Antioxidants

Vitiligo, an acquired depigmentation disorder, is characterized by the loss of functional melanocytes and epidermal melanin. In recent years, research has focused on promoting melanin biosynthesis and protecting melanocytes to reduce stress-related damage for the purpose of applying it to vitiligo treatment. Ruta graveolens L. has been utilized as a medicinal herb in diverse traditional medicine systems to address conditions like vitiligo. In this investigation, we isolated and purified 16 unique alkaloid compounds from the chloroform extracts of R. graveolens, encompassing a new quinoline alkaloid and several recognized compounds. Bioactivity analysis showed that compound 13, an alkaloid derived from R. graveolens, promotes melanin production while protecting PIG3V melanocytes against 4-tert-butylphenol (4-TBP)-induced oxidative damage by downregulating endoplasmic reticulum (ER) stress and pro-inflammatory cytokines through interleukin-6 (IL-6) regulation. Additionally, the compound suppressed the expression of Bip, IRE1, p-IRE1, and XBP-1 proteins, suggesting a potential antioxidant function. These findings suggest that compound 13 isolated from R. graveolens can augment melanogenesis in melanocytes, reduce endoplasmic reticulum (ER) stress, and ameliorate vitiligo exacerbation. The melanogenic activity observed in the chloroform fraction emphasizes R. graveolens’s potential as a novel therapeutic target for vitiligo treatment, warranting further exploration in future studies. Full article

In this study, D-mannose was used to synthesize poly-D-mannose using a one-pot method. The molecular weight, degree of branching, monosaccharide composition, total sugar content, and infrared spectrum were determined. In addition, we evaluated the safety and bioactivity of poly-D-mannose including anti-pathogen biofilm, antioxidant, and anti-inflammatory activity. The results showed that poly-D-mannose was a mixture of four components with different molecular weights. The molecular weight of the first three components was larger than 410,000 Da, and that of the fourth was 3884 Da. The branching degree of poly-D-mannose was 0.53. The total sugar content was 97.70%, and the monosaccharide was composed only of mannose. The infrared spectra showed that poly-D-mannose possessed characteristic groups of polysaccharides. Poly-D-mannose showed no cytotoxicity or hemolytic activity at the concentration range from 0.125 mg/mL to 8 mg/mL. In addition, poly-D-mannose had the best inhibition effect on Salmonella typhimurium at the concentration of 2 mg/mL (68.0% ± 3.9%). The inhibition effect on Escherichia coli O157:H7 was not obvious, and the biofilm was reduced by 37.6% ± 2.9% at 2 mg/mL. For Staphylococcus aureus and Bacillus cereus, poly-D-mannose had no effect on biofilms at low concentration; however, 2 mg/mL of poly-D-mannose showed inhibition rates of 33.7% ± 6.4% and 47.5% ± 4%, respectively. Poly-D-mannose showed different scavenging ability on free radicals. It showed the best scavenging effect on DPPH, with the highest scavenging rate of 74.0% ± 2.8%, followed by hydroxyl radicals, with the scavenging rate of 36.5% ± 1.6%; the scavenging rates of superoxide anion radicals and ABTS radicals were the lowest, at only 10.1% ± 2.1% and 16.3% ± 0.9%, respectively. In lipopolysaccharide (LPS)-stimulated macrophages, poly-D-mannose decreased the secretion of nitric oxide (NO) and reactive oxygen species (ROS), and down-regulated the expression of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Therefore, it can be concluded that poly-D-mannose prepared in this research is safe and has certain biological activity. Meanwhile, it provides a new idea for the development of novel prebiotics for food and feed industries or active ingredients used for pharmaceutical production in the future. Full article

Preeclampsia (PE) is a pregnancy-specific syndrome affecting 5–7% of patients. There is no effective treatment available. Early abnormal placental development is associated with oxidative stress (OS) and a release of reactive oxygen species (ROS) in the placenta. This phenomenon leads to downstream signaling, Hypoxia Inducible Factor 1A (HIF1A) stabilization and transcription of the anti-angiogenic factors soluble fms-like tyrosine kinase 1 (sFLT1) and soluble endoglin (sEng), which are known to cause endothelial and trophoblast dysfunction and cardinal features of PE: hypertension, proteinuria and, in severe cases, eclampsia. We tested whether 3-(Hydroxymethyl)-1-oxy-2,2,5,5-tetramethylpyrrolidine (HMP)—a nitroxide-type antioxidant molecule—can reduce placental OS and mitigate PE symptoms in vitro. We induced OS in human trophoblast (HTR-8/SVneo) cells with hydrogen peroxide (H₂O₂) and assessed whether modulating cell redox function with HMP reduces cell injury, mitochondrial stress and HIF1A and sFLT1 production. Pre-treatment with HMP reduced mitochondrial-derived ROS production, restored LC3B expression and reduced HIF1A and sFLT1 expression in H₂O₂-exposed HTR-8/SVneo trophoblast cells. HMP improved the mitochondrial electron chain enzyme activity, indicating that a reduction in OS alleviates mitochondrial stress and also reduces anti-angiogenic responses. In reducing placental trophoblast OS, HMP presents a potential novel therapeutic approach for the treatment of PE. Future investigation is warranted regarding the in vivo use of HMP. Full article

Proteins have been extensively studied for their outstanding functional properties, while polyphenols have been shown to possess biological activities such as antioxidant properties. There is increasing clarity about the enhanced functional properties as well as the potential application prospects for the polyphenol–protein complexes with antioxidant properties. It is both a means of protein modification to provide enhanced antioxidant capacity and a way to deliver or protect polyphenols from degradation. This review shows that polyphenol–protein complexes could be formed via non-covalent or covalent interactions. The methods to assess the complex’s antioxidant capacity, including scavenging free radicals and preventing lipid peroxidation, are summarized. The combination mode, the type of protein or polyphenol, and the external conditions will be the factors affecting the antioxidant properties of the complexes. There are several food systems that can benefit from the enhanced antioxidant properties of polyphenol–protein complexes, including emulsions, gels, packaging films, and bioactive substance delivery systems. Further validation of the cellular and in vivo safety of the complexes and further expansion of the types and sources of proteins and polyphenols for forming complexes are urgently needed to be addressed. The review will provide effective information for expanding applications of proteins and polyphenols in the food industry. Full article

Loss of skeletal muscle mass and function has detrimental effects on quality of life, morbidity, and mortality, and is particularly relevant in aging societies. The enhancement of mitochondrial function has shown promise in promoting muscle differentiation and function. Ginsenoside Rc (gRc), a major component of ginseng, has various pharmacological activities; however, its effect on muscle loss remains poorly explored. In this study, we examined the effects of gRc on the hydrogen peroxide (H₂O₂)-induced reduction of cell viability in C2C12 myoblasts and myotubes and H₂O₂-induced myotube degradation. In addition, we investigated the effects of gRc on the production of intracellular reactive oxygen species (ROS) and mitochondrial superoxide, ATP generation, and peroxisome proliferator-activated receptor-gamma co-activator 1α (PGC-1α) activity in myoblasts and myotubes under H₂O₂ treatment. Furthermore, to elucidate the mechanism of action of gRc, we conducted a transcriptome analysis of myotubes treated with or without gRc under H₂O₂ treatment. gRc effectively suppressed H₂O₂-induced cytotoxicity, intracellular ROS, and mitochondrial superoxide production, restored PGC-1α promoter activity, and increased ATP synthesis. Moreover, gRc significantly affected the expression levels of genes involved in maintaining mitochondrial mass and biogenesis, while downregulating genes associated with muscle degradation in C2C12 myotubes under oxidative stress. We provide compelling evidence supporting the potential of gRc as a promising treatment for muscle loss and weakness. Further investigations of the pharmacological effects of gRc under various pathological conditions of muscle loss will contribute to the clinical development of gRc as a therapeutic intervention. Full article

