astaxanthin treatment could protect retinal ganglion cells (RGCs) from death [...] Read more.
Astaxanthin, a xanthophyll belonging to the family of carotenoids, is a potent antioxidant. However, much less is known about its protective effects on the oxidative stress of ischemic optic nerve. We hypothesized that astaxanthin treatment could protect retinal ganglion cells (RGCs) from death via anti-oxidative and anti-apoptotic responses. Adult male Wistar rats were fed astaxanthin (100 mg/kg/day) by daily gavage for seven consecutive days, either before or after inducing oxidative stress in the retina by photodynamic treatment. The visual function, RGC apoptosis, macrophage infiltration in the optic nerve, expression of p-Akt, p-mTOR, SGK1, pS6K, Nrf2, p62, TNFα, Il1β in retinas were investigated. The visual function and the RGC densities were significantly higher in both pre- and post-treatment groups. The numbers of apoptotic RGCs and extrinsic macrophage infiltration in the optic nerve were significantly decreased in both astaxanthin-treated groups. Furthermore, pre- and post-treatment of astaxanthin showed a higher expression of p-Akt, p-mTOR, Nrf2 and superoxide dismutase activity, and a lower expression of cleaved caspase-3, suggesting anti-apoptotic and anti-oxidative roles. Our findings indicate that astaxanthin can preserve visual function and reduce RGC apoptosis after ischemic insults. Including astaxanthin in daily diet as a supplement may be beneficiary for ischemic optic neuropathy. Full article
(This article belongs to the Special Issue Astaxanthin: A Potential Therapeutic Agent)
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15 pages, 5146 KiB  
Article
Effects of Astaxanthin from Shrimp Shell on Oxidative Stress and Behavior in Animal Model of Alzheimer’s Disease
by Takunrat Taksima, Pennapa Chonpathompikunlert, Morakot Sroyraya, Pilaiwanwadee Hutamekalin, Maruj Limpawattana and Wanwimol Klaypradit
Mar. Drugs 2019, 17(11), 628; https://doi.org/10.3390/md17110628 - 04 Nov 2019
Cited by 36 | Viewed by 4962
Abstract
This study aimed to investigate the effect of astaxanthin (ASX) extracted and ASX powder from shrimp (Litopenaeus vannamei) shells on Wistar rats with Alzheimer’s disease, induced by amyloid-β (1-42) peptides. In this task, the rats were divided into eight groups: (1) [...] Read more.
This study aimed to investigate the effect of astaxanthin (ASX) extracted and ASX powder from shrimp (Litopenaeus vannamei) shells on Wistar rats with Alzheimer’s disease, induced by amyloid-β (1-42) peptides. In this task, the rats were divided into eight groups: (1) Control, (2) sham operate, (3) negative control (vehicle) + Aβ1-42, (4) ASX extract+Aβ1-42, (5) commercial ASX + Aβ1-42, (6) ASX powder + Aβ1-42, (7) blank powder + Aβ1-42, and (8) vitamin E + Aβ1-42. All treatments were orally administrated for 30 days. At 14- and 29-days post injection, animals were observed in behavioral tests. On the 31st day, animals were sacrificed; the hippocampus and cortex were collected. Those two brain areas were then homogenized and stored for biochemical and histological analysis. The results showed that the Aβ1-42 infused group significantly reduced cognitive ability and increased memory loss, as assessed by the Morris water maze test, novel object recognition test, and novel object location test. Moreover, the Aβ1-42 infused group exhibited a deterioration of oxidative markers, including glutathione peroxidase enzymes (GPx), lipid peroxidation (MDA), products of protein oxidation, and superoxide anion in the cortex and the hippocampus. Meanwhile, ASX powder (10 mg/kg body weight) showed a significant reduction in cognitive and memory impairments and oxidative stress which is greater than ASX extract in the same dose of compound or vitamin E (100 mg/kg body weight). Our study indicates the beneficial properties of ASX in alleviation of cognitive functions and reducing neurodegeneration in Wistar rats induced by amyloid-β (1-42) peptides. Full article
(This article belongs to the Special Issue Astaxanthin: A Potential Therapeutic Agent)
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16 pages, 2180 KiB  
Article
Development and Characterization of Astaxanthin-Containing Whey Protein-Based Nanoparticles
by Francesca Zanoni, Martina Vakarelova and Gianni Zoccatelli
Mar. Drugs 2019, 17(11), 627; https://doi.org/10.3390/md17110627 - 04 Nov 2019
Cited by 28 | Viewed by 4119
Abstract
Astaxanthin (ASX) is a carotenoid of great interest due to its potential health benefits. However, its use in the food, feed, and pharmaceutical fields is limited due to low bioavailability, poor stability during thermochemical treatments, susceptibility to oxidation, and poor organoleptic characteristics. The [...] Read more.
