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Plasma response to a single dose of dietary beta-cryptoxanthin esters from papaya (Carica papaya L.) or non-esterified beta-cryptoxanthin in adult human subjects: a comparative study.

Many orange-coloured fruits contain beta-cryptoxanthin in its non-esterified as well as its esterified form. Information concerning the absorption of beta-cryptoxanthin, especially with regard to the metabolism of its fatty acid esters, is rather scarce. The present study assessed the plasma concentration reached after consumption of a single dose of native beta-cryptoxanthin esters from papaya (Carica papaya L.) or non-esterified beta-cryptoxanthin in equal total amounts. In a randomized, single-blind crossover study, twelve subjects were served a portion of yoghurt containing esterified or non-esterified beta-cryptoxanthin (1.3 mg absolute) together with a balanced breakfast. Between the two intervention days, there was a 2-week depletion period. After a fasting blood sample had been taken, futher samples were taken from the subjects at 3, 6, 9, 12 and 24 h. The concentration of non-esterified beta-cryptoxanthin in the whole plasma was determined by HPLC; beta-cryptoxanthin identification was confirmed by liquid chromatography-atmospheric pressure chemical ionization-MS analyses. Irrespective of the consumed diet, the plasma beta-cryptoxanthin concentrations increased significantly (P=0.05) and peaked after 6-12 h. The concentration curves, as well as the areas under the curves, were not distinguishable according to two-sided F and t tests (P=0.05). Standardization of beta-cryptoxanthin concentrations to plasma triacylglycerol and cholesterol had no impact on the results. Thus, the present study indicates comparable bioavailability of both non-esterified beta-cryptoxanthin and mixtures of beta-cryptoxanthin esters. The results support the existence of an effective enzymatic cleavage system accepting various beta-cryptoxanthin esters.

Adult↗

Frequent intake of tropical fruits that are rich in beta-cryptoxanthin is associated with higher plasma beta-cryptoxanthin concentrations in Costa Rican adolescents.

Dietary tocopherols and carotenoids may play a role in preventing cancer and cardiovascular diseases. Because these may begin to develop during adolescence, dietary patterns during this period could influence long-term risk. The objective of this study was to examine the intake and plasma concentrations of the major carotenoids and tocopherols in 159 adolescents (mean +/- SD, 15.5 +/- 2.5 y old) living in Costa Rica. All participants completed a 135-item food-frequency questionnaire and provided a fasting blood sample. Carotenoid and tocopherol intakes were adjusted for total energy and plasma concentrations for total cholesterol. The relative abundance of carotenoids in the diet was similar to their distribution in plasma; lycopene was the most abundant, followed by beta-carotene and lutein + zeaxanthin. gamma-Tocopherol was more abundant than alpha-tocopherol in the diet, but alpha-tocopherol was approximately sevenfold higher in plasma. The highest diet-plasma correlations (adjusted for age, sex and body mass index) were 0.38 for beta-cryptoxanthin, 0.33 for gamma-tocopherol and 0.17 for lutein + zeaxanthin (all P < 0.05). All other correlations were r < 0.15. Papaya intake was the best food predictor of plasma beta-cryptoxanthin concentrations (r = 0.41). Subjects that frequently (> or =3/d) consumed tropical fruits with at least 50 micro g/100 g beta-cryptoxanthin (papaya, tangerine, orange and watermelon) had twofold the plasma beta-cryptoxanthin concentrations of those with intakes of <4/wk (P for trend = 0.0009). In sum, the diet-plasma carotenoid and tocopherol correlations were generally low in Costa Rican adolescents. Intakes of beta-cryptoxanthin and papaya, a tropical fruit frequently consumed in Latin America, were the best predictors of beta-cryptoxanthin concentrations in plasma.

