Combined conventional/antioxidant ＂Astaxanthin＂ treatment for male infertility： a double blind, randomized trial

Aim： To evaluate the treatment of male infertility with a strong natural antioxidant, in addition to conventional treatment. Methods： Using a double blind, randomized trial design, 30 men with infertility of ≥12 months and female partners with no demonstrable cause of infertility received conventional treatment according to the guidelines of the World Health Organization （WHO）, and either a strong antioxidant Astaxanthin 16 rag/day （AstaCarox, AstaReal AB, Gustavsberg, Sweden） or placebo for 3 months. The effects of treatment on semen parameters, reactive oxygen species （ROS）, zona-free hamster oocyte test, serum hormones including testosterone, luteinizing hormone （LH）, follicle stimulating hormone （FSH） and Inhibin B, and spontaneous or intrauterine insemination （IUI）-induced pregnancies were evaluated. Results： ROS and Inhibin B decreased significantly and sperm linear velocity increased in the Astaxanthin group （n = 11）, but not in the placebo group （n = 19）. The results of the zona-free hamster oocyte test tended to improve in the Astaxanthin group in contrast with the placebo group, though not reaching statistical significance. The total and per cycle pregnancy rates among the placebo cases （10.5 % and 3.6 %） were lower compared with 54.5 % and 23. 1% respectively in the Astaxanthin group （P=0.028; P=0.036）. Conclusion： Although the present study suggests a positive effect of Astaxanthin on sperm parameters and fertility, the results need to be confirmed in a larger trial before recommending Astaxanthin for the complementary treatment of infertile men. （Asian J Androl 2005 Sep; 7： 257-262）     

虾青素抗去势雌性大鼠骨质疏松症实验研究

目的:探讨虾青素对去卵巢骨质疏松模型大鼠股骨的密度、骨矿含量的影响及机制.方法:将72只15周龄SD大鼠随机分为6组,空白组做假手术,其余5组做卵巢切除术,术后用药12周后处死,测定右侧股骨骨密度、骨矿含量、血清雌二醇、碱性磷酸酶含量及子宫湿重.结果:虾青素高、中、低剂量(20、15、10 mg/kg)组、尼尔雌醇(1.05 mg/kg)组能对抗骨密度、骨矿含量、血清雌二醇的下降、血清碱性磷酸酶的升高(与模型组相比P＜0.05);各剂量组、尼尔雌醇组能对抗子宫指数的减轻(与模型组相比P＜0.05).结论:虾青素可以改善骨质量,抑制大鼠去卵巢骨质疏松的发生,具有类似雌激素的效应.     

虾青素的来源、功能及应用

虾青素是一种非维生素A原的类胡萝卜素，天然存在于甲壳纲动物（如虾、蟹壳）、鱼类（如红鳟鱼）、鸟类（如红鹤）和某些微藻中。虾青素的化学名为3，3’-二羟基-β，β’-胡萝卜素-4，4’-二酮，分子式C40H52O4，相对分子质量596．86，是一种萜烯类不饱和化合物，其结构式如图1所示。其化学结构南4个异戊二烯单位以共轭双键形式连接，在其两端有2个异戊二烯单位组成的六元环结构，和β-胡萝卜素的结构相似。     

Anti-inflammatory effects of astaxanthin in the human gingival keratinocyte line NDUSD-1

Oral lichen planus is a chronic inflammatory disease that affects the mucous membrane of the oral cavity and can contribute to the development of other diseases. Inflammation in oral lichen planus is a T-cell-mediated autoimmune disease that acts through cytotoxic CD8⁺ T cells to trigger apoptosis of keratinocytes. However, the specific cause of oral lichen planus remains unknown and no effective medical treatment has yet been established. Astaxanthin is a carotenoid pigment with capacity for anti-inflammatory and anti-oxidant activities. In this study, we evaluated whether astaxanthin could be used to improve the pathology of oral lichen planus by reducing inflammation. In particular, the anti-inflammatory effects of astaxanthin on the chronic inflammation caused by lipopolysaccharide derived from Escherichia coli O55 in human gingival keratinocytes (NDUSD-1) were evaluated. Following astaxanthin treatment, localization of nuclear factor κB/p65 and the level of inflammatory cytokines (interleukin-6, tumor necrosis factor-α) tended to decrease, and cell proliferation significantly increased in vitro. These results suggest that astaxanthin could be useful for improving chronic inflammation such as that associated with oral lichen planus.     

