[The use of antioxidants in combination therapy of chronic prostatitis].

Currently, the significance of the chronic prostatitis (CP) is undoubted. Oxidative stress is considered as one of the standard mechanisms of cellular damage that is associated with inflammatory diseases such as CP. When choosing the combination therapy for this group of patients, a correction of oxidative stress is pathogenetically justified. Literature data about the pathogenetic feasibility and prospects of using a biologically active complex containing flavonoids and carotenoids quercetin, lycopene and naringin as part of the combination treatment of patients with CP are presented in the article. Considering the various effects of the biologically active complex Querceprost, containing quercetin, lycopene and naringin, among which antioxidant, anti-inflammatory, antimicrobial and immunomodulatory are of greatest importance, as well as taking into account the synergistic effect of flavonoids and carotenoids, we suggest that Querceprost is promising component of combination treatment of patients with CP.

Protective role of crocin against sepsis-induced injury in the liver, kidney and lungs via inhibition of p38 MAPK/NF-κB and Bax/Bcl-2 signalling pathways.

CONTEXT: Crocin has been reported to have multiple bioactivities. However, the effect of crocin administration on caecal ligation and puncture (CLP)-induced sepsis remains unknown. OBJECTIVE: We investigated the effects of crocin on CLP-induced sepsis in mice and the underlying mechanism of action. MATERIALS AND METHODS: Five experimental groups (n = 10) of BALB/c mice were used: control, CLP (normal saline) and CLP + crocin (50, 100 and 250 mg/kg, 30 min prior to CLP). Mice were sacrificed 24 h after CLP. Liver, kidney and lung histopathology, indicator levels, apoptotic status, pro-inflammatory cytokines and relative protein levels were evaluated. RESULTS: Compared to the CLP group, crocin treatment significantly increased the survival rate (70%, 80%, 90% vs. 30%). Crocin groups exhibited protection against liver, kidney and lung damage with mild-to-moderate morphological changes and lower indicator levels: liver (2.80 ± 0.45, 2.60 ± 0.55, 1.60 ± 0.55 vs. 5.60 ± 0.55), kidney (3.00 ± 0.71, 2.60 ± 0.55, 1.40 ± 0.55 vs. 6.20 ± 0.84) and lungs (8.00 ± 1.59, 6.80 ± 1.64, 2.80 ± 0.84 vs. 14.80 ± 1.79). The proinflammatory cytokines (IL-1ß, TNF-α, IL-6 and IL-10 levels in the crocin groups) were distinctly lower and the apoptotic index showed a significant decrease. Crocin administration significantly suppressed p38 MAPK phosphorylation and inhibited NF-κB/IκBα and Bcl-2/Bax activation. DISCUSSION AND CONCLUSIONS: Pre-treatment with crocin confers protective effects against CLP-induced liver, kidney and lung injury, implying it to be a potential therapeutic agent.

The apparent inverse association between dietary carotene intake and risk of cardiovascular mortality disappeared after adjustment for other cardioprotective dietary intakes: The Japan collaborative cohort study.

BACKGROUND AND PURPOSE: An effect of dietary carotenes on risk of cardiovascular disease (CVD) is uncertain. We aimed to investigate whether the association between dietary carotenes intake and risk of CVD mortality will persist after controlling for the intakes of potential cardioprotective dietary factors that correlate with dietary alpha- and/or beta-carotenes. METHODS AND RESULTS: We followed up a total of 58,646 Japanese between 1988 and 1990 and 2009. We used a food frequency questionnaire (FFQ) to determine the dietary intakes of carotenes, and estimated the hazard ratios (HRs) and 95% confidence intervals (CIs) of CVD mortality in relation to carotene intake by the proportional hazard regression developed by David Cox. During 965,970 person-years of follow-up (median 19.3 years), we identified 3388 total CVD deaths. After adjusting for demographic and lifestyle factors, dietary intakes of alpha-carotene were significantly associated with the reduced risk of mortality from coronary heart disease (CHD); adjusted HR (95% CI) in the highest versus lowest quintiles of intake was 0.75 (0.58-0.96; P-trend = 0.02) and dietary intakes of beta-carotene were significantly associated with the reduced risk of mortality from CVD, CHD, and other CVD; adjusted HRs (95% CIs) were 0.88 (0.79-0.98; P-trend = 0.04), 0.78 (0.61-0.99; P-trend = 0.01), and 0.81 (0.67-0.98; P-trend = 0.04), respectively. However, after further adjusting for the dietary intakes of potassium, calcium, vitamins C, E, or K, these associations disappeared. CONCLUSIONS: -Dietary alpha- and beta-carotene intakes were not associated with risk of CVD mortality after controlling for intakes of other potential cardioprotective nutrients.

