Astaxanthin   中文名称: 虾青素

虾青素（50、100、150 和 200 µM；48 小时）抑制 DU145 细胞生长（IC50<200 µM）[1]。通过防止增殖、促进细胞凋亡、阻碍迁移和侵袭，虾青素（200 µM；24 小时）可降低 STAT3 和相关通路蛋白的表达（在蛋白和 mRNA 水平）[1]。此外，虾青素通过在蛋白质水平下调 VEGF 来保护 RPE 细胞免受氧化应激和高葡萄糖引起的异常激活 [2]。在 K562 细胞中，虾青素（1-50 µM；72 小时）以剂量和时间依赖性方式增加 PPARγ 蛋白的表达 [3]。

在不穿衣服的小鼠中，虾青素（200 mg/kg；每天一次灌胃，持续三周）可防止肿瘤异种移植物 (DU145) 的形成 [1]。在大鼠中，虾青素（125 或 500 mg/kg；在动物饲料中；7 天）可显着降低氧化应激并提供心脏保护作用 [4]。

细胞凋亡分析 [1]
细胞类型： DU145 细胞
测试浓度： 200 µM（预孵育）
孵育持续时间：24小时
实验结果：凋亡细胞百分比从8.5%增加到13.1%（与空白对照相比）。

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细胞迁移测定[1]
细胞类型： DU145 细胞
测试浓度： 200 µM
孵育时间：24小时
实验结果：DU145细胞表现出迁移和侵袭减弱（大约41%的细胞不能从一个室移动到另一个室，36%的细胞不能从一个室移动到另一个室）与对照组相比， 的细胞无法通过 Transwell 膜）。

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细胞增殖测定[2]
细胞类型： ARPE-19 细胞
测试浓度： 50 µM（孵育前）
孵育时间：7天
实验结果：当暴露于高葡萄糖时，细胞增殖显着减弱。

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蛋白质印迹分析[1]
细胞类型： DU145 细胞
测试浓度： 200 µM
孵育时间： 24 h
实验结果： STAT3在蛋白和mRNA水平上的表达均减少（下调JAK2、BCL-2和NF-κB的蛋白表达） , 上调 BAX , 蛋白表达

Animal/Disease Models: Nude mouse (approximately 20 grams; DU145 tumor xenograft model) [1].
Doses: 200 mg/kg
Route of Administration: intragastric (po) (po)administration; one time/day for 3 weeks.
Experimental Results: It has a significant inhibitory effect on tumor growth.

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Animal/Disease Models: Female C57BL/6 mice (7 weeks old) [4].
Doses: 125 or 500 mg/kg
Route of Administration: Animal feed; 7 days.
Experimental Results: The mean infarct size was Dramatically diminished to 45.1% and 39.1% in the two treatment groups (125 and 500 mg/kg), respectively. The myocardial salvage rates in the 125 mg/kg group and 500 mg/kg group were 26% and 36%, respectively. 9-HETE levels were Dramatically diminished in a dose-dependent manner. 9-HETE is a regioisomer oxidation product of arachidonic acid and is thought to be a product of free radical-mediated oxidation.