Adolescent↗

beta-Cryptoxanthin selectively increases in human chylomicrons upon ingestion of tangerine concentrate rich in beta-cryptoxanthin esters.

beta-Cryptoxanthin is a major source of vitamin A, often second only to beta-carotene, and is present in fruits such as oranges, tangerines, and papayas. Here, we studied the uptake of this carotenoid upon ingestion of tangerine juice concentrate, rich in beta-cryptoxanthin esters. Increasing amounts of free beta-cryptoxanthin were detected in chylomicrons and serum. Peak levels in chylomicrons were reached at t = 6 h, and the concentration returned toward basal levels at t = 9 h. No beta-cryptoxanthin esters were detected in chylomicrons or serum, indicating efficient cleavage in the intestine before the carotenoid is incorporated into lipoproteins by the liver. Other xanthophyll esters, e.g., of zeaxanthin and lutein, were present in low amounts in the tangerine concentrate. As with beta-cryptoxanthin, no esters appeared in serum or chylomicrons, suggesting that the cleavage of carotenoid esters prior to release into the lymphatic circulation occurs generally in human oxocarotenoid biokinetics.

Absorption↗

LDL susceptibility to copper-induced oxidation after administration of a single dose of free or esterified beta-cryptoxanthin.

BACKGROUND: The oxidative modification of LDL is believed to be an initial step in atherosclerosis. Thus, antioxidative substances such as carotenoids may have a role in the prevention of coronary heart disease. We examined the susceptibility of LDL to Cu2+ oxidation in young adults before and after a single dose of beta-cryptoxanthin. METHODS: 1.3 mg of beta-cryptoxanthin was administered to 12 apparently healthy young volunteers. Six of the volunteers received esters, the other six free beta-cryptoxanthin. The plasma concentration of beta-cryptoxanthin and the susceptibility of LDL to copper-induced oxidation ex vivo in terms of the duration of lag time were measured before and 12 h after beta-cryptoxanthin ingestion. RESULTS: A single dose of beta-cryptoxanthin significantly increased the mean plasma beta-cryptoxanthin concentration and the mean cholesterol adjusted beta-cryptoxanthin concentration by 117 and 133%, respectively. No effect on the length of lag time was assessed. However, in LDL isolated from plasma 12 h after beta-cryptoxanthin administration the lengths of lag time correlated significantly with the plasma beta-cryptoxanthin concentration and with the cholesterol adjusted beta-cryptoxanthin levels. The lag time did not differ significantly between volunteers who received esters and those who received the same dosage as free beta-cryptoxanthin. At both measuring points, smokers, male volunteers and women using oral contraceptives tended to exhibit lower beta-cryptoxanthin concentrations and lower cholesterol adjusted beta-cryptoxanthin concentrations as well as increased LDL oxidizability compared to nonsmokers and women not using oral contraceptives. CONCLUSION: A single dose of beta-cryptoxanthin does not enhance the duration of LDL lag time ex vivo in healthy young subjects.

Adult↗

Beta-cryptoxanthin suppresses the growth of immortalized human bronchial epithelial cells and non-small-cell lung cancer cells and up-regulates retinoic acid receptor beta expression.

Recent findings of an inverse association between beta-cryptoxanthin and lung cancer risk in several observational epidemiologic studies suggest that beta-cryptoxanthin could potentially act as a chemopreventive agent against lung cancer. However, the biological activity of beta-cryptoxanthin and molecular mechanism(s) by which beta-cryptoxanthin affects lung tumourigenesis have not been studied. In the present study, we found that beta-cryptoxanthin inhibited the growth of A549 cells, a non-small-cell lung cancer cell line and BEAS-2B cells, an immortalized human bronchial epithelial cell line in a dose-dependent manner. beta-Cryptoxanthin suppressed the protein levels of cyclin D1 and cyclin E, up-regulated the cell cycle inhibitor p21, increased the number of lung cancer cells in the G1/G0 phase and decreased those in the S phase of the cell cycle. Consistent with inhibition of the lung cancer cell growth, beta-cryptoxanthin induced the mRNA levels of retinoic acid receptor beta (RARbeta) in BEAS-2B cells, although this effect was less pronounced in A549 cells. Furthermore, beta-cryptoxanthin transactivated RAR-mediated transcription activity of the retinoic acid response element. These findings suggest a mechanism of anti-proliferative action of beta-cryptoxanthin and indicate that beta-cryptoxanthin may be a promising chemopreventive agent against lung cancer.

Anticarcinogenic Agents↗

beta-Cryptoxanthin stimulates cell proliferation and transcriptional activity in osteoblastic MC3T3-E1 cells.

