Combined Ingestion of Tea Catechin and Citrus ß-Cryptoxanthin Improves Liver Function via Adipokines in Chronic Obesity.

Recently, there has been an increase in the number of obese individuals, which has elevated the risk of related diseases. Although several studies have been performed to develop a definitive treatment for obesity, no solution has yet been achieved. Recent evidence suggests that tea catechins possess antiobesity effects; however, an impractical amount of catechin may be required to achieve antiobesity effects in humans. Moreover, studies are yet to elucidate the effects of the combined treatment of tea catechins with other substances. Here, we investigated the synergistic effects of catechins and ß-cryptoxanthin in high-calorie diet-induced mice. Combined treatment with catechins and ß-cryptoxanthin significantly suppressed obesity-induced weight gain and adipocyte size and area, restoring serum parameters to normal. Additionally, combined treatment with catechins and ß-cryptoxanthin suppressed inflammatory responses in adipocytes, restored adiponectin levels to normal, protected the liver against obesity-induced damage, and restored normal liver function. Moreover, activin E level was restored to normal, possibly affecting the energy metabolism of brown adipocytes. Overall, these results suggest that the combined ingestion of tea catechins and ß-cryptoxanthin was not only effective against obesity but may also help to prevent obesity-related diseases, such as diabetes and cardiovascular diseases.

Anti-Obesity and Anti-Inflammatory Synergistic Effects of Green Tea Catechins and Citrus ß-Cryptoxanthin Ingestion in Obese Mice.

Chronic obesity causes various diseases, leading to an urgent need for its treatment and prevention. Using monosodium-glutamate-induced obesity mice, the present study investigated the synergistic obesity-reducing effects of tea catechins and the antioxidant ß-cryptoxanthin present in mandarin oranges. The results show that the obese mice that ingested both tea catechin and ß-cryptoxanthin for 4 weeks had a significantly decreased body weight, with no difference in body weight compared with control mice. Moreover, the blood biochemical test results were normal, and the body fat percentage was significantly decreased according to the histopathological analysis. Additionally, the abundance of M1 macrophages, which release pro-inflammatories, was significantly reduced in adipose tissue. Indeed, a significant decrease was detected in M1-macrophage-secreted tumor necrosis factor-alpha levels. Meanwhile, M2 macrophage levels were recovered, and adiponectin, which is released from adipocytes and involved in suppressing metabolic syndrome, was increased. Collectively, these results suggest that the combination of tea catechins and antioxidant foods can alleviate chronic obesity, indicating that a combination of various ingredients in foods might contribute to reducing chronic obesity.

ß-Cryptoxanthin Attenuates Cigarette-Smoke-Induced Lung Lesions in the Absence of Carotenoid Cleavage Enzymes (BCO1/BCO2) in Mice.

High dietary intake of ß-cryptoxanthin (BCX, an oxygenated provitamin A carotenoid) is associated with a lower risk of lung disease in smokers. BCX can be cleaved by ß-carotene-15,15'-oxygenase (BCO1) and ß-carotene-9',10'-oxygenase (BCO2) to produce retinol and apo-10'-carotenoids. We investigated whether BCX has protective effects against cigarette smoke (CS)-induced lung injury, dependent or independent of BCO1/BCO2 and their metabolites. Both BCO1-/-/BCO2-/- double knockout mice (DKO) and wild type (WT) littermates were supplemented with BCX 14 days and then exposed to CS for an additional 14 days. CS exposure significantly induced macrophage and neutrophil infiltration in the lung tissues of mice, regardless of genotypes, compared to the non-exposed littermates. BCX treatment significantly inhibited CS-induced inflammatory cell infiltration, hyperplasia in the bronchial epithelium, and enlarged alveolar airspaces in both WT and DKO mice, regardless of sex. The protective effects of BCX were associated with lower expression of IL-6, TNF-α, and matrix metalloproteinases-2 and -9. BCX treatment led to a significant increase in hepatic BCX levels in DKO mice, but not in WT mice, which had significant increase in hepatic retinol concentration. No apo-10'-carotenoids were detected in any of the groups. In vitro BCX, at comparable doses of 3-OH-ß-apo-10'-carotenal, was effective at inhibiting the lipopolysaccharide-induced inflammatory response in a human bronchial epithelial cell line. These data indicate that BCX can serve as an effective protective agent against CS-induced lung lesions in the absence of carotenoid cleavage enzymes.