Absorption, Distribution and Excretion
Apparent astaxanthin (3,3'-dihydroxy-beta,beta-carotene-4,4'-dione) digestibility coefficients (ADC) and carotenoid compositions of the muscle, liver, whole kidney and plasma were compared in Atlantic salmon (Salmo salar) and Atlantic halibut (Hippoglossus hippoglossus) fed a diet supplemented with 66 mg astaxanthin kg(-1) dry matter for 112 days. The astaxanthin source consisted of 75% all-E-, 3% 9Z- and 22% 13Z-astaxanthin, of (3R,3'R)-, (3R,3'S; meso)-, and (3S,3'S)-astaxanthin in a 1:2:1 ratio. The ADC of astaxanthin was significantly higher in Atlantic halibut than in Atlantic salmon after 56 and 112 days of feeding (P < 0.05). The ADC of all-E-astaxanthin was significantly higher than ADC of 9Z-astaxanthin (P < 0.05). Considerably more carotenoids were present in all plasma and tissue samples of salmon than in halibut. Retention of astaxanthin in salmon muscle was 3.9% in salmon and 0 in halibut. All-E-astaxanthin accumulated selectively in the muscle of salmon, and in plasma of salmon and halibut compared with diet. 13Z-astaxanthin accumulated selectively in liver and whole kidney of salmon and halibut, when compared with plasma. A reductive pathway for astaxanthin metabolism in halibut similar to that of salmon was shown by the presence of 3',4'-cis and trans glycolic isomers of idoxanthin (3,3',4'-trihydroxy-beta,beta-carotene-4'-one) in plasma, liver and whole kidney. In conclusion, the higher ADC of astaxanthin in halibut than Atlantic salmon may be explained by lower feed intake in halibut, and the lower retention of astaxanthin by a higher capacity to transform astaxanthin metabolically.
The present studies were performed to investigate the metabolism of astaxanthin (Ax) in Atlantic salmon, especially in the liver of salmon. The investigations were undertaken in vivo salmon that were fed a diet containing 60 ppm 15, 15' (14)C-labelled Ax prior to sacrifice. The samples of blood, bile, liver, gastrointestinal tract and contents, muscle, skin, remaining carcass and feces were taken for scintillation counting. The highest radioactivity (71.36%) of (14)C-labelled Ax was found in the gastrointestinal contents and feces, 7.13% in the bile and 10.68% in the samples of liver, muscle, and skin at the end of the experiments. The metabolites of (14)C-labelled Ax were extracted from the bile of the salmon and analyzed using thin-layer chromatography (TLC) and high performance liquid chromatography (HPLC). Predominant (14)C-labelled Ax and its cis-isomers were found and no conjugation of (14)C-labelled Ax was observed. These results indicate that (14)C-labelled Ax was not conjugated into larger colorless compound in Atlantic salmon liver.

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Metabolism / Metabolites
One force-fed meal containing labelled (14)C-astaxanthin and (3)H-canthaxanthin or (3)H-zeaxanthin was given to eight mature female rainbow trout. Ninety-six hours after the test meal ingestion, trout were killed and liver, skin, muscle and ovaries were dissected out. Astaxanthin accumulated slightly more in muscle than canthaxanthin but in all tissues astaxanthin and canthaxanthin were very significantly more concentrated than zeaxanthin. (3)H-zeaxanthin metabolites were found only in the liver, whereas (14)C-phoenicoxanthin was the only metabolic pigment from (14)C-astaxanthin detected and was found in all investigated tissues. (3)H-astaxanthin was found in the liver of all trout indicating that (3)H-canthaxanthin and (3)H-zeaxanthin were astaxanthin precursors, and that salmonids probably possess carotenoid oxidative pathways unknown until now. Labelled retinol1 and retinol2 were detected only in the liver and (3)H-zeaxanthin was largely the predominant precursor of these two vitamin A forms.
The effects of feed intake, growth rate and temperature (8 and 12 degrees C) on apparent digestibility coefficients (ADC), blood uptake of individual astaxanthin E/Z isomers and metabolism of astaxanthin (3,3'-dihydroxy-beta,beta-carotene-4,4'-dione) were determined in Atlantic salmon. Accumulation of idoxanthin (3,4,3'-trihydroxy-beta,beta-carotene-4-one) in plasma was used to indicate metabolic transformation of astaxanthin.

Interactions
The present study investigated the in vivo protective effect of astaxanthin isolated from the Xanthophyllomyces dendrorhous mutant against ethanol-induced gastric mucosal injury in rats. The rats were treated with 80% ethanol for 3 d after pretreatment with two doses of astaxanthin (5 and 25 mg/kg of body weight respectively) for 3 d, while the control rats received only 80% ethanol for 3 days. The oral administration of astaxanthin (5 and 25 mg/kg of body weight) showed significant protection against ethanol-induced gastric lesion and inhibited elevation of the lipid peroxide level in gastric mucosa. In addition, pretreatment with astaxanthin resulted in a significant increase in the activities of radical scavenging enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. A histologic examination clearly indicated that the acute gastric mucosal lesion induced by ethanol nearly disappeared after pretreatment with astaxanthin.

[1]. Anti-Tumor Effects of Astaxanthin by Inhibition of the Expression of STAT3 in Prostate Cancer. Mar Drugs. 2020 Aug 7;18(8):415.

