Effect Of Zeaxanthin Research Articles

Effects of Zeaxanthin on the Insulin Resistance and Gut Microbiota of High-Fat-Diet-Induced Obese Mice

Obesity-induced insulin resistance (IR) can precipitate metabolic disorders such as diabetes. Zeaxanthin, a crucial member of the carotenoid family, has been found to mitigate the damage caused by obesity. However, reports on the effects of zeaxanthin on obesity-induced IR are lacking. Our objective was to examine the metabolic regulatory impacts of zeaxanthin on mice subjected to a high-fat diet (HFD) that triggered IR and to explore their influence on gut microbiota regulation. This study constructed a mouse model of metabolic dysfunction caused by lipid-rich nutritional patterns to investigate physiological and biochemical indices, liver pathway expression, and the intestinal microbiota. The mechanisms by which zeaxanthin improved both IR and glucose metabolic disorders were elucidated. The results demonstrate that zeaxanthin effectively suppressed obesity. The fasting blood glucose, area under curve of oral glucose tolerance test and insulin tolerance test, and homeostatic model assessment–insulin resistance (HOMA-IR) indices in the HFDZEA group decreased by 14.9%, 25.2%, 28.9%, and 29.8%. Additionally, zeaxanthin improved the lipid metabolism and alleviated damage to the liver and pancreas while also activating the PI3K/Akt pathway, regulating hepatic gluconeogenesis and the glycogen metabolism. The number of OTUs in the HFDZEA group increased by 29.04%. Zeaxanthin improved the structure and profile of the gastrointestinal microbiome and enhanced its diversity, increasing probiotics abundance, decreasing pathogen abundance, and thereby ameliorating the dysbiosis of enteric microbial communities in rodents with obesity resulting from excessive fat consumption. The outcomes of our analysis provide a rational basis for advancing zeaxanthin-based nutritional products.

Association between Advanced Glycation End-Products, Carotenoids, and Severe Erectile Dysfunction.

To investigate the association between skin advanced glycation end-products (AGEs) levels, blood antioxidative vitamin and carotenoid concentrations, and severe erectile dysfunction (ED) in community-dwelling men. This cross-sectional study used the 5-Item International Index of Erectile Function to identify 335 community-dwelling men with ED. The accumulation of skin AGEs was assessed noninvasively by measuring skin autofluorescence. Background-adjusted multivariable logistic regression analyses using the inverse probability of treatment weighting method were performed to evaluate the effects of AGEs, vitamins, and carotenoids on severe ED. Moreover, multiple linear regression analyses were performed to assess the association between skin AGEs levels and serum carotenoid concentrations. The median age of study participants was 57 years. Of the 335 men, 289 (86.3%) and 46 (13.7%) were classified into the mild/moderate and severe ED groups, respectively. Multivariable analyses revealed that skin AGEs levels, blood vitamins C and E, lutein, zeaxanthin, β-cryptoxanthin, α-carotene, β-carotene, total lycopene, and cis-lycopenes concentrations were significantly associated with severe ED, whereas all-trans lycopene concentrations were not. In the multiple linear regression analyses, serum zeaxanthin concentrations were negatively and significantly correlated with skin AGEs levels. Higher skin AGEs levels and lower blood antioxidative vitamin and carotenoid concentrations were significantly associated with severe ED. Serum zeaxanthin levels were negatively and significantly correlated with skin AGEs levels, suggesting the possible effects of zeaxanthin on ED by decreasing tissue AGEs levels.

Provitamin A carotenoids from an engineered high-carotenoid maize are bioavailable and zeaxanthin does not compromise β-carotene absorption in poultry.