ß-Cryptoxanthin Maintains Mitochondrial Function by Promoting NRF2 Nuclear Translocation to Inhibit Oxidative Stress-Induced Senescence in HK-2 Cells.

The mechanisms of acute kidney injury and chronic kidney disease remain incompletely revealed, and drug development is a pressing clinical challenge. Oxidative stress-induced cellular senescence and mitochondrial damage are important biological events in a variety of kidney diseases. As a type of carotenoid, ß-Cryptoxanthin (BCX) has various biological functions, which means it is a potential therapeutic candidate for the treatment of kidney disease. However, the role of BCX in the kidney is unclear, and the effect of BCX on oxidative stress and cellular senescence in renal cells is also unknown. Therefore, we conducted a series of studies on human renal tubular epithelial (HK-2) cells in vitro. In the present study, we investigated the effect of BCX pretreatment on H2O2-induced oxidative stress and cellular senescence and explored the potential mechanism of BCX action. The results showed that BCX attenuated H2O2-induced oxidative stress and cellular senescence in HK-2 cells. Moreover, BCX promoted NRF2 nuclear expression, maintained mitochondrial function, and reduced mitochondrial damage in HK-2 cells. In addition, silencing NRF2 altered the protective effect of BCX on mitochondria and significantly reversed the anti-oxidative stress and anti-senescence effects of BCX in HK-2 cells. We concluded that BCX maintained mitochondrial function by promoting NRF2 nuclear translocation to inhibit oxidative stress-induced senescence in HK-2 cells. In light of these findings, the application of BCX might be a promising strategy for the prevention and treatment of kidney diseases.

ß-cryptoxanthin alleviates myocardial ischaemia/reperfusion injury by inhibiting NF-κB-mediated inflammatory signalling in rats.

The present study aimed to explore the function and molecular mechanism of ß-cryptoxanthin on myocardial ischaemia-reperfusion injury (MIRI). Left anterior descending coronary artery ligation with reperfusion was utilised to establish a MIRI rat model. The results indicated that ß-cryptoxanthin decreases infarct size and ameliorates signs of pathological histology in MIRI. TNF-α, IL-1ß, and IL-6 levels in the serum were attenuated in response to ß-cryptoxanthin treatment, serum LDH and CK-MB activities were also decreased. Immunohistochemical analysis and western blot results suggested that p65 was translocated to the nucleus in the I/R injury rat model. However, in the ß-cryptoxanthin administration group, p65 expression and activity in the nucleus were decreased in a dose-dependent manner. Furthermore, p-p38 MAPK levels in response to ß-cryptoxanthin were decreased, indicating that MAPK is involved in NF-κB signalling pathway regulation. In conclusion, ß-cryptoxanthin alleviates myocardial ischaemia/reperfusion injury by inhibiting NF-κB-mediated inflammatory signalling in rats.

Different Doses of ß-Cryptoxanthin May Secure the Retina from Photooxidative Injury Resulted from Common LED Sources.