[2]. Effect of astaxanthin on retinal pigment epithelial cells in high glucose: an in-vitro study. Biomed Res, 2017, 28(15): 6839-6843.

[3]. Carotenoids inhibit proliferation and regulate expression of peroxisome proliferators-activated receptor gamma (PPARγ) in K562 cancer cells. Arch Biochem Biophys. 2011 Aug 1;512(1):96-106.

[4]. Seven day oral supplementation with Cardax (disodium disuccinate astaxanthin) provides significant cardioprotection and reduces oxidative stress in rats. Mol Cell Biochem. 2006 Feb;283(1-2):23-30.

[5]. Multiple Mechanisms of Anti-Cancer Effects Exerted by Astaxanthin. Mar Drugs. 2015 Jul 14;13(7):4310-30.

Astaxanthin is a carotenone that consists of beta,beta-carotene-4,4'-dione bearing two hydroxy substituents at positions 3 and 3' (the 3S,3'S diastereomer). A carotenoid pigment found mainly in animals (crustaceans, echinoderms) but also occurring in plants. It can occur free (as a red pigment), as an ester, or as a blue, brown or green chromoprotein. It has a role as an anticoagulant, an antioxidant, a food colouring, a plant metabolite and an animal metabolite. It is a carotenone and a carotenol. It derives from a hydride of a beta-carotene.
Astaxanthin is a keto-carotenoid in the terpenes class of chemical compounds. It is classified as a xanthophyll but it is a carotenoid with no vitamin A activity. It is found in the majority of aquatic organisms with red pigment. Astaxanthin has shown to mediate anti-oxidant and anti-inflammatory actions. It may be found in fish feed or some animal food as a color additive.
Astaxanthin has been reported in Agrobacterium aurantiacum, Phaffia rhodozyma, and other organisms with data available.
Astaxanthin is a natural and synthetic xanthophyll and nonprovitamin A carotenoid, with potential antioxidant, anti-inflammatory and antineoplastic activities. Upon administration, astaxanthin may act as an antioxidant and reduce oxidative stress, thereby preventing protein and lipid oxidation and DNA damage. By decreasing the production of reactive oxygen species (ROS) and free radicals, it may also prevent ROS-induced activation of nuclear factor-kappa B (NF-kB) transcription factor and the production of inflammatory cytokines such as interleukin-1beta (IL-1b), IL-6 and tumor necrosis factor-alpha (TNF-a). In addition, astaxanthin may inhibit cyclooxygenase-1 (COX-1) and nitric oxide (NO) activities, thereby reducing inflammation. Oxidative stress and inflammation play key roles in the pathogenesis of many diseases, including cardiovascular, neurological, autoimmune and neoplastic diseases.

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Drug Indication
Investigated for use/treatment in eye disorders/infections, cancer/tumors (unspecified), and asthma.