High-carotenoid (HC) maize, a biofortified staple crop which accumulates β-carotene, β-cryptoxanthin, lutein and zeaxanthin, was used as a feed component in a chicken feeding trial to assess the bioavailability of provitamin A (PVA) carotenoids in the kernel matrix compared to the synthetic and natural color additives routinely used in the poultry industry. We found that the PVA carotenoids in HC maize were not metabolized in the same manner: β-carotene was preferentially converted into retinol in the intestine whereas β-cryptoxanthin accumulated in the liver. We also considered the effect of zeaxanthin on the absorption of PVA carotenoids because zeaxanthin is the major carotenoid component of HC maize. We found that chickens fed on diets with low levels of zeaxanthin accumulated higher levels of retinol in the liver, suggesting that zeaxanthin might interfere with the absorption of β-carotene, although this observation was not statistically significant. Our results show that HC maize provides bioavailable carotenoids, including PVA carotenoids, and is suitable for use as a feed component.

The Effect of Zeaxanthin on the Visual Acuity of Zebrafish.

Oral supplementation of carotenoids such as zeaxanthin or lutein which naturally occur in human retina have been shown to improve vision and prevent progression of damage to advanced AMD in some studies. The zebrafish eye shares many physiological similarities with the human eye and is increasingly being used as model for vision research. We hypothesized that injection of zeaxanthin into the zebrafish eye would improve the visual acuity of the zebrafish over time. Visual acuity, calculated in cycles per degree, was measured in adult zebrafish to establish a consistent baseline using the optokinetic response. Zeaxanthin dissolved into phosphate buffered saline (PBS) or PBS only was injected into the anterior chamber of the right and left eyes of the Zebrafish. Visual acuities were measured at 1 week and 3, 8 and 12 weeks post-injection to compare to baseline values. Repeated measures ANOVA was used to compare visual acuities between fish injected with PBS and zeaxanthin. A significant improvement in visual acuity, 14% better than before the injection (baseline levels), was observed one week after injection with zeaxanthin (p = 0.04). This improvement peaked at more than 30% for some fish a few weeks after the injection and improvement in vision persisted at 3 weeks after injection (p = 0.006). The enhanced visual function was not significantly better than baseline at 8 weeks (p = 0.19) and returned to baseline levels 12 weeks after the initial injection (p = 0.50). Zeaxanthin can improve visual acuity in zebrafish eyes. Further studies are required to develop a better understanding of the role zeaxanthin and other carotenoids play during normal visual function.

Abstract 3812: Induction of apoptosis by zeaxanthin in human uveal melanoma cells

Abstract INTRODUCTION Uveal melanoma is the highly malignant tumor of the eye and frequently leads to metastatic death. Depending on size and other parameters, traditional treatment of the primary tumor has been enucleation. However, alternative treatments to preserve the eye have been devised, including cryotherapy, radioactive therapy, transpupillary thermotherapy, surgical resection and photocoagulation. Despite these advances in treatment, mortality varies considerably, to more than 50% in high-risk patients, primarily due to metastasis to the liver. Therefore, it is critical to develop drugs that are non-toxic and can be administered for potentially extended periods to patients who have diagnosed with primary uveal melanoma. In recent years, Zeaxanthin, a naturally occurring carotenoid alcohol highly enriched in green leaves, has been used in medicine to treat various diseases. Epidemiological studies have shown that higher intake and higher blood levels of zeaxanthin appear to be associated with a lower risk of occurrence of various cancers. It has also been reported that zeaxanthin may inhibit cell growth or induce apoptosis of several tumor cell lines in vitro. The present study was designed to investigate the effect of zeaxanthin on human uveal melanoma cells. Methods Human uveal melanoma cells isolated from tissues of enucleated eyes were treated with zeaxanthin in a dose- and time-dependent manner. After zeaxanthin treatment, cell viability was measured using MTT assay. The proapoptotic and antiproliferative effects were evaluated by -annexin V staining and flow cytometry respectively. Mitochondrial transmembrane potential was measured as a function of drug treatment using 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethyl-benzamidazolocarbocyanin iodide (JC-1). Immunoblotting was used to evaluate the expression of apoptosis-related proteins. Caspase-9 and -3 activities were determined by spectroflurometry. Results Zeaxanthin induced apoptosis in dose- and time-dependent manner. Decrease in the level of Bcl-2 and increase in the level of Bax were observed in zeaxanthin-treated in human uveal melanoma cells. Preceding cell death, zeaxanthin evoked a rapid dissipation of mitochondrial transmembrane potential. This was followed by the release of cytochrome c into the cytoplasm and a substantial increase in the activities of caspase-9 and -3. Conclusions These results demonstrate that zeaxanthin induces apoptosis through the regulation of Bcl-2 family protein and activation of intrinsic mitochondrial pathway. This may warrant further exploration as an adjuvant to conventional anticancer therapies for uveal melanoma. Citation Format: Sandeep Goswami, Arpna Srivastava, Neelam Pushker, Mandeep Singh Bajaj, Seema Kashyap, Jasbir Kaur. Induction of apoptosis by zeaxanthin in human uveal melanoma cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3812. doi:10.1158/1538-7445.AM2015-3812