Astaxanthin (ASX) is a carotenoid of great interest due to its potential health benefits. However, its use in the food, feed, and pharmaceutical fields is limited due to low bioavailability, poor stability during thermochemical treatments, susceptibility to oxidation, and poor organoleptic characteristics. The aim of this work was to develop a method to stabilize astaxanthin extracted from the microalgae Haematococcus pluvialis (H.p.) and to improve its nutritional and functional properties through nanoencapsulation. Nanoparticles (NPs) were produced by emulsification–solvent evaporation technique starting from H.p. oleoresin using whey proteins concentrate (WPC) as stabilizer. The efficiency of encapsulation was 96%. The particle size (Z-average) was in the range of 80–130 nm and the superficial charge (measured as zeta-potential) was negative (−20 to −30 mV). The stability of the NPs upon resuspension in water was assayed through a panel of stress tests, i.e., extreme pH, UV radiation, Fe3+ exposition, and heating at 65 °C, that always showed a superior performance of encapsulated ASX in comparison to oleoresin, even if NPs tended to precipitate at pH 3.5–5.5. Simulated gastroenteric digestion was conducted to study the release of ASX in physiological conditions, and showed a maximum bioaccessibility of 76%, with 75% ASX converted into the more bioavailable free form. The collected data suggest that NPs might have possible future applications as supplements for human and animal diets. Full article
(This article belongs to the Special Issue Astaxanthin: A Potential Therapeutic Agent)
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12 pages, 1619 KiB  
Article
Improved Astaxanthin Production with Corynebacterium glutamicum by Application of a Membrane Fusion Protein
by Nadja A. Henke and Volker F. Wendisch
Mar. Drugs 2019, 17(11), 621; https://doi.org/10.3390/md17110621 - 31 Oct 2019
Cited by 35 | Viewed by 4709
Abstract
Astaxanthin is one of the strongest natural antioxidants and a red pigment occurring in nature. This C40 carotenoid is used in a broad range of applications such as a colorant in the feed industry, an antioxidant in cosmetics or as a supplement in [...] Read more.
Astaxanthin is one of the strongest natural antioxidants and a red pigment occurring in nature. This C40 carotenoid is used in a broad range of applications such as a colorant in the feed industry, an antioxidant in cosmetics or as a supplement in human nutrition. Natural astaxanthin is on the rise and, hence, alternative production systems are needed. The natural carotenoid producer Corynebacterium glutamicum is a potent host for industrial fermentations, such as million-ton scale amino acid production. In C. glutamicum, astaxanthin production was established through heterologous overproduction of the cytosolic lycopene cyclase CrtY and the membrane-bound β-carotene hydroxylase and ketolase, CrtZ and CrtW, in previous studies. In this work, further metabolic engineering strategies revealed that the potential of this GRAS organism for astaxanthin production is not fully exploited yet. It was shown that the construction of a fusion protein comprising the membrane-bound β-carotene hydroxylase and ketolase (CrtZ~W) significantly increased astaxanthin production under high glucose concentration. An evaluation of used carbon sources indicated that a combination of glucose and acetate facilitated astaxanthin production. Moreover, additional overproduction of cytosolic carotenogenic enzymes increased the production of this high value compound. Taken together, a seven-fold improvement of astaxanthin production was achieved with 3.1 mg/g CDW of astaxanthin. Full article
(This article belongs to the Special Issue Astaxanthin: A Potential Therapeutic Agent)
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9 pages, 1717 KiB  
Communication
Astaxanthin from Shrimp Cephalothorax Stimulates the Immune Response by Enhancing IFN-γ, IL-10, and IL-2 Secretion in Splenocytes of Helicobacter Pylori-Infected Mice
by Sergio Davinelli, Heidi Mikkelsen Melvang, Leif Percival Andersen, Giovanni Scapagnini and Michael Engelbrecht Nielsen
Mar. Drugs 2019, 17(7), 382; https://doi.org/10.3390/md17070382 - 26 Jun 2019
Cited by 27 | Viewed by 3834
Abstract
Infection with Helicobacter pylori is a critical cause of gastrointestinal diseases. A crucial host response associated with H. pylori infection includes gastric inflammation, which is characterized by a sustained recruitment of T-helper (Th) cells to the site of infection and distinct patterns of [...] Read more.