Oral Bioavailability of Omega-3 Fatty Acids and Carotenoids from the Microalgae Phaeodactylum tricornutum in Healthy Young Adults.

The microalgae Phaeodactylum tricornutum (PT) contains valuable nutrients such as proteins, polyunsaturated omega-3 fatty acids (n-3 PUFA), particularly eicosapentaenoic acid (EPA) and some docosahexaenoic acid (DHA), carotenoids such as fucoxanthin (FX), and beta-glucans, which may confer health benefits. In a randomized intervention trial involving 22 healthy individuals, we administered for two weeks in a crossover manner the whole biomass of PT (5.3 g/day), or fish oil (FO) containing equal amounts of EPA and DHA (together 300 mg/day). In an additional experiment, sea fish at 185 g/week resulting in a similar EPA and DHA intake was administered in nine individuals. We determined the bioavailability of fatty acids and carotenoids and assessed safety parameters. The intake of PT resulted in a similar increase in the n-3 PUFA and EPA content and a decrease in the PUFA n-6:n-3 ratio in plasma. PT intake caused an uptake of FX that is metabolized to fucoxanthinol (FXOH) and amarouciaxanthin A (AxA). No relevant adverse effects occurred following PT consumption. The study shows that PT is a safe and effective source of EPA and FX-and likely other nutrients-and therefore should be considered as a future sustainable food item.

Mixed carotenoid supplementation and dysmetabolic obesity: gaps in knowledge.

Dysmetabolic obesity during childhood and adolescence currently represents one of the greatest therapeutic challenge for healthcare systems worldwide. The global rates of obesity have more than doubled in the last 30 years. Recent meta-analysis from national surveys and food composition studies suggest an inverse association between lower carotenoid levels and the prevalence of Metabolic Syndrome in the general population, independent of serum retinol (vitamin A) levels. In children, two double-blind randomised placebo-controlled studies describing the effects of diet vs. mixed carotenoid supplementation on insulin resistance, adipokines and the rate of accrual of subcutaneous abdominal fat, implicate supplementation of these compounds to achieve targetable levels may be useful in the management of obesity accrual in this population. We will discuss the role of carotenoids and their conversion products (retinoids) in adipogenesis, lipolysis, insulin resistance and the pathophysiology of the metabolic syndrome and review the animal studies, which help support these findings.

Microencapsulation of Bioactive Ingredients for Their Delivery into Fermented Milk Products: A Review.

The popularity and consumption of fermented milk products are growing. On the other hand, consumers are interested in health-promoting and functional foods. Fermented milk products are an excellent matrix for the incorporation of bioactive ingredients, making them functional foods. To overcome the instability or low solubility of many bioactive ingredients under various environmental conditions, the encapsulation approach was developed. This review analyzes the fortification of three fermented milk products, i.e., yogurt, cheese, and kefir with bioactive ingredients. The encapsulation methods and techniques alongside the encapsulant materials for carotenoids, phenolic compounds, omega-3, probiotics, and other micronutrients are discussed. The effect of encapsulation on the properties of bioactive ingredients themselves and on textural and sensory properties of fermented milk products is also presented.

The Zebrafish Embryo as a Model to Test Protective Effects of Food Antioxidant Compounds.