Zeaxanthin inhibits hypoxia-induced VEGF secretion by RPE cells through decreased protein levels of hypoxia-inducible factors-1α.

Hypoxia is the most important stimulus leading to upregulation of VEGF in the retina and this is caused by accumulation of hypoxia-inducible factors-1α (HIF-1α) protein. The effects of zeaxanthin, a natural phytochemical, on the VEGF and HIF-1α expression in the primary culture of human retinal pigment epithelial (RPE) cells were studied. An in vitro RPE cell hypoxia model was established by placing cells under 1% oxygen pressure or by adding cobalt chloride (CoCl2) to the culture medium. RPE cells and conditioned media were collected from cultures treated with and without zeaxanthin under normoxic and hypoxic conditions. VEGF and HIF-1α protein and RNA levels were measured by ELISA kits and RT-PCR, respectively. Hypoxia caused a significant increase of VEGF expression and accumulation of HIF-1α in RPE cells. Zeaxanthin at 50–150 μM significantly inhibited the expression of VEGF and accumulation of HIF-1α protein caused by hypoxia but did not affect expression of VEGF and HIF-1α under normoxic conditions. This is the first report on the effect of zeaxanthin on VEGF and HIF-1α levels in cultured RPE cells and suggests that zeaxanthin may have potential value in the prevention and treatment of various retinal diseases associated with vascular leakage and neovascularization.

Effects of Zeaxanthin on Growth and Invasion of Human Uveal Melanoma in Nude Mouse Model.

Uveal melanoma cells were inoculated into the choroid of nude mice and treated with or without intraocular injection of zeaxanthin. After 21 days, mice were sacrificed and the eyes enucleated. Histopathological analysis was performed in hematoxylin and eosin stained frozen sections. Melanoma developed rapidly in the control group (without treatment of zeaxanthin). Tumor-bearing eye mass and tumor mass in the control group were significantly greater than those in zeaxanthin treated group. Melanoma in the controlled eyes occupied a large part of the eye, was epithelioid in morphology, and was with numerous mitotic figures. Scleral perforation and extraocular extension were observed in half of the eyes. Melanomas in zeaxanthin treated eyes were significantly smaller with many necrosis and apoptosis areas and no extraocular extension could be found. Quantitative image analysis revealed that the tumor size was reduced by 56% in eyes treated with low dosages of zeaxanthin and 92% in eyes treatment with high dosages of zeaxanthin, as compared to the controls. This study demonstrated that zeaxanthin significantly inhibits the growth and invasion of human uveal melanoma in nude mice, suggesting that zeaxanthin may be a promising agent to be explored for the prevention and treatment of uveal melanoma.

Effect of Zeaxanthin and Antioxidant Supplementation on Vascular Endothelial Growth Factor (VEGF) Expression in Apolipoprotein-E Deficient Mice

