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1.
Int J Mol Sci ; 25(7)2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38612498

ABSTRACT

Sericin derived from the white cocoon of Bombyx mori has been attracting more attention for its utilization in food, cosmetics, and biomedicine. The potential health benefits of natural carotenoids for humans have also been well-established. Some rare strains of Bombyx mori (B. mori) produce yellow-red cocoons, which endow a potential of natural carotenoid-containing sericin. We hypothesized that natural carotenoid-containing sericin from yellow-red cocoons would exhibit better properties compared with white cocoon sericin. To investigate the physicochemical attributes of natural carotenoid-containing sericin, we bred two silkworm strains from one common ancestor, namely XS7 and XS8, which exhibited different cocoon colors as a result of the inconsistent distribution of lutein and ß-carotene. Compared with white cocoon sericin, the interaction between carotenoids and sericin molecules in carotenoid-containing sericin resulted in a unique fluorescence emission at 530, 564 nm. The incorporation of carotenoids enhanced the antibacterial effect, anti-cancer ability, cytocompatibility, and antioxidant of sericin, suggesting potential wide-ranging applications of natural carotenoid-containing sericin as a biomass material. We also found differences in fluorescence characteristics, antimicrobial effects, anti-cancer ability, and antioxidants between XS7 and XS8 sericin. Our work for the first time suggested a better application potential of natural carotenoid-containing sericin as a biomass material than frequently used white cocoon sericin.


Subject(s)
Bombyx , Sericins , Humans , Animals , Carotenoids/pharmacology , Sericins/pharmacology , Antioxidants/pharmacology , beta Carotene/pharmacology
2.
Adv Nutr ; 15(5): 100211, 2024 May.
Article in English | MEDLINE | ID: mdl-38493875

ABSTRACT

A systematic review and meta-analysis was conducted to assess the relationship between the common dietary antioxidants vitamin C, vitamin E, and ß-carotene and type 2 diabetes (T2D) and related traits. MEDLINE, Embase, and the Cochrane Library were searched for relevant publications up until May 2023. Studies were eligible if they had a cohort, case-control, or randomized controlled trial (RCT) design and examined dietary intake, supplementation, or circulating levels of these antioxidants as exposure, and insulin resistance, ß-cell function, or T2D incidence as outcomes. Summary relative risks (RR) or mean differences (MD) with 95% confidence intervals (CI) were estimated using random-effects models. The certainty of the evidence was assessed with the Grading of Recommendations, Assessment, Development and Evaluations framework. Among 6190 screened records, 25 prospective observational studies and 15 RCTs were eligible. Inverse associations were found between dietary and circulating antioxidants and T2D (observational studies). The lowest risk was seen at intakes of 70 mg/d of vitamin C (RR: 0.76; CI: 0.61, 0.95), 12 mg/d of vitamin E (RR: 0.72; CI: 0.61, 0.86), and 4 mg/d of ß-carotene (RR: 0.78; CI: 0.65, 0.94). Supplementation with vitamin E (RR: 1.01; CI: 0.93, 1.10) or ß-carotene (RR: 0.98; CI: 0.90, 1.07) did not have a protective effect on T2D (RCTs), and data on vitamin C supplementation was limited. Regarding insulin resistance, higher dietary vitamin C (RR: 0.85; CI: 0.74, 0.98) and vitamin E supplementation (MD: -0.35; CI: -0.65, -0.06) were associated with a reduced risk. The certainty of evidence was high for the associations between T2D and dietary vitamin E and ß-carotene, and low to moderate for other associations. In conclusion, moderate intakes of vitamins C, E, and ß-carotene may lower risk of T2D by reducing insulin resistance. Lack of protection with supplementation in RCTs suggests that adequate rather than high intakes may play a role in T2D prevention. This systematic review and meta-analysis was registered in PROSPERO with registration number CRD42022343482.


Subject(s)
Antioxidants , Ascorbic Acid , Diabetes Mellitus, Type 2 , Dietary Supplements , Vitamin E , beta Carotene , Diabetes Mellitus, Type 2/prevention & control , Diabetes Mellitus, Type 2/blood , Humans , beta Carotene/administration & dosage , beta Carotene/pharmacology , beta Carotene/blood , Ascorbic Acid/administration & dosage , Ascorbic Acid/pharmacology , Vitamin E/administration & dosage , Vitamin E/pharmacology , Antioxidants/administration & dosage , Insulin Resistance , Diet , Risk Factors , Male , Female , Middle Aged , Adult , Aged
3.
Neurobiol Aging ; 133: 16-27, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38381472

ABSTRACT

A significant progressive decline in beta-carotene (ßC) levels in the brain is associated with cognitive impairment and a higher prevalence of Alzheimer's disease (AD). In this study, we investigated whether the administration of 9-cis beta-carotene (9CBC)-rich powder of the alga Dunaliella bardawil, the best-known source of ßC in nature, inhibits the development of AD-like neuropathology and cognitive deficits. We demonstrated that in 3 AD mouse models, Tg2576, 5xFAD, and apoE4, 9CBC treatment improved long- and short-term memory, decreased neuroinflammation, and reduced the prevalence of ß-amyloid plaques and tau hyperphosphorylation. These findings suggest that 9CBC has the potential to be an effective preventive and symptomatic AD therapy.


