虾青素生理活性的研究进展

虾青素是一种天然的萜烯类不饱和化合物,具有许多种对人类健康有益的生理活性。虾青素分子结构中有两个β-紫罗酮环和11个共轭双键,具有极强的抗氧化性和良好的生理活性,能够有效淬灭单线态氧、清除氧自由基、防紫外线辐射等,因而在食品、药品、化妆品等行业都有重要的应用。本论文介绍了虾青素的主要来源和结构特征,并对虾青素的一系列生理活性及其作用机制进行了综述,详细整理汇总了近年来虾青素在抗氧化、抗肿瘤、防癌症、光保护、视力保护、中枢神经的保护、抗炎症、预防心血管疾病等多方面新的研究成果,为虾青素未来的研究开发和综合利用提供依据。     

虾青素药理作用的研究进展

虾青素是一种天然的类胡萝卜素,国外对其抗氧化、抗高血压、抗炎症、抗癌、抗辐射和增强免疫等药理作用进行了广泛研究。本文对近年来虾青素在药理作用方面的研究进展进行综述。     

虾青素调控Nrf2通路发挥心血管保护作用的研究进展

氧化应激在多种心血管疾病的发病机制中起着重要作用。核因子E2相关因子2(Nrf2)是机体调节氧化应激的关键转录因子，也是氧化应激相关疾病的新兴治疗靶点。虾青素是类胡萝卜素的一种，具有极强的抗炎、抗氧化作用，被认为在心血管疾病中发挥良好的保护作用。多项研究表明虾青素能通过激活Nrf2通路改善血脂、血糖异常，抑制血管钙化，延缓动脉粥样硬化的发展，减轻心肌损伤并改善心力衰竭，在防治心血管疾病方面具有广阔前景。     

虾青素临床研究现状及其在特医食品开发中的应用前景

虾青素是一种酮式类胡萝卜素,具有广泛的临床应用价值,在糖尿病、心血管系统疾病、眼科疾病、神经疾病及肿瘤的预防和治疗等多方面体现一定的改善作用。特殊医学用途配方食品（特医食品）是为了满足特定疾病状态人群对营养素或膳食的特殊需要,专门加工配制而成的配方食品,能辅助临床治疗。本文对虾青素的临床及临床前研究进行综述,为未来基于虾青素的特医食品开发及进一步深入研究提供参考。     

虾青素促进丙烯酰胺所致大鼠海马神经细胞损伤的恢复

目的从细胞水平上研究虾青素对丙烯酰胺所致海马神经细胞损伤恢复的影响。方法通过B27无血清培养法进行SD乳鼠的大脑海马神经细胞的分离、培养及其鉴定;MTT法检测细胞存活率,比色法测定细胞内抗氧化酶SOD、CAT、GSH-Px的活性,线粒体的MDA及NO的含量。结果虾青素能提高丙烯酰胺损伤过的海马神经细胞的存活率,提高了丙烯酰胺损伤后细胞SOD、CAT活性、GSH-Px的活力,并降低了细胞线粒体中的MDA和NO的含量。结论虾青素对丙烯酰胺造成的高海马神经细胞损伤有促进恢复的作用。     

虾青素可能通过H~+传递功能保护NaN_3损伤的人胎肝L-02细胞

观察虾青素(astaxanthin)对呼吸链复合体Ⅳ抑制剂叠氮钠(NaN3)损伤的人胎肝L-02细胞保护作用,并初步探讨其作用机制。100 mmol·L-1 NaN3用于构建肝损伤细胞模型,通过测定不同浓度虾青素(0.01、0.10、1.00及10.00 nmol·L-1)对损伤细胞存活率(MTT检测)、细胞内活性氧(reactive oxygen species,ROS)水平(DCFH-DA检测)、细胞凋亡率(Annexin V-FITC/PI双染法)以及线粒体膜电位(mitochondrial membrane potential,MMP)水平(JC-1法)的影响,发现虾青素能抑制损伤细胞晚期凋亡;对细胞存活率和MMP的保护作用呈现先增加后降低的非剂量依赖性关系,其中0.10 nmol·L-1虾青素表现为较强的保护作用;实验浓度范围内的虾青素并不能显著降低细胞内ROS水平(P>0.05)。为进一步探讨虾青素对损伤细胞的保护作用,人工制备平面双层磷脂膜(planar bilayer lipid membrane,BLM)模拟线粒体膜,测定不同浓度虾青素(0.1%、2.0%、10.0%)对H+的传递能力。结果...     