Infection with Helicobacter pylori is a critical cause of gastrointestinal diseases. A crucial host response associated with H. pylori infection includes gastric inflammation, which is characterized by a sustained recruitment of T-helper (Th) cells to the site of infection and distinct patterns of cytokine production. Adequate nutritional status, especially frequent consumption of dietary antioxidants, appears to protect against infection with H. pylori. The aim of the present study was to investigate whether astaxanthin (AXT) from shrimp cephalothorax may modulate cytokine release of splenocytes in H. pylori-infected mice (n = 60). Six- to eight-week-old female mice were divided into three groups (n = 20 per group) to receive a daily oral dose of 10 or 40 mg of AXT for six weeks. After six weeks, a trend toward interferon gamma (IFN-γ) upregulation was found (40 mg; p < 0.05) and a significant dose-dependent increase of interleukin 2 (IL-2) and IL-10 (both p < 0.05) was observed. These results suggest that AXT induces higher levels of IL-2 and a shift to a balanced Th1/Th2 response by increasing IFN-γ and augmenting IL-10. We concluded that AXT may influence the pattern of cytokines during H. pylori infection. Full article
(This article belongs to the Special Issue Astaxanthin: A Potential Therapeutic Agent)
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17 pages, 5104 KiB  
Article
Astaxanthin Complexes to Attenuate Muscle Damage after In Vivo Femoral Ischemia-Reperfusion
by Marisol Zuluaga Tamayo, Laurence Choudat, Rachida Aid-Launais, Olivier Thibaudeau, Liliane Louedec, Didier Letourneur, Virginie Gueguen, Anne Meddahi-Pellé, Anne Couvelard and Graciela Pavon-Djavid
Mar. Drugs 2019, 17(6), 354; https://doi.org/10.3390/md17060354 - 14 Jun 2019
Cited by 18 | Viewed by 4102
Abstract
(1) Background: Reperfusion injury refers to the cell and tissue damage induced, when blood flow is restored after an ischemic period. While reperfusion reestablishes oxygen supply, it generates a high concentration of radicals, resulting in tissue dysfunction and damage. Here, we aimed to [...] Read more.