Protective effects of astaxanthin from Paracoccus carotinifaciens on murine gastric ulcer models

The purpose of this study was to investigate the effect of astaxanthin extracted from Paracoccus carotinifaciens on gastric mucosal damage in murine gastric ulcer models. Mice were pretreated with astaxanthin for 1 h before ulcer induction. Gastric ulcers were induced in mice by oral administration of hydrochloride (HCl)/ethanol or acidified aspirin. The effect of astaxanthin on lipid peroxidation in murine stomach homogenates was also evaluated by measuring the level of thiobarbituric acid reactive substance (TBARS). The free radical scavenging activities of astaxanthin were also measured by electron spin resonance (ESR) measurements. Astaxanthin significantly decreased the extent of HCl/ethanol‐ and acidified aspirin‐induced gastric ulcers. Astaxanthin also decreased the level of TBARS. The ESR measurement showed that astaxanthin had radical scavenging activities against the 1,1‐diphenyl‐2‐picrylhydrazyl radical and the superoxide anion radical. These results suggest that astaxanthin has antioxidant properties and exerts a protective effect against ulcer formation in murine models. Copyright © 2011 John Wiley & Sons, Ltd.     

虾青素对1型糖尿病大鼠代谢性白内障的预防作用及其机制

背景 糖尿病性白内障的发病机制尚未完全明了,研究认为多种代谢通路参与其发病,其中包括氧化应激机制.研究表明虾青素有强大的抗氧化作用,可有效抑制氧化应激损伤及脂质过氧化,但目前鲜见虾青素对糖尿病性白内障防治作用研究的相关报道. 目的 观察虾青素对1型糖尿病大鼠代谢性白内障的预防作用及其机制.方法 将38只SPF级6周龄雄性SD大鼠纳入研究,其中30只大鼠用一次性腹腔内注射质量分数1％链脲佐菌素(STZ)方法制备糖尿病大鼠模型,连续3d血糖值＞16.7 mol/L者为造模成功,应用随机数字表法将造模成功的24只大鼠随机分为糖尿病模型组、低剂量虾青素组和高剂量虾青素组,正常对照组8只大鼠同法注射等容量生理盐水.低剂量虾青素组和高剂量虾青素组大鼠分别给予50mg/(kg·d)和100 mg/(kg·d)虾青素以及橄榄油和饲料混合物连续喂养3个月,糖尿病模型组大鼠以等容量橄榄油混合饲料喂养,正常对照组以正常饲料喂养.造模后用裂隙灯显微镜行眼前节照相并对晶状体混浊的严重程度分为1～5级;收集大鼠双侧眼球制备晶状体切片,采用苏木精-伊红染色法观察大鼠晶状体的组织病理学改变;采用免疫组织化学法观察晶状体中糖基化终末产物(AGEs)的阳性表达并进行定量分析;采用ELISA双抗体夹心法测定各组大鼠晶状体内AGEs质量浓度、丙二醛(MDA)浓度、过氧化氢酶(CAT)、超氧化物歧化酶(SOD)水平以及谷胱甘肽(GSH)质量浓度.结果 造模后2、4、6、8、10和12周糖尿病模型组、低剂量虾青素组和高剂量虾青素组大鼠血糖水平均明显高于正常对照组,差异均有统计学意义(均P＜0.05),而糖尿病模型组、低剂量虾青素组和高剂量虾青素组间大鼠血糖水平的差异均无统计学意义(均P＞0.05).正常对照组大鼠晶状体透明,为1级,糖尿病模型组晶状体混浊均为5级,不同剂量虾青素组大鼠晶状体混浊度多为3～4级.低剂量虾青素组和高剂量虾青素组大鼠晶状体匀浆内的AGEs质量浓度分别为(7.23±0.50) μg/ml和(7.01±0.37) μg/ml,MDA浓度分别为(1.43±0.22) mmol/L和(1.35±0.16)mmol/L,均低于糖尿病模型组的(7.61±0.45) μg/ml和(1.62±0.42) mmol/L,差异均有统计学意义(均P＜0.05).低剂量虾青素组和高剂量虾青素组大鼠晶状体中GSH质量浓度分别为(272.70±12.53) ng/L和(283.52±16.17) ng/L,SOD含量分别为(55.45±6.47)μmol/(min·L)和(56.73 ±5.12) μmol/(min·L),CAT含量分别为(2.91±0.41) μmol/(min· L)和(3.02±0.13) μmol/(min·L),均明显高于糖尿病模型组的(241.52±15.13) ng/L、(51.67±5.45) μmol/(min·L)和(2.72±0.27)μmol/(min·L),差异均有统计学意义(均P＜0.05),低剂量虾青素组大鼠晶状体中GSH质量浓度和SOD含量明显低于高剂量虾青素组,差异均有统计学意义(均P＜0.05). 结论 虾青素能够延缓1型糖尿病大鼠代谢性白内障的发生和发展,其作用机制与其抗氧化应激反应有关.     