The carotenoid beta-cryptoxanthin has been shown to have a stimulatory effect on bone formation in rat bone tissues in vitro. The effect of beta-cryptoxanthin in osteoblastic cells in vitro was investigated. Osteoblastic MC3T3-E1 cells were cultured for 72 h in alpha-minimal essential medium containing 10% fetal bovine sereum (FBS) to reach subconfluent monolayers. After culture, the medium was changed, then beta-cryptoxanthin (10(-8) to 10(-6) M) was added in the culture medium without FBS, and the cells were cultured for an additional 24, 48, or 72 h. The proliferation of osteoblastic cells was significantly enhanced in the presence of beta-cryptoxanthin (10(-8) to 10(-6) M), when it was cultured for 48 or 72 h in medium containing 10% FBS. When osteoblastic cells with subconfluency were cultured for 48 or 72 h in FBS free-medium containing beta-cryptoxanthin (10(-8) to 10(-6) M), alkaline phosphatase activity or deoxyribonucleic acid (DNA) content in the cells was significantly increased. Also, protein content in the cells was significantly increased by culture with 10(-6) M beta-cryptoxanthin for 48 or 72 h. The effect of beta-cryptoxanthin (10(-6) M) in increasing protein content, alkaline phosphatase activity, or DNA content in the cells was significantly blocked in the presence of staurosporine (10(-6) M) or PD98059 (10(-6) M), which is an inhibitor of protein kinases. The stimulatory effect of beta-cryptoxanthin (10(-6) M) on cellular biochemical components was completely prevented in the presence of cycloheximide (10(-6) M), an inhibitor of protein synthesis, or 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB; 10(-9) M), an inhibitor of transcriptional activity. The expressions of insulin-like growth factor (IGF)-I and transforming growth factor (TGF)-beta1 mRNAs were demonstrated by reverse transcription-polymerase chain reaction (RT-PCR) analysis in osteoblastic cells using mouse IGF-I or TGF-beta1-specific primers. These expressions were significantly raised in the presence of beta-cryptoxanthin (10(-6) M). This study demonstrates that beta-cryptoxanthin has a stimulatory effect on cell proliferation and biochemical components in osteoclastic MC3T3-E1 cells, and that the carotenoid can stimulate transcriptional activity in the cells.

3T3 Cells↗

beta-cryptoxanthin stimulates cell differentiation and mineralization in osteoblastic MC3T3-E1 cells.

The effect of beta-cryptoxanthin, a kind of carotenoid, on cell differentiation and mineralization in osteoblastic MC3T3-E1 cells was investigated. Cells were cultured for 72 h in a minimum essential medium containing 10% fetal bovine serum (FBS), and the cells with subconfluency were changed to a medium containing either vehicle or beta-cryptoxanthin (10(-8) to 10(-6) M) without FBS. Cells were cultured for 3 to 21 days. Gene expression in osteoblastic cells was determined using reverse transcription-polymerase chain reaction (RT-PCR). Culture with beta-cryptoxanthin (10(-7) or 10(-6) M) for 3 days caused a significant increase in Runx2 type 1, Runx2 type 2, alpha1 (I) collagen, and alkaline phosphatase mRNA levels in osteoblastic cells. These increases were completely blocked in the presence of cycloheximide, an inhibitor of protein synthesis, or 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB), an inhibitor of transcriptional activity. Meanwhile, vitamin A (10(-6) M) did not have a significant effect on Runx2 type 1 mRNA expression in the cells. The effect of beta-cryptoxanthin (10(-6) M) in stimulating Runx2 type 1 and alpha1 (I) collagen mRNA levels, protein content, and alkaline phosphatase activity in the cells was also seen in the presence of vitamin A (10(-6) M), suggesting that the mode of beta-cryptoxanthin action differs from that of vitamin A. Prolonged culture with beta-cryptoxanthin (10(-6) M) for 3 to 21 days caused a significant increase in cell number, deoxyribonucleic acid (DNA) content, protein content, and alkaline phosphatase activity in osteoblastic cells, suggesting that beta-cryptoxanthin stimulates cell proliferation and differentiation. Moreover, culture with beta-cryptoxanthin (10(-7) or 10(-6) M) for 5 to 21 days caused a remarkable increase in mineralization. This study demonstrates that beta-cryptoxanthin has a stimulatory effect on cell differentiation and mineralization due to enhancing gene expression of proteins, which involve in bone formation in osteoblastic MC3T3-E1 cells.