Subject(s)
Alzheimer Disease , Neuroinflammatory Diseases , Animals , Mice , beta Carotene/pharmacology , beta Carotene/therapeutic use , Alzheimer Disease/drug therapy , Diet , Cognition , Disease Models, Animal , Plaque, Amyloid
4.
Elife ; 122024 Feb 06.
Article in English | MEDLINE | ID: mdl-38319073

ABSTRACT

ß-Carotene oxygenase 1 (BCO1) catalyzes the cleavage of ß-carotene to form vitamin A. Besides its role in vision, vitamin A regulates the expression of genes involved in lipid metabolism and immune cell differentiation. BCO1 activity is associated with the reduction of plasma cholesterol in humans and mice, while dietary ß-carotene reduces hepatic lipid secretion and delays atherosclerosis progression in various experimental models. Here we show that ß-carotene also accelerates atherosclerosis resolution in two independent murine models, independently of changes in body weight gain or plasma lipid profile. Experiments in Bco1-/- mice implicate vitamin A production in the effects of ß-carotene on atherosclerosis resolution. To explore the direct implication of dietary ß-carotene on regulatory T cells (Tregs) differentiation, we utilized anti-CD25 monoclonal antibody infusions. Our data show that ß-carotene favors Treg expansion in the plaque, and that the partial inhibition of Tregs mitigates the effect of ß-carotene on atherosclerosis resolution. Our data highlight the potential of ß-carotene and BCO1 activity in the resolution of atherosclerotic cardiovascular disease.


Subject(s)
Atherosclerosis , beta Carotene , Mice , Humans , Animals , beta Carotene/pharmacology , beta Carotene/metabolism , Vitamin A/metabolism , Liver/metabolism , Atherosclerosis/drug therapy , Atherosclerosis/metabolism , Lipids
5.
Yakugaku Zasshi ; 144(2): 203-222, 2024.
Article in Japanese | MEDLINE | ID: mdl-38296498

ABSTRACT

Normal differentiation and proliferation of cells are essential for maintaining homeostasis. Following the successful completion of whole genome sequencing, protein modification has been attracted increasing attention in order to understand the roles of protein diversification in protein function and to elucidate molecular targets in mechanisms of signal transduction. Vitamin A is an essential nutrient for health maintenance. It is present as ß-carotene in green and yellow vegetables and retinyl ester in animal products and absorbed into the body from the intestines. After ingestion, it is converted to retinol and oxidized in target cells to retinal, which plays critical roles in vision. It is then further oxidized to retinoic acid (RA), which exhibits a number of effects prior to being metabolized by cytochrome P450 and excreted from the body. Since RA exhibits cell differentiation-inducing actions, it is used as a therapeutic agent for patients with acute promyelocytic leukemia. The current paper describes: (1) HL60 cell differentiation and cell differentiation induction therapy by RA; (2) roles played by RA and retinal and their mechanisms of action; (3) retinoylation, post-translational protein-modified by RA, a novel non-genomic RA mechanism of action without RA receptor; (4) new actions of ß-carotene and retinol in vivo and (5) potent anticancer effects of p-dodecylaminophenol (p-DDAP), a novel vitamin A derivative created from the RA derivative fenretinide. We propose that nutritional management of vitamin A can be effective at preventing and treating diseases, and that p-DDAP is a promising anticancer drug.


Subject(s)
Neoplasms , Vitamin A , Animals , Humans , Vitamin A/pharmacology , beta Carotene/pharmacology , Tretinoin/pharmacology , Tretinoin/therapeutic use , Cell Differentiation , Cell Proliferation , Neoplasms/drug therapy , Neoplasms/etiology , Neoplasms/prevention & control
6.
Int J Mol Sci ; 25(2)2024 Jan 19.
Article in English | MEDLINE | ID: mdl-38279214