虾青素对过氧化氢所致HepG2细胞线粒体氧化损伤及生存能力下降的保护作用

目的探讨虾青素对H_2O_2导致的HepG2细胞线粒体氧化损伤及生存能力下降的保护作用。方法采用H_2O_2损伤HepG2细胞,测定细胞内Ca~(2+)浓度及线粒体膜电位、胞浆中细胞色素c(Cyt-c)的阳性表达率变化考察了虾青素对活性氧所致线粒体氧化损伤的保护作用;测定细胞存活率、乳酸脱氢酶(LDH)释放率考察了虾青素对活性氧所致细胞生存能力下降的保护作用。结果虾青素(1.0×10~(-7)、1.0×10~(-6)、1.0×10~(-5)mol·L~(-1))能明显抑制H_2O_2导致的细胞内Ca~(2+)浓度升高、线粒体膜电位降低、Cyt-c的释放增加;以及细胞存活率下降、LDH释放率增加。结论虾青素对H_2O_2所致细胞线粒体氧化损伤及细胞生存能力下降具有明显的保护作用,其机制可能与其抗氧化作用有关。     

红球藻提取物大鼠90d喂养试验与致畸试验研究

正天然虾青素在食品添加剂、保健品、制药业、化妆品等方面都有广泛的应用。国内外关于虾青素致畸试验的报道较少,有研究发现虾青素未引起胎兔畸形率的增加[1]。红球藻富含虾青素,是商业虾青素产品的良好来源。但关于红球藻提取物尚缺乏系统的毒理学     

虾青素对过氧化氢所致质膜氧化损伤的保护作用

目的探讨虾青素对H_2O_2所致质膜氧化损伤的保护作用。方法采用H_2O_2导致红细胞膜氧化损伤,以细胞形态学、细胞溶血率、丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性、膜封闭能力及流动性为指标,观察一定浓度的虾青素(1.0×10~(-7)、1.0×10~(-6)、1.0×10~(-5)mol·L~(-1))对H_2O_2所致质膜氧化损伤的保护作用。结果H_2O_2能导致红细胞溶血率和MDA含量增加、SOD活性、膜封闭能力及膜流动性下降。而经过一定浓度的虾青素预处理后,红细胞溶血率和MDA含量明显降低、SOD活性、膜封闭能力及膜流动性显著增强。结论虾青素对H_2O_2引起的质膜氧化损伤具有明显的保护作用,其机制可能与其抗氧化作用有关。     

虾青素抑制NF-κB的激活减轻大鼠心肌梗死后的交感神经重构的研究

目的探讨虾青素对心肌梗死后的交感神经重构的影响以及可能的作用机制。方法心肌梗死组和虾青素组大鼠结扎冠状动脉前降支制作心肌梗死模型;假手术组开胸后剪开心包腔,不结扎冠状动脉。虾青素组按100 mg/(kg·d)的剂量于术前1日开始灌胃,1次·d-1;心肌梗死对照组和假手术组灌胃等量无菌蒸馏水。28 d后用HE染色观察细胞形态,采用蛋白免疫印迹法检测心肌梗死周边NF-κB核移位、p-CX43蛋白的表达。采用免疫组化方法检测心肌梗死周边神经生长因子(NGF)、生长相关蛋白43(GAP43)、酪氨酸羟化酶(TH)的分布。结果与心肌梗死组相比,虾青素抑制了NF-κB核移位,p-CX43蛋白水平表达增多,虾青素组GAP-43与TH阳性的密度及NGF的含量明显减少。结论虾青素可减轻心肌梗死周边的交感神经重构,可能是通过抑制NF-κB的激活。     

Effect of astaxanthin on the hepatotoxicity, lipid peroxidation and antioxidative enzymes in the liver of CCl4-treated rats

Astaxanthin is one of many carotenoids present in marine animals, vegetables and fruits. Since carotenoids are known to have antioxidant properties, we tested to determine if astaxanthin could have protective effects in the CCl4-treated rat liver by activating the antioxidant system. Astaxanthin blocked the increase of glutamate-oxalacetate transaminase (GOT) and glutamate-pyruvate transaminase (GTP) activity and thiobarbituric acid reactive substances (TBARS) in response to carbon tetrachloride (CCl4), while causing an increase in glutathione (GSH) levels and superoxide dismutase (SOD) activities in the CCl4-treated rat liver. These results suggest that astaxanthin protects liver damage induced by CCl4 by inhibiting lipid peroxidation and stimulating the cellular antioxidant system.     

