carotenoidI recommend eating colored fruits and vegetables. There are dietary supplements that have anti-aging properties as they contain carotenoid. Below are Pubmed information about inflammation and dietary modifications (foods/supplements rich in carotenoids, tocopherols, anti-oxidants).

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Connie Dello Buono

Br J Nutr. 2014 Oct;112(8):1341-52. doi: 10.1017/S0007114514001962.

Patterns of dietary intake and serum carotenoid and tocopherol status are associated with biomarkers of chronic low-grade systemic inflammation and cardiovascular risk.

Wood AD1, Strachan AA1, Thies F1, Aucott LS1, Reid DM1, Hardcastle AC2, Mavroeidi A3, Simpson WG1, Duthie GG4, Macdonald HM1.

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Dietary modification may affect inflammatory processes and protect against chronic disease. In the present study, we examined the relationship between dietary patterns, circulating carotenoid and tocopherol concentrations, and biomarkers of chronic low-grade systemic inflammation in a 10-year longitudinal study of Scottish postmenopausal women. Diet was assessed by FFQ during 1997-2000 (n 3237, mean age 54·8 (sd 2·2) years). Participants (n 2130, mean age 66·0 (sd 2·2) years) returned during 2007-11 for follow-up. Diet was assessed by FFQ (n 1682) and blood was collected for the analysis of serum high-sensitivity C-reactive protein (hs-CRP), IL-6, serum amyloid A, E-selectin, lipid profile and dietary biomarkers (carotenoids, tocopherols and retinol). Dietary pattern and dietary biomarker (serum carotenoid) components were generated by principal components analysis. A past ‘prudent’ dietary pattern predicted serum concentrations of hs-CRP and IL-6 (which decreased across the quintiles of the dietary pattern; P= 0·002 and P= 0·001, respectively; ANCOVA). Contemporary dietary patterns were also associated with inflammatory biomarkers. The concentrations of hs-CRP and IL-6 decreased across the quintiles of the ‘prudent’ dietary pattern (P= 0·030 and P= 0·006, respectively). hs-CRP concentration increased across the quintiles of a ‘meat-dominated’ dietary pattern (P= 0·001). Inflammatory biomarker concentrations decreased markedly across the quintiles of carotenoid component score (P< 0·001 for hs-CRP and IL-6, and P= 0·016 for E-selectin; ANCOVA). Prudent dietary pattern and carotenoid component scores were negatively associated with serum hs-CRP concentration (unstandardised β for prudent component: – 0·053, 95 % CI – 0·102, – 0·003; carotenoid component: – 0·183, 95 % CI – 0·233, – 0·134) independent of study covariates. A prudent dietary pattern (which reflects a diet high in the intakes of fish, yogurt, pulses, rice, pasta and wine, in addition to fruit and vegetable consumption) and a serum carotenoid profile characteristic of a fruit and vegetable-rich diet are associated with lower concentrations of intermediary markers that are indicative of CVD risk reduction.

PMID: 25313576 [PubMed – in process]

 J Nutr Biochem. 2014 Sep 16. pii: S0955-2863(14)00168-5. doi: 10.1016/j.jnutbio.2014.07.004. [Epub ahead of print]

Preventive supplementation with fresh and preserved peach attenuates CCl4-induced oxidative stress, inflammation and tissue damage.

Gasparotto J1, Somensi N2, Bortolin RC2, Girardi CS2, Kunzler A2, Rabelo TK2, Schnorr CE2, Moresco KS2, Bassani VL3, Yatsu FK3, Vizzotto M4, Raseira MD4, Zanotto-Filho A2, Moreira JC2, Gelain DP2.

