cryptoxanthins and Inflammation

β-Cryptoxanthin, a carotenoid, and hesperidin, a flavonoid, possess inhibitory effects on carcinogenesis in several tissues. We recently have prepared a pulp (CHRP) and citrus juices (MJ2 and MJ5) from a satsuma mandarin (Citrus unshiu Mar.) juice (MJ). They contain high amounts of β-cryptoxanthin and hesperidin. We have demonstrated that CHRP and/or MJs inhibit chemically induced rat colon, rat tongue, and mouse lung tumorigenesis. Gavage with CHRP resulted in an increase of activities of detoxifying enzymes in the liver, colon, and tongue rats'. CHRP and MJs were also able to suppress the expression of proinflammatory cytokines and inflammatory enzymes in the target tissues. This paper describes the findings of our in vivo preclinical experiments to develop a strategy for cancer chemoprevention of colon, tongue, and lung neoplasms by use of CHRP and MJs.

Topics: Animal Feed; Animals; Anticarcinogenic Agents; Beverages; Cell Line, Tumor; Citrus; Colonic Neoplasms; Cryptoxanthins; Cytokines; Hesperidin; Humans; Inflammation; Lung Neoplasms; Mice; Models, Chemical; Neoplasm Transplantation; Rats; Rats, Inbred F344; Tongue Neoplasms; Xanthophylls

The efficacy of β-cryptoxanthin (BCX), a high-protein diet (HPD), or both in reducing oxidative stress and inflammation in nonalcoholic fatty liver disease (NAFLD) has never been examined within a randomized controlled trial (RCT). Thus, we aimed to assess the efficacy of an energy-restricted HPD supplemented with BCX in alleviating these conditions in NAFLD in an RCT design. We hypothesized that this combination may improve oxidative stress and inflammation in NAFLD as compared to a standard energy-restricted diet. Ninety-two ultrasonographically confirmed overweight/obese adult NAFLD patients attending an outpatient clinic in Ahvaz, Iran, were recruited for this 12-week, single-center, parallel-group, double-blind RCT from 2017 to 2018. Subjects were randomized into 4 equal groups (n = 23): HPD-BCX (energy-restricted HPD + BCX), HPD (energy-restricted HPD + placebo), BCX (standard energy-restricted diet + BCX), and control (standard energy-restricted diet + placebo). Serum levels of oxidative stress- and inflammation-related markers, as primary outcome measures, were determined at baseline and at the study end point. The 1-way analysis of covariance models in the intention-to-treat population (N = 92) showed that the HPD-BCX group achieved greater 12-week reductions in malondialdehyde, high-sensitivity C-reactive protein, interleukin-6, and total cytokeratin-18 (CK18-M65) but higher increases in total antioxidant capacity and adiponectin compared to the control group (mean differences for malondialdehyde, high-sensitivity C-reactive protein, interleukin-6, total cytokeratin-18, total antioxidant capacity, and adiponectin were -1.9 nmol/mL, -1.0 mg/L, -2.0 ng/L, -270.9 ng/L, 2.5 U/mL, and 1.9 mg/L, respectively; all P < .001). These results show that an energy-restricted HPD supplemented with BCX more efficaciously alleviates oxidative stress and inflammation in NAFLD as compared to a standard energy-restricted diet.

Topics: Adult; Beta-Cryptoxanthin; Biomarkers; Caloric Restriction; Combined Modality Therapy; Diet, High-Protein; Dietary Supplements; Double-Blind Method; Female; Humans; Inflammation; Iran; Male; Non-alcoholic Fatty Liver Disease; Oxidative Stress; Provitamins; Treatment Outcome

Epidemiological evidence supports a positive relationship between fruit and vegetable (FV) intake, lung function and chronic obstructive pulmonary disease (COPD). Increasing FV intake may attenuate the oxidative stress and inflammation associated with COPD. An exploratory randomised controlled trial to examine the effect of increased consumption of FV on oxidative stress and inflammation in moderate-to-severe COPD was conducted. 81 symptomatically stable patients with a habitually low FV intake (two or fewer portions of FV per day) were randomised to the intervention group (five or more portions of FV per day) or the control group (two or fewer portions of FV per day). Each participant received self-selected weekly home deliveries of FV for 12 weeks. 75 participants completed the intervention. There was a significant between-group change in self-reported FV intake and biomarkers of FV intake (zeaxanthin (p = 0.034) and β-cryptoxanthin (p = 0.015)), indicating good compliance; post-intervention intakes in intervention and control groups were 6.1 and 1.9 portions of FV per day, respectively. There were no significant changes in biomarkers of airway inflammation (interleukin-8 and myeloperoxidase) and systemic inflammation (C-reactive protein) or airway and systemic oxidative stress (8-isoprostane). This exploratory study demonstrated that patients with moderate-to-severe COPD were able to comply with an intervention to increase FV intake; however, this had no significant effect on airway or systemic oxidative stress and inflammation.