Retinal damage associated with loss of photoreceptors is a hallmark of eye diseases such as age-related macular degeneration (AMD) and diabetic retinopathy. Potent nutritional antioxidants were previously shown to abate the degenerative process in AMD. ß-Cryptoxanthin (BCX) is an essential dietary carotenoid with antioxidant, anti-inflammatory, and provitamin A activity. It is a potential candidate for developing intervention strategies to delay the development/progression of AMD. In the current study, the effect of a novel, highly purified BCX oral formulation on the rat retinal damage model was evaluated. Rats were fed with BCX for four weeks at the doses of 2 and 4 mg/kg body weight in the form of highly bioavailable oil suspension, followed by retinal damage by exposing to the bright light-emitting diode (LED) light (750 lux) for 48 hrs. Animals were sacrificed after 48 hours, and eyes and blood samples were collected and analyzed. BCX supplementations (2 and 4 mg/kg) showed improvements in the visual condition as demonstrated by histopathology of the retina and measured parameters such as total retinal thickness and outer nuclear layer thickness. BCX supplementation helped reduce the burden of oxidative stress as seen by decreased serum and retinal tissue levels of malondialdehyde (MDA) and restored the antioxidant enzyme activities in BCX groups. Further, BCX supplementation modulated inflammatory markers (IL-1ß, IL-6, and NF-κB), apoptotic proteins (Bax, Bcl-2, caspase 3), growth proteins and factors (GAP43, VEGF), glial and neuronal proteins (GFAP, NCAM), and heme oxygenase-1 (HO-1), along with the mitochondrial stress markers (ATF4, ATF6, Grp78, Grp94) in the rat retinal tissue. This study indicates that oral supplementation of BCX exerts a protective effect on light-induced retinal damage in the rats via reducing oxidative stress and inflammation, also protected against mitochondrial DNA damage and cellular death.

ß-Cryptoxanthin Improves p62 Accumulation and Muscle Atrophy in the Soleus Muscle of Senescence-Accelerated Mouse-Prone 1 Mice.

We investigated the effects of ß-cryptoxanthin on skeletal muscle atrophy in senescence-accelerated mouse-prone 1 (SAMP1) mice. For 15 weeks, SAMP1 mice were intragastrically administered vehicle or ß-cryptoxanthin. At 35 weeks of age, the skeletal muscle mass in SAMP1 mice was reduced compared with that in control senescence-accelerated mouse-resistant 1 (SAMR1) mice. ß-cryptoxanthin increased muscle mass with an increase in the size of muscle fibers in the soleus muscle of SAMP1 mice. The expressions of autophagy-related factors such as beclin-1, p62, LC3-I, and LC3-II were increased in the soleus muscle of SAMP1 mice; however, ß-cryptoxanthin administration inhibited this increase. Unlike in SAMR1 mice, p62 was punctately distributed throughout the cytosol in the soleus muscle fibers of SAMP1 mice; however, ß-cryptoxanthin inhibited this punctate distribution. The cross-sectional area of p62-positive fiber was smaller than that of p62-negative fiber, and the ratio of p62-positive fibers to p62-negative fibers was increased in SAMP1 mice. ß-cryptoxanthin decreased this ratio in SAMP1 mice. Furthermore, ß-cryptoxanthin decreased the autophagy-related factor expression in murine C2C12 myotube. The autophagy inhibitor bafilomycin A1, but not the proteasome inhibitor MG132, inhibited the ß-cryptoxanthin-induced decrease in p62 and LC3-II expressions. These results indicate that ß-cryptoxanthin inhibits the p62 accumulation in fibers and improves muscle atrophy in the soleus muscle of SAMP1 mice.

Carotenoids Inhibit Fructose-Induced Inflammatory Response in Human Endothelial Cells and Monocytes.