ABSTRACT

Alcohol is believed to harm acinar cells, pancreatic ductal epithelium, and pancreatic stellate cells. After giving ethanol and/or ß-carotene to C57BL/6 mice, our goal was to evaluate their biochemistry, histology, and morpho-quantitative features. There were six groups of C57BL/6 mice: 1. Group C (control), 2. Group LA (low-dose alcohol), 3. Group MA (moderate-dose alcohol), 4. Group B (ß-carotene), 5. Group LA + B (low-dose alcohol combined with ß-carotene), and 6. Group MA + B (moderate-dose alcohol combined with ß-carotene). After the animals were euthanized on day 28, each specimen's pancreatic tissue was taken. Lipase, uric acid, and amylase were assessed using biochemical assessment. Furthermore, the examination of the pancreatic structure was conducted using Ammann's fibrosis scoring system. Finally, the morpho-quantitative characteristics of the pancreatic islets and acinar cells were determined. In the serum of the MA + B group, there were higher amounts of total amylase (825.953 ± 193.412 U/L) and lower amounts of lipase (47.139 ± 6.099 U/L) (p < 0.05). Furthermore, Ammann's fibrosis punctuation in the pancreas revealed significant variations between the groups (p < 0.001). Finally, the stereological analysis of pancreatic islets showed that the groups were different (p < 0.001). These findings suggest that antioxidant treatments might help decrease the negative effects of ethanol exposure in animal models.


Subject(s)
Pancreas , beta Carotene , Mice , Animals , beta Carotene/pharmacology , Mice, Inbred C57BL , Pancreas/pathology , Ethanol , Lipase , Amylases , Fibrosis , Dietary Supplements
7.
Cryobiology ; 114: 104851, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38237749

ABSTRACT

Sperm quality is preserved through the crucial involvement of antioxidants, which play a vital role in minimizing the occurrence of reactive oxygen species (ROS) during the cryopreservation process. The suitability of the type and concentration of antioxidants are species-dependent, and this study is crucial in order to improve the quality of the climbing perch sperm post-cryopreservation. Therefore, this study aimed to determine the best type and concentration of antioxidants for cryopreservation of climbing perch Anabas testudineus sperm. To achieve this, 6 types of antioxidants, namely, ascorbic acid, beta-carotene, glutathione, butylated hydroxytoluene (BHT), myo-inositol, and alpha-tocopherol, with inclusion of a control were tested in 3 replications at three concentration levels of 0 mg/L (control), 20 mg/L, 40 mg/L, and 60 mg/L. Sperm was diluted in a glucose-base extender at a ratio of 1:60 (sperm: glucose base), then 10 % DMSO and 5 % egg yolk was added before cryopreservation for two weeks. The results showed that the type and concentration of antioxidants had a significant effect on the motility and viability of cryopreserved climbing perch sperm (P < 0.05), where the best results for ascorbic acid, beta-carotene, glutathione, myo-inositol, and alpha-tocopherol were obtained at a concentration of 60 mg/L, while BHT was at a concentration of 20 mg/L. The best results for glutathione, myo-inositol, and alpha-tocopherol were significantly different from other treatments, while the best results for ascorbic acid and beta-carotene (60 mg/L) were not significantly different from the 40 mg/L concentration, while the best results for BHT were not significantly different from the control treatments. Therefore, the best concentration of glutathione, myo-inositol, and alpha-tocopherol was 60 mg/L, while for ascorbic acid and beta-carotene it was 40 mg/L, and BHT was not recommended. DNA integrity analysis indicated the absence of fragmentation in all samples, including fresh, control, and treated sperm. Based on practical and economic considerations, myo-inositol at 60 mg/L was recommended for cryopreservation of climbing perch A. testudineus sperm.


Subject(s)
Perches , Semen Preservation , Animals , Male , Antioxidants/pharmacology , Sperm Motility , alpha-Tocopherol/pharmacology , beta Carotene/pharmacology , Cryopreservation/methods , Semen , Semen Preservation/veterinary , Semen Preservation/methods , Spermatozoa , Ascorbic Acid/pharmacology , Glutathione/pharmacology , DNA , Glucose/pharmacology , Inositol/pharmacology
8.
Cell Biochem Biophys ; 82(1): 291-302, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38082173

ABSTRACT

This experiment successfully isolated the rat colonic epithelial cells and established a TNF-α-induced intestinal inflammation model. Western Blot was used to detect the related protein expression levels of the MAPKs signaling pathway. QPCR technology was used to detect the expression of aquaporins, intestinal mucosal repair factor, and inflammatory factors. The results show that 25 µM ß-carotene pretreatment at 24 h can inhibit MAPKs signaling pathway activated by TNF-α, change the relative mRNA expression of inflammatory cytokines, intestinal mucosal repair factors, and aquaporins, and the phosphorylated protein expression of p38, ERK, and NF-κB were attenuated to reduce inflammatory damage. After inhibiting p38 and ERK, the effect of ß-carotene was reduced significantly (P < 0.05). In conclusion, ß-carotene can alleviate the abnormal expression of aquaporins caused by inflammation through the MAPKs signaling pathway. This is for ß-carotene as a functional nutrient that provides new insights.