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Therapeutic Uses
For the current study, it was hypothesized that oral Cardax /disodium disuccinate astaxanthin/ administration would inhibit oxidative damage of multiple relevant biological targets in a representative, well-characterized murine peritoneal inflammation model. A previously developed mass spectrometry-based (LC/ESI/MS/MS) approach was used to interrogate multiple distinct pathways of oxidation in a black mouse (C57/BL6) model system. In vivo markers of oxidant stress from peritoneal lavage samples (supernatants) were evaluated in mice on day eight (8) after treatment with either Cardax or vehicle (lipophilic emulsion without drug) orally by gavage at 500 mg/kg once per day for seven (7) days at five (5) time points: (1) baseline prior to treatment (t=0); (2) 16 h following intraperitoneal (i.p.) injection with thioglycollate to elicit a neutrophilic infiltrate; (3) 4 h following i.p. injection of yeast cell wall (zymosan; t=16 h/4 h thioglycollate+zymosan); (4) 72 h following i.p. injection with thioglycollate to elicit monocyte/macrophage infiltration; and (5) 72 h/4 h thioglycollate+zymosan. A statistically significant sparing effect on the arachidonic acid (AA) and linoleic acid (LA) substrates was observed at time points two and five. When normalized to the concentration of the oxidative substrates, statistically significant reductions of 8-isoprostane-F(2alpha) (8-iso-F(2alpha)) at time point three (maximal neutrophil recruitment/activation), and 5-HETE, 5-oxo-EET, 11-HETE, 9-HODE, and PGF(2alpha) at time point five (maximal monocyte/macrophage recruitment/activation) were observed. Subsequently, the direct interaction of the optically inactive stereoisomer of Cardax (meso-dAST) with human 5-lipoxygenase (5-LOX) was evaluated in vitro with circular dichroism (CD) and electronic absorption (UV/Vis) spectroscopy, and subsequent molecular docking calculations were made using mammalian 15-LOX as a surrogate (for which XRC data has been reported). The results suggested that the meso-compound was capable of interaction with, and binding to, the solvent-exposed surface of the enzyme. These preliminary studies provide the foundation for more detailed evaluation of the therapeutic effects of this compound on the 5-LOX enzyme, important in chronic diseases such as atherosclerosis, asthma, and prostate cancer in humans. /Disodium disuccinate astaxanthin/
The composition of atherosclerotic plaques, not just macroscopical lesion size, has been implicated in their susceptibility to rupture and the risk of thrombus formation. By focusing on the quality of lipids, macrophages, apoptosis, collagen, metalloproteinase expression and plaque integrity, we evaluated the possible anti-atherosclerotic effect of the antioxidants alpha-tocopherol and astaxanthin in Watanabe heritable hyperlipidemic (WHHL) rabbits. Thirty-one WHHL rabbits were divided into three groups and were fed a standard diet, as controls (N =10), or a standard diet with the addition of 500 mg alpha-tocopherol per kg feed (N =11) or 100 mg astaxanthin per kg feed (N =10) for 24 weeks. We found that both antioxidants, particularly astaxanthin, significantly decreased macrophage infiltration in the plaques although they did not affect lipid accumulation. All lesions in the astaxanthin-treated rabbits were classified as early plaques according to the distribution of collagen and smooth muscle cells. Both antioxidants also improved plaque stability and significantly diminished apoptosis, which mainly occurred in macrophages, matrix metalloproteinase three expressions and plaque ruptures. Although neither antioxidant altered the positive correlations between the lesion size and lipid accumulation, the lesion size and apoptosis were only positively correlated in the control group. Astaxanthin and alpha-tocopherol may improve plaque stability by decreasing macrophage infiltration and apoptosis in this atherosclerotic setting. Apoptosis reduction by alpha-tocopherol and astaxanthin may be a new anti-atherogenic property of these antioxidants.
Exptl Ther: Astaxanthin, a carotenoid without vitamin A activity, may exert antitumor activity through the enhancement of immune responses. Here, we determined the effects of dietary astaxanthin on tumor growth and tumor immunity against transplantable methylcholanthrene-induced fibrosarcoma (Meth-A tumor) cells. These tumor cells express a tumor antigen that induces T cell-mediated immune responses in syngenic mice. BALB/c mice were fed astaxanthin (0.02%, 40 micrograms/kg body wt/day in a beadlet form) mixed in a chemically defined diet starting zero, one, and three weeks before subcutaneous inoculation with tumor cells (3 x 10(5) cells, 2 times the minimal tumorigenic dose). Three weeks after inoculation, tumor size and weight were determined. We also determined cytotoxic T lymphocyte (CTL) activity and interferon-gamma (IFN-gamma) production by tumor-draining lymph node (TDLN) and spleen cells by restimulating cells with Meth-A tumor cells in culture. The astaxanthin-fed mice had significantly lower tumor size and weight than controls when supplementation was started one and three weeks before tumor inoculation. This antitumor activity was paralleled with higher CTL activity and IFN-gamma production by TDLN and spleen cells in the astaxanthin-fed mice. CTL activity by TDLN cells was highest in mice fed astaxanthin for three weeks before inoculation. When the astaxanthin-supplemented diet was started at the same time as tumor inoculation, none of these parameters were altered by dietary astaxanthin, except IFN-gamma production by spleen cells. Total serum astaxanthin concentrations were approximately 1.2 mumol/l when mice were fed astaxanthin (0.02%) for four weeks and appeared to increase in correlation with the length of astaxanthin supplementation. Our results indicate that dietary astaxanthin suppressed Meth-A tumor cell growth and stimulated immunity against Meth-A tumor antigen.
Exptl Ther: In the current study, the improved oral bioavailability of a synthetic astaxanthin derivative (Cardax; disodium disuccinate astaxanthin) was utilized to evaluate its potential effects as a cardioprotective agent after 7-day subchronic oral administration as a feed supplement to Sprague-Dawley rats. Animals received one of two concentrations of Cardax in feed (0.1 and 0.4%; approximately 125 and 500 mg/kg/day, respectively) or control feed without drug for 7 days prior to the infarct study carried out on day 8. Thirty minutes of occlusion of the left anterior descending (LAD) coronary artery was followed by 2 hr of reperfusion prior to sacrifice, a regimen which resulted in a mean infarct size (IS) as a percentage (%) of the area at risk (AAR; IS/AAR,%) of 61 + or - 1.8%. The AAR was quantified by Patent blue dye injection, and IS was determined by triphenyltetrazolium chloride (TTC) staining. Cardax at 0.1 and 0.4% in feed for 7 days resulted in a significant mean reduction in IS/AAR,% to 45 + or - 2.0% (26% salvage) and 39 + or - 1.5% (36% salvage), respectively. Myocardial levels of free astaxanthin achieved after 7-day supplementation at each of the two concentrations (400 + or - 65 nM and 1634 + or - 90 nM, respectively) demonstrated excellent solid-tissue target organ loading after oral supplementation. Parallel trends in reduction of plasma levels of multiple lipid peroxidation products with disodium disuccinate astaxanthin supplementation were observed, consistent with the documented in vitro antioxidant mechanism of action. These results extend the potential utility of this compound for cardioprotection to the elective human cardiovascular patient population, for which 7-day oral pre-treatment (as with statins) provides significant reductions in induced periprocedural infarct size. /Disodium disuccinate astaxanthin/
For more Therapeutic Uses (Complete) data for ASTAXANTHINE (7 total), please visit the HSDB record page.