The antioxidant activity of food compounds is one of the properties generating the most interest, due to its health benefits and correlation with the prevention of chronic disease. This activity is usually measured using in vitro assays, which cannot predict in vivo effects or mechanisms of action. The objective of this study was to evaluate the in vivo protective effects of six phenolic compounds (naringenin, apigenin, rutin, oleuropein, chlorogenic acid, and curcumin) and three carotenoids (lycopene B, ß-carotene, and astaxanthin) naturally present in foods using a zebrafish embryo model. The zebrafish embryo was pretreated with each of the nine antioxidant compounds and then exposed to tert-butyl hydroperoxide (tBOOH), a known inducer of oxidative stress in zebrafish. Significant differences were determined by comparing the concentration-response of the tBOOH induced lethality and dysmorphogenesis against the pretreated embryos with the antioxidant compounds. A protective effect of each compound, except ß-carotene, against oxidative-stress-induced lethality was found. Furthermore, apigenin, rutin, and curcumin also showed protective effects against dysmorphogenesis. On the other hand, ß-carotene exhibited increased lethality and dysmorphogenesis compared to the tBOOH treatment alone.

Long-Term Intake of Dietary Carotenoids Is Positively Associated with Late-Life Subjective Cognitive Function in a Prospective Study in US Women.

BACKGROUND: A protective association of dietary carotenoids with cognitive function has been suggested, but most studies have been relatively small with limited periods of follow-up. OBJECTIVES: We examined prospectively long-term intakes of carotenoids in relation to subjective cognitive function (SCF), a self-reported, validated indicator of cognitive dysfunction. METHODS: Among 49,493 female registered nurses with a mean age of 48 y in 1984, we used multinomial logistic regression to estimate the ORs and 95% CIs relating intakes of carotenoids to self-reported SCF in 2012 and 2014. Mean intakes of carotenoids were calculated from 7 repeated FFQs collected in 1984, 1986, and every 4 y afterwards until 2006. Self-reported SCF was assessed by a 7-item questionnaire on changes in memory and cognition; validity was supported by strong associations with Apolipoprotein E (APOE) ε4 genotype and concurrent cognitive function and cognitive decline measured by telephone-based neuropsychological tests. The mean values of scores assessed in 2012 and 2014 were categorized as "good" (0 points, 40.8%), "moderate" (0.5-2.5 points, 46.9%), and "poor" (3-7 points, 12.3%). RESULTS: Higher intake of total carotenoids was associated with substantially lower odds of moderate or poor cognitive function after controlling for other dietary and nondietary risk factors and total energy intake. Comparing the top with the bottom quintile of total carotenoids, the multivariable ORs were 0.86 (95% CI: 0.80, 0.93; P-trend < 0.001) for moderate SCF and 0.67 (95% CI: 0.60, 0.75; P-trend < 0.001) for poor SCF. This lower OR was also seen for carotenoids consumed 28 y before SCF assessment. Similar associations were found for total ß-carotene, dietary ß-carotene, α-carotene, lycopene, lutein + zeaxanthin, and ß-cryptoxanthin. The significant associations for ß-cryptoxanthin, lycopene, and lutein + zeaxanthin persisted after mutual adjustment for each other. CONCLUSIONS: Our findings support a long-term beneficial role of carotenoid consumption on cognitive function in women.

Overlapping Vitamin A Interventions with Provitamin A Carotenoids and Preformed Vitamin A Cause Excessive Liver Retinol Stores in Male Mongolian Gerbils.