Subject(s)
Aquaporins , Tumor Necrosis Factor-alpha , Rats , Animals , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism , beta Carotene/pharmacology , beta Carotene/metabolism , Signal Transduction , NF-kappa B/metabolism , Epithelial Cells/metabolism , Inflammation/chemically induced , Inflammation/metabolism , Aquaporins/metabolism
9.
J Oleo Sci ; 72(11): 1027-1035, 2023.
Article in English | MEDLINE | ID: mdl-37914264

ABSTRACT

Acute liver injury (ALI), posing a serious threaten to our life, has emerged as a public health issue around the world. ß-carotene has plenty of pharmacologic effects, such as anti-inflammatory, antioxidant, and antitumor activities. In this study, we focused on studying the protective role and potential molecular mechanisms of ß-carotene against D-galactosamine (D-GalN) and lipopolysaccharide (LPS) induced ALI. Our results indicated that ß-carotene pretreatment effectively hindered abnormal changes induced by LPS/D-GalN in liver histopathology. Meanwhile, serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were downgraded with ß-carotene pretreatment. ß-carotene pretreatment also decreased malondialdehyde content and myeloperoxidase activity, increased glutathione peroxidase and superoxide dismutase levels, and reduced the levels of tumor necrosis factor-a (TNF-α) and interleukin 6 (IL-6) in liver tissues. Further investigations found that ß-carotene mediated multiple signaling pathways in LPS/D-GalN-induced ALI, inhibiting NF-κB and MAPK signaling and upregulating the expression of Nrf2 and HO-1 proteins. All findings indicate that ß-carotene appears to protect mice against LPS/D-GalN induced ALI by reducing oxidative stress and inflammation, possibly via regulating NF-κB, MAPK, and Nrf2 signaling.


Subject(s)
Chemical and Drug Induced Liver Injury , NF-kappa B , Animals , Mice , Antioxidants/pharmacology , Antioxidants/metabolism , beta Carotene/pharmacology , Chemical and Drug Induced Liver Injury/prevention & control , Galactosamine/toxicity , Galactosamine/metabolism , Lipopolysaccharides , Liver/metabolism , NF-E2-Related Factor 2/metabolism , NF-kappa B/metabolism , Tumor Necrosis Factor-alpha/metabolism
10.
J Agric Food Chem ; 71(48): 18696-18708, 2023 Dec 06.
Article in English | MEDLINE | ID: mdl-38012857

ABSTRACT

Deoxynivalenol (DON), one of the most polluted mycotoxins in the environment and food, has been proven to have strong embryonic and reproductive toxicities. However, the effects of DON on placental impairment and effective interventions are still unclear. This study investigated the effect of ß-carotene on placental functional impairment and its underlying molecular mechanism under DON exposure. Adverse pregnancy outcomes were caused by intraperitoneal injection of DON from 13.5 to 15.5 days of gestation in mice, resulting in higher enrichment of DON in placenta than in other tissue samples. Interestingly, 0.1% ß-carotene dietary supplementation could significantly alleviate DON-induced pregnancy outcomes. Additionally, in vivo and in vitro placental barrier models demonstrated the association of DON-induced placental function impairment with placental permeability barrier disruption, angiogenesis impairment, and oxidative stress induction. Moreover, ß-carotene regulated DON-induced placental toxicity by activating the expressions of claudin 1, zonula occludens-1, and vascular endothelial growth factor-A through retinoic acid-peroxisome proliferator-activated receptor α signaling.


Subject(s)
PPAR alpha , Placenta , Pregnancy , Female , Animals , Mice , Placenta/metabolism , PPAR alpha/metabolism , beta Carotene/pharmacology , beta Carotene/metabolism , Vascular Endothelial Growth Factor A/metabolism , Tretinoin/metabolism
11.
Int J Mol Sci ; 24(14)2023 Jul 22.
Article in English | MEDLINE | ID: mdl-37511557

ABSTRACT

As the use of antioxidant compounds in the domains of health, nutrition and well-being is exponentially rising, there is an urgent need to quantify antioxidant power quickly and easily, ideally within living cells. We developed an Anti Oxidant Power in Yeast (AOPY) assay which allows for the quantitative measurement of the Reactive Oxygen Species (ROS) and free-radical scavenging effects of various molecules in a high-throughput compatible format. Key parameters for Saccharomyces cerevisiae were investigated, and the optimal values were determined for each of them. The cell density in the reaction mixture was fixed at 0.6; the concentration of the fluorescent biosensor (TO) was found to be optimal at 64 µM, and the strongest response was observed for exponentially growing cells. Our optimized procedure allows accurate quantification of the antioxidant effect in yeast of well-known antioxidant molecules: resveratrol, epigallocatechin gallate, quercetin and astaxanthin added in the culture medium. Moreover, using a genetically engineered carotenoid-producing yeast strain, we realized the proof of concept of the usefulness of this new assay to measure the amount of ß-carotene directly inside living cells, without the need for cell lysis and purification.