In vivo protective efficacy of astaxanthin against ionizing radiation-induced DNA damage

Astaxanthin, a carotenoid pigment, is believed to be effective in the repair of DNA damage. Our study evaluates the effect of astaxanthin on DNA damage in rats exposed to whole-body radiotherapy using the comet assay. Thirty-two male rats were randomly divided into four groups (control, ionizing radiation, astaxanthin, and radiation+astaxanthin). The radiation and radiation+astaxanthin groups were exposed to X-rays at a dose of 8 gray (0.62 gray/min). Astaxanthin was administered at 4 mg/kg by gavage for 7 days starting from irradiation. The %TailDNA parameter was chosen as an indicator of DNA damage and the results were compared using one-way ANOVA. %TailDNA was 3.24 ± 3.12 in the control group, 2.85 ± 2.73 in the astaxanthin group, 4.11 ± 7.90 in the radiation group, and 3.59 ± 4.05 in the radiation+astaxanthin group. There was a significant increase in DNA damage in the radiation group, compared with the control and astaxanthin groups (p < .001). DNA damage was reduced in the radiation+astaxanthin group compared with the radiation group (p < .05). Although this decrease did not reduce damage to the level of the control group, it was significant. The decrease in radiation-induced DNA damage by astaxanthin administration in our study supports the hypothesis that astaxanthin is a promising agent for against/reducing DNA damage.     

Effects of astaxanthin supplementation on exercise-induced fatigue in mice

The present study was designed to determine the effect of astaxanthin on endurance capacity in male mice aged 4 weeks. Mice were given orally either vehicle or astaxanthin (1.2, 6, or 30 mg/kg body weight) by stomach intubation for 5 weeks. The astaxanthin group showed a significant increase in swimming time to exhaustion as compared to the control group. Blood lactate concentration in the astaxanthin groups was significantly lower than in the control group. In the control group, plasma non-esterfied fatty acid (NEFA) and plasma glucose were decreased by swimming exercise, but in the astaxanthin group, NEFA and plasma glucose were significantly higher than in the control group. Astaxanthin treatment also significantly decreased fat accumulation. These results suggest that improvement in swimming endurance by the administration of astaxanthin is caused by an increase in utilization of fatty acids as an energy source.     

Astaxanthin ameliorates lung fibrosis in vivo and in vitro by preventing transdifferentiation,inhibiting proliferation,and promoting apoptosis of activated cells

Astaxanthin, a member of the carotenoid family, is the only known ketocarotenoid transported into the brain by transcytosis through the blood–brain barrier. However, whether astaxanthin has antifibrotic functions is unknown. In this study, we investigated the effects of astaxanthin on transforming growth factor β1-mediated and bleomycin-induced pulmonary fibrosis in vitro and in vivo. The results showed that astaxanthin significantly improved the structure of the alveoli and alleviated collagen deposition in vivo. Compared with the control group, the astaxanthin-treated groups exhibited downregulated protein expressions of α-smooth muscle actin, vimentin, hydroxyproline, and B cell lymphoma/leukemia-2 as well as upregulated protein expressions of E-cadherin and p53 in vitro and in vivo. Astaxanthin also inhibited the proliferation of activated A549 and MRC-5 cells at median inhibitory concentrations of 40 and 30 μM, respectively. In conclusion, astaxanthin could relieve the symptoms and halt the progression of pulmonary fibrosis, partly by preventing transdifferentiation, inhibiting proliferation, and promoting apoptosis of activated cells.     

Oral bioavailability of the antioxidant astaxanthin in humans is enhanced by incorporation of lipid based formulations.