C40H52O4

596.8385

596.386

472-61-7

5281224

Dark purple to black solid powder

1.1±0.1 g/cm3

774.0±60.0 °C at 760 mmHg

215-216ºC

435.8±29.4 °C

0.0±6.0 mmHg at 25°C

1.595

8.16

74.6

2

4

10

44

1340

2

CC1=C(C(C[C@@H](C1=O)O)(C)C)/C=C/C(=C/C=C/C(=C/C=C/C=C(/C=C/C=C(/C=C/C2=C(C(=O)[C@H](CC2(C)C)O)C)\C)\C)/C)/C

MQZIGYBFDRPAKN-UWFIBFSHSA-N

InChI=1S/C40H52O4/c1-27(17-13-19-29(3)21-23-33-31(5)37(43)35(41)25-39(33,7)8)15-11-12-16-28(2)18-14-20-30(4)22-24-34-32(6)38(44)36(42)26-40(34,9)10/h11-24,35-36,41-42H,25-26H2,1-10H3/b12-11+,17-13+,18-14+,23-21+,24-22+,27-15+,28-16+,29-19+,30-20+/t35-,36-/m0/s1

(6S)-6-Hydroxy-3-[(1E,3E,5E,7E,9E,11E,13E,15E,17E)-18-[(4S)-4-hydroxy-2,6,6-trimethyl-3-oxo-1-cyclohexenyl]-3,7,12,16-tetramethyloctadeca-1,3,5,7,9,11,13,15,17-nonaenyl]-2,4,4-trimethyl-1-cyclohex-2-enone

Astaxanthin

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： (1). 本产品在运输和储存过程中需避光。  (2). 请将本产品存放在密封且受保护的环境中（例如氮气保护），避免吸湿/受潮。  (3). 该产品在溶液状态不稳定，请现配现用。

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~2 mg/mL (~3.35 mM)
Acetone :< 1 mg/mL

配方 1 中的溶解度: 3.33 mg/mL (5.58 mM) in 0.5% CMC-Na/saline water (这些助溶剂从左到右依次添加，逐一添加), 悬浮液； 超声和加热处理
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: 3.33 mg/mL (5.58 mM) in 20% HP-β-CD in Saline (这些助溶剂从左到右依次添加，逐一添加), 悬浮液； 超声和加热处理
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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