Subject(s)
Antioxidants , Saccharomyces cerevisiae , Antioxidants/pharmacology , Carotenoids/pharmacology , beta Carotene/pharmacology , Reactive Oxygen Species
12.
Anim Biotechnol ; 34(9): 4978-4988, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37300519

ABSTRACT

This experiment was conducted to evaluate the growth performance, growth regulating factors, and liver morphology of chicks hatched from egg-laying breeding hens dietary supplemented with additives (ß-carotene). Hy-line breeding hens were allocated into three groups with three replicates/group. The dietary treatments were as follows: basal diet as a control (Con), basal diet supplemented with 120 (ßc-L) or 240 (ßc-H) mg/kg of ß-carotene diet. After 6 weeks, the eggs were collected and incubated. The hatched chicks were fed the same diet. The results showed that chicks in the ßc-L group increased in body weight at 21 days (p < 0.01). At 42 days, chicks in the ßc-H group showed a significant increase in tibia length (p < 0.05). The liver index increased in the ßc-L and ßc-H groups at 7 days (p < 0.05). Serum HGF (7, 14, 21, and 42 days) and leptin (14 days) were significantly increased in the group supplemented with ßc. Hepatic GHR (14 days), IGF-1R (14 days), and LEPR (21 days) mRNA expression were significantly increased. In addition, there was an increase in PCNA-positive cells in the liver of chicks in the ßc group. In conclusion, the addition of ß-carotene to the diet of laying breeder hens was more advantageous in terms of growth performance and liver development of the offspring.


Subject(s)
Chickens , beta Carotene , Animals , Female , Chickens/genetics , beta Carotene/pharmacology , beta Carotene/metabolism , Diet/veterinary , Dietary Supplements , Animal Feed/analysis , Liver
13.
Free Radic Biol Med ; 205: 25-46, 2023 08 20.
Article in English | MEDLINE | ID: mdl-37270031

ABSTRACT

Endoplasmic reticulum (ER) and mitochondria are the main sites for the storage and regulation of Ca2+ homeostasis. An imbalance of Ca2+ homeostasis can cause ER stress and mitochondrial dysfunction, thereby inducing apoptosis. The store-operated calcium entry (SOCE) is the main channel for extracellular calcium influx. Mitochondria-associated endoplasmic reticulum (MAM) is an important agent for Ca2+ transfer from the ER to the mitochondria. Therefore, regulation of SOCE and MAMs has potential therapeutic value for disease prevention and treatment. In this study, bovine mammary epithelial cells (BMECs) and mice were used as models to explore the mechanisms of ß-carotene to relieve ER stress and mitochondrial dysfunction. BAPTA-AM, EGTA (Ca2+ inhibitor), and BTP2 (SOCE channel inhibitor) alleviated ER stress and mitochondrial oxidative damage induced by increased intracellular Ca2+ levels after lipopolysaccharide (LPS) stimulation. Furthermore, inhibition of ER stress by 4-PBA (ER stress inhibitor), 2-APB (IP3R inhibitor), and ruthenium red (mitochondrial calcium uniporter (MCU) inhibitor) restored mitochondrial function by reducing mitochondrial ROS. Our data also confirm that ß-carotene targeted STIM1 and IP3R channels to repair LPS-induced ER stress and mitochondrial disorders. Consistent with the in vitro study, in vito experiments in mice further showed that ß-carotene attenuated LPS-induced ER stress and mitochondrial oxidative damage by inhibiting the expression of STIM1 and ORAI1, and reducing the level of Ca2+ in mouse mammary glands. Therefore, ER stress-mitochondrial oxidative damage mediated by the STIM1-ER-IP3R/GRP75/VDAC1-MCU axis plays an vital role in the development of mastitis. Our results provided novel ideas and therapeutic targets for the prevention and treatment of mastitis.


Subject(s)
Lipopolysaccharides , beta Carotene , Animals , Mice , Cattle , Lipopolysaccharides/toxicity , Lipopolysaccharides/metabolism , beta Carotene/pharmacology , Calcium/metabolism , Mitochondria/metabolism , Calcium Signaling/physiology , Oxidative Stress
14.
PLoS One ; 18(5): e0285180, 2023.
Article in English | MEDLINE | ID: mdl-37195965

ABSTRACT

Lettuce (Lactuca sativa) is commonly produced in vertical farms. The levels of nutritionally important phytochemicals such as beta-carotene (precursor to vitamin A) are generally low in lettuce. In this study, we investigated the benefits of variable lighting strategy (i.e., varying the light quality during production) on maintaining plant growth and increasing the biosynthesis of beta-carotene and anthocyanin. We tested two variable lighting methods, using green and red romaine lettuce, namely (i) providing growth lighting (supports vegetative growth) initially (21 days) followed by a high percentage of blue light (supports biosynthesis of phytochemicals) at final stages (10 days) and (ii) providing a high percentage of blue light initially followed by growth lighting at final stages. Our results indicate that the variable lighting method with initial growth lighting and high percentage of blue at final stages can maintain vegetative growth and enhance phytochemicals such as beta-carotene in green romaine lettuce while both variable lighting methods were not effective in red romaine lettuce. In green romaine lettuce, we did not observe a significant reduction in shoot dry weight but there was an increase in beta-carotene (35.7%) in the variable compared to the fixed lighting method with growth lighting for the entire duration. The physiological bases for differences in vegetative growth and synthesis of beta-carotene and anthocyanin in the variable and fixed lighting methods are discussed.