BACKGROUND: Vitamin A (VA) deficiency is a public health problem in some countries. Fortification, supplementation, and increased provitamin A consumption through biofortification are efficacious, but monitoring is needed due to risk of excessive VA intake when interventions overlap. OBJECTIVES: Two studies in 28-36-d-old male Mongolian gerbils simulated exposure to multiple VA interventions to determine the effects of provitamin A carotenoid consumption from biofortified maize and carrots and preformed VA fortificant on status. METHODS: Study 1 was a 2 × 2 × 2 factorial design (n = 85) with high-ß-carotene maize, orange carrots, and VA fortification at 50% estimated gerbil needs, compared with white maize and white carrot controls. Study 2 was a 2 × 3 factorial design (n = 66) evaluating orange carrot and VA consumption through fortification at 100% and 200% estimated needs. Both studies utilized 2-wk VA depletion, baseline evaluation, 9-wk treatments, and liver VA stores by HPLC. Intestinal scavenger receptor class B member 1 (Scarb1), ß-carotene 15,15'-dioxygenase (Bco1), ß-carotene 9',10'-oxygenase (Bco2), intestine-specific homeobox (Isx), and cytochrome P450 26A1 isoform α1 (Cyp26a1) expression was analyzed by qRT-PCR in study 2. RESULTS: In study 1, liver VA concentrations were significantly higher in orange carrot (0.69 ± 0.12 µmol/g) and orange maize groups (0.52 ± 0.21 µmol/g) compared with baseline (0.23 ± 0.069 µmol/g) and controls. Liver VA concentrations from VA fortificant alone (0.11 ± 0.053 µmol/g) did not differ from negative control. In study 2, orange carrot significantly enhanced liver VA concentrations (0.85 ± 0.24 µmol/g) relative to baseline (0.43 ± 0.14 µmol/g), but VA fortificant alone (0.42 ± 0.21 µmol/g) did not. Intestinal Scarb1 and Bco1 were negatively correlated with increasing liver VA concentrations (P < 0.01, r2 = 0.25-0.27). Serum retinol concentrations did not differ. CONCLUSIONS: Biofortified carrots and maize without fortification prevented VA deficiency in gerbils. During adequate provitamin A dietary intake, preformed VA intake resulted in excessive liver stores in gerbils, despite downregulation of carotenoid absorption and cleavage gene expression.

Dietary carotenoids in cancer chemoprevention and chemotherapy: A review of emerging evidence.

In recent years, natural products have reemerged as biotherapeutic options, with several dietary carotenoids, viz. astaxanthin, fucoxanthin, siphonaxanthin, ß-cryptoxanthin, α-carotene, ß-carotene, and lycopene, developing as potential candidates for chemoprevention and chemotherapeutics of breast, colorectal, lung, and prostate cancers. The potent cytotoxic and antiproliferative effects of carotenoids against various cancer cells are mediated by a wide range of molecular mechanisms modulating oxidative stress and redox balance, mitogen-activated protein kinases (MAPK) and other cellular signaling proteins, transcription factors, caspase cascade pathways of apoptosis, cell cycle progression and proliferation, angiogenesis, metastasis, gap junction intercellular communication (GJIC), and multidrug resistance (MDR). This review discusses recent evidence demonstrating the crucial roles of carotenoids in these cellular and molecular events of cancer cell cytotoxicity. In addition, recent case-control and cohort studies are discussed to support the potential role of carotenoids in cancer prevention and therapy.

Diet Quality and Biomarker Profiles Related to Chronic Disease Prevention: The Multiethnic Cohort Study.

Objective: To understand how diet quality affects chronic disease etiology, the associations of 4 a priori diet quality indices with blood levels of lipid-soluble micronutrients and biomarkers of inflammation, lipid, and glucose metabolism were examined in 5 ethnic groups.Methods: In a cross-sectional design, the Adiposity Phenotype Study, a subset of the Multiethnic Cohort in Hawaii and Los Angeles, recruited participants of white, African American, Native Hawaiian, Japanese American, and Latino ancestry. A total of 896 men and 910 women completed a validated quantitative food frequency questionnaire and anthropometric measurements and donated a fasting blood sample. Using general linear models, covariate-adjusted mean levels of lipid-soluble micronutrients (total carotenes, lycopene, total tocopherols, total lutein, cryptoxanthins), biomarkers of inflammation (C-reactive protein [CRP], tumor necrosis factor-[Formula: see text]), adipokines (adiponectin, leptin), lipids (total cholesterol, high-density lipoprotein cholesterol [HDL-C], triglycerides), and glucose metabolism (glucose, insulin, homeostatic model assessment of insulin resistance [HOMA-IR]) were computed across tertiles of 4 a priori dietary indices Healthy Eating Index (HEI)-2010, Alternative HEI (AHEI)-2010, alternate Mediterranean Diet (aMED), Dietary Approaches to Stop Hypertension (DASH); trends were evaluated in models with diet quality scores as continuous variables.Results: With better diet quality, levels of carotenes, lutein, cryptoxanthin, adiponectin, and HDL-C were significantly higher (ptrend < 0.01), whereas levels of CRP, leptin, total cholesterol, triglycerides, glucose, insulin, and HOMA-IR were inversely associated (ptrend < 0.05) with diet quality. With the exception of cryptoxanthins and triglycerides, the associations were consistent across ethnic groups.Conclusions: These findings confirm the association between diet quality and nutrition-related biomarkers and support the idea that a high-quality diet positively influences biologic pathways involved in chronic disease etiology across different ethnic groups.

Differential effect of a carotenoid-rich diet on retina function in non-diabetic and diabetic rats.

Objective: This study was designed to examine the supplementation of a carotenoid-rich carrot powder, on retina function and carotenoid metabolism in non-diabetic control and type 1 diabetic animals. Methods: Male Wistar rats (n = 30) were randomly assigned to diets supplemented with (n = 15) or without (n = 15) carrot powder enriched diets (150 g/kg diet). After 3 weeks of diet adaptation, 8 rats in each group were treated with streptozotocin (iv) to induce type 1 diabetes and fed for a further 9 wk. Retinal function was assessed with the electroretinogram (ERG). Hepatic and plasma retinoids and carotenoids were measured by ultra-performance liquid chromatography. Results: Non-diabetic control rats fed the carrot diet had significantly (p < 0.02) higher rod- and cone- driven post-synaptic b-wave amplitudes, respectively, compared to those fed the control diet. These functional changes correlated with higher (p < 0.05) liver levels of carotenoids (α- and ß- carotene) and retinoids. In diabetic rats, carrot diet exacerbated retina dysfunction; the amplitudes for most of rod- and cone-driven ERG components were the lowest amplitudes among all groups (p < 0.02). Diabetic rats fed the carrot diet had lower hepatic retinol and retinyl palmitate, while having higher α- and ß-carotene levels, indicating diminished hepatic conversion of carotenoids into retinoids. Discussion: Dietary supplementation of high dose dietary carotenoids plays a beneficial role on healthy rat retina function, but exerts a detrimental effect in diabetes, which warrants undertaking detailed mechanistic studies.

Crocin-protected malathion-induced spatial memory deficits by inhibiting TAU protein hyperphosphorylation and antiapoptotic effects.

Organophosphorus compounds are widely used in agriculture. Epidemiological studies propose that pesticide exposure is a risk factor for Alzheimer's disease (AD), but the mechanisms are unclear. Here, we investigated the impact of malathion exposure on the cognitive ability and the underlying mechanisms in rats. Moreover, we studied whether crocin reduced malathion-induced cognitive and memory loss in rats. Malathion (100 mg/kg) and crocin (10, 20 and 40 m/kg) were administered into the rats once a day for 14 days via i.p. Also vitamin E was used as positive control. Malathion exhibited spatial memory deficits as assessed by Morris water maze (MWM). Malathion increased the latency to reach the platform and decreased time spent and swimming distance of animals in target quadrant in probe trial. These effects were protected by crocin. Malathion exposure induced spatial learning and memory deficits with a simultaneous decrease of PSD93 and TAU hyperphosphorylation at multiple AD-related phosphorylation sites with activation of glycogen synthase kinase-3ß (GSK-3ß) and inhibition of protein phosphatase-2A (PP2A). Additionally, the elevation of malondialdehyde (MDA), TNF α and IL-6 levels, amelioration of reduced glutathione (GSH) in the hippocampus and reduction of plasma acetylcholinesterase activity were observed upon administration of the malathion. Also, malathion-induced apoptosis in the hippocampus. Crocin or vitamin E improved memory damages and antagonized the effects of malathion. According to the data of this study, crocin mitigated malathion-induced neurological alterations and cognitive impairment by reducing oxidative stress and inflammation, inhibiting TAU protein hyperphosphorylation and antiapoptotic effects.

