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Background: Rheumatoid arthritis (RA), is a typical autoimmune disease affecting nearly 1% of the world's population. The dysfunctional hyperproliferation of synