Alkylresorcinols Research Articles

Fast blue B functionalized silica-polymer composite to evaluate 3,5-dihydroxyhydrocinnamic acid as biomarker of gluten intake

Celiac disease is an immune-mediated systemic disorder elicited by gluten and related prolamines in genetically susceptible individuals. The current treatment is a strict and lifelong gluten-free diet. However, compliance with the gluten-free diet is not always adequate and many food products contain low concentrations of gluten. The determination of dietary transgressions is a challenge for patients, physicians and dietitians. Alkylresorcinols (AR) have been proposed as sensitive and specific biomarkers of gluten consumption. In this work silica–polymer composites doped with fast blue B reagent (FB) have been used to estimate alkylresorcinols in biological samples. The proposed colorimetric device was synthetized by immobilizing FB into polydimethylsiloxane-tetraethylortosilicate composite. The assay was based on the spontaneous release of FB to the solution containing AR (3,5-dihydroxyhydrocinnamic acid, DHCA) and the azocomplexe formation (520 nm). The response was evaluated with UV-vis spectroscopy and chromatography (in-tube SPME-Capillary LC-DAD) to isolate DHCA signal. The spectroscopic analysis can be used as a screening tool to differentiate positive and negative samples. Meanwhile, the chromatographic assay was necessary to isolate DHCA response in positive samples. LOD was 60 ng mL -1 by adding a SPE step. Precision provided adequate results (RSD < 15%). Preliminary studies in urine samples displayed successful results, showing DHCA can be used as biomarker of gluten intake. The here proposed methodology clearly simplifies the dietary transgression evaluation thanks to the development of a pre-screening tool before the chromatographic analysis.

Higher Alkylresorcinol Concentrations, a Consequence of Whole-Grain Intake, are Inversely Associated with Gestational Diabetes Mellitus in Iceland

BackgroundA diet rich in whole grains may provide benefits for pregnant women due to whole grains’ high nutritional value and dietary fiber content. ObjectivesTo study the associations of whole-grain consumption, as well as the plasma alkylresorcinol concentration, a whole-grain consumption biomarker, in early pregnancy with gestational diabetes mellitus (GDM) diagnoses. MethodsSubjects were women from the prospective study Pregnant Women in Iceland II (PREWICE II; n = 853) who attended their ultrasound appointment in gestational weeks 11–14 during the period from October 2017 to March 2018. During that visit, whole-grain consumption was estimated using a diet screening questionnaire, and blood samples were collected for analysis of plasma alkylresorcinols (ARs). Information on GDM diagnoses was later extracted from medical records. Multivariate log-binomial regression was used to evaluate the association of dietary whole-grain and AR concentrations with GDM. ResultsIn total, 14.9% of the women adhered to the national food-based dietary guidelines (n = 127), which recommend 2 portions of whole grains daily. GDM was diagnosed in 127 women (14.9%). The frequency of whole-grain consumption was lower in women who were later diagnosed with GDM compared to the women without GDM (median, 5 times/week vs. 6 times/week, respectively; P = 0.02). This difference was reflected in the lower median concentration of total AR in women diagnosed with GDM (163 nmol/L vs. 209 nmol/L, respectively; P < 0.01). The quartile with the highest concentrations of AR had a RR of 0.50 (95% CI: 0.27–0.90) of being diagnosed with GDM, in comparison to the lowest quartile. There was a significant dose response in the GDM risk with higher AR levels. ConclusionsWe found that a higher consumption of whole grains, reflected both by reported consumption according to the FFQ and AR biomarkers, was associated with a decreased risk of receiving a GDM diagnosis.

Evaluating an Intervention to Increase Cereal Fiber Intake in Children: A Randomized Controlled Feasibility Trial

ABSTRACTBackgroundObservational studies have shown that higher cereal fiber intake is associated with reduced type 2 diabetes risk. However, it remains uncertain whether this association is causal.ObjectiveThis study evaluated the feasibility of an intervention to increase cereal fiber intake in children using breakfast cereals.MethodsThe study was a 2-arm parallel group randomized controlled trial in 9–10-y-old children, who received free supplies of high-fiber breakfast cereals (>3.5 g/portion) or low-fiber breakfast cereals (<1.0 g/portion) to eat daily for 1 mo with behavioral support to promote adherence. Children provided baseline and 1-mo fasting blood samples, physical measurements, and 24-h dietary recalls. The primary outcome was the group difference in change in plasma total alkylresorcinol (AR) concentration; secondary outcomes were group differences in nutrient intakes and adiposity indices. Analyses (complete case and multiple imputation) were conducted by regressing the final AR concentration on baseline AR in models adjusted for sex, ethnicity, age, and school (random effect).ResultsTwo-hundred seventy-two children were randomly assigned (137 receiving a low-fiber and 135 a high-fiber diet) and 193 (71%) provided fasting blood samples at baseline and follow-up. Among randomized participants, median (IQR) of baseline AR was 43.1 (24.6–85.5) nmol/L and of cereal fiber intake was 4.5 (2.7–6.4) g; 87% of participants reported consuming the cereal on most or all days. Compared with changes in the low-fiber group, the high-fiber group had greater increases in AR (40.7 nmol/L; 95% CI: 21.7, 59.8 nmol/L, P < 0.0001) and in reported cereal fiber intake (2.9g/d; 95% CI: 2.0, 3.7 g; P < 0.0001). There were no appreciable differences in other secondary outcomes.ConclusionsWe have developed a simple and acceptable nutritional intervention that increases markers of daily cereal fiber intake in children. This intervention could be used to test whether increases in cereal fiber intake in children might reduce insulin resistance. This trial was registered at www.isrctn.com as ISRCTN33260236.

Neuroprotective Effect of Alkylresorcinols from Wheat Bran in HT22 Cells: Correlation with in vitro Antioxidant Activity

Alkylresorcinols (ARs), which are phenolic lipids found in wheat bran, have attracted a considerable amount of attention because of their antioxidant properties. However, the mechanism of ARs for regulating neuroprotective activity remains unclear. The correlation between the cellular neuroprotective effects of ARs in HT22 cells and their in vitro antioxidant activity were investigated. The results showed that two main constituents of crude ARs were C19:0 and C21:0, which was identified by high-performance liquid chromatography-atmospheric pressure chemical ionization tandem mass spectrometry. Pre-treatment with 400 μg/mL crude ARs could protect from H2O2-induced cellular damage involving low cell viability, leakage of lactate dehydrogenase and decreased superoxide dismutase activity. The maximum radical scavenging ability of DPPH•, ABTS•+, • and •OH– was 85.45%, 88.89%, 84.42% and 87.36%. The neuroprotection effect of ARs was significantly correlated with in vitro antioxidant capacity, confirmed by the maximum correlation coefficients being 0.9988, –0.9974 and 0.9972. The antioxidation of ARs potentially promoted neuroprotective effect and further study is needed to clarify the other mechanism behind ARs benefits.

Straightforward synthesis of cytosporone analogs AMS35AA and AMS35BB.

Cytosporones, a class of octaketide resorcinolic lipids, have drawn the attention of researchers for exhibiting a number of notable biological properties. Herein, we describe routes to synthesize the bioactive synthetic resorcinolic lipids AMS35AA and AMS35BB with excellent overall yields using 3,5-dimethoxybenzoic acid as the starting material. The methods proved remarkably efficient to achieve the target compounds and comprise the synthesis of AMS35AA catalyzed by ascorbic acid (vitamin C).

Research Article Short Alkyl Chain-Length Resorcinol Olivetol Protects Against Obesity with Mitochondrial Activation by Pgc-1α Deacetylation

Summary: The deacetylation of PGC-1α by the activation of sirtuins (SIRTs) with resveratrol (Res) promotes mitochondrial function and metabolic homeostasis. However, Res may not have the ability to specifically promote the deacetylation of PGC-1α by activating SIRT1. We investigated whether the specific deacetylation of PGC-1α is enhanced by increasing the rate of the enzyme-catalyzed reaction of SIRT1 and affects mitochondrial function and metabolic homeostasis. We previously demonstrated that alkylresorcinols (ARs) raised the Vmax of recombinant SIRT1 for NAD+ and extended the Drosophila melanogaster lifespan. Herein, we observed that treatment with the short alkyl chain-length resorcinol olivetol protected mice against diet-induced obesity with SIRT1 activation for PGC-1α. These olivetol effects were superior to Res for all parameters. Olivetol effects were associated with an induction of genes for lipid metabolism and were largely explained by PGC-1α deacetylation. Olivetol specifically activated PGC-1α deacetylation, increased mitochondrial numbers, and accelerated fat burning.

Effect of alkylresorcinols on the formation of Nε‐(carboxymethyl)lysine and sensory profile of wheat bread

Alkylresorcinols (ARs) are important bioactive components in wheat bran which have been used as biomarkers for whole grain wheat consumption. In this study, the impact of ARs on the formation of Nε‐(carboxymethyl)lysine (CML), the main component of dietary advanced glycation end products which could induce chronic disease was analyzed. Moreover, the influence of the addition of ARs on the sensory profiles of wheat bread was evaluated. ARs supplementation (0.03%, 0.1%, and 0.3% w/w) could significantly decrease the formation of CML by 21.70%, 35.11%, and 42.18%, respectively, compared with the control. Moreover, ARs‐supplemented bread achieved a higher score in overall acceptability and buttery‐like aroma through sensory evaluation. The volatile compounds in bread supplemented with ARs were characterized by headspace solid phase microextraction‐gas chromatography‐mass spectrometry (HS‐SPME‐GC‐MS), among which acetoin, 2,3‐butanedione, 3‐methyl‐1‐butanol, 2‐phenylethanol, and 2‐methylbutanal were confirmed as the main volatile compounds through determination of odor activity value. In addition, ARs supplementation had no negative impact on the chewiness, hardness, and springiness of bread. These findings demonstrated that ARs could be applied as potential food additives to improve the quality and sensory profile of bread.

Influence of kernel thermal pre-treatments on 5-n-alkylresorcinols, polyphenols and antioxidant activity of durum and einkorn wheat

Nowadays by-products and waste originated from agro-food processes are considered a source of bioactive molecules. The recovery of the greatest amount of these compounds using advantageous processes is important from an economic perspective. In this work, three different thermal pre-treatments, i.e. hydrothermal, hot air-drying (at three different temperatures) and freeze drying, were applied on intact kernels of durum and einkorn wheat to investigate their effects on the recovery and on the homologue chains composition of alkylresorcinols (AR), on total soluble phenolic (TSP) compounds and on total antioxidant capacity (TAC). The results of this preliminary study showed that thermal processing generally improved AR extractability and caused changes in AR homologue composition, whereas a decrease in TSP content was observed in both wheat species. TAC was not affected by the treatments, suggesting that other antioxidant compounds besides TSP contribute to the total antioxidant capacity of wheat. These findings indicate that just modulating the physical parameters of the thermal pre-processes, it could be possible to promote the recovery of specific bioactive compounds most involved in the biological activities.

Monitoring of changes in 5-n-alkylresorcinols during wheat seedling development.

For seven days of wheat growth, caryopsis remained the main source of 5-n-alkylresorcinols with C19 and/or C21 homolog as a main compound. Shoot contained small amount of these phenolic lipids; their average content was 3.23% of level obtained in the whole seedling. Moreover, 41.38% of resorcinolic lipids of seven-day-old shoot was accumulated in part of leaf covered by coleoptile. Interestingly, a removal of 1.07% of the primary pool of kernel alkylresorcinols by short-term washing (10s) of wheat seed with acetone before planting decreased their level only in seed of seven-day old seedling. Compared to the respective controls, this treatment did not affect the amount of these lipids in the green part of seedling that proved that de novo synthesis of 5-n-alkylresorcinols takes place in shoots. The very similar homolog profiles of these lipids in four- and seven-day-old shoots turned out to be markedly less diversified than those found in respective seed samples. Compared to the mature wheat caryopsis, the rise in the content of very-long-chain homologs was observed only in the oldest shoot. Their increased accumulation was probably connected with formation of cuticular layer providing the defensive barrier against various phytopathogens.

Long-term whole-grain rye and wheat consumption and their associations with selected biomarkers of inflammation, endothelial function, and cardiovascular disease.

Whole-grain (WG) intake has been associated with a lowered risk of developing type 2 diabetes, cardiovascular disease, and some cancers in epidemiological studies. Reduced subclinical inflammation could be one important mechanism behind such associations. This study investigated whether high long-term WG rye and wheat intakes were associated with lower concentrations of biomarkers of inflammation, endothelial function, and protein biomarkers associated with cardiovascular disease. We assessed WG intake by food frequency questionnaire (FFQ) and by measuring alkylresorcinols (ARs) in plasma and adipose tissue, respectively. Selected biomarkers in free-living 109 women and 149 men were analyzed from two clinical subcohort studies (Swedish Mammography Cohort-Clinical (SMC-C) and Cohort of Swedish Men-Clinical (COSM-C), respectively. Total WG rye and wheat (WGRnW) and the ratio of WG rye to WG rye and wheat (WGR/WGRnW) were estimated from FFQs. ARs were measured in plasma and adipose tissue by gas chromatography-mass spectrometry (GC-MS) and the biomarkers by ELISA. We found no consistent associations between WG intake assessed by different methods and the selected biomarkers. However, WGRnW intake was inversely associated with cathepsin S (P-trend < 0.05) and total AR and C17:0/C21:0 in plasma were inversely associated with the endostatin concentration (P-trend < 0.05) adjusted for BMI, age, and sex. The results give limited support to the hypothesis that a high WG wheat and rye intake is associated with lower concentrations of common biomarkers of inflammation and CVD that have previously been reported inversely associated with WG intake or an overall healthy lifestyle.

Benzoxazinoid and alkylresorcinol content, and their antioxidant potential, in a grain of spring and winter wheat cultivated under different production systems

The health-promoting properties of the grains of common wheat (Triticum aestivum L.) are associated with the presence of unique phytochemicals. This study determines the profile of alkylresorcinols (ARs) and benzoxazinoids (BXs) in T. aestivum spring and winter cultivars grown in Poland under the two different production systems: conventional and organic. Wheat grain extracts were subjected to qualitative and quantitative UPLC-UV-MS/MS analyses. The ARs profile consisted of five 5-n-alkylresorcinol derivatives, among which 5-n-heneicosylresorcinol (C21:0) and 5-n-nonadecanylresorcinol (C19:0) predominated; while six different BXs were determined in hydrothermally treated grains. Our research shows significant differences in the contents of ARs and BXs among wheat cultivars, as well as the two production systems used. Organically grown varieties had their total contents of ARs and BXs significantly higher than those grown conventionally. Another aim of the study was to determine the antioxidant capacity of alkylresorcinol extracts from tested wheat cultivars. The quantitative TLC-DPPH• method for determining the antiradical capacity of wheat ARs extracts was developed. We observed a positive relationship between the free radical scavenging activity of extracts and the total amount of ARs. The biological activity research is important for developing value-added wheat cultivars, having an improved profile and composition of nutritional substances.

A Straightforward Method for Synthesizing Bioactive Resorcinolic Lipid Analogues

Neste trabalho, foi planejada a sintese de lipideos resorcinolicos analogos as citosporonas utilizando metodos classicos de sintese orgânica. O objetivo principal foi a preparacao dos compostos: acido 2,4-dihidroxi-6-octil-benzoico ( 6 ) e 2,4-diidroxi-6-(8-oxooctil)-benzoico ( 7 ). Foram estudadas rotas de sintese visando a producao desses compostos, foi possivel obtencao de tres intermediarios avancados, com sucesso: 2,4 dimetoxi-6-octil-benzoato de etila ( 8 ), 2-hidroxi-4-metoxi-6-octil-benzoato de etila ( 9 ) e acido 2-hidroxi-4-metoxi-6-octil-benzoico ( 10 ), os quais tiveram suas estruturas determinadas por tecnicas de espectroscopia de RMN de 1 H e de 13 C, e no caso de ( 10 ) incluindo tecnicas bidimensionais (HSQC e HMBC).

Bioavailability and Bioactivity of Alkylresorcinols from Different Cereal Products

Cereal products are the most important dietary source for energy intake and several bioactive compounds with high concentrations in the bran and the germ. Different cereal products provide a rich source of bioactive phytochemicals, namely, phenolic acids, carotenoids, tocopherols, alkylresorcinols, benzoxazines, phytosterols, and lignans. The bioactive substance alkylresorcinols (ARs) present in the whole cereal can inhibit enzyme activity, prevent bacterial or fungal infection, reduce cholesterol absorption, prevent cancer, and resist oxidation. In this paper, we discussed the biological activity of ARs in whole cereal products. Understanding the effects of processing on cereal phytochemicals will help us to develop improved processes for processing cereal foods with higher retention rates of bioactive compounds.

The Active Components in Whole Grain Wheat for Colon Cancer Prevention: Synergistic Effects Between Phytochemical Alkylresorcinols and Fiber Microbial Metabolite Butyrate

Abstract Objectives Wheat bran (WB) is a rich source of dietary fiber and phytochemicals with health-promoting properties. However, the active components especially the interaction between different components in whole grain (WG) wheat have not been fully explored. This study aimed to investigate whether WB phytochemicals, alkylresorcinols (ARs), and the active intestinal microbial metabolite of fiber, butyrate, could synergistically suppress human colon cancer cells. Methods Cell viability was determined by MTT assay in HCT-116 and HT-29 cells after the treatments of the combination of ARs, C21 and C19, and NaB, respectively. Apoptosis was determined by Cell Death ELISA Kit. The further mechanism was investigated by western blot associated with apoptosis, autophagy, and ER stress pathways. The C21 levels in gastrointestinal tract were measured by HPLC in mice treated with human-relevant doses of C21. Isobologram analysis was employed for the determination of synergistic or additive anticancer effects of the co-treatments of AR and NaB. Results The combination of C21 or C19 and butyrate synergistically inhibited the growth of colon cancer cells and induced apoptosis. Further mechanistic studies demonstrated that the co-treatment of C21 and butyrate induced significant upregulations in cleaved Poly(ADP-ribose) polymerase (PARP), cleaved caspase 3, p53 upregulated modulator of apoptosis (PUMA), cytochrome C, lipid-conjugated membrane-bound form of microtubule-associated protein 1A/1B-light chain 3 (LC3-II), and C/EBP homologous protein (CHOP) expressions. Notably, the C21 concentrations in the large intestinal tract of mice treated with human-relevant doses of C21, were from 0.86 to 1.78 μmol/g, suggesting the C21 doses used in vitro may be achievable after daily WG wheat intake. Conclusions We demonstrated for the first time that phytochemical component ARs and the microbial metabolites of WB fiber exhibit synergistic anticancer effects in human colon cancer cells, which may be associated with the induction of apoptosis, autophagy, and ER stress pathways. The present study provides novel insights into the understanding of the chemo-preventive effects of WG wheat against CRC. However, the mechanism of the synergistic anticancer effect of phytochemicals and fiber is complicated and still needs to be further investigated in vivo. Funding Sources USDA NIFA R01.

Natural Function and Structural Modification of Climacostol, a Ciliate Secondary Metabolite.

The review highlights the main results of two decades of research on climacostol (5-[(2Z)-non-2-en-1-yl]benzene-1,3-diol), the resorcinolic lipid produced and used by the ciliated protozoan Climacostomum virens for chemical defense against a wide range of predators, and to assist its carnivorous feeding. After the first studies on the physiological function of climacostol, the compound and some analogues were chemically synthesized, thus allowing us to explore both its effect on different prokaryotic and eukaryotic biological systems, and the role of its relevant structural traits. In particular, the results obtained in the last 10 years indicate climacostol is an effective antimicrobial and anticancer agent, bringing new clues to the attempt to design and synthesize additional novel analogues that can increase or optimize its pharmacological properties.

Effects of 3-Heptyl-3,4,6-trimethoxy-3H-isobenzofuran-1-one alone or/in association with cyclophosphamide on testicular function.

Chemotherapy for cancer treatment may result in a temporary or long-term gonadal damage resulting in subfertility or infertility. Cyclophosphamide (CY) is a cytotoxic alkylating agent that has been widely used in the treatment of cancer. Recent studies have shown that synthetic resorcinol lipid AMS35AA (3-Heptyl-3,4,6-trimethoxy-3H-isobenzofuran-1-one) may be an important adjuvant chemotherapy that potentiates mutagenic damage and increases apoptosis caused by CY. The present study investigates the action of AMS35AA alone or/in association with CY on testicular function. Animals were divided into four groups: (a) control group: received only water; (b) CY group: received 150μg/g of CY b.w., i.p.; (c) AMS35AA group: received 10μg/g of AMS35AA b.w., i.p; and (d) associated group: received 10μg/g of AMS35AA+150μg/g of CY b.w., i.p. Four weeks after the treatment, the results showed that testes weight of CY and associated groups decreased. However, the number of Sertoli cell and Leydig cell per testis was similar in control and treated groups. Our findings provide strong evidence that the AMS35AA alone or in CY association is not toxic to spermatogenesis. The absence of toxicity of AMS35AA supports the view that the resorcinolic lipid could be used associated with CY chemotherapy without causing adverse effects to testes function.

Simplified method for the measurement of plasma alkylresorcinols: Biomarkers of whole-grain intake.

Consumption of whole grains is negatively associated with cardiovascular disease (CVD) risk but quantification of whole-grain intake is challenging. Alkylresorcinols (ARs) are biomarkers of whole-grain intake. Current methods for AR quantification involve a time-consuming multi-step separation process that hampers applicability in large-scale studies. We developed a streamlined method to quantify ARs in human plasma based on protein precipitation and direct injection into an ultra-high-performance liquid chromatograph coupled to a quadrupole time-of-flight mass spectrometer operating in atmospheric pressure chemical ionization negative ion mode. Separation of five major ARs was achieved, with linearity in the 5 to 550 nmol/L range and a lower limit of detection (LOD) of 0.5 nmol/L and quantification (LOQ) of 5 nmol/L. The within-run and between-run precision and accuracy were below 15%, and recoveries above 90%. Once validated, the method was applied to measure concentrations of plasma ARs in subjects who participated in a randomized, crossover trial evaluating the effect of carbohydrate type on CVD risk factors. The unrefined carbohydrate diet with the highest fiber content resulted in the highest plasma AR concentration (93 ± 78 nmol/L), and was significantly different (p <0.01) from lower fiber diets (18 ± 26 nmol/L and 19 ± 26 nmol/L, simple and unrefined carbohydrate, respectively). This method offers a simplified approach to measure concentrations of plasma ARs as an objective biomarker of whole-grain intake that can be applied to large-scale cohort studies.

Resorcinolic Lipids from Yucatecan Propolis

Propolis is a material produced by bees from a combination of plant exudates and wax, used to fill out cracks in the beehive and to defend against intruders and pathogenic microorganisms; it is recognized for its many biological activities and its chemical composition depends on the botanical sources close to the beehive. The objective of this investigation was to isolate and identify metabolites with antioxidant activity present in a propolis sample collected in Yucatan, Mexico. Purification of the bioactive metabolites was carried out using argentation chromatography, while the combination of 1H nuclear magnetic resonance (NMR), laser desorption ionization (LDI), gas chromatography-mass spectrometry (GC-MS) and biosynthetic origin data allowed their identification as resorcinolic lipids. Finally, the resin of Mangifera indica was identified as the botanical source of these metabolites.

Alkylresorcinols (biomarkers of whole grain intake), cereal fibre intake and metabolic profile - results from a European study

AbstractBackground:High intakes of whole-grains and cereal fiber have been consistently associated with lower risk of cardiometabolic diseases in observational studies. Yet, improved understanding about the underlying mechanisms is needed. We hypothesized that cereal fiber and whole-grain are associated with beneficial metabolic marker profiles.Aim:To investigate if cereal fiber intake, estimated by food frequency questionnaires and plasma total alkylresorcinols concentrations as well as the C17:0/C21:0-ratio in plasma as biomarkers of whole-grain wheat and rye intake or the relative whole-grain rye to wheat intake, respectively, were associated with metabolic biomarkers.Design:A cross-sectional study conducted to investigate the associations between alkylresorcinols as biomarker of whole-grain wheat and rye intake, cereal fiber and selected metabolic biomarkers among 954 participants of the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Cereal fiber intake was assessed by FFQ and whole grain wheat and rye were reflected by biomarkers analyzed in plasma samples, i.e. total alkylresorcinol (AR). Moreover, the ratio of two of the five measured alkylresorcinols (AR C17:0/C21:0 ratio) was used as an indicator of whole-grain source (wheat or rye). Metabolic biomarkers (HbA1c, C-peptide, IGFBP-1, IGFBP-2, total cholesterol, LDL, HDL, triglycerides, apolipoprotein A-I (apoA), apolipoprotein B (ApoB) and CRP) were measured in blood samples. All biomarkers were already measured for nested case-control studies of colorectal cancer matched based on sex, study center, age at blood collection, date and time of blood collection, fasting status. Women were further matched by menopausal status, phase of menstrual cycle, and use of oral contraceptives or hormone replacement therapy at time of blood collection. Multivariable linear regression analysis was used to investigate the relationship between exposure variables metabolic biomarkers adjusted for case-control status and common confounders.Results:No associations were found between cereal fiber intake and the metabolic markers. However, whole-grain wheat and rye intake, reflected by total AR, was associated with a lower concentration of the inflammation marker CRP. The alkylresorcinol C17:0/C21:0 ratio was not associated with any of the measured metabolic markers in this cohort.Conclusion:Overall, we found no support for an association between cereal fibre intake, whole grain wheat and rye intake reflected by biomarkers and metabolic markers in the present cohort. One exception was the finding of an inverse association between whole grain biomarkers and CRP. Prospective studies or RCTs are warranted to confirm our findings.

5-Heptadecylresorcinol attenuates oxidative damage and mitochondria-mediated apoptosis through activation of the SIRT3/FOXO3a signaling pathway in neurocytes.

5-Heptadecylresorcinol (AR-C17) is a main component of the alkylresorcinols (ARs), and has been widely used as a biomarker for whole grain rye consumption. In the present study, the neuroprotective effect and potential defense mechanisms of AR-C17 against hydrogen peroxide (H2O2)-induced apoptosis and mitochondrial dysfunction were investigated in PC-12 cells. The results showed that AR-C17 treatment significantly suppressed oxidative damage to cells, and ROS-mediated cells apoptosis. Furthermore, AR-C17 improved multiple mitochondrial bioactivities, reducing mitochondrial ROS levels, maintaining the mitochondrial membrane potential and enhancing mitochondrial respiration, leading to an elevation in the cellular ATP production, maximal respiration and spare respiratory capacity. In addition, AR-C17 exposure dramatically increased the protein expression of SIRT3 and its downstream functional gene FOXO3a. The cytoprotective effect of AR-C17 was abolished by the SIRT3 inhibitor 3-TYP, which led to increased cell apoptosis. Taken together, our findings demonstrate that AR-C17 could be used as a potential nutraceutical in reducing neuronal oxidative damage.