Orally administered mixed carotenoids protect human skin against ultraviolet A-induced skin pigmentation: A double-blind, placebo-controlled, randomized clinical trial.

BACKGROUND: Photoprotection of human skin is determined as the capacity of sunscreens to prevent ultraviolet (UV) B radiation-induced erythema and UVA radiation-induced pigmentation. It is unequivocal that, in addition to sunscreens, oral supplementation with carotenoids can protect human skin against UVB radiation-induced erythema. It is not known if this is also the case for UVA radiation-induced pigmentation. OBJECTIVE: To clinically evaluate the photoprotective effects of daily supplementation with carotenoids against UVA radiation-induced pigmentation. METHODS: In this double-blind, placebo-controlled trial, 60 subjects (Fitzpatrick types II-IV) were randomized to receive Nutrilite™ Multi Carotene supplement or placebo for 12 weeks. UVB-induced minimal erythemal dose (MED), UVA-induced minimal persistent pigmentation dose (MPPD) and skin carotenoid levels were measured at baseline, 4, 8, and 12 weeks of intervention. Skin color was evaluated by expert clinical graders and by colorimetry. Carotenoid levels in the skin were measured by the Biozoom® device. RESULTS: In the intervention group, a significant increase in comparison with the placebo group was observed in (a) skin carotenoid levels, (b) UVB-induced MED, and (c) UVA-induced MPPD values obtained by colorimetry. CONCLUSION: Daily supplementation with carotenoids protects human skin against both UVB-induced erythema and UVA-induced pigmentation.

Properties of Carotenoids in Fish Fitness: A Review.

Carotenoids, one of the most common types of natural pigments, can influence the colors of living organisms. More than 750 kinds of carotenoids have been identified. Generally, carotenoids occur in organisms at low levels. However, the total amount of carotenoids in nature has been estimated to be more than 100 million tons. There are two major types of carotenoids: carotene (solely hydrocarbons that contain no oxygen) and xanthophyll (contains oxygen). Carotenoids are lipid-soluble pigments with conjugated double bonds that exhibit robust antioxidant activity. Many carotenoids, particularly astaxanthin (ASX), are known to improve the antioxidative state and immune system, resulting in providing disease resistance, growth performance, survival, and improved egg quality in farmed fish without exhibiting any cytotoxicity or side effects. ASX cooperatively and synergistically interacts with other antioxidants such as α-tocopherol, ascorbic acid, and glutathione located in the lipophilic hydrophobic compartments of fish tissue. Moreover, ASX can modulate gene expression accompanying alterations in signal transduction by regulating reactive oxygen species (ROS) production. Hence, carotenoids could be used as chemotherapeutic supplements for farmed fish. Carotenoids are regarded as ecologically friendly functional feed additives in the aquaculture industry.

Antitumour Effects of Astaxanthin and Adonixanthin on Glioblastoma.

Several antitumour drugs have been isolated from natural products and many clinical trials are underway to evaluate their potential. There have been numerous reports about the antitumour effects of astaxanthin against several tumours but no studies into its effects against glioblastoma. Astaxanthin is a red pigment found in crustaceans and fish and is also synthesized in Haematococcus pluvialis; adonixanthin is an intermediate product of astaxanthin. It is known that both astaxanthin and adonixanthin possess radical scavenging activity and can confer a protective effect on several damages. In this study, we clarified the antitumour effects of astaxanthin and adonixanthin using glioblastoma models. Specifically, astaxanthin and adonixanthin showed an ability to suppress cell proliferation and migration in three types of glioblastoma cells. Furthermore, these compounds were confirmed to transfer to the brain in a murine model. In the murine orthotopic glioblastoma model, glioblastoma progression was suppressed by the oral administration of astaxanthin and adonixanthin at 10 and 30 mg/kg, respectively, for 10 days. These results suggest that both astaxanthin and adonixanthin have potential as treatments for glioblastoma.