Subject(s)
Lactuca , beta Carotene , Farms , beta Carotene/pharmacology , Anthocyanins/pharmacology , Light , Agriculture , Nutritive Value , Plant Leaves
15.
Sci Rep ; 13(1): 8555, 2023 05 26.
Article in English | MEDLINE | ID: mdl-37237040

ABSTRACT

Oxidative stress has been considered the main contributor to liver injury. Dietary antioxidants would be expected to improve liver function. The hepatoprotective effects of antioxidants are controversial. In the present study, the associations of some dietary antioxidants and the levels of serum liver enzymes were examined. This cross-sectional study was conducted using the Rafsanjan Cohort Study (RCS) data as a population-based prospective cohort which is a part of the Prospective Epidemiological Research Studies in IrAN (PERSIAN). A total of 9942 participants aged 35-70 years old were included in this study. Among this population, 4631 (46.59%) were male, and 5311 (53.42%) were female. Dietary intakes were collected by a validated food frequency questionnaire (FFQ) with 128 items. Aspartate transaminase (AST), Alanine transaminase (ALT), γ-glutamyl transferase (GGT), and Alkaline phosphatase (ALP) were measured by a biotecnica analyzer. Dichotomous logistics regression models were used to investigate the association between the elevated liver enzymes and intake of dietary antioxidants using crude and adjusted models. In the adjusted model, in subjects with higher consumption of Se, Vit A, Vit E, ß-carotene, α-carotene, and ß-cryptoxanthin, the odds ratios of elevated ALP were decreased compared to the reference group (ORs 0.79 (0.64-0.96), 0.80 (0.66-0.98), 0.73 (0.60-0.89), 0.79 (0.64-0.96), 0.78 (0.64-0.95), 0.80 (0.66-0.98), and 0.79 (0.64-0.98), respectively). Subjects with higher consumption of Se, Vit A, Vit E, and provitamin A carotenoids (ß-carotene, α-carotene, ß-cryptoxanthin) showed decreased odds of elevated ALP. These findings support the hypothesis that Se, Vit A, Vit E, and provitamin A carotenoids may be associated with improvements in ALP and act as suppressors against the development of liver injury.


Subject(s)
Antioxidants , beta Carotene , Male , Humans , Female , Adult , Middle Aged , Aged , Antioxidants/pharmacology , beta Carotene/pharmacology , Cohort Studies , Prospective Studies , Beta-Cryptoxanthin , Provitamins/pharmacology , Cross-Sectional Studies , Iran , Carotenoids/pharmacology , Vitamin E/pharmacology , Liver , Vitamin A/pharmacology , Alanine Transaminase
16.
Front Endocrinol (Lausanne) ; 14: 1148954, 2023.
Article in English | MEDLINE | ID: mdl-37143734

ABSTRACT

Introduction: Naringenin, a peroxisome proliferator-activated receptor (PPAR) activator found in citrus fruits, upregulates markers of thermogenesis and insulin sensitivity in human adipose tissue. Our pharmacokinetics clinical trial demonstrated that naringenin is safe and bioavailable, and our case report showed that naringenin causes weight loss and improves insulin sensitivity. PPARs form heterodimers with retinoic-X-receptors (RXRs) at promoter elements of target genes. Retinoic acid is an RXR ligand metabolized from dietary carotenoids. The carotenoid ß-carotene reduces adiposity and insulin resistance in clinical trials. Our goal was to examine if carotenoids strengthen the beneficial effects of naringenin on human adipocyte metabolism. Methods: Human preadipocytes from donors with obesity were differentiated in culture and treated with 8µM naringenin + 2µM ß-carotene (NRBC) for seven days. Candidate genes involved in thermogenesis and glucose metabolism were measured as well as hormone-stimulated lipolysis. Results: We found that ß-carotene acts synergistically with naringenin to boost UCP1 and glucose metabolism genes including GLUT4 and adiponectin, compared to naringenin alone. Protein levels of PPARα, PPARγ and PPARγ-coactivator-1α, key modulators of thermogenesis and insulin sensitivity, were also upregulated after treatment with NRBC. Transcriptome sequencing was conducted and the bioinformatics analyses of the data revealed that NRBC induced enzymes for several non-UCP1 pathways for energy expenditure including triglyceride cycling, creatine kinases, and Peptidase M20 Domain Containing 1 (PM20D1). A comprehensive analysis of changes in receptor expression showed that NRBC upregulated eight receptors that have been linked to lipolysis or thermogenesis including the ß1-adrenergic receptor and the parathyroid hormone receptor. NRBC increased levels of triglyceride lipases and agonist-stimulated lipolysis in adipocytes. We observed that expression of RXRγ, an isoform of unknown function, was induced ten-fold after treatment with NRBC. We show that RXRγ is a coactivator bound to the immunoprecipitated PPARγ protein complex from white and beige human adipocytes. Discussion: There is a need for obesity treatments that can be administered long-term without side effects. NRBC increases the abundance and lipolytic response of multiple receptors for hormones released after exercise and cold exposure. Lipolysis provides the fuel for thermogenesis, and these observations suggest that NRBC has therapeutic potential.