Topics: Aged; Aged, 80 and over; Anticarcinogenic Agents; Biomarkers; C-Reactive Protein; Cryptoxanthins; Diet; Dinoprost; Feeding Behavior; Female; Fruit; Humans; Inflammation; Interleukin-8; Male; Middle Aged; Oxidative Stress; Patient Compliance; Peroxidase; Pulmonary Disease, Chronic Obstructive; Severity of Illness Index; Sputum; Vegetables; Xanthophylls; Zeaxanthins

This research is aimed at determining the vascular health characteristics of carotenoids by evaluating their effect on excessive inflammatory response in endothelial and monocyte cells, the main factors of atherosclerosis.. Human umbilical vein endothelial cells (HUVECs) or U937 monocytes were treated with escalating concentrations (0.1, 0.5, and 1 . Carotenoids repressed monocyte adhesion to fructose-stimulated ECs dose dependently via decreasing primarily the expression of endothelial VCAM-1. In ECs and monocytes, three carotenoids, i.e.,. Our results show that carotenoids have a variety of anti-inflammatory and antiatherosclerosis activities, which can help prevent or reduce fructose-induced inflammatory vascular diseases.

Topics: Atherosclerosis; Beta-Cryptoxanthin; Carotenoids; Cell Adhesion; Cytokines; Endothelial Cells; Fructose; Human Umbilical Vein Endothelial Cells; Humans; Inflammation; Lipid Peroxidation; Lutein; Lycopene; Monocytes; Oxidative Stress; Reactive Oxygen Species; U937 Cells

Recent nutritional epidemiological surveys showed that serum β-cryptoxanthin inversely associates with the risks for insulin resistance and liver dysfunction. Consumption of β-cryptoxanthin possibly prevents nonalcoholic steatohepatitis (NASH), which is suggested to be caused by insulin resistance and oxidative stress from nonalcoholic fatty liver disease. To evaluate the effect of β-cryptoxanthin on diet-induced NASH, we fed a high-cholesterol and high-fat diet (CL diet) with or without 0.003% β-cryptoxanthin to C56BL/6J mice for 12 weeks. After feeding, β-cryptoxanthin attenuated fat accumulation, increases in Kupffer and activated stellate cells, and fibrosis in CL diet-induced NASH in the mice. Comprehensive gene expression analysis showed that although β-cryptoxanthin histochemically reduced steatosis, it was more effective in inhibiting inflammatory gene expression change in NASH. β-Cryptoxanthin reduced the alteration of expression of genes associated with cell death, inflammatory responses, infiltration and activation of macrophages and other leukocytes, quantity of T cells, and free radical scavenging. However, it showed little effect on the expression of genes related to cholesterol and other lipid metabolism. The expression of markers of M1 and M2 macrophages, T helper cells, and cytotoxic T cells was significantly induced in NASH and reduced by β-cryptoxanthin. β-Cryptoxanthin suppressed the expression of lipopolysaccharide (LPS)-inducible and/or TNFα-inducible genes in NASH. Increased levels of the oxidative stress marker thiobarbituric acid reactive substances (TBARS) were reduced by β-cryptoxanthin in NASH. Thus, β-cryptoxanthin suppresses inflammation and the resulting fibrosis probably by primarily suppressing the increase and activation of macrophages and other immune cells. Reducing oxidative stress is likely to be a major mechanism of inflammation and injury suppression in the livers of mice with NASH.

Topics: Animals; Antigens, Differentiation; Cholesterol; Cryptoxanthins; Dietary Fats; Gene Expression Regulation; Inflammation; Insulin Resistance; Macrophages; Male; Mice; Non-alcoholic Fatty Liver Disease; T-Lymphocytes

We examined the effects of β-cryptoxanthin, a typical carotenoid, on inflammatory periodontitis. β-Cryptoxanthin suppressed lipopolysaccharide (LPS)-induced osteoclast formation in co-cultures of bone marrow cells and osteoblasts. In a mouse model of periodontitis, it suppressed bone resorption in the mandibular alveolar bone in vitro and restored alveolar bone loss induced by LPS in vivo. β-Cryptoxanthin might protect against periodontal disease.

Topics: Animals; Bone Marrow Cells; Bone Resorption; Cryptoxanthins; Disease Models, Animal; Humans; Inflammation; Mice; NIH 3T3 Cells; Osteoblasts; Osteoclasts; Periodontitis; Xanthophylls

In epidemiologic studies, high intake of β-cryptoxanthin has been associated with a decreased risk of lung cancer, particularly among current smokers. However, data are not available from well-controlled animal studies to examine the effects of β-cryptoxanthin on cigarette smoke-induced lung lesions, and the biological mechanisms by which β-cryptoxanthin might affect lung carcinogenesis. We evaluated the effects of β-cryptoxanthin supplementation on cigarette smoke-induced squamous metaplasia, inflammation, and changes in protein levels of proinflammatory cytokine [tumor necrosis factor alpha (TNFα)] and transcription factors [nuclear factor kappa B (NF-κB) and activator protein-1 (AP-1)], as well as on smoke-induced oxidative DNA damage [8-hydroxy-2'-deoxyguanosine (8-OHdG)] in the lung tissue of ferrets. Thirty-six male ferrets were assigned to cigarette smoke exposure or no exposure and to low-dose, or high-dose β-cryptoxanthin, or no dose (2 × 3 factorial design) for 3 months. β-Cryptoxanthin supplementation dose-dependently increased plasma and lung β-cryptoxanthin levels in ferrets, whereas cigarette smoke exposure lowered plasma and lung β-cryptoxanthin levels. β-Cryptoxanthin at both doses significantly decreased smoke-induced lung squamous metaplasia and inflammation. β-Cryptoxanthin also substantially reduced smoke-elevated TNFα levels in alveolar, bronchial, bronchiolar, and bronchial serous/mucous gland epithelial cells and in lung macrophages. Moreover, β-cryptoxanthin decreased smoke-induced activation of NF-κB, expression of AP-1 and levels of 8-OHdG. The beneficial effects of β-cryptoxanthin were stronger for high-dose β-cryptoxanthin than for low-dose β-cryptoxanthin. Data from this study indicate that β-cryptoxanthin provides a beneficial effect against cigarette smoke-induced inflammation, oxidative DNA damage and squamous metaplasia in the lungs.

Topics: Animals; Cryptoxanthins; Cytokines; Dietary Supplements; DNA Damage; Ferrets; Genetic Markers; Immunohistochemistry; Inflammation; Lung; Male; Metaplasia; Nicotiana; Oxidative Stress; Smoking; Xanthophylls

The exact pathogenesis of liver injury and fibrosis in chronic hepatitis C (CHC) is unclear. Free radicals play a role in CHC liver damage. Antioxidants (AO) (enzymatic and nonenzymatic) scavenge free radicals and prevent tissue injury. The aims of our study were to estimate serum levels of malondialdehyde (MDA), serum and liver levels of nonenzymatic fat-soluble AO, and to correlate the liver AO levels with the degree of inflammation and fibrosis on biopsy.. AO levels were estimated by high-pressure liquid chromatography in the pretreatment serum and liver biopsy specimen of 20 treatment-naïve patients with CHC who were not on vitamin supplements. Serum levels of MDA were measured as a marker of increased oxidative stress. Twenty-two healthy individuals with no history of vitamin supplementation served as controls. AO analyzed were: retinol, alpha- and gamma-tocopherol, lutein, beta-cryptoxanthin, lycopene, and alpha- and beta-carotene.. Twenty CHC patients (11 men, nine women, mean age 48.5 +/- 7.9 yr) were studied. Patients and controls were comparable in age and sex. Serum MDA levels were significantly higher in CHC patients compared with controls (1.62 +/- 0.57 vs 0.23 +/- 0.15 micromol/L, p = < 0.0000). Serum levels of all AO except lutein were significantly decreased in CHC patients, and their levels were two to ten times lower than serum levels in controls. Liver levels of alpha-carotene (p = 0.0004), beta-carotene (p = 0.006), and lutein (p = 0.002) correlated with the serum levels, whereas the levels of retinol, alpha-tocopherol, lycopene, and beta-cryptoxanthin showed no correlation. Serum MDA levels were significantly higher in patients with moderate-to-severe inflammation or fibrosis compared with those with mild inflammation or fibrosis. The levels of all liver AO except alpha-carotene were significantly lower in patients with moderate-to-severe fibrosis. The severity of inflammation (portal or lobular) did not affect liver AO levels.. Our findings suggest that increased oxidative stress is present in patients with CHC. Micronutrient AO are severely depleted in serum and liver tissue of patients with CHC, and liver levels of some AO appear to reflect serum levels. Increasing fibrosis is associated with decreased liver AO levels indicating that severe disease may be a consequence of AO depletion or decreased liver storage resulting from fibrosis.

Topics: Adult; Antioxidants; beta Carotene; Carotenoids; Cryptoxanthins; Female; Fibrosis; Hepatitis C, Chronic; Humans; Inflammation; Liver; Lutein; Lycopene; Male; Malondialdehyde; Micronutrients; Middle Aged; Oxidative Stress; Tocopherols; Vitamin A; Xanthophylls