OBJECTIVE: This research is aimed at determining the vascular health characteristics of carotenoids by evaluating their effect on excessive inflammatory response in endothelial and monocyte cells, the main factors of atherosclerosis. METHODS: Human umbilical vein endothelial cells (HUVECs) or U937 monocytes were treated with escalating concentrations (0.1, 0.5, and 1 µM) of five most common carotenoids in human plasma, i.e., α-carotene, ß-carotene, ß-cryptoxanthin, lutein, and lycopene prior to stimulation with 2 mM fructose. We examined the monocyte adhesion to endothelial cells (ECs) and relevant endothelial adhesion molecules. Chemokine and proinflammatory cytokine production as well as intracellular oxidative stress were also assessed in fructose-stimulated ECs and monocytes. RESULTS: Carotenoids repressed monocyte adhesion to fructose-stimulated ECs dose dependently via decreasing primarily the expression of endothelial VCAM-1. In ECs and monocytes, three carotenoids, i.e., ß-cryptoxanthin, lutein, and lycopene, suppressed the fructose-induced expression of chemokines MCP-1, M-CSF, and CXCL-10 and inflammatory cytokines TNF-α and IL-1ß, with CXCL-10 being the most repressed inflammatory mediator. ß-Cryptoxanthin, lutein, and lycopene dramatically downregulated the fructose-induced CXCL-10 expression in vascular cells. The reduction in the inflammatory response was associated with a slight but significant decrease of intracellular oxidative stress. CONCLUSIONS: Our results show that carotenoids have a variety of anti-inflammatory and antiatherosclerosis activities, which can help prevent or reduce fructose-induced inflammatory vascular diseases.

Xanthophyll ß-Cryptoxanthin Inhibits Highly Refined Carbohydrate Diet-Promoted Hepatocellular Carcinoma Progression in Mice.

SCOPE: ß-Cryptoxanthin (BCX) can be cleaved by both ß-carotene 15,15'-oxygenase (BCO1) and ß-carotene 9',10'-oxygenase (BCO2), generating biological active vitamin A and apocarotenoids. We examined whether BCX feeding could inhibit diethylnitrosamine (DEN)-initiated, highly refined carbohydrate diet (HRCD)-promoted hepatocellular carcinoma (HCC) development, dependent or independent of BCO1/BCO2 activity. METHODS AND RESULTS: Two-week-old male wild-type (WT) and BCO1-/- /BCO2-/- double knockout (DKO) mice are given a single intraperitoneal injection of DEN (25 mg kg-1 body weight) to initiate hepatic carcinogenesis. At 6 weeks of age, all animals are fed HRCD (66.5% of energy from carbohydrate) with or without BCX for 24 weeks. BCX feeding increases hepatic vitamin A levels in WT mice, but not in DKO mice that shows a significant accumulation of hepatic BCX. Compared to their respective HRCD littermates, both WT and DKO fed BCX have significantly lower HCC multiplicity, average tumor size, and total tumor volume, and the steatosis scores. The chemopreventive effects of BCX are associated with increased p53 protein acetylation and decreased protein levels of lactate dehydrogenase and hypoxia-inducible factor-1α in tumors. CONCLUSION: This study suggests that BCX feeding may alleviate HRCD-promoted HCC progression by modulating the acetylation of p53, hypoxic tumor microenvironment, and glucose metabolism, independent of BCO1/BCO2.

Influence of Βeta-Cryptoxanthin Supplementation on Ovarian Reserve and Fertility Status in Aged Wistar Rats.

Previous observational studies have suggested that ß-cryptoxanthin, a micronutrient present in yellow and orange fruit and vegetables, may help delay the onset of menopause. Given the widespread social trend of delaying pregnancy, the possibility that ß-cryptoxanthin supplementation may delay age-related loss of fertility and onset of menopause is of significant interest. In a parallel study, either saline or ß-cryptoxanthin (5 µg/kg rat/day) was delivered to Wistar albino rats via an osmotic pump from 4 to 7 months of age. All control and ß-cryptoxanthin-treated dams were fertile at 7 months of age, with no differences in litter size, sex ratio, or pup viability at the time of mating at 7, 9, 11, and 15 months of age (p ≥ .05 for all). As expected, over time there was a pronounced decrease in litter size and serum anti-Müllerian hormone (AMH), but with no significant differences between the two groups at any time point. Overall, there was a positive correlation between litter size and AMH (r = 0.324, p = .012), confirming a link between this serum marker of ovarian reserve status and fertility potential. At 16 months, bilateral oophorectomies were performed at necropsy, before conducting follicle density assessments of ovarian reserve. The total number and stage of follicle development were similar between the ß-cryptoxanthin and control groups (13.8 ± 3.2 cf 10.2 ± 4.8, respectively, p > .05). ß-cryptoxanthin supplementation for 3 months early in reproductive life was not effective in delaying ovarian senescence or enhancing fertility in rats later in life, contrary to the association suggested by observational studies in humans.