Subject(s)
Adipocytes, White , Insulin Resistance , Humans , Adipocytes, White/metabolism , beta Carotene/pharmacology , beta Carotene/metabolism , Lipolysis , PPAR gamma/metabolism , Obesity/metabolism , Phenotype , Hormones , Triglycerides , Glucose
17.
J Anim Sci ; 1012023 Jan 03.
Article in English | MEDLINE | ID: mdl-37010193

ABSTRACT

Finishing pigs (N = 224; 28.66 ± 1.90 kg bodyweight) were randomly assigned across 56 pens of either four barrows or gilts, and assigned to one of four diets: control (7,656 IU vitamin A/kg), control supplemented with vitamin A (4.36 ppm, Rovimix A 1000, DSM, Parsippany, NJ, USA), control supplemented with beta-carotene (163.28 ppm, Rovimix ß-Carotene 10%, DSM, Parsippany), or control supplemented with oxidized beta-carotene (40 ppm; 10% active ingredient, Avivagen, Ottawa, ON, Canada). Pigs and feeder weights were obtained at the start of the study (d 0), and end of each phase (d 21, 42, and 63). A subset of gilts had a blood sample taken via jugular venipuncture on d 0, a blood sample and vaccinations of Lawsonia intracellularis and porcine circovirus type 2 (PCV2) on d 18, a blood sample and booster vaccination of PCV2 on d 39, a blood sample on day 60, and a final blood sample on day 63. Gilts were euthanized at the end of the study to obtain a liver (entire right lobe) and a jejunum sample (15.24 cm at 10% of length). Additionally, the second and fourth right anterior mammary were collected to assess anterior mammary tissues. Data were analyzed in SAS 9.4 (Statistical Analysis System, Cary, NC) via GLIMMIX procedure. Oxidized beta-carotene supplementation increased (P = 0.02) ADG across phases over vitamin A supplementation, although there were no differences (P = 0.18) in the body weight of pigs. There was no effect (P > 0.05) of diet on plasma or hepatic retinol, IgG or IgM levels, or immune cell presence in developing mammary tissue. Supplemented vitamin A tended (P = 0.05) to increase the mRNA abundance of retinol binding protein in the jejunum, but other mRNA abundance for genes (alcohol dehydrogenase class 1, lecithin retinol acyltransferase phosphatidylcholine-retinol O-acyltransferase, and beta-carotene oxygenase 1) were not affected (P > 0.05) by dietary treatments. A diet by time interaction (P = 0.04) was noted for the circovirus S/P ratio, where vitamin A supplementation had the best ratio compared to other diets. Analyzed titer levels for the circovirus vaccine had an interaction (P < 0.01) for diet by time, where vitamin A supplementation had the highest titer at the end of the study. Thus, pigs supplemented with oxidized beta-carotene had an improved ADG over vitamin A supplemented pigs, but pigs supplemented with vitamin A seemed to have an improved immune status.


Vitamin A, beta-carotene, and oxidized beta-carotene were supplemented to finishing pigs to determine if feeding vitamin A, beta-carotene, or oxidized beta-carotene influences growth performance and the proliferation of immune cell populations in the developing mammary gland in prepubertal gilts. When evaluating overall growth parameters, there were no differences across the dietary treatments and no differences in the circulating immunoglobulin production. Supplementing vitamin A did increase the amount of retinol binding protein that was expressed in the small intestine. Pigs supplemented with oxidized beta-carotene did have an increase in average daily gain (ADG) during a health challenge over pigs supplemented with vitamin A. However, gilts that received vitamin A supplementation had an improved sample-to-positive ratio (S/P ratio) and titer response to porcine circovirus 2 vaccines, indicating that vitamin A supplemented gilts have an improved immune response to vaccinations.