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The present study was elaborated to comparatively evaluate the preventive effect of different peach-derived products obtained from preserved fruits (Syrup and Preserve Pulp Peach [PPP]) and from fresh peels and pulps (Peel and Fresh Pulp Peach [FPP]) in a model of liver/renal toxicity and inflammation induced by carbon tetrachloride (CCl4) in rats. Tissue damage (carbonyl, thiobarbituric acid reactive species and sulfhydril), antioxidant enzymes activity (catalase and superoxide dismutase) and inflammatory parameters [tumor necrosis factor (TNF)-α and interleukin (IL)-1β levels, and receptor for advanced glycation end-products (RAGE) and nuclear factor (NF)κB-p65 immunocontent] were investigated. Our findings demonstrated that Peel, PPP and FPP (200 or 400 mg/kg) daily administration by oral gavage for 30 days conferred a significant protection against CCl4-induced antioxidant enzymes activation and, most importantly, oxidative damage to lipids and proteins as well as blocked induction of inflammatory mediators such as TNF-α, IL-1β, RAGE and NFκB. This antioxidant/anti-inflammatory effect seems to be associated with the abundance of carotenoids and polyphenols present in peach-derived products, which are enriched in fresh-fruit-derived preparations (Peel and FPP) but are also present in PPP. The Syrup – which was the least enriched in antioxidants – displayed no protective effect in our experiments. These effects cumulated in decreased levels of transaminases and lactate dehydrogenase leakage into serum and maintenance of organ architecture. Therefore, the herein presented results show evidence that supplementation with peach products may be protective against organ damage caused by oxidative stress, being interesting candidates for production of antioxidant-enriched functional foods.

Copyright © 2014. Published by Elsevier Inc.

Nutr Res. 2014 Jul 18. pii: S0271-5317(14)00117-1. doi: 10.1016/j.nutres.2014.07.010. [Epub ahead of print]

Carotenoids, inflammation, and oxidative stress-implications of cellular signaling pathways and relation to chronic disease prevention.

Kaulmann A1, Bohn T2.

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Several epidemiologic studies have shown that diets rich in fruits and vegetables reduce the risk of developing several chronic diseases, such as type 2 diabetes, atherosclerosis, and cancer. These diseases are linked with systemic, low-grade chronic inflammation. Although controversy persists on the bioactive ingredients, several secondary plant metabolites have been associated with these beneficial health effects. Carotenoids represent the most abundant lipid-soluble phytochemicals, and in vitro and in vivo studies have suggested that they have antioxidant, antiapoptotic, and anti-inflammatory properties. Recently, many of these properties have been linked to the effect of carotenoids on intracellular signaling cascades, thereby influencing gene expression and protein translation. By blocking the translocation of nuclear factor κB to the nucleus, carotenoids are able to interact with the nuclear factor κB pathway and thus inhibit the downstream production of inflammatory cytokines, such as interleukin-8 or prostaglandin E2. Carotenoids can also block oxidative stress by interacting with the nuclear factor erythroid 2-related factor 2 pathway, enhancing its translocation into the nucleus, and activating phase II enzymes and antioxidants, such as glutathione-S-transferases. In this review, which is organized into in vitro, animal, and human investigations, we summarized current knowledge on carotenoids and metabolites with respect to their ability to modulate inflammatory and oxidative stress pathways and discuss potential dose-health relations. Although many pathways involved in the bioactivity of carotenoids have been revealed, future research should be directed toward dose-response relations of carotenoids, their metabolites, and their effect on transcription factors and metabolism.

J Neuroinflammation. 2014 Jul 1;11:117. doi: 10.1186/1742-2094-11-117.

Cerebrospinal fluid levels of inflammation, oxidative stress and NAD+ are linked to differences in plasma carotenoid concentrations.

Guest J, Grant R1, Garg M, Mori TA, Croft KD, Bilgin A.

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The consumption of foods rich in carotenoids that possess significant antioxidant and inflammatory modulating properties has been linked to reduced risk of neuropathology. The objective of this study was to evaluate the relationship between plasma carotenoid concentrations and plasma and cerebrospinal fluid (CSF) markers of inflammation, oxidative stress and nicotinamide adenine dinucleotide (NAD+) in an essentially healthy human cohort.