Anti-stress Effect of ß-Cryptoxanthin in Satsuma Mandarin Orange on Females.

Beta-cryptoxanthin (ß-CRX, (3R)-ß, ß-caroten-3-ol) is an oxygenated carotenoid and a potent antioxidant that is abundant in Satsuma mandarin orange (Citrus unshiu MARC.), which is the most popular fruit in Japan. Since our preliminary data suggested that the ingestion of ß-CRX had an anti-stress effect in female participants, the effect was evaluated in another set of female participants. The study design was a double-blind group comparison and participants (n = 23) were randomly assigned to ß-CRX-rich orange juice or placebo (ß-CRX was removed from orange juice) groups. ß-CRX or placebo juice (125 mL, after breakfast) were consumed from 1 week prior to pharmacy practice and continued for 5 d into the practice period. Salivary α-amylase activity (sAA), a marker of sympathetic nervous system activity, was significantly higher in the evening than in the morning in the placebo-group during pharmacy practice, but not in the ß-CRX-group. This result supports the anti-stress effect of ß-CRX. The dose-dependency of ß-CRX was observed in male mice that were loaded with stress. These results indicate that the ingestion of ß-CRX is helpful to reduce stress.

ß-Cryptoxanthin induced anti-proliferation and apoptosis by G0/G1 arrest and AMPK signal inactivation in gastric cancer.

ß-Cryptoxanthin has been associated with reduced-risk of some cancers. However, the mechanisms of ß-cryptoxanthin still remain unclearly understood in gastric cancer (GC). In this study, we examined the effect of ß-cryptoxanthin on AMPK signal in human gastric cancer cells. AGS and SGC-7901 cells were treated with ß-cryptoxanthin (0-40 µM) and AGS cells were injected in BALB/c (nu/nu) mice to analyze the effect of ß-cryptoxanthin on GC. We found that ß-cryptoxanthin induced inhibitory effect on the cell viability in a time- and concentration-dependent manner. The number of migrated cells and protein levels of matrix metalloproteinase (MMP) -2 and MMP-9 were obviously decreased. ß-Cryptoxanthin treatment induced G0/G1 arrest, and reduced the expression of Cyclin E, Cyclin D1, cyclin-dependent kinases (CDK) of CDK4 and CDK6, and increased the expression of p53 and p21 in the two GC cells. Additionally, ß-cryptoxanthin induced apoptosis and increased the expression of cleaved caspase-3, -8, -9 as well as cytochrome C (cyt C). ß-Cryptoxanthin induced AMP-activated protein kinase (AMPK) signal inactivation by the down-regulation of protein kinase A (PKA), p-AMPK, eukaryotic elongation factor 2 kinase (eEF2k). Furthermore, ß-cryptoxanthin inhibited tumor growth through suppressing the tumor volume and weight, inducing apoptotic cells. Besides, ß-cryptoxanthin induced significant reductions of vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9). In conclusion, our data provide the novel evidence to understand the mechanism of anti-pcancer of ß-cryptoxanthin and indicate that ß-cryptoxanthin can serve as a promising chemopreventive agent against gastric cancer.

Beta-Cryptoxanthin Inhibits Lipopolysaccharide-Induced Osteoclast Differentiation and Bone Resorption via the Suppression of Inhibitor of NF-κB Kinase Activity.