Subject(s)
Vitamin A , beta Carotene , Swine , Animals , Female , Vitamin A/pharmacology , beta Carotene/pharmacology , Dietary Supplements/analysis , Sus scrofa , Diet/veterinary , Animal Feed/analysis
18.
Trop Anim Health Prod ; 55(3): 175, 2023 Apr 26.
Article in English | MEDLINE | ID: mdl-37099042

ABSTRACT

This study was aimed at investigating the effects of vitamin A (VITA), vitamin E (VITE), and combined ß-carotene plus vitamin E (ßCAR+VITE) injections on some fertility parameters in ewes. Estrus synchronization was performed by treating the ewes with intravaginal FGA sponges impregnated with 30 mg of fluorogestone acetate. On the days of the insertion and withdrawal of the intravaginal sponges, groups VITA, VITE, and ßCAR+VITE were administered with 500 000 IU of vitamin A, 50 mg of vitamin E, and a combination of ß-carotene plus vitamin E, respectively. The ewes in the control group (C) were maintained for control purposes. Statistically significant differences were determined between groups VITA and ßCAR+VITE, groups VITE and ßCAR+VITE, and groups C and ßCAR+VITE, as well as groups VITE and C, groups VITA and C for the multiple birth rates. While significant differences were determined between groups VITA and C, groups VITE and C, and groups ßCAR+VITE and C for the lambing rates, it was ascertained that the ratio of newborn lambs to delivered ewes (litter size) significantly differed between groups VITA and ßCAR+VITE, groups VITA and C, groups VITE and ßCAR+VITE, groups VITE and C, and groups ßCAR+VITE and C. The highest MDA level and lowest GSH level were determined on day 20 after mating in the control group. In conclusion, it is suggested that both multiple birth rates and litter size can be increased by the combined administration of ß-carotene and vitamin E.


Subject(s)
Fertility , Sheep , Vitamin A , Vitamin E , beta Carotene , Animals , Female , Pregnancy , beta Carotene/pharmacology , Estrus Synchronization , Fertility/drug effects , Injections/veterinary , Sheep/physiology , Vitamin A/pharmacology , Vitamin E/pharmacology , Male
19.
Int J Mol Sci ; 24(6)2023 Mar 08.
Article in English | MEDLINE | ID: mdl-36982248

ABSTRACT

The aggregation of amyloid beta (Aß) into fibrillar aggregates is a key feature of Alzheimer's disease (AD) pathology. ß-carotene and related compounds have been shown to associate with amyloid aggregates and have direct impact on the formation of amyloid fibrils. However, the precise effect of ß-carotene on the structure of amyloid aggregates is not known, which poses a limitation towards developing it as a potential AD therapeutic. In this report, we use nanoscale AFM-IR spectroscopy to probe the structure of Aß oligomers and fibrils at the single aggregate level and demonstrate that the main effect of ß-carotene towards modulating Aß aggregation is not to inhibit fibril formation but to alter the secondary structure of the fibrils and promote fibrils that lack the characteristic ordered beta structure.


Subject(s)
Alzheimer Disease , Amyloid beta-Peptides , Humans , Amyloid beta-Peptides/chemistry , beta Carotene/pharmacology , Alzheimer Disease/pathology , Amyloid/chemistry , Protein Structure, Secondary , Peptide Fragments/chemistry
20.
Mol Pharm ; 20(5): 2326-2340, 2023 05 01.
Article in English | MEDLINE | ID: mdl-36976623

ABSTRACT

Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. Despite recent therapeutic advancements, resistance to 5-fluorouracil (5-FU) remains a major obstacle to the successful treatment of this disease. We have previously identified the ribosomal protein uL3 as a key player in the cell response to 5-FU, and loss of uL3 is associated with 5-FU chemoresistance. Natural products, like carotenoids, have shown the ability to enhance cancer cell response to drugs and may provide a safer choice to defeat chemoresistance in cancer. Transcriptome analysis of a cohort of 594 colorectal patients revealed a correlation between uL3 expression and both progression-free survival and response to treatment. RNA-Seq data from uL3-silenced CRC cells demonstrated that a low uL3 transcriptional state was associated with an increased expression of specific ATP-binding cassette (ABC) genes. Using two-dimensional (2D) and three-dimensional (3D) models of 5-FU-resistant CRC cells stably silenced for uL3, we investigated the effect of a novel therapeutic strategy by combining ß-carotene and 5-FU using nanoparticles (NPs) as a drug delivery system. Our results indicated that the combined treatment might overcome 5-FU chemoresistance, inducing cell cycle arrest in the G2/M phase and apoptosis. Furthermore, the combined treatment significantly reduced the expression levels of analyzed ABC genes. In conclusion, our findings suggest that ß-carotene combined with 5-FU may be a more effective therapeutic approach for treating CRC cells with low levels of uL3.


Subject(s)
Colorectal Neoplasms , beta Carotene , Humans , beta Carotene/pharmacology , beta Carotene/metabolism , beta Carotene/therapeutic use , Tumor Suppressor Protein p53/genetics , Drug Resistance, Neoplasm/genetics , Cell Line, Tumor , Fluorouracil/pharmacology , Fluorouracil/therapeutic use , Apoptosis , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Gene Expression Regulation, Neoplastic
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