Effect of Diets Supplemented with Different Sources of Astaxanthin on the Gonad of the Sea Urchin Anthocidaris crassispina

The effect of the microalgae Haematococcus pluvialis and Chorella zofingiensis, and synthetic astaxanthin on the gonad of the sea urchin Anthocidaris crassispina was studied. The basal diet was supplemented with H. pluvialis, C. zofingiensis, or synthetic astaxanthin, at two levels of astaxanthin (approximately 400 mg/kg and 100 mg/kg), to obtain the experimental diets HP1, HP2, CZ1, CZ2, AST1, and AST2, respectively, for two months of feeding experiment. The results showed that the concentrations of astaxanthin in the gonads of the sea urchins fed these experimental diets ranged from 0.15 to 3.01 mg/kg dry gonad weight. The higher astaxanthin levels (>2.90 mg/kg) were found in the gonads of the sea urchins fed the diets HP1 (containing 380 mg/kg of astaxanthins, mostly mono- and diesters) and AST1 (containing 385 mg/kg of synthetic astaxanthin). The lowest astaxanthin level (0.15 mg/kg) was detected in the gonads of the sea urchins fed the diet CZ2 (containing 98 mg/kg of astaxanthins, mostly diesters). Furthermore, the highest canthaxanthin level (7.48 mg/kg) was found in the gonads of the sea urchins fed the diet CZ1 (containing 387 mg/kg of astaxanthins and 142 mg/kg of canthaxanthin), suggesting that astaxanthins, especially astaxanthin esters, might not be assimilated as easily as canthaxanthin by the sea urchins. Our results show that sea urchins fed diets containing astaxanthin pigments show higher incorporation of these known antioxidant constituents, with the resultant seafood products therefore being of potential higher nutritive value.     