Beta-cryptoxanthin (ß-cry) is a typical carotenoid found abundantly in fruit and vegetables such as the Japanese mandarin orange, persimmon, papaya, paprika, and carrot, and exerts various biological activities (e.g., antioxidant effects). We previously reported that ß-cry suppressed lipopolysaccharide (LPS)-induced osteoclast differentiation via the inhibition of prostaglandin (PG) E2 production in gingival fibroblasts and restored the alveolar bone loss in a mouse model for periodontitis in vivo. In this study, we investigated the molecular mechanism underlying the inhibitory effects of ß-cry on osteoclast differentiation. In mouse calvarial organ cultures, LPS-induced bone resorption was suppressed by ß-cry. In osteoblasts, ß-cry inhibited PGE2 production via the downregulation of the LPS-induced mRNA expression of cyclooxygenase (COX)-2 and membrane-bound PGE synthase (mPGES)-1, which are PGE synthesis-related enzymes, leading to the suppression of receptor activator of NF-κB ligand (RANKL) mRNA transcriptional activation. In an in vitro assay, ß-cry directly suppressed the activity of the inhibitor of NF-κB kinase (IKK) ß, and adding ATP canceled this IKKß inhibition. Molecular docking simulation further suggested that ß-cry binds to the ATP-binding pocket of IKKß. In Raw264.7 cells, ß-cry suppressed RANKL-mediated osteoclastogenesis. The molecular mechanism underlying the involvement of ß-cry in LPS-induced bone resorption may involve the ATP-competing inhibition of IKK activity, resulting in the suppression of NF-κB signaling.

ß-Cryptoxanthin Reduces Body Fat and Increases Oxidative Stress Response in Caenorhabditis elegans Model.

ß-Cryptoxanthin (BCX) is a major dietary pro-vitamin A carotenoid, found mainly in fruits and vegetables. Several studies showed the beneficial effects of BCX on different aspects of human health. In spite of the evidence, the molecular mechanisms of action of BCX need to be further investigated. The Caenorhabditis elegans model was used to analyze in vivo the activity of BCX on fat reduction and protection to oxidative stress. Dose-response assays provided evidence of the efficacy of BCX at very low dose (0.025 µg/mL) (p < 0.001) on these processes. Moreover, a comparative analysis with other carotenoids, such as lycopene and ß-carotene, showed a stronger effect of BCX. Furthermore, a transcriptomic analysis of wild-type nematodes supplemented with BCX revealed upregulation of the energy metabolism, response to stress, and protein homeostasis as the main metabolic targets of this xanthophyll. Collectively, this study provides new in vivo evidence of the potential therapeutic use of BCX in the prevention of diseases related to metabolic syndrome and aging.

ß-Cryptoxanthin-Biofortified Hen Eggs Enhance Vitamin A Status When Fed to Male Mongolian Gerbils.

Background: Consumption of provitamin A carotenoid biofortified crops, such as maize, supports vitamin A (VA) status in animals and humans. Laying hens that consume ß-cryptoxanthin-biofortified maize deposit ß-cryptoxanthin into egg yolk. Objective: We investigated whether ß-cryptoxanthin-biofortified egg consumption would affect VA status of male Mongolian gerbils (Meriones unguiculatus) compared with white-yolked eggs. Methods: ß-Cryptoxanthin-biofortified egg yolk, produced in hens fed biofortified orange maize or tangerine-fortified maize feeds, was freeze-dried and fed to gerbils. White-yolked eggs were produced by feeding white maize to hens. Gerbils (n = 57) were fed VA-deficient feed for 28 d. After baseline (n = 7), treatments (n = 10/group) included oil control (VA-); 16.7% orange maize-biofortified, tangerine-fortified, or white-yolk egg feeds; or retinyl acetate as positive control (VA+) matched to daily preformed retinol intake from the eggs for 30 d. Preformed retinol did not differ between the egg yolks. Gerbil liver retinol, lipid, fatty acids, and cholesterol were determined. Results: Liver retinol concentration (0.13 ± 0.03 µmol/g) and total hepatic VA (0.52 ± 0.12 µmol) were higher in gerbils fed orange maize-biofortified eggs than in all other groups. The VA- group was severely VA deficient (0.018 ±0.010 µmol/g; P < 0.05). Liver retinol was similar among VA+, tangerine-egg-, and white-egg-fed gerbils, but retinol reserves were higher in tangerine-egg-fed gerbils (0.35 ± 0.11 µmol) than in VA+ or VA- gerbils or at baseline (P < 0.05). Liver fat was 3.6 times (P < 0.0001) and cholesterol was 2.1 times (P < 0.004) higher in egg-fed groups that experienced hepatosteatosis. Liver fatty acid profiles reflected feed, but retinyl ester fatty acids did not. Conclusions: The preformed retinol in the eggs enhanced gerbil VA status, and the ß-cryptoxanthin-biofortified eggs from hens fed orange maize prevented deficiency. Biofortified maize can enhance VA status when consumed directly or through products from livestock fed orange maize.