Thirty-eight matched CSF and plasma samples were collected from consenting participants who required a spinal tap for the administration of anaesthetic. Plasma concentrations of carotenoids and both plasma and cerebrospinal fluid (CSF) levels of NAD(H) and markers of inflammation (IL-6, TNF-α) and oxidative stress (F2-isoprostanes, 8-OHdG and total antioxidant capacity) were quantified.


The average age of participants was 53 years (SD=20, interquartile range=38). Both α-carotene (P=0.01) and β-carotene (P<0.001) correlated positively with plasma total antioxidant capacity. A positive correlation was observed between α-carotene and CSF TNF-α levels (P=0.02). β-cryptoxanthin (P=0.04) and lycopene (P=0.02) inversely correlated with CSF and plasma IL-6 respectively. A positive correlation was also observed between lycopene and both plasma (P<0.001) and CSF (P<0.01) [NAD(H)]. Surprisingly no statistically significant associations were found between the most abundant carotenoids, lutein and zeaxanthin and either plasma or CSF markers of oxidative stress.


Together these findings suggest that consumption of carotenoids may modulate inflammation and enhance antioxidant defences within both the central nervous system (CNS) and systemic circulation. Increased levels of lycopene also appear to moderate decline in the essential pyridine nucleotide [NAD(H)] in both the plasma and the CSF.

PMID: 24985027 [PubMed – in process] PMCID: PMC4096526 Free PMC Article


Glob Adv Health Med. 2014 Mar;3(2):34-9. doi: 10.7453/gahmj.2013.098.

A Phytochemical-rich Multivitamin-multimineral Supplement Is Bioavailable and Reduces Serum Oxidized Low-density Lipoprotein, Myeloperoxidase, and Plasminogen Activator Inhibitor-1 in a Four-week Pilot trial of Healthy Individuals.

Lerman RH1, Desai A1, Lamb JJ1, Chang JL1, Darland G1, Konda VR2.

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A multivitamin-multimineral supplement combined with a diverse blend of bioactive phytochemicals may provide additional antioxidant capacity and anti-inflammatory property for overall health. This convenient feature may be useful for individuals who want to increase their intake of phytochemicals.


We conducted a pilot study in 15 healthy individuals (8 women and 7 men, mean age 41.7±14.9 years, mean body mass index 28.0±5.6) to investigate the effects of this novel formulation on biomarkers associated with oxidative stress and inflammation. After a 2-week diet that limited intake of fruits and vegetables to 2 servings/day, participants continued with the same restricted diet but began consuming 2 tablets of the study product for the subsequent 4 weeks. Fasting blood samples collected at Week 2 and Week 6 were analyzed and compared using paired t-tests for levels of carotenoids, folate, vitamin B12, homocysteine, oxidized low-density lipoprotein cholesterol (oxLDL), high-sensitivity C-reactive protein (hs-CRP), F2-isoprostane, plasminogen activator inhibitor-1 (PAI-1), and myeloperoxidase. Noninvasive peripheral arterial tonometry (EndoPAT) was also measured.


After 4 weeks of supplementation, plasma levels of carotenoids, folate, and vitamin B12, but not homocysteine, were significantly increased (P<.05). Serum levels of oxLDL, PAI-1 and myeloperoxidase were significantly reduced (P<.05), but F2-isoprostane, hs-CRP, and EndoPAT measures were unchanged compared with baseline. The study product was well tolerated.


This nutritional supplement is bioavailable as indicated by the significant increase in plasma carotenoids, vitamin B12, and folate levels and may provide health benefits by significantly reducing serum levels of oxLDL, myeloperoxidase, and PAI-1 in healthy individuals.


Multivitamin; cardiovascular disease; low-density lipoprotein; multimineral

PMID: 24808980 [PubMed] PMCID: PMC4010963 [Available on 2015/3/1]

J Surg Res. 2014 Nov;192(1):206-13. doi: 10.1016/j.jss.2014.05.029. Epub 2014 May 21.