Crocin Alleviates Pain Hyperalgesia in AIA Rats by Inhibiting the Spinal Wnt5a/ß-Catenin Signaling Pathway and Glial Activation.

At present, most of the drugs have little effect on the pathological process of rheumatoid arthritis (RA). Analgesia is an important measure in the treatment of RA and is also one of the criteria to determine the therapeutic effects of the disease. Some studies have found that crocin, a kind of Chinese medicine, can effectively alleviate pain sensitization in pain model rats, but the mechanism is not clear. Emerging evidence indicates that crocin may inhibit the metastasis of lung and liver cancer cells from the breast by inhibiting Wnt/ß-catenin and the Wnt signaling pathway is closely related to RA. Wnt5a belongs to the Wnt protein family and was previously thought to be involved only in nonclassical Wnt signaling pathways. Recent studies have shown that Wnt5a has both stimulatory and inhibitory effects on the classical Wnt signaling pathway, and so, Wnt5a has attracted increasing attention. This study demonstrated that crocin significantly increased the mechanical thresholds of adjuvant-induced arthritis (AIA) rats, suggesting that crocin can alleviate neuropathic pain. Crocin significantly decreased the levels of pain-related factors and glial activation. Foxy5, activator of Wnt5a, inhibited the above effects of crocin in AIA rats. In addition, intrathecal injection of a Wnt5a inhibitor significantly decreased hyperalgesia in AIA rats. This research shows that crocin may alleviate neuropathic pain in AIA rats by inhibiting the expression of pain-related molecules through the Wnt5a/ß-catenin pathway, elucidating the mechanism by which crocin relieves neuropathic pain and provides a new way of thinking for the treatment of AIA pain.

Oral and ocular administration of crocetin prevents retinal edema in a murine retinal vein occlusion model.

Purpose: We investigated the effects of oral and ocular administration of crocetin in a murine retinal vein occlusion (RVO) model. Crocetin is a type of carotenoid contained in the fruit of gardenia (Gardenia jasminoides Ellis) and the stigma of saffron (Crocus staruts L). Methods: This study was performed on a murine RVO model, which was created by laser irradiation of retinal veins. We evaluated the retinal thickness after the oral administration of crocetin (100 mg/kg) 1 and 6 h before laser irradiation, and immediately, 6 h, 12 h, and 18 h after laser irradiation in the murine RVO model. In addition, we measured the retinal layer thickness after administration of crocetin eye drops (0.03% or 0.10%) immediately, 6 h, and 12 h after laser irradiation. Western blotting of retinal tissue was used to determine the expression levels of matrix metalloproteinase (MMP-9), tumor nuclear factor (TNF-α), and occludin after oral administration of crocetin. Results: Oral and ocular administration of crocetin improved retinal edema in the murine RVO model. Crocetin administration statistically significantly suppressed overexpression of MMP-9 and TNF-α, and reversed the reduction of occludin. Conclusions: These findings indicate that crocetin can protect retinal tight junctions by suppressing retinal edema through an anti-inflammatory effect, which suggests that crocetin may be useful for RVO disease.

No CFH or ARMS2 Interaction with Omega-3 Fatty Acids, Low versus High Zinc, or ß-Carotene versus Lutein and Zeaxanthin on Progression of Age-Related Macular Degeneration in the Age-Related Eye Disease Study 2: Age-Related Eye Disease Study 2 Report No. 18.