Higher dietary and serum carotenoid levels are associated with lower carotid intima-media thickness in middle-aged and elderly people.

Several studies have suggested that higher carotenoid levels may be beneficial for atherosclerosis patients, but few studies have examined this relationship in the Chinese population. This cross-sectional study examined the association between the levels of carotenoids in diet and serum and carotid intima-media thickness (IMT) in Chinese adults aged 50-75 years in Guangzhou, China. Dietary intake was assessed using a FFQ. HPLC was used to assay the serum concentrations of α-carotene, ß-carotene, lutein+zeaxanthin, ß-cryptoxanthin and lycopene. The IMT at the common carotid artery (CCA) and bifurcation of the carotid artery was measured by B-mode ultrasound. A total of 3707 and 2947 participants were included in the analyses of dietary and serum carotenoids. After adjustment for demographic, socio-economic and lifestyle factors, all the serum carotenoids levels except lycopene were found to be inversely associated with the IMT at the CCA and bifurcation (P trend<0·001 to 0·013) in both men and women. The absolute mean differences in the IMT between the subjects in the extreme quartiles of serum carotenoid levels were 0·034 mm (α-carotene), 0·037 mm (ß-carotene), 0·032 mm (lutein+zeaxanthin), 0·030 mm (ß-cryptoxanthin), 0·015 mm (lycopene) and 0·035 mm (total carotenoids) at the CCA; the corresponding values were 0·025, 0·053 0·043, 0·050, 0·011 and 0·042 mm at the bifurcation. The favourable associations were also observed between dietary carotenoids (except lycopene) and the CCA IMT. In conclusion, elevated carotenoid levels in diet and serum are associated with lower carotid IMT values (particular at the CCA) in Chinese adults.

Antioxidant ß-cryptoxanthin enhances porcine oocyte maturation and subsequent embryo development in vitro.

Oxidative stress is partly responsible for the poor quality of IVM oocytes. The present study investigated the effects of the antioxidant ß-cryptoxanthin on the IVM of porcine oocytes and the in vitro development of the ensuing embryos. Oocytes were matured in IVM medium containing different concentrations of ß-cryptoxanthin (0, 0.1, 1, 10 or 100µM). Treatment with 1µM ß-cryptoxanthin (Group 1B) improved polar body extrusion and the expression of maturation-related genes in cumulus cells and oocytes compared with control. In addition, levels of reactive oxygen species decreased significantly in Group 1B, whereas there were significant increases in glutathione levels and expression of the antioxidant genes superoxide dismutase 1 and peroxiredoxin 5 in this group. After parthenogenetic activation, although the cleavage rate did not differ between the control and 1B groups, the blastocyst formation rate was higher in the latter. Moreover, the total number of cells per blastocyst and relative mRNA levels of pluripotency marker and antioxidant genes were significantly higher in the 1B compared with control group. These results demonstrate that ß-cryptoxanthin decreases oxidative stress in porcine oocytes and improves their quality and developmental potential.

Effects of Plant Sterols or ß-Cryptoxanthin at Physiological Serum Concentrations on Suicidal Erythrocyte Death.