Astaxanthin offers neuroprotection and reduces neuroinflammation in experimental subarachnoid hemorrhage.

Zhang XS1, Zhang X2, Wu Q1, Li W1, Wang CX1, Xie GB1, Zhou XM1, Shi JX1, Zhou ML3.



Neuroinflammation has been proven to play a crucial role in early brain injury pathogenesis and represents a target for treatment of subarachnoid hemorrhage (SAH). Astaxanthin (ATX), a dietary carotenoid, has been shown to have powerful anti-inflammation property in various models of tissue injury. However, the potential effects of ATX on neuroinflammation in SAH remain uninvestigated. The goal of this study was to investigate the protective effects of ATX on neuroinflammation in a rat prechiasmatic cistern SAH model.


Rats were randomly distributed into multiple groups undergoing the sham surgery or SAH procedures, and ATX (25 mg/kg or 75 mg/kg) or equal volume of vehicle was given by oral gavage at 30 min after SAH. All rats were sacrificed at 24 h after SAH. Neurologic scores, brain water content, blood-brain barrier permeability, and neuronal cell death were examined. Brain inflammation was evaluated by means of expression changes in myeloperoxidase, cytokines (interleukin-1β, tumor necrosis factor-α), adhesion molecules (intercellular adhesion molecule-1), and nuclear factor kappa B DNA-binding activity.


Our data indicated that post-SAH treatment with high dose of ATX could significantly downregulate the increased nuclear factor kappa B activity and the expression of inflammatory cytokines and intercellular adhesion molecule-1 in both messenger RNA transcription and protein synthesis. Moreover, these beneficial effects lead to the amelioration of the secondary brain injury cascades including cerebral edema, blood-brain barrier disruption, neurological dysfunction, and neuronal degeneration.


These results indicate that ATX treatment is neuroprotective against SAH, possibly through suppression of cerebral inflammation.

Nutr J. 2013 Dec 5;12(1):157. doi: 10.1186/1475-2891-12-157.

Extracellular micronutrient levels and pro-/antioxidant status in trauma patients with wound healing disorders: results of a cross-sectional study.

Blass SC, Goost H, Burger C, Tolba RH, Stoffel-Wagner B, Stehle P, Ellinger S1.



Disorders in wound healing (DWH) are common in trauma patients, the reasons being not completely understood. Inadequate nutritional status may favor DWH, partly by means of oxidative stress. Reliable data, however, are lacking. This study should investigate the status of extracellular micronutrients in patients with DWH within routine setting.


Within a cross-sectional study, the plasma/serum status of several micronutrients (retinol, ascorbic acid, 25-hydroxycholecalciferol, α-tocopherol, β-carotene, selenium, and zinc) were determined in 44 trauma patients with DWH in addition to selected proteins (albumin, prealbumin, and C-reactive protein; CRP) and markers of pro-/antioxidant balance (antioxidant capacity, peroxides, and malondialdehyde). Values were compared to reference values to calculate the prevalence for biochemical deficiency. Correlations between CRP, albumin and prealbumin, and selected micronutrients were analyzed by Pearson’s test. Statistical significance was set at P < 0.05.


Mean concentrations of ascorbic acid (23.1 ± 15.9 μmol/L), 25-hydroxycholecalciferol (46.2±30.6 nmol/L), β-carotene (0.6 ± 0.4 μmol/L), selenium (0.79±0.19 μmol/L), and prealbumin (24.8 ± 8.2 mg/dL) were relatively low. Most patients showed levels of ascorbic acid (<28 μmol/L; 64%), 25-hydroxycholecalciferol (<50 μmol/L; 59%), selenium (≤ 94 μmol/L; 71%) and β-carotene (<0.9 μmol/L; 86%) below the reference range. Albumin and prealbumin were in the lower normal range and CRP was mostly above the reference range. Plasma antioxidant capacity was decreased, whereas peroxides and malondialdehyde were increased compared to normal values. Inverse correlations were found between CRP and albumin (P < 0.05) and between CRP and prealbumin (P < 0.01). Retinol (P < 0.001), ascorbic acid (P < 0.01), zinc (P < 0.001), and selenium (P < 0.001) were negatively correlated with CRP.