Astaxanthin is a carotenoid with antioxidant properties, synthesised by plants and algae, and distributed in marine seafood. Astaxanthin is also available as a food supplement, but, like other carotenoids, is a very lipophilic compound and has low oral bioavailability. However, bioavailability can be enhanced in the presence of fat. There is not much information in the literature about the pharmacokinetics of oral astaxanthin in humans. In this open parallel study, healthy male volunteers received a single dose of 40 mg astaxanthin, as lipid based formulations or as a commercially available food supplement, followed by blood sampling for further analysis of plasma concentrations. Pharmacokinetic parameters were calculated to evaluate the extent and rate of absorption from each formulation. The elimination half-life was 15.9+/-5.3 h (n=32), and showed a mono-phasic curve. Three lipid based formulations: long-chain triglyceride (palm oil) and polysorbate 80 (formulation A), glycerol mono- and dioleate and polysorbate 80 (formulation B), and glycerol mono- and dioleate, polysorbate 80 and sorbitan monooleate (formulation C), all showed enhanced bioavailability, ranging from 1.7 to 3.7 times that of the reference formulation. The highest bioavailability was observed with formulation B, containing a high content of the hydrophilic synthetic surfactant polysorbate 80.     

Safety assessment of astaxanthin derived from engineered Escherichia coli K-12 using a 13-week repeated dose oral toxicity study and a prenatal developmental toxicity study in rats

Astaxanthin is a natural carotenoid with strong antioxidant activity that has been used for decades as a nutrient/color additive and it has recently been marketed as a health supplement. Astaxanthin can be synthesized in a wide range of microalgae, yeast, and bacteria. As genes directing astaxanthin biosynthesis in various organisms have been cloned, this study assessed the safety of astaxanthin crystal produced by Escherichia coli K-12 harboring plasmids carrying astaxanthin biosynthetic genes. The astaxanthin crystal contains a total carotenoid content of 950 mg/g and an astaxanthin content of 795 mg/g. Subchronic oral toxicity and prenatal developmental toxicity of the astaxanthin in rats were conducted in accordance with the Guidelines of Health Food Safety Assessment promulgated by Food and Drug Administration of Taiwan which is based on OECD guidelines 408 and 414. Both male and female Sprague-Dawley (SD) rats (12 for each gender) receiving the astaxanthin crystal at 1.2, 240.0, or 750.0 mg/kg/day in olive oil via oral gavage for 90 days showed no changes in body weight gains, hematology and serum chemistry values and hepatic enzyme stability, organ integrity and organ weight. Except the higher food consumption observed in rats receiving 750.0 mg/g astaxanthin crystal, administration of the astaxanthin crystal to 25–27 pregnant female rats in each group throughout the period of organogenesis (G6-G15) produced no adverse effects on fetal organogenesis. Based on the results, we propose that the no-observable-adverse-effect level (NOAEL) of the astaxanthin crystal extracted from genetically modified E. coli K-12 is 750.0 mg/kg bw/day.     

虾青素对大鼠乙酸性胃溃疡的治疗作用

This study is to investigate therapeutic effect of astaxanthin on acetic acid-induced gastric ulcer in rats.  Rats were divided into control group, ulcer control group, and astaxanthin (5, 10, and 25 mg·kg^-1) groups at random, 8 rats in each group.  After administered for 10 days consecutively, all the rats were sacrificed.  The area of ulcer and the levels of MDA, SOD, CAT and GSH-Px in gastric mucosa were measured.  Compared with ulcer control group, in astaxanthin (5, 10, and 25 mg·kg^-1) groups, the area of ulcer was decreased significantly.  Level of MDA decreased while activities of SOD, CAT and GSH-Px increased (P < 0.05).  Astaxanthin has good therapeutic effect on acetic acid-induced gastric ulcer in rats.  Eliminating free radical and improving local blood circulation of the ulcer may be the mechanism of action.     

虾青素-胶原蛋白耦合物改善小鼠皮肤光老化作用研究

目的 在制备虾青素-胶原蛋白耦合物的基础上,探讨耦合物对小鼠皮肤光老化的改善作用。方法 将来源于雨生红球藻的虾青素单体和均一分子量胶原蛋白多肽在一定条件下反应后生成耦合物,将耦合物与适当基质混合后制成外用乳膏。采用UV灯照射Balb/c小鼠背部裸露皮肤,建立动物光老化模型,随机分为正常对照组、模型对照组、基质对照组、虾青素组、胶原蛋白多肽组、耦合物组和维生素E组,每天UV照射前进行药物涂抹。6周后观察小鼠皮肤形态、测定皮肤厚度变化及进行皮肤组织病理学检测等。结果 虾青素和胶原蛋白可结合生成具有特征吸收波长的水溶性耦合物,耦合物可有效缓解皮肤厚度增生,修复皮肤胶原纤维和弹性纤维网状结构。结论 虾青素-胶原蛋白多肽耦合物可有效改善UV引起的皮肤光老化损伤。