The eryptotic and hemolytic effects of a phytosterol (PS) mixture (ß-sitosterol, campesterol, stigmasterol) or ß-cryptoxanthin (ß-Cx) at physiological serum concentration and their effect against oxidative stress induced by tert-butylhydroperoxide (tBOOH) (75 and 300 µM) were evaluated. ß-Cryptoxanthin produced an increase in eryptotic cells, cell volume, hemolysis, and glutathione depletion (GSH) without ROS overproduction and intracellular Ca2+ influx. Co-incubation of both bioactive compounds protected against ß-Cx-induced eryptosis. Under tBOOH stress, PS prevented eryptosis, reducing Ca2+ influx, ROS overproduction and GSH depletion at 75 µM, and hemolysis at both tBOOH concentrations. ß-Cryptoxanthin showed no cytoprotective effect. Co-incubation with both bioactive compounds completely prevented hemolysis and partially prevented eryptosis as well as GSH depletion induced by ß-Cx plus tBOOH. Phytosterols at physiological serum concentrations help to prevent pro-eryptotic and hemolytic effects and are promising candidate compounds for ameliorating eryptosis-associated diseases.

ß-Cryptoxanthin Inhibits Angiogenesis in Human Umbilical Vein Endothelial Cells Through Retinoic Acid Receptor.

SCOPE: ß-Cryptoxanthin is an abundant carotenoid in fruits and vegetables that can be quantified in human blood serum. Yet, contrary to other carotenoids, its effects on endothelial cells and angiogenesis remain unknown. METHODS AND RESULTS: Human umbilical vein endothelial cells (HUVEC) are treated with 0.01, 0.1, or 1 µm of ß-cryptoxanthin. Antioxidant activity is determined by its free radical scavenging and oxygen-radical absorbance capacity. The effect on migration and formation of tubular structures is studied. Additionally, effect on angiogenesis is also analyzed using an in vivo model. ß-Cryptoxanthin exhibits scavenging ability, having an antioxidant effect on HUVEC. Interestingly, ß-cryptoxanthin reduces their migration and angiogenesis, even in the presence of vascular endothelial growth factor (VEGF). Additionally, such carotenoid inhibits in vivo angiogenesis induced by VEGF. In addition, treatment of HUVEC with LE540 (retinoic acid receptor [RAR] panantagonist) inhibits ß-cryptoxanthin antiangiogenic effect on HUVEC. CONCLUSION: ß-Cryptoxanthin inhibits angiogenesis through RAR. Thus, this carotenoid and food containing it may be useful for the prevention and treatment of angiogenic pathologies. That includes tumoral growth and wet macular degeneration associated with aging. To the best of our knowledge, this is the first report of the antioxidant effect and antiangiogenic activity of this carotenoid on HUVEC, both in vitro and in vivo.

Encapsulation of Nutraceutical Ingredients in Liposomes and Their Potential for Cancer Treatment.

At present, cancer is one of the major diseases in the world affecting numerous lives. There have been various approaches to combat the disease, particularly involving chemical interventions (chemotherapy). However, owing to serious side effects of chemotherapy, employment of natural supplements in cancer therapy has been long desired. Nutraceuticals are currently being studied as a medicament, to act as both preventive and curative measure. Nutraceuticals provide both nutrition and therapeutic benefits; besides, they are natural and biocompatible, and therefore pose no side effects. This facilitates their ready acceptance as dietary supplements with no requirements of special dosage and concerns over long-term usage. Nutraceuticals can be derived from the natural resources such as spices, fruits, vegetables, and plants. However, nutraceuticals are vulnerable to environmental stresses that necessitate encapsulation for long-term storage and required bioavailability. The review collates the findings on encapsulated nutraceuticals in liposomes for cancer therapy. The article provides a coherent overview of the research conducted on liposomal administration of nutraceuticals to target various forms of cancer, explaining the advances made.