(1) Background: Reperfusion injury refers to the cell and tissue damage induced, when blood flow is restored after an ischemic period. While reperfusion reestablishes oxygen supply, it generates a high concentration of radicals, resulting in tissue dysfunction and damage. Here, we aimed to challenge and achieve the potential of a delivery system based on astaxanthin, a natural antioxidant, in attenuating the muscle damage in an animal model of femoral hind-limb ischemia and reperfusion. (2) Methods: The antioxidant capacity and non-toxicity of astaxanthin was validated before and after loading into a polysaccharide scaffold. The capacity of astaxanthin to compensate stress damages was also studied after ischemia induced by femoral artery clamping and followed by varied periods of reperfusion. (3) Results: Histological evaluation showed a positive labeling for CD68 and CD163 macrophage markers, indicating a remodeling process. In addition, higher levels of Nrf2 and NQO1 expression in the sham group compared to the antioxidant group could reflect a reduction of the oxidative damage after 15 days of reperfusion. Furthermore, non-significant differences were observed in non-heme iron deposition in both groups, reflecting a cell population susceptible to free radical damage. (4) Conclusions: Our results suggest that the in situ release of an antioxidant molecule could be effective in improving the antioxidant defenses of ischemia/reperfusion (I/R)-damaged muscles. Full article
(This article belongs to the Special Issue Astaxanthin: A Potential Therapeutic Agent)
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10 pages, 1135 KiB  
Article
Xanthophyllomyces dendrorhous-Derived Astaxanthin Regulates Lipid Metabolism and Gut Microbiota in Obese Mice Induced by A High-Fat Diet
by Jihui Wang, Shiwen Liu, Han Wang, Shan Xiao, Cheng Li, Ying Li and Bingnan Liu
Mar. Drugs 2019, 17(6), 337; https://doi.org/10.3390/md17060337 - 05 Jun 2019
Cited by 42 | Viewed by 3543
Abstract
Astaxanthin is an important antioxidant with many biological activities such as anti-tumor, anti-obesity, cardioprotective, and immuno-modulatory activities. Most of these biological activities are derived from (3S,3′S)-astaxanthin, while the activities of (3R,3′R)-astaxanthin are rarely reported. The purpose of this study was to investigate the [...] Read more.
Astaxanthin is an important antioxidant with many biological activities such as anti-tumor, anti-obesity, cardioprotective, and immuno-modulatory activities. Most of these biological activities are derived from (3S,3′S)-astaxanthin, while the activities of (3R,3′R)-astaxanthin are rarely reported. The purpose of this study was to investigate the effect of (3R,3′R)-astaxanthin on lipid metabolism and gut microbiota in mice fed with a high-fat diet. In this work, 40 male C57BL/6 mice were divided into 8 groups fed a high-fat diet supplemented or not with (3R,3′R)-astaxanthin or Xanthophyllomyces dendrorhous for 8 weeks. The weight gain, energy intake, fat index, plasma triacylglycerol and cholesterol, liver triacylglycerol and cholesterol, and gut microbiota were determined. The results showed that the addition of (3R,3′R)-astaxanthin/X. dendrorhous to the high-fat diet as a supplement prevented weight gain, reduced plasma and liver triacylglycerol, and decreased plasma and liver total cholesterol. The addition of (3R,3′R)-astaxanthin/X. dendrorhous also regulated the gut microbiota of the mice, which optimized the ratio of Bacteroides to Firmicutes and increased the content of Verrucomicrobia, especially Akkermansia. The changes in the gut microflora achieved a healthier structure, thus reducing the incidence of obesity. Thus (3R,3′R)-Astaxanthin has the function of regulating lipid metabolism and gut microbiota to prevent obesity caused by a high-fat diet. The production strain of (3R,3′R)-astaxanthin, X. dendrorhous, has the same function as astaxanthin in preventing obesity caused by a high-fat diet, which reflects its potential ability as a probiotic drug. Full article
(This article belongs to the Special Issue Astaxanthin: A Potential Therapeutic Agent)
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18 pages, 24871 KiB  
Article
Astaxanthin Ameliorates Lipopolysaccharide-Induced Neuroinflammation, Oxidative Stress and Memory Dysfunction through Inactivation of the Signal Transducer and Activator of Transcription 3 Pathway
by Ji Hye Han, Yong Sun Lee, Jun Hyung Im, Young Wan Ham, Hee Pom Lee, Sang Bae Han and Jin Tae Hong
Mar. Drugs 2019, 17(2), 123; https://doi.org/10.3390/md17020123 - 18 Feb 2019
Cited by 46 | Viewed by 5574
Abstract
Astaxanthin (AXT), a xanthophyll carotenoid compound, has potent antioxidant, anti-inflammatory and neuroprotective properties. Neuroinflammation and oxidative stress are significant in the pathogenesis and development of Alzheimer’s disease (AD). Here, we studied whether AXT could alleviate neuroinflammation, oxidative stress and memory loss in lipopolysaccharide [...] Read more.
Astaxanthin (AXT), a xanthophyll carotenoid compound, has potent antioxidant, anti-inflammatory and neuroprotective properties. Neuroinflammation and oxidative stress are significant in the pathogenesis and development of Alzheimer’s disease (AD). Here, we studied whether AXT could alleviate neuroinflammation, oxidative stress and memory loss in lipopolysaccharide (LPS) administered mice model. Additionally, we investigated the anti-oxidant activity and the anti-neuroinflammatory response of AXT in LPS-treated BV-2 microglial cells. The AXT administration ameliorated LPS-induced memory loss. This effect was associated with the reduction of LPS-induced expression of inflammatory proteins, as well as the production of reactive oxygen species (ROS), nitric oxide (NO), cytokines and chemokines both in vivo and in vitro. AXT also reduced LPS-induced β-secretase and Aβ1–42 generation through the down-regulation of amyloidogenic proteins both in vivo and in vitro. Furthermore, AXT suppressed the DNA binding activities of the signal transducer and activator of transcription 3 (STAT3). We found that AXT directly bound to the DNA- binding domain (DBD) and linker domain (LD) domains of STAT3 using docking studies. The oxidative stress and inflammatory responses were not downregulated in BV-2 cells transfected with DBD-null STAT3 and LD-null STAT3. These results indicated AXT inhibits LPS-induced oxidant activity, neuroinflammatory response and amyloidogenesis via the blocking of STAT3 activity through direct binding. Full article
(This article belongs to the Special Issue Astaxanthin: A Potential Therapeutic Agent)
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Review

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25 pages, 635 KiB  
Review
Recent Advances in Astaxanthin Micro/Nanoencapsulation to Improve Its Stability and Functionality as a Food Ingredient
by Óscar Martínez-Álvarez, Marta M. Calvo and Joaquín Gómez-Estaca
Mar. Drugs 2020, 18(8), 406; https://doi.org/10.3390/md18080406 - 01 Aug 2020
Cited by 64 | Viewed by 6044
Abstract
Astaxanthin is a carotenoid produced by different organisms and microorganisms such as microalgae, bacteria, yeasts, protists, and plants, and it is also accumulated in aquatic animals such as fish and crustaceans. Astaxanthin and astaxanthin-containing lipid extracts obtained from these sources present an intense [...] Read more.
Astaxanthin is a carotenoid produced by different organisms and microorganisms such as microalgae, bacteria, yeasts, protists, and plants, and it is also accumulated in aquatic animals such as fish and crustaceans. Astaxanthin and astaxanthin-containing lipid extracts obtained from these sources present an intense red color and a remarkable antioxidant activity, providing great potential to be employed as food ingredients with both technological and bioactive functions. However, their use is hindered by: their instability in the presence of high temperatures, acidic pH, oxygen or light; their low water solubility, bioaccessibility and bioavailability; their intense odor/flavor. The present paper reviews recent advances in the micro/nanoencapsulation of astaxanthin and astaxanthin-containing lipid extracts, developed to improve their stability, bioactivity and technological functionality for use as food ingredients. The use of diverse micro/nanoencapsulation techniques using wall materials of a different nature to improve water solubility and dispersibility in foods, masking undesirable odor and flavor, is firstly discussed, followed by a discussion of the importance of the encapsulation to retard astaxanthin release, protecting it from degradation in the gastrointestinal tract. The nanoencapsulation of astaxanthin to improve its bioaccessibility, bioavailability and bioactivity is further reviewed. Finally, the main limitations and future trends on the topic are discussed. Full article
(This article belongs to the Special Issue Astaxanthin: A Potential Therapeutic Agent)
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21 pages, 3167 KiB  
Review
Impact of Astaxanthin on Diabetes Pathogenesis and Chronic Complications
by Rebecca Landon, Virginie Gueguen, Hervé Petite, Didier Letourneur, Graciela Pavon-Djavid and Fani Anagnostou
Mar. Drugs 2020, 18(7), 357; https://doi.org/10.3390/md18070357 - 09 Jul 2020
Cited by 76 | Viewed by 7018
Abstract
Oxidative stress (OS) plays a pivotal role in diabetes mellitus (DM) onset, progression, and chronic complications. Hyperglycemia-induced reactive oxygen species (ROS) have been shown to reduce insulin secretion from pancreatic β-cells, to impair insulin sensitivity and signaling in insulin-responsive tissues, and to alter [...] Read more.