虾青素调控AMPK-SIRT1通路对七氟醚诱导HT22神经细胞损伤的影响

目的研究虾青素对七氟醚诱导的海马神经元HT22细胞活力和细胞凋亡的作用与机制。方法体外培养HT22细胞分为对照组、七氟醚组、七氟醚+虾青素(1.25、2.50、5.00μmol/L)组;七氟醚组给予4%七氟醚刺激细胞6 h;七氟醚+虾青素组七氟醚刺激细胞前给予不同浓度的虾青素处理2 h。采用MTT实验检测各组HT22细胞存活率,DCFH-DA荧光探针和硫代巴比妥酸法分别检测各组细胞内的活性氧(ROS)水平和丙二醛(MDA)含量,流式细胞术和TUNEL检测各组细胞凋亡,Western blotting检测各组细胞中CyclinD1、Cleaved Caspase-3、Bax和Bcl-2、AMPK、p-AMPK、SIRT1蛋白的表达。结果与对照组比较,七氟醚组HT22细胞存活率显著下降和细胞凋亡率显著增加(P0.05),CyclinD1、Bcl-2、p-AMPK和SIRT1蛋白表达减少(P0.05),Cleaved Caspase-3、Bax蛋白表达增加(P0.05),ROS活性和MDA含量降低(P0.05)。与模型组比较,七氟醚+虾青素HT22细胞Cleaved Caspase-3、Bax蛋白表达下调(P0.05),CyclinD1、Bcl-2、p-AMPK和SIRT1蛋白表达上调(P0.05),ROS活性和MDA含量降低(P0.05),且呈剂量相关性。结论虾青素对七氟醚诱导的HT22细胞凋亡和氧化应激损伤具有保护作用,其机制可能与调控AMPK-SIRT1通路有关。     

NEWS FROM EU RESEARCH: Preparation of active packaging with antioxidant and antimicrobial activity based on astaxanthin and chitosan

The project ‘Preparation of active packaging with antioxidant and antimicrobial activity based on astaxanthin and chitosan’ (PAPAAABAC, in Spanish PEACAABAQ) brings together a multi‐disciplinary team from Mexico, Spain and Portugal, with expertise in different areas of food and polymer sciences. The working programme includes optimisation of the extraction and characterisation of astaxanthin and chitosan from shrimp waste, and incorporation of these compounds into plastic (polymeric matrices), in order to obtain new packaging with antioxidant and antimicrobial properties (active packaging) and finally control‐release studies which are carried out in order to determine the quantity of active compounds that should be included in the packaging. This is a 2‐year project which started in 2009 and is funded by FONCYCIT (Fund for International Cooperation of Science and Technology EU‐Mexico; Fondo de Cooperación Internacional de Ciencia y Tecnologia Unión Europea‐Mexico) under the coordination of Professor Jaime López Cervantes from the Technological Institute of Sonora (ITSON).     

Astaxanthin protects against MPTP/MPP+-induced mitochondrial dysfunction and ROS production in vivo and in vitro

Astaxanthin (AST) is a powerful antioxidant that occurs naturally in a wide variety of living organisms. We have investigated the role of AST in preventing 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced apoptosis of the substantia nigra (SN) neurons in the mouse model of Parkinson’s disease (PD) and 1-methyl-4-phenylpyridinium (MPP+)-induced cytotoxicity of SH-SY5Y human neuroblastoma cells. In in vitro study, AST inhibits MPP+-induced production of intracellular reactive oxygen species (ROS) and cytotoxicity in SH-SY5Y human neuroblastoma cells. Preincubation of AST (50 μM) significantly attenuates MPP+-induced oxidative damage. Furthermore, AST is able to enhance the expression of Bcl-2 protein but reduce the expression of α-synuclein and Bax, and suppress the cleavage of caspase-3. Our results suggest that the protective effects of AST on MPP+-induced apoptosis may be due to its anti-oxidative properties and anti-apoptotic activity via induction of expression of superoxide dismutase (SOD) and catalase and regulating the expression of Bcl-2 and Bax. Pretreatment with AST (30 mg/kg) markedly increases tyrosine hydroxylase (TH)-positive neurons and decreases the argyrophilic neurons compared with the MPTP model group. In summary, AST shows protection from MPP+/MPTP-induced apoptosis in the SH-SY5Y cells and PD model mouse SN neurons, and this effect may be attributable to upregulation of the expression of Bcl-2 protein, downregulation of the expression of Bax and α-synuclein, and inhibition of the activation of caspase-3. These data indicate that AST may provide a valuable therapeutic strategy for the treatment of progressive neurodegenerative disease such as Parkinson’s disease.