Alkaline Phosphatase↗

Beta-cryptoxanthin stimulates apoptotic cell death and suppresses cell function in osteoclastic cells: change in their related gene expression.

The effect of beta-cryptoxanthin, a kind of carotenoid, on osteoclastic cells in mouse marrow culture system in vitro was investigated. The macrophage colony-stimulating factor (M-CSF)-dependent bone marrow macrophages were cultured in the presence of M-CSF (10 ng/ml) and receptor activator of NF-kappaB ligand (RANKL; 25 ng/ml) for 4 days. The osteoclastic cells formed were further cultured in medium containing either vehicle or beta-cryptoxanthin (10(-8)-10(-6) M) with or without M-CSF (10 ng/ml) and RANKL (50 ng/ml) for 24-72 h. Osteoclastic cells were significantly decreased with culture of beta-cryptoxanthin (10(-7) or 10(-6) M) with or without M-CSF and RANKL for 24, 48, or 72 h. beta-Cryptoxanthin (10(-8) M)-induced decrease in osteoclastic cells were significantly inhibited in the presence of caspase-3 inhibitor (10(-8) or 10(-7) M). Agarose gel electrophoresis showed the presence of low-molecular-weight deoxyribonucleic acid (DNA) fragments of adherent cells cultured with beta-cryptoxanthin (10(-7) or 10(-6) M) for 24 or 48 h, indicating that the carotenoid induces apoptotic cell death. Apoptosis-related gene expression was determined using reverse transcription-polymerase chain reaction (RT-PCR). Culture with beta-cryptoxanthin (10(-7) or 10(-6) M) for 24 or 48 h caused a significant increase in caspase-3 mRNA expression in the presence or absence of M-CSF and RANKL, while Bcl-2 and Apaf-2 mRNA expressions were significantly increased with culture of beta-cryptoxanthin (10(-7) or 10(-6) M) without M-CSF and RANKL for 24 or 48 h. Akt-1 mRNA expression was not significantly changed with culture of the carotenoid (10(-7) or 10(-6) M) for 24 or 48 h. Moreover, tartrate-resistant acid phosphatase (TRACP) activity, or TRACP and cathepsin K mRNA expressions were significantly decreased with culture of beta-cryptoxanthin (10(-6) M) in the presence or absence of M-CSF and RANKL for 48 h. This study demonstrates that beta-cryptoxanthin has stimulatory effects on apoptotic cell death and suppressive effects on osteoclastic cell function.

Acid Phosphatase↗

Inhibitory effect of beta-cryptoxanthin on osteoclast-like cell formation in mouse marrow cultures.