Oxidative stress initiates various degenerative diseases, and it is caused by excessive reactive oxygen species (ROS) production. Oxidative stress is a key factor that causes infertility by inducing ovarian dysfunction, characterized by irregular hormone levels, lower quality of mature follicles, and loss of follicles. Hence, stem cell therapy has been actively studied as an approach to overcome the side effects of hormone replacement therapy (HRT) on ovarian dysfunction. However, there is a lack of evidence about the appropriate number of cells required for stem cell therapy. Therefore, based on the antioxidant effects investigated in this study, we focused on determining the appropriate dose of stem cells for transplantation in an animal model with ovarian dysfunction. One week after half-ovariectomy, placenta-derived mesenchymal stem cells (PD-MSCs, 1 × 10⁵ cells, 5 × 10⁵ cells, or 2.5 × 10⁶ cells) were injected intravenously into the Tx groups through the tail vein. As a result, the mRNA expression of hAlu gradually increased as the transplanted cell concentration increased. Compared with no transplantation (NTx), the transplantation of PD-MSCs improved folliculogenesis, including the levels of secreted hormones and numbers of follicles, by exerting antioxidant effects. Also, the levels of oxidized glutathione in the serum of animal models after transplantation were significantly increased (* p < 0.05). These results indicated that PD-MSC transplantation improved ovarian function in half-ovariectomized rats by exerting antioxidant effects. According to our data, increasing the number of transplanted cells did not proportionally increase the effectiveness of the treatment. We suggest that low-dose PD-MSC transplantation has the same therapeutic effect as described in previous studies. These findings provide new insights for further understanding reproductive systems and provide evidence for related clinical trials. Full article

This study aimed to evaluate and compare the effects of treatment with gold nanoparticles (GNPs) reduced with Curcumin (Curcuma longa L.) or Açai (Euterpe oleracea) to a standard commercial treatment of the pharmacological type (Omcilon^®) and an electrophysical agent (photobiomodulation) in the palatal wounds of rats. As for the in vitro assay, a cell viability test was performed to assess the toxicity of the synthesized nanoparticles. In vivo assay: 60 Wistar rats were divided into five groups (n = 12): I. Palatal Wound (PW); II. PW + Photobiomodulation (PBM); III. PW + Omcilon^®; IV. PW + GNPs-Cur (0.025 mg/mL); V. PW + GNPs-Açai (0.025 mg/mL). Animals were first anesthetized, and circular lesions in the palatine mucosa were induced using a 4 mm-diameter punch. The first treatment session started 24 h after the injury and occurred daily for 5 days. The animals were euthanized, and the palatal mucosa tissue was removed for histological, biochemical, and molecular analysis. GNPs-Açai were able to significantly reduce pro-inflammatory cytokines and increase anti-inflammatory ones, reduce oxidant markers, and reduce inflammatory infiltrate while increasing the collagen area and contraction rate of the wound, along with an improved visual qualification. The present study demonstrated that the proposed therapies of GNPs synthesized greenly, thus associating their effects with those of plants, favor the tissue repair process in palatal wounds. Full article

Kombucha is traditional drink made from the fermentation of a black tea infusion, and is believed to offer a variety of health benefits. Recently, exploring kombucha made from alternative substrates has become a research hotspot. In this paper, two novel kombucha beverages were produced with bamboo leaf or mulberry leaf for the first time. Moreover, the effects of fermentation with leaf residues (infusion plus residues) or without leaf residues (only infusion) on the antioxidant properties of kombucha were compared. The ferric-reducing antioxidant power assay, Trolox equivalent antioxidant capacity assay, Folin–Ciocalteu method, and high-performance liquid chromatography were utilized to measure the antioxidant capacities, total phenolic contents, as well as some compound concentrations of the kombucha. The results showed that two types of kombucha had high antioxidant capacities. Moreover, kombucha fermented with bamboo leaf residues (infusion plus residues) significantly enhanced its antioxidant capabilities (maximum increase 83.6%), total phenolic content (maximum increase 99.2%), concentrations of some compounds (luteolin-6-C-glucoside and isovitexin), and sensory acceptability, compared to that without residues (only infusion). In addition, fermentation with leaf residues had no significant effect on mulberry leaf kombucha. Overall, the bamboo leaf was more suitable for making kombucha with residues, while the mulberry leaf kombucha was suitable for fermentation with or without residues. Full article

Low testosterone (T) levels are a major cause of male infertility, as this hormone is crucial for several processes throughout the entire male reproductive tract. Leydig cells (LC) produce T through testicular steroidogenesis. Disrupted LC function can hinder steroid production and fertility. Among the factors that affect steroidogenesis, endocrine-disrupting chemicals (EDCs) raise concerns, as they disturb hormonal signaling. Chromium is classified as an EDC, and its main forms are hexavalent (Cr(VI)) and trivalent chromium (Cr(III)). While Cr(III) is controversially regarded as an essential metal, its compound Cr(III) picolinate (CrPic₃) is used as a nutritional supplement due to its antidiabetic and antioxidant properties. This review aims to identify the possible effects of CrPic₃ on testicular steroidogenesis and thus, on male fertility. The detriments caused by CrPic₃ in LC include the inhibition of enzymes involved in steroidogenesis, and, as in other cells, the induction of mutagenesis and apoptosis. Remarkably, CrPic₃ impacts male fertility through the alteration of reactive oxygen species (ROS), T levels, and sperm parameters (sperm motility and abnormal sperm count). However, gaps and inconsistencies exist in the literature concerning its effects on male fertility. Thus, further research is imperative to comprehend the underlying mechanisms of CrPic₃ in the physiological processes relevant to male fertility, ensuring the supplement’s safety for use by men. Full article

Due to the limitations in the use of antibiotic agents, researchers are constantly seeking natural bioactive compounds that could benefit udder health status but also milk quality characteristics in dairy animals. The aim of the current study was therefore to examine the effects of a standardized mixture of plant bioactive components (MPBC) originated from thyme, anise and olive on milk yield, composition, oxidative stability and somatic cell count in dairy ewes. Thirty-six ewes approximately 75 days after parturition were randomly allocated into three experimental treatments, which were provided with three diets: control (C); without the addition of the mixture, B1; supplemented with MPBC at 0.05% and B2; supplemented with rumen protected MPBC at 0.025%. The duration of the experiment was 11 weeks, and milk production was weekly recorded, while individual milk samples for the determination of composition, oxidative stability, somatic cell count (SCC), pH and electric conductivity were collected. Every two weeks, macrophage, lymphocyte, and polymorphonuclear leukocyte counts were also determined in individual milk samples. It was observed that milk yield was the greatest in the B2 group, with significant differences within the seventh and ninth week (p < 0.05), whereas no significant differences were found for milk composition, with the exception of the seventh week, when protein, lactose and non-fat solid levels were lower in MPBC groups (p < 0.05). Oxidative stability was improved in the groups that received the MPBC, with significant differences at the third, seventh, tenth and eleventh week (p < 0.05). SCC was also significantly lower at the second, eighth and ninth week in B2 compared to the other groups (p < 0.05), while no significant effects on the macrophage, lymphocyte, and polymorphonuclear leukocyte counts were observed. In conclusion, the MPBC addition had a positive effect on sheep milk yield, oxidative stability and somatic cell count, without any negative effect on its composition. Full article

Hydrogen sulfide (H₂S), originally known as toxic gas, has now attracted attention as one of the gasotransmitters involved in many reactions in the human body. H₂S has been assumed to play a role in the pathogenesis of many chronic diseases, of which the exact pathogenesis remains unknown. One of them is inflammatory bowel disease (IBD), a chronic intestinal disease subclassified as Crohn’s disease (CD) and ulcerative colitis (UC). Any change in the amount of H₂S seems to be linked to inflammation in this illness. These changes can be brought about by alterations in the microbiota, in the endogenous metabolism of H₂S and in the diet. As both too little and too much H₂S drive inflammation, a balanced level is needed for intestinal health. The aim of this review is to summarize the available literature published until June 2023 in order to provide an overview of the current knowledge of the connection between H₂S and IBD. Full article

Alterations in the circulating concentrations of uric acid and its degradation product, allantoin, might account for the systemic pro-oxidant state and the increased cardiovascular risk in rheumatoid arthritis (RA). We sought to address this issue by conducting a systematic review and meta-analysis of the association between the plasma/serum concentrations of uric acid and allantoin and RA. We searched PubMed, Scopus, and Web of Science from inception to 20 June 2023 for studies comparing plasma/serum concentrations of uric acid and allantoin between RA patients and healthy controls. We assessed the risk of bias with the JBI Critical Appraisal Checklist for analytical studies and the certainty of evidence with the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) Working Group system. In the 19 studies selected for analysis, there were non-significant differences in uric acid concentrations between RA patients and controls (standard mean difference, SMD = 0.11, 95% CI −0.07 to 0.30, p = 0.22; I² = 87.9%, p < 0.001; low certainty of evidence). By contrast, the concentrations of allantoin were significantly higher in RA patients (SMD = 1.10, 95% CI 0.66 to 1.55, p < 0.001; I² = 55.6%, p = 0.08; extremely low certainty of evidence). In meta-regression, a significant association was observed between the SMD of uric acid concentrations and body mass index, a risk factor for atherosclerosis and cardiovascular disease (t = 3.35, p = 0.007). Our study has shown a significant increase in the concentrations of the oxidative stress biomarker allantoin in patients with RA. Further research is warranted to investigate the interplay between uric acid, allantoin, redox balance, and cardiovascular disease in this group. (PROSPERO registration number: CRD42023441127). Full article

The progression of an abdominal aortic aneurysm (AAA) is an important issue, especially as AAA is becoming more common, and potentially life-threatening. This study aimed to understand better the mechanisms underlying AAA progression. For this purpose, we have focused on assessing the selected biomarkers whose potentially common denominator is the NRF2 (nuclear factor erythroid 2-related factor 2) transcription factor, that determines the selected antioxidant enzymes’ activation. The study group consisted of 44 AAA male patients (71.41 ± 7.80 years aged). They were divided into three groups based on the aneurism diameter: group I (below 55 mm), group II (between 55 and 70 mm), and group III (over 70 mm). The laboratory analyses of PON1 (paraoxonase-1), NRF2, and HO-1 (heme oxygenase 1) were performed based on commercial ELISA tests; Blb (bilirubin) and hsCRP (high sensitivity C-reactive protein) were assessed during routine morphology examinations after admission to the hospital. Multiple linear regression showed that both bilirubin and NRF2 determined the PON1 concentration in the entire study group. The correlations between the examined parameters within the three studied groups suggest the capitulation of NRF2-dependent antioxidant mechanisms to pro-inflammatory processes. We showed that HO-1 and hsCRP may play a crucial role in the development of inflammation aneurism progression. Moreover, in patients with medium-sized aneurysms, antioxidant mechanisms were depressed, and inflammatory processes began to dominate, which may lead to uncontrolled growth aneurysm rupture. Our study is one of the first to indicate that the chronically activated antioxidant pathway using NRF2 may be a source of reduction stress. Full article

Chronic liver disease (CLD) constitutes a growing global health issue, with no effective treatments currently available. Oxidative stress closely interacts with other cellular and molecular processes to trigger stress pathways in different hepatic cells and fuel the development of liver fibrosis. Therefore, inhibition of reactive oxygen species (ROS)-mediated effects and modulation of major antioxidant responses to counteract oxidative stress-induced damage have emerged as interesting targets to prevent or ameliorate liver injury. Although many preclinical studies have shown that dietary supplements with antioxidant properties can significantly prevent CLD progression in animal models, this strategy has not proved effective to significantly reduce fibrosis when translated into clinical trials. Novel and more specific therapeutic approaches are thus required to alleviate oxidative stress and reduce liver fibrosis. We have reviewed the relevant literature concerning the crucial role of alterations in redox homeostasis in different hepatic cell types during the progression of CLD and discussed current pharmacological approaches to ameliorate fibrosis by reducing oxidative stress focusing on selective modulation of enzymatic oxidant sources, antioxidant systems and ROS-mediated pathogenic processes. Full article

Diabetes mellitus is recognized as the leading contributor to cardiovascular disease and associated mortality rates worldwide. Despite the use of pharmaceutical drugs to treat diabetes, its prevalence continues to rise alarmingly. Therefore, exploring remedies with a lower toxicity profile is crucial while remaining safe and effective in addressing this global public health crisis. Punica granatum Linn (pomegranate), known for its properties and safety profile, has been investigated in applied research and preclinical and clinical trials. However, conflicting reports still exist regarding its effects in diabetes. According to our knowledge, no systematic review has been conducted to critically analyze evidence from preclinical and clinical trials simultaneously, explicitly focusing on oxidative stress, inflammation, and endothelial function in diabetes. Therefore, in this systematic review, we searched for evidence on the impact of pomegranate in diabetes using databases such as PubMed, Scopus, and Google Scholar. Our inclusion criteria were limited to studies published in English. Of the 170 retrieved studies, 46 were deemed relevant and underwent critical analysis. The analyzed evidence suggests that pomegranate has the potential to alleviate oxidative stress, inflammation, and endothelial dysfunction in diabetes. Although a beneficial impact was noted in these markers, the endothelial function evidence still requires validation through further clinical trials with a powered sample size. Full article