Trauma patients with DWH frequently suffer from protein malnutrition and reduced plasma concentrations of several micronutrients probably due to inflammation, increased requirement, and oxidative burden. Thus, adequate nutritional measures are strongly recommended to trauma patients.

PMID: 24314073 [PubMed – indexed for MEDLINE] PMCID: PMC4028853

J Biomed Biotechnol. 2012;2012:524019. doi: 10.1155/2012/524019. Epub 2012 Oct 2.

Antioxidant, antinociceptive, and anti-inflammatory effects of carotenoids extracted from dried pepper (Capsicum annuum L.).

Hernández-Ortega M1, Ortiz-Moreno A, Hernández-Navarro MD, Chamorro-Cevallos G, Dorantes-Alvarez L, Necoechea-Mondragón H.


Carotenoids extracted from dried peppers were evaluated for their antioxidant, analgesic, and anti-inflammatory activities. Peppers had a substantial carotenoid content: guajillo 3406 ± 4 μg/g, pasilla 2933 ± 1 μg/g, and ancho 1437 ± 6 μg/g of sample in dry weight basis. A complex mixture of carotenoids was discovered in each pepper extract. The TLC analysis revealed the presence of chlorophylls in the pigment extract from pasilla and ancho peppers. Guajillo pepper carotenoid extracts exhibited good antioxidant activity and had the best scavenging capacity for the DPPH(+) cation (24.2%). They also exhibited significant peripheral analgesic activity at 5, 20, and 80 mg/kg and induced central analgesia at 80 mg/kg. The results suggest that the carotenoids in dried guajillo peppers have significant analgesic and anti-inflammatory benefits and could be useful for pain and inflammation relief.

PMID: 23091348 [PubMed – indexed for MEDLINE] PMCID: PMC3468166

Biochimie. 2012 Dec;94(12):2723-33. doi: 10.1016/j.biochi.2012.08.013. Epub 2012 Aug 24.

A dietary colorant crocin mitigates arthritis and associated secondary complications by modulating cartilage deteriorating enzymes, inflammatory mediators and antioxidant status.

Hemshekhar M1, Sebastin Santhosh M, Sunitha K, Thushara RM, Kemparaju K, Rangappa KS, Girish KS.


Articular cartilage degeneration and inflammation are the hallmark of progressive arthritis and is the leading cause of disability in 10-15% of middle aged individuals across the world. Cartilage and synovium are mainly degraded by either enzymatic or non-enzymatic ways. Matrix metalloproteinases (MMPs), hyaluronidases (HAases) and aggrecanases are the enzymatic mediators and inflammatory cytokines and reactive oxygen species being non-enzymatic mediators. In addition, MMPs and HAases generated end-products act as inflammation inducers via CD44 and TLR-4 receptors involved NF-κB pathway. Although several drugs have been used to treat arthritis, numerous reports describe the side effects of these drugs that may turn fatal. On this account several medicinal plants and their isolated molecules have been involved in modern medicine strategies to fight against arthritis. In view of this, the present study investigated the antiarthritic potentiality of Crocin, a dietary colorant carotenoid isolated from stigma of Crocus sativus. Crocin effectively neutralized the augmented serum levels of enzymatic (MMP-13, MMP-3 and MMP-9 and HAases) and non-enzymatic (TNF-α, IL-1β, NF-κB, IL-6, COX-2, PGE(2) and ROS) inflammatory mediators. Further, Crocin re-established the arthritis altered antioxidant status of the system (GSH, SOD, CAT and GST). It also protected the bone resorption by inhibiting the elevated levels of bone joint exoglycosidases, cathepsin-D and tartrate resistant acid phosphatases. Taken together, Crocin revitalized the arthritis induced cartilage and bone deterioration along with inflammation and oxidative damage that could be accredited to its antioxidant nature. Thus, Crocin could be an effective antiarthritic agent which can equally nullify the arthritis associated secondary complication.

Cell Stress Chaperones. 2014 Mar;19(2):183-91. doi: 10.1007/s12192-013-0443-x. Epub 2013 Jul 14.

Astaxanthin reduces hepatic endoplasmic reticulum stress and nuclear factor-κB-mediated inflammation in high fructose and high fat diet-fed mice.

Bhuvaneswari S1, Yogalakshmi B, Sreeja S, Anuradha CV.


We recently showed that astaxanthin (ASX), a xanthophyll carotenoid, activates phosphatidylinositol 3-kinase pathway of insulin signaling and improves glucose metabolism in liver of high fructose-fat diet (HFFD)-fed mice. The aim of this study is to investigate whether ASX influences phosphorylation of c-Jun-N-terminal kinase 1 (JNK1), reactive oxygen species (ROS) production, endoplasmic reticulum (ER) stress, and inflammation in liver of HFFD-fed mice. Adult male Mus musculus mice were fed either with control diet or HFFD for 15 days. After this period, mice in each group were divided into two and administered ASX (2 mg/kg/day, p.o) in 0.3 ml olive oil or 0.3 ml olive oil alone for the next 45 days. At the end of 60 days, liver tissue was excised and examined for lipid accumulation (Oil red O staining), intracellular ROS production, ER stress, and inflammatory markers. Elevated ROS production, lipid accumulation, and increased hepatic expression of ER stress markers such as Ig-binding protein, PKR-like ER kinase, phosphorylated eukaryotic initiation factor 2α, X-box binding protein 1, activating transcription factor 6, and the apoptotic marker caspase 12 were observed in the liver of the HFFD group. ASX significantly reversed these changes. This reduction was accompanied by reduced activation of JNK1 and I kappa B kinase β phosphorylation and nuclear factor-kappa B p65 nuclear translocation in ASX-treated HFFD mice. These findings suggest that alleviation of inflammation and ER stress by ASX could be a mechanism responsible for its beneficial effect in this model. ASX could be a promising treatment strategy for insulin resistant patients.

PMID: 23852435 [PubMed – indexed for MEDLINE] PMCID: PMC3933623

Clin Nutr. 2012 Oct;31(5):659-65. doi: 10.1016/j.clnu.2012.01.013. Epub 2012 Feb 25.

Higher serum concentrations of dietary antioxidants are associated with lower levels of inflammatory biomarkers during the year after hip fracture.

D’Adamo CR1, Miller RR, Shardell MD, Orwig DL, Hochberg MC, Ferrucci L, Semba RD, Yu-Yahiro JA, Magaziner J, Hicks GE.



Chronic inflammation impairs recovery among the 1.6 million people who suffer from hip fracture annually. Vitamin E and the carotenoids are two classes of dietary antioxidants with profound anti-inflammatory effects, and the goal of this study was to assess whether higher post-fracture concentrations of these antioxidants were associated with lower levels of interleukin 6 (IL-6) and the soluble receptor for tumor necrosis factor-alpha (sTNF-αR1), two common markers of inflammation.


Serum concentrations of the dietary antioxidants and inflammatory markers were assessed at baseline and 2, 6, and 12 month follow-up visits among 148 hip fracture patients from The Baltimore Hip Studies. Generalized estimating equations modeled the relationship between baseline and time-varying antioxidant concentrations and inflammatory markers.


Higher post-fracture concentrations of vitamin E and the carotenoids were associated with lower levels of inflammatory markers. Associations were strongest at baseline, particularly between the α-tocopherol form of vitamin E and sTNF-αR1 (p = 0.05) and total carotenoids and both sTNF-αR1(p = 0.01) and IL-6 (p = 0.05). Higher baseline and time-varying α-carotene and time-varying lutein concentrations were also associated with lower sTNF-αR1 at all post-fracture visits (p ≤ 0.05).


These findings suggest that a clinical trial increasing post-fracture intake of vitamin E and the carotenoids may be warranted.

Copyright © 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

PMID: 22365613 [PubMed – indexed for MEDLINE] PMCID: PMC3412071

Mar Drugs. 2012 Apr;10(4):890-9. doi: 10.3390/md10040890. Epub 2012 Apr 10.

Astaxanthin treatment reduced oxidative induced pro-inflammatory cytokines secretion in U937: SHP-1 as a novel biological target.

Speranza L1, Pesce M, Patruno A, Franceschelli S, de Lutiis MA, Grilli A, Felaco M.


It has been suggested that oxidative stress activates various intracellular signaling pathways leading to secretion of a variety of pro-inflammatory cytokines and chemokines. SHP-1 is a protein tyrosine phosphatase (PTP) which acts as a negative regulator of immune cytokine signaling. However, intracellular hydrogen peroxide (H(2)O(2)), generated endogenously upon stimulation and exogenously from environmental oxidants, has been known to be involved in the process of intracellular signaling through inhibiting various PTPs, including SHP-1. In this study, we investigated the potential role of astaxanthin, an antioxidant marine carotenoid, in re-establishing SHP-1 negative regulation on pro-inflammatory cytokines secretion in U-937 cell line stimulated with oxidative stimulus. ELISA measurement suggested that ASTA treatment (10 µM) reduced pro-inflammatory cytokines secretion (IL-1β, IL-6 and TNF-α) induced through H(2)O(2), (100 µM). Furthermore, this property is elicited by restoration of basal SHP-1 protein expression level and reduced NF-κB (p65) nuclear expression, as showed by western blotting experiments.


SHP-1 protein; astaxanthin; carotenoids; inflammation

PMID: 22690149 [PubMed – indexed for MEDLINE] PMCID: PMC3366681

Mol Cell Biol. 2012 Dec;32(24):5103-15. doi: 10.1128/MCB.00820-12. Epub 2012 Oct 15.

Retinol-binding protein 4 induces inflammation in human endothelial cells by an NADPH oxidase- and nuclear factor kappa B-dependent and retinol-independent mechanism.

Farjo KM1, Farjo RA, Halsey S, Moiseyev G, Ma JX.


Serum retinol-binding protein 4 (RBP4) is the sole specific vitamin A (retinol) transporter in blood. Elevation of serum RBP4 in patients has been linked to cardiovascular disease and diabetic retinopathy. However, the significance of RBP4 elevation in the pathogenesis of these vascular diseases is unknown. Here we show that RBP4 induces inflammation in primary human retinal capillary endothelial cells (HRCEC) and human umbilical vein endothelial cells (HUVEC) by stimulating expression of proinflammatory molecules involved in leukocyte recruitment and adherence to endothelium, including vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), E-selectin, monocyte chemoattractant protein 1 (MCP-1), and interleukin-6 (IL-6). We demonstrate that these novel effects of RBP4 are independent of retinol and the RBP4 membrane receptor STRA6 and occur in part via activation of NADPH oxidase and NF-κB. Importantly, retinol-free RBP4 (apo-RBP4) was as potent as retinol-bound RBP4 (holo-RBP4) in inducing proinflammatory molecules in both HRCEC and HUVEC. These studies reveal that RBP4 elevation can directly contribute to endothelial inflammation and therefore may play a causative role in the development or progression of vascular inflammation during cardiovascular disease and microvascular complications of diabetes.

PMID: 23071093 [PubMed – indexed for MEDLINE] PMCID: PMC3510526