The carotenoid beta-cryptoxanthin has been shown to have an inhibitory effect on bone-resorping factor-stimulated bone resorption in rat bone tissues in vitro. The effect of beta-cryptoxanthin on osteoclast-like cell formation in mouse marrow culture in vitro was investigated. The bone marrow cells were cultured for 7 days in alpha-minimal essential medium containing a bone-resorbing agent [parathyroid hormone (1-34) (PTH), prostaglandin E(2), 1,25-dihydroxyvitamin D(3), lipopolysaccharide, or tumor necrosis factor-alpha (TNFalpha)] with an effective concentration. Osteoclast-like cell formation was estimated by staining for tartrate-resistant acid phosphatase, a marker enzyme of osteoclasts. The presence of PTH (10(-7)M), prostaglandin E(2) (10(-5)M), 1,25-dihydroxyvitamin D(3) (10(-7)M), lipopolysaccharide (10 microg/mL), or TNFalpha (10 ng/mL) induced a remarkable increase in osteoclast-like multinucleated cells. These increases were significantly inhibited in the presence of beta-cryptoxanthin (10(-8) to 10(-6)M). beta-Cryptoxanthin (10(-7) and 10(-6)M) significantly inhibited dibutyryl cyclic adenosine monophosphate (DcAMP) (10(-5)M) or phorbol 12-myristate 13-acetate (PMA) (10(-5)M), an activator of protein kinase C, induced osteoclast-like cell formation. Also, beta-cryptoxanthin (10(-7) and 10(-6)M) had a significant inhibitory effect on osteoclast-like formation induced by receptor activator of NF-kappaB ligand (RANKL) (10 and 20 ng/mL) in the presence of macrophage colony-stimulating factor (M-CSF) (10 and 20 ng/mL). The stimulatory effect of RANKL and M-CSF on osteoclast-like cell formation was significantly enhanced in the presence of PMA, while such an effect was not seen by DcAMP. beta-Cryptoxanthin (10(-6)M) significantly inhibited osteoclast-like cell formation induced by RANKL and M-CSF in the presence of PMA or DcAMP. Moreover, the inhibitory effect of beta-cryptoxanthin on RANKL plus M-CSF-, PTH-, or TNFalpha-induced osteoclast-like cell formation was not observed in the presence of cycloheximide (10(-7)M), an inhibitor of protein synthesis at translational process, or 5,6-dichloro-1-beta-d-ribofuranosylbenzimidazole (10(-6)M), an inhibitor of transcription. This study demonstrates that beta-cryptoxanthin has a potent inhibitory effect on osteoclast-like cell formation in mouse marrow culture. The inhibitory action of beta-cryptoxanthin may partly involve in a newly synthesized protein component which is related to RANKL stimulation in osteoclastogenesis.

Animals↗

Cryptoxanthin structural isomers in oranges, orange juice, and other fruits.

Citrus fruits contain a wide range of bioactive compounds. Their carotenoid fraction is inter alia dominated by structural cryptoxanthin isomers as beta-cryptoxanthin and zeinoxanthin. Both xanthophylls were identified in saponified citrus fruit extracts by comparison to reference compounds extracted from corn and by their typical fragmentation pattern in LC-(APCI)MS analyses. alpha-Cryptoxanthin, another structural cryptoxanthin isomer usually found in carrot leaves, was not identified in the citrus fruits studied. Cryptoxanthin concentrations of direct orange juices (D) and reconstituted juices (C) were compared. Although the respective mean values [beta-cryptoxanthin, 62 (C) versus 110 microg/100 g (D); zeinoxanthin, 22 (C) versus 37 microg/100 g (D)] were statistically distinguishable (P < 0.05%), a doubtless classification is not possible because the concentration ranges overlap. To identify esters of structural cryptoxanthin isomers in native orange juice extracts, four saturated acyl esters were synthesized. LC-(APCI)MS studies revealed for the first time that the dominant acylation partners of both xanthophylls were C12:0, C14:0, and C16:0 in nearly equal amounts of roughly one-third, whereas C10:0 and C18:1 were present at lower extents of 5-14%; other acylation partners were not identified. The presented method is appropriate to gain deeper insight into the pattern of structural cryptoxanthin isomers of citrus fruits. Knowledge of acylated cryptoxanthin isomers may be important in the evaluation of the bioavailability of individual esters in future human digestion studies.

Beverages↗

Oral administration of beta-cryptoxanthin induces anabolic effects on bone components in the femoral tissues of rats in vivo.

The effect of beta-cryptoxanthin on bone components in the femoral tissues of rats was investigated. Beta-cryptoxanthin was isolated from Satsuma mandarin (Citrus unshiu MARC.). Bone tissues were cultured for 48 h in serum-free Dulbecco's modified Eagle's medium containing either vehicle or beta-cryptoxanthin (10(-7) or 10(-6) M). The presence of beta-cryptoxanthin (10(-7) or 10(-6) M) caused a significant increase in calcium content and alkaline phosphatase activity in the femoral-diaphyseal and femoral-metaphyseal tissues. These increases were completely abolished in the presence of cycloheximide (10(-6) M), an inhibitor of protein synthesis. Thus beta-cryptoxanthin had an anabolic effect on bone calcification in vitro. Moreover, beta-cryptoxanthin (10, 25, or 50 microg/100 g body weight) was orally administered once daily for 7 d to young male rats. The administration of beta-cryptoxanthin (10, 25, or 50 microg/100 g body weight) caused a significant increase in calcium content and alkaline phosphatase activity in the femoral-diaphyseal and femoral-metaphyseal tissues. Femoral-diaphyseal and femoral-metaphyseal DNA contents were significantly increased by the dose of 25 or 50 microg/100 g body weight. A significant increase in metaphyseal DNA content was also seen with the dose of 10 microg/100 g body weight of beta-cryptoxanthin. This study demonstrates that beta-cryptoxanthin has an anabolic effect on bone components in rats in vitro and in vivo.