PURPOSE: To assess whether genotypes at 2 major loci associated with age-related macular degeneration (AMD), complement factor H (CFH), or age-related maculopathy susceptibility 2 (ARMS2), modify the response to oral nutrients for the treatment of AMD in the Age-Related Eye Disease Study 2 (AREDS2). DESIGN: Post hoc analysis of a randomized trial. PARTICIPANTS: White AREDS2 participants. METHODS: AREDS2 participants (n = 4203) with bilateral large drusen or late AMD in 1 eye were assigned randomly to lutein and zeaxanthin, omega-3 fatty acids, both, or placebo, and most also received the AREDS supplements. A secondary randomization assessed modified AREDS supplements in 4 treatment arms: lower zinc dosage, omission of ß-carotene, both, or no modification. To evaluate the progression to late AMD, fundus photographs were obtained at baseline and annual study visits, and history of treatment for late AMD was obtained at study visits and 6-month interim telephone calls. Participants were genotyped for the single-nucleotide polymorphisms rs1061170 in CFH and rs10490924 in ARMS2. Bivariate frailty models using both eyes were conducted, including a gene-supplement interaction term and adjusting for age, gender, level of education, and smoking status. The main treatment effects, as well as the direct comparison between lutein plus zeaxanthin and ß-carotene, were assessed for genotype interaction. MAIN OUTCOME MEASURES: The interaction between genotype and the response to AREDS2 supplements regarding progression to late AMD, any geographic atrophy (GA), and neovascular AMD. RESULTS: Complete data were available for 2775 eyes without baseline late AMD (1684 participants). The participants (mean age ± standard deviation, 72.1±7.7 years; 58.5% female) were followed up for a median of 5 years. The ARMS2 risk allele was associated significantly with progression to late AMD and neovascular AMD (P = 2.40 × 10-5 and P = 0.002, respectively), but not any GA (P = 0.097). The CFH risk allele was not associated with AMD progression. Genotype did not modify significantly the response to any of the AREDS2 supplements. CONCLUSIONS: CFH and ARMS2 risk alleles do not modify the response to the AREDS2 nutrient supplements with respect to the progression to late AMD (GA and neovascular AMD).

Carrot Leaves Maintain Liver Vitamin A Concentrations in Male Mongolian Gerbils Regardless of the Ratio of α- to ß-Carotene When ß-Carotene Equivalents Are Equalized.

BACKGROUND: Carrots are an important horticultural crop that contain provitamin A carotenoids (PACs). Orange carrots have high concentrations of α-carotene, which upon central cleavage yields 1 retinal and 1 α-retinal molecule. The leaves of carrot plants are a source of PACs when consumed. OBJECTIVE: Male Mongolian gerbils aged 27-30 d were used to assess the bioefficacy of carrot leaves to maintain vitamin A (VA) status and investigate whether the ratio of α- to ß-carotene (α:ß-carotene) affected bioefficacy. METHODS: After 3 wk depletion, baseline gerbils were killed (n = 6) and the remaining gerbils (n = 60) were divided into 6 groups to receive 4 VA-deficient, carrot leaf-fortified feeds (1:1.4, 1:2.5, 1:5.0, and 1:80 α:ß-carotene ratio) equalized to 4.8 nmol/g ß-carotene equivalents (ßCEs), or VA-deficient feed with (VA+) or without (VA-) retinyl acetate supplements. Carrot-leaf powder from 4 carrot plants with differing α:ß-carotene ratios was used. After 4 wk, gerbils were killed and tissues were collected and analyzed for retinoids by HPLC. RESULTS: VA+ had higher total liver VA (means ± SD 0.91 ± 0.29 µmol) than all other groups (range: 0.40-0.62) (P ≤ 0.03), and the carrot leaf treatments did not differ from baseline (0.55 ± 0.09 µmol). VA- (0.40 ± 0.23 µmol VA/liver) did not differ from the leaf-fed groups, but 30% became VA deficient (defined as <0.1 µmol VA/g liver). α-Retinol accumulated in livers and lungs and was correlated to total α-carotene consumption (R2 = 0.83 and 0.88, respectively; P < 0.0001). Bioefficacy factors ranged from 4.2 to 6.2 µg ßCE to 1 µg retinol. CONCLUSIONS: Carrot leaves maintain VA status and prevent deficiency in gerbils regardless of the α:ß-carotene ratio. The bioconversion of PACs from carrot leaves to retinol is similar to what has been reported for other green leafy vegetables, making the consumption of carrot leaves a viable method to improve dietary PAC intake.