An M. salmoides fish meal diet was supplemented with 0 (CHL0, Control), 38 (CHL38), 76 (CHL76), 114 (CHL114), and 152 (CHL152) mg/kg C. vulgaris for 60 days, and their serum and intestinal samples were analyzed. The results showed that the albumin (ALB) and total protein (TP) contents were observably enhanced in the CHL76 group compared with the Control group. The intestinal glutathione (GSH) and glutathione peroxidase (GSH-Px) contents were enhanced significantly in the CHL76 group, while the total antioxidant capacity (T-AOC) was enhanced in the CHL38 group, compared with the Control group. However, supplementation of >76 g/kg C. vulgaris significantly inhibited the superoxide dismutase (SOD) activity in the intestines of M. salmoides. Moreover, the malondialdehyde (MDA) content was observably dropped in the CHL-supplemented groups compared with the Control group. Transcriptome analysis of the CHL76 and Control groups displayed a total of 1384 differentially expressed genes (DEGs). KEGG analysis revealed that these DEGs were enriched in apoptosis, cytokine–cytokine receptor interaction, tight junction (TJ), and phagosome signaling pathways, which were associated with improved intestinal immunity in the CHL76 group. Additionally, the DEGs enriched in the above pathways were also correlated with the antioxidant parameters, such as catalase (CAT), GSH, GSH-Px, SOD, T-AOC, and MDA. Therefore, our study found that dietary supplementation of C. vulgaris effectively enhanced the intestinal antioxidant capacity of M. salmoides by increasing antioxidant enzyme activity and decreasing MDA content. Additionally, dietary supplementation of C. vulgaris improved the intestinal immune status of M. salmoides by reducing proapoptotic and proinflammatory factors, increasing intestinal TJs- and phagosome-related genes expressions, and increasing the serum ALB and TP contents. Lastly, quadratic regression analysis of the serum biochemical indices (ALB and TP) and intestinal antioxidant parameters (GSH-Px and GSH) revealed that the optimal supplemental level of C. vulgaris in the M. salmoides diet was 58.25–77.7 g/kg. Full article

Although the trigger for the neurodegenerative disease process is unknown, the relevance of aging stands out as a major risk for the development of neurodegeneration. In this review, we highlighted the relationship between the different cellular mechanisms that occur as a consequence of aging and transcription factor nuclear factor erythroid-2-related factor 2 (NRF2) and the connection with the TAU protein. We focused on the relevance of NRF2 in the main processes involved in neurodegeneration and associated with aging, such as genomic instability, protein degradation systems (proteasomes/autophagy), cellular senescence, and stem cell exhaustion, as well as inflammation. We also analyzed the effect of aging on TAU protein levels and its aggregation and spread process. Finally, we investigated the interconnection between NRF2 and TAU and the relevance of alterations in the NRF2 signaling pathway in both primary and secondary tauopathies. All these points highlight NRF2 as a possible therapeutic target for tauopathies. Full article

The consumption of extra virgin olive oil (EVOO) has been linked to various health benefits, including a reduced risk of cardiovascular disease. EVOO contains triglycerides and unsaturated fatty acids, as well as minor compounds, such as polar phenols and tocopherols, which play a crucial nutritional and biological role. The composition of these minor compounds is affected by various factors that distinguish EVOOs from lower-quality olive oils. The European Parliament approved Regulation 1924/2006 that governs the use of health claims on food products based on EFSA reports. Currently, there are several authorized health claims related to unsaturated fatty acids, vitamin E, and polyphenol content that can be used for commercial reasons on EVOO labels. Consumers can easily take enough grams of EVOO per day to receive the beneficial effects of the nutrient in question; nevertheless, the use of these health claims is subject to a required concentration of specific nutrients throughout the shelf life of olive oil. Few studies have examined the evolution of these compounds along the shelf life of EVOO to meet health claims. This work aims to evaluate the nutritional profile of several EVOOs with potential health claims and the evolution of related nutrients during storage in darkness at different temperatures. This study proposes an accelerated method to determine the end of the EVOO shelf life based on the loss of its nutraceutical capacity and the inability to comply with the stated health claims. Full article