Purpose: Apolipoprotein E-/- deficient (apoE-/-) mice develop hypercholesterolemia, atherosclerosis, and retinal alterations. We studied the oxidative status and vascular endothelial growth factor (VEGF) expression in murine retinal pigment epithelium-choroid (RPE) and Bruch's membrane (BM) ultrastructure and the effect of zeaxanthin. Methods: Ten 6-month-old C57BL/6 and 40 apoE-/- mice were divided into four groups (n = 10 each) and fed different diets for 12 weeks based on body weight: wild type (WT) and apoE-/- (AE-Con) mice standard rodent chow; apoE-/- mice (AES) standard rodent chow with ascorbate (800 mg/kg), tocopherol (1053 mg/kg), and zinc (135 mg/kg); and apoE-/- mice the last diet plus zeaxanthin with either 0.4 g/kg (AES-Z04) or 4 g/kg feed (AES-Z4). Results: Plasma total cholesterol (TC) and triglycerides (TG) and urine lipid peroxidation (isoprostanes) were measured. VEGF expression was determined in RPE-choroid homogenates. Zeaxanthin uptake was assessed in liver and retina by high-performance liquid chromatography; the retinal ultrastructure was analyzed by electron microscopy. AE-Con mice had higher plasma TC (p < 0.001) and TG (p < 0.001) values than WT mice. AE-Con mice had higher RPE-choroid-VEGF levels than WT mice (p < 0.05), BM thickness (p < 0.001) and presence of basal laminar deposits (BLamD). AES-Z4 resulted in lower urinary isoprostanes (p = 0.054) and lower VEGF expression in the RPE-choroid (p < 0.01). BM in the AES-Z4 animals had less confluent BLamD than AE-Con, AES, or AES-Z04 animals. Conclusions: We have reported that supplementation with zeaxanthin and antioxidants may delay or reverse alterations in the RPE and deposits in BM, and reduced VEGF expression observed in apoE-/- mice.

Carotenoids and Related Polyenes. Part 9. Total Synthesis of Thermozeaxanthin and Thermocryptoxanthin and the Stabilizing Effect of Thermozeaxanthin on Liposomes.

Thermozeaxanthin and thermocryptoxanthin are efficiently synthesized via β-selective glucosidation of (3R)-3-hydroxy-β-ionone 7, and the stabilizing effects of zeaxanthin 5, its glucoside 3 and thermozeaxanthin-15 1a on liposomes are also examined.

Time-resolved fluorescence analysis of the recombinant photosystem II antenna complex CP29. Effects of zeaxanthin, pH and phosphorylation

Nonradiative dissipation of excitation energy is the major photoprotective mechanism in plants. The formation of zeaxanthin in the antenna of photosystem II has been shown to correlate with the onset of nonphotochemical quenching in vivo. We have used recombinant CP29 protein, over-expressed in Escherichia coli and refolded in vitro with purified pigments, to obtain a protein indistinguishable from the native complex extracted from thylakoids, binding either violaxanthin or zeaxanthin together with lutein. These recombinant proteins and the native CP29 were used to measure steady-state chlorophyll fluorescence emission and fluorescence decay kinetics. We found that the presence of zeaxanthin bound to CP29 induces a ≈ 35% decrease in fluorescence yield with respect to the control proteins (the native and zeaxanthin-free reconstituted proteins). Fluorescence decay kinetics showed that four components are always present but lifetimes (τ) as well as relative fluorescence quantum yields (rfqy) of the two long-lived components (τ3 and τ4) are modified by the presence of zeaxanthin. The most relevant changes are observed in the rfqy of τ3 and in the average lifetime (≈ 2.4 ns with zeaxanthin and 3.2–3.4 ns in the control proteins). When studied in vitro, no significant effect of acidic pH (5.2–5.3) is observed on chlorophyll a fluorescence yield or kinetics. The data presented show that recombinant CP29 is able to bind zeaxanthin and this protein-bound zeaxanthin induces a significant quenching effect.

The effect of zeaxanthin on the thickness of dimyristoylphosphatidylcholine bilayer: X-ray diffraction study

Multilayers of dimyristoylphosphatidylcholine (DMPC) modified with a carotenoid pigment zeaxanthin were analyzed by means of small-angle X-ray diffractometry. The results are discussed in terms of the superlattice theory developed recently for metallic multilayers. Inclusion of zeaxanthin to a DMPC bilayer increases thickness of the hydrophobic core by about 3 A in the whole lipid-pigment miscibility range. The thickness increases very sharply as pigment concentration approaches the threshold of miscibility. Zeaxanthin aggregation within a layer causes further changes in the thickness of the membrane: a local decrease followed by a gradual rise.