Oxidative stress (OS) plays a pivotal role in diabetes mellitus (DM) onset, progression, and chronic complications. Hyperglycemia-induced reactive oxygen species (ROS) have been shown to reduce insulin secretion from pancreatic β-cells, to impair insulin sensitivity and signaling in insulin-responsive tissues, and to alter endothelial cells function in both type 1 and type 2 DM. As a powerful antioxidant without side effects, astaxanthin (ASX), a xanthophyll carotenoid, has been suggested to contribute to the prevention and treatment of DM-associated pathologies. ASX reduces inflammation, OS, and apoptosis by regulating different OS pathways though the exact mechanism remains elusive. Based on several studies conducted on type 1 and type 2 DM animal models, orally or parenterally administrated ASX improves insulin resistance and insulin secretion; reduces hyperglycemia; and exerts protective effects against retinopathy, nephropathy, and neuropathy. However, more experimental support is needed to define conditions for its use. Moreover, its efficacy in diabetic patients is poorly explored. In the present review, we aimed to identify the up-to-date biological effects and underlying mechanisms of ASX on the ROS-induced DM-associated metabolic disorders and subsequent complications. The development of an in-depth research to better understand the biological mechanisms involved and to identify the most effective ASX dosage and route of administration is deemed necessary. Full article
(This article belongs to the Special Issue Astaxanthin: A Potential Therapeutic Agent)
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18 pages, 1038 KiB  
Review
Astaxanthin as a Putative Geroprotector: Molecular Basis and Focus on Brain Aging
by Vincenzo Sorrenti, Sergio Davinelli, Giovanni Scapagnini, Bradley J. Willcox, Richard C. Allsopp and Donald C. Willcox
Mar. Drugs 2020, 18(7), 351; https://doi.org/10.3390/md18070351 - 05 Jul 2020
Cited by 35 | Viewed by 13062
Abstract
In recent years, the scientific interest in natural compounds with geroprotective activities has grown exponentially. Among the various naturally derived molecules, astaxanthin (ASX) represents a highly promising candidate geroprotector. By virtue of the central polyene chain, ASX acts as a scavenger of free [...] Read more.
In recent years, the scientific interest in natural compounds with geroprotective activities has grown exponentially. Among the various naturally derived molecules, astaxanthin (ASX) represents a highly promising candidate geroprotector. By virtue of the central polyene chain, ASX acts as a scavenger of free radicals in the internal membrane layer and simultaneously controls oxidation on the membrane surface. Moreover, several studies have highlighted ASX’s ability to modulate numerous biological mechanisms at the cellular level, including the modulation of transcription factors and genes directly linked to longevity-related pathways. One of the main relevant evolutionarily-conserved transcription factors modulated by astaxanthin is the forkhead box O3 gene (FOXO3), which has been recognized as a critical controller of cell fate and function. Moreover, FOXO3 is one of only two genes shown to robustly affect human longevity. Due to its tropism in the brain, ASX has recently been studied as a putative neuroprotective molecule capable of delaying or preventing brain aging in different experimental models of brain damage or neurodegenerative diseases. Astaxanthin has been observed to slow down brain aging by increasing brain-derived neurotrophic factor (BDNF) levels in the brain, attenuating oxidative damage to lipids, protein, and DNA and protecting mitochondrial functions. Emerging data now suggest that ASX can modulate Nrf2, FOXO3, Sirt1, and Klotho proteins that are linked to longevity. Together, these mechanisms provide support for a role of ASX as a potential geroneuroprotector. Full article
(This article belongs to the Special Issue Astaxanthin: A Potential Therapeutic Agent)
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22 pages, 590 KiB  
Review
Astaxanthin Modulation of Signaling Pathways That Regulate Autophagy
by Suhn Hyung Kim and Hyeyoung Kim
Mar. Drugs 2019, 17(10), 546; https://doi.org/10.3390/md17100546 - 23 Sep 2019
Cited by 39 | Viewed by 5121
Abstract
Autophagy is a lysosomal pathway that degrades and recycles unused or dysfunctional cell components as well as toxic cytosolic materials. Basal autophagy favors cell survival. However, the aberrant regulation of autophagy can promote pathological conditions. The autophagy pathway is regulated by several cell-stress [...] Read more.