Administration, Oral↗

Reduction in photostability by the esterification of beta-cryptoxanthin.

Liposomes, in which beta-carotene, beta-cryptoxanthin, zeaxanthin, beta-cryptoxanthin palmitate or beta-cryptoxanthin acetate had been embedded, were irradiated by UVA, and the rate of degradation of each carotenoid was measured. There was no significant difference in the degradation rate between beta-carotene, beta-cryptoxanthin and zeaxanthin. The degradation rates of beta-cryptoxanthin palmitate and beta-cryptoxanthin acetate were faster than that of beta-cryptoxanthin, and the degradation rate of beta-cryptoxanthin palmitate was faster than that of beta-cryptoxanthin acetate.

Carotenoids↗

Carotenoid esters in vegetables and fruits: a screening with emphasis on beta-cryptoxanthin esters.

Carotenoids are found in food plants in free form or as fatty acid esters. Most studies have been carried out after saponification procedures, so the resulting data do not represent the native carotenoid composition of plant tissues. Therefore, nonsaponified extracts of 64 fruits and vegetables have been screened to determine the amount of carotenoid esters in food plants. Because one of the major problems in the quantitation of carotenoids is the availability of pure standard material, the total carotenoid ester content was calculated as lutein dimyristate equivalents. Lutein dimyristate was independently synthesized from lutein and myristoyl chloride. The highest ester concentrations were found in red chili (17.1 mg/100 g) and orange pepper (9.2 mg/100 g); most of the investigated fruits and vegetables showed concentrations up to 1.5 mg/100 g. Special attention was dedicated to beta-cryptoxanthin esters. To enable an accurate detection of the beta-cryptoxanthin ester content, beta-cryptoxanthin was purified from papaya and used for synthesis of beta-cryptoxanthin laurate, myristate, and palmitate, representing the major beta-cryptoxanthin esters in food plants. The study proved tropical and subtropical fruits to be an additional source of beta-cryptoxanthin esters in the human diet. The contents ranged from 8 microg/100 g beta-cryptoxanthin laurate in Tunisian orange to 892 microg/100 g beta-cryptoxanthin laurate in papaya.

Anticarcinogenic Agents↗

beta-Cryptoxanthin stimulates bone formation and inhibits bone resorption in tissue culture in vitro.

The effect of beta-cryptoxanthin, which is greatly present in fruits, has not been clarified so far on bone metabolism. The effect of beta-cryptoxanthin on bone formation and bone resorption was investigated in tissue culture in vitro. Rat femoral-diaphyseal (cortical bone) and -metaphyseal (trabecular bone) tissues were cultured for 48 h in Dulbecco's modified Eagle's medium (high glucose, 4.5%) supplemented with antibiotics and bovine serum albumin. The experimental cultures contained 10(-8)-10(-5) M beta-cryptoxanthin. The presence of beta-cryptoxanthin (10(-6) or 10(-5) M) caused a significant increase in calcium content, alkaline phosphatase activity and deoxyribonucleic acid (DNA) content in the diaphyseal and metaphyseal tissues. These increases were completely prevented in the presence of cycloheximide (10(-6) M), an inhibitor of protein synthesis. beta-Carotene (10(-6) or 10(-5) M) or xantine (10(-6) or 10(-5) M) had no effect on the diaphyseal and metaphyseal calcium contents. The bone-resorbing factors parathyroid hormone (1-34) (PTH; 10(-7) M) or prostaglandin E2 (PGE2; 10(-5) M) caused a significant decrease in calcium content in the diaphyseal and metaphyseal tissues. The decrease in bone calcium content induced by PTH or PGE2 was completely inhibited by beta-cryptoxanthin (10(-8)-10(-6) M). In addition, beta-cryptoxanthin (10(-8)-10(-6) M) completely inhibited the PTH (10(-7) M)- or PGE, (10(-5) M)-induced increase in medium glucose consumption and lactic acid production by diaphyseal and metaphyseal tissues. The inhibitory effect of beta-cryptoxanthin (10(-7) M) on PTH (10(-7) M)- or PGE2 (10(-5) M)-stimulated decrease in the diaphyseal calcium content was significantly prevented in the presence of 10(-3) M vanadate, an inhibitor of protein tyrosine phosphatase. Vanadate (10(-3) M) did not have a significant effect on calcium content and lactic acid production in control bone tissues. The present study demonstrates that beta-cryptoxanthin has a direct stimulatory effect on bone formation and an inhibitory effect on bone resorption in tissue culture in vitro.

Alkaline Phosphatase↗

Synergistic effect of beta-cryptoxanthin and zinc sulfate on the bone component in rat femoral tissues in vitro: the unique anabolic effect with zinc.

The effect of the combination of beta-cryptoxanthin and zinc sulfate (zinc) on bone components in the femoral-diaphyseal and -metaphyseal tissues of young rats in vitro was investigated. Bone tissues were cultured for 48 h in a serum-free Dulbecco's modified Eagle's medium containing either vehicle, beta-cryptoxanthin (10(-9)-10(-7) M) or zinc sulfate (10(-6)-10(-4) M). The presence of beta-cryptoxanthin (10(-9) M) or zinc (10(-6) M) did not have a significant effect on calcium content in the femoral-diaphyseal or -metaphyseal tissues. However, culture which combined beta-cryptoxanthin (10(-9) M) and zinc (10(-6) M) caused a significant increase in calcium content in the femoral-diaphyseal and -metaphyseal tissues. Such an effect was not observed by the combination of beta-cryptoxanthin (10(-9) M) plus genistein (10(-6) M) or menaquinone-7 (10(-6) M), or zinc (10(-6) M) plus genistein (10(-6) M) or menaquinone-7 (10(-6) M). Also, the combination of beta-cryptoxanthin (10(-9) M) plus zinc (10(-6) M) caused a remarkable increase in alkaline phosphatase activity and deoxyribonucleic acid (DNA) in the femoral-diaphyseal and -metaphyseal tissues, while their application alone did not have an effect on the enzyme activity or DNA content in the femoral tissues. The effect of the combination of beta-cryptoxanthin (10(-9) M) plus zinc (10(-6) M) in increasing calcium content, alkaline phosphatase activity, and DNA content in the femoral-diaphyseal and -metaphyseal tissues was completely prevented in the presence of cycloheximide (10(-6) M), an inhibitor of protein synthesis, or 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DBR), an inhibitor of transcriptional activity. This study demonstrates that the combination of beta-cryptoxanthin and zinc at a lower concentration has a synergistic effect on bone components in vitro.

Alkaline Phosphatase↗

Dietary cryptoxanthin and reduced risk of lung cancer: the Singapore Chinese Health Study.

High prediagnostic serum beta-cryptoxanthin levels have been found to be associated with reduced risk of lung cancer in a recent cohort study of Chinese men in Shanghai, China. Data on dietary beta-cryptoxanthin, and other specific carotenoids and antioxidants in relation to lung cancer, particularly in non-Western populations, are scarce. The aim of the present study was to assess the roles of dietary antioxidants in the development of lung cancer. Between April 1993 and December 1998, 63,257 Chinese men and women ages 45-74 years in Singapore participated in a prospective study of diet and cancer. At baseline, an in-person interview was conducted using a structured questionnaire for information on usual dietary habits, tobacco smoking, and other lifestyle factors. A Singapore food composition database was used to estimate intake of alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, lutein/zeaxanthin, vitamins A, C, and E, and folate in study subjects. During the first 8 years of follow-up, 482 lung cancer cases occurred among cohort members. High levels of dietary beta-cryptoxanthin were associated with reduced risk of lung cancer; relative to the lowest quintile, the self-reported smoking adjusted relative risks (95% confidence intervals) for the highest quintile were 0.73 (0.54-0.98) among all of the subjects and 0.63 (0.41-0.99) among current smokers. Before adjustment for cigarette smoking, dietary vitamin C was associated with a statistically significant reduction in risk of lung cancer. However the inverse vitamin C-lung cancer association was largely explained by smoking and dietary beta-cryptoxanthin. Other carotenoids (alpha-carotene, beta-carotene, lycopene, and lutein/zeaxanthin), vitamins A and E, and folate were not associated significantly with lung cancer risk after adjustment for cigarette smoking. We recognized that potential measurement errors in cigarette smoking may exert an effect on the dietary beta-cryptoxanthin-lung cancer association. After additional adjustments were made for the residual confounding by smoking using statistical models, about 15-40% reduction in risk of lung cancer was seen for subjects in the highest versus lowest 10th percentile of dietary beta-cryptoxanthin. The present study lends additional credence to prior experimental and epidemiological data in support of the hypothesis that dietary beta-cryptoxanthin is a chemopreventive agent for lung cancer in humans.

Aged↗

Oral administration of beta-cryptoxanthin prevents bone loss in streptozotocin-diabetic rats in vivo.

The effects of beta-cryptoxanthin, a carotenoid, on bone components in the femoral-diaphyseal and -metaphyseal tissues of streptozotocin (STZ)-diabetic rats was investigated. Rats received a single subcutaneous administration of STZ (6.0 mg/100 g body weight), and then the animal were orally administered beta-cryptoxanthin (5 or 10 microg/100 g body weight) once daily for 7 or 14 d. The administration of STZ caused a significant decrease in body weight and a significant increase in serum glucose, triglyceride, and calcium levels, indicating a diabetic state. These alterations were significantly prevented by the administration of beta-cryptoxanthin (5 or 10 microg/100 g) for 14 d. The administration of beta-cryptoxanthin (5 or 10 microg/100 g) to normal rats for 14 d did not have a significant effect on body weight or on serum glucose, triglyceride, and calcium levels. Calcium content, alkaline phosphatase activity, and DNA content in the femoral-diaphyseal and -metaphyseal tissues were significantly decreased in STZ-diabetic rats. These decreases were significantly prevented by the administration of beta-cryptoxanthin (5 or 10 microg/100 g) for 14 d. The administration of beta-cryptoxanthin to normal rats for 14 d caused a significant increase in calcium content, alkaline phosphatase activity, and DNA content in the femoral-diaphyseal and -metaphyseal tissues. This study demonstrates that the intake of beta-cryptoxanthin has a preventive effect on bone loss in STZ-diabetic rats.

Animals↗

Oral administration in combination with zinc enhances beta-cryptoxanthin-induced anabolic effects on bone components in the femoral tissues of rats in vivo.

The effects of combined beta-cryptoxanthin and zinc on bone components in the femoral-diaphyseal (cortical bone) and -metaphyseal (trabecular bone) tissues of rats in vivo were investigated. Rats were orally administered either vehicle, beta-cryptoxanthin (5 or 10 microg/100 g body weight), zinc sulfate (0.1 or 0.5 mg Zn/100 g), or their combination once a day for 7 d. Calcium content, alkaline phosphatase activity, and DNA content in the femoral-diaphyseal tissues was not significantly altered by the administration of beta-cryptoxanthin (5 microg/100 g) or zinc (0.1 or 0.5 mg/100 g). Combined administration of beta-cryptoxanthin (5 microg/100 g) and zinc (0.1 or 0.5 mg/100 g) caused a synergistic increase in calcium content, alkaline phosphatase activity, and DNA content in the diaphyseal tissues. The effect of beta-cryptoxanthin (5 or 10 microg/100 g) in increasing calcium and DNA contents in the metaphyseal tissues was significantly enhanced by the combined administration of zinc (0.1 or 0.5 mg/100 g), but did not have a significant effect on the metaphyseal components. The metaphyseal alkaline phosphatase activity was markedly increased by the combination of beta-cryptoxanthin (5 microg/100 g) and zinc (0.1 or 0.5 mg/100 g). This study demonstrates that the oral administration of the combination of zinc at lower doses synergistically enhances beta-cryptoxanthin-induced anabolic effects on bone components in the femoral tissues of rats in vivo.

Administration, Oral↗