Autophagy is a lysosomal pathway that degrades and recycles unused or dysfunctional cell components as well as toxic cytosolic materials. Basal autophagy favors cell survival. However, the aberrant regulation of autophagy can promote pathological conditions. The autophagy pathway is regulated by several cell-stress and cell-survival signaling pathways that can be targeted for the purpose of disease control. In experimental models of disease, the carotenoid astaxanthin has been shown to modulate autophagy by regulating signaling pathways, including the AMP-activated protein kinase (AMPK), cellular homolog of murine thymoma virus akt8 oncogene (Akt), and mitogen-activated protein kinase (MAPK), such as c-Jun N-terminal kinase (JNK) and p38. Astaxanthin is a promising therapeutic agent for the treatment of a wide variety of diseases by regulating autophagy. Full article
(This article belongs to the Special Issue Astaxanthin: A Potential Therapeutic Agent)
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12 pages, 690 KiB  
Review
Astaxanthin as a Peroxisome Proliferator-Activated Receptor (PPAR) Modulator: Its Therapeutic Implications
by Chang-Ik Choi
Mar. Drugs 2019, 17(4), 242; https://doi.org/10.3390/md17040242 - 23 Apr 2019
Cited by 41 | Viewed by 5255
Abstract
Peroxisome proliferator-activated receptors (PPARs) are part of the nuclear hormone receptors superfamily that plays a pivotal role in functions such as glucose and lipid homeostasis. Astaxanthin (ASX) is a lipid-soluble xanthophyll carotenoid synthesized by many microorganisms and various types of marine life that [...] Read more.
Peroxisome proliferator-activated receptors (PPARs) are part of the nuclear hormone receptors superfamily that plays a pivotal role in functions such as glucose and lipid homeostasis. Astaxanthin (ASX) is a lipid-soluble xanthophyll carotenoid synthesized by many microorganisms and various types of marine life that is known to possess antioxidant, anti-inflammatory, antidiabetic, anti-atherosclerotic, and anticancer activities. As such, it is a promising nutraceutical resource. ASX-mediated modulation of PPARs and its therapeutic implications in various pathophysiological conditions are described in this review. ASX primarily enhances the action of PPARα and suppresses that of PPARβ/δ and PPARγ, but it has also been confirmed that ASX displays the opposite effects on PPARs, depending on the cell context. Anti-inflammatory effects of ASX are mediated by PPARγ activation, which induces the expression of pro-inflammatory cytokines in macrophages and gastric epithelial cells. The PPARγ-agonistic effect of ASX treatment results in the inhibition of cellular growth and apoptosis in tumor cells. Simultaneous and differential regulation of PPARα and PPARγ activity by ASX has demonstrated a hepatoprotective effect, maintaining hepatic lipid homeostasis and preventing related hepatic problems. Considering additional therapeutic benefits of ASX such as anti-gastric, cardioprotective, immuno-modulatory, neuroprotective, retinoprotective, and osteogenic effects, more studies on the association between ASX-mediated PPAR regulation and its therapeutic outcomes in various pathophysiological conditions are needed to further elucidate the role of ASX as a novel nutraceutical PPAR modulator. Full article
(This article belongs to the Special Issue Astaxanthin: A Potential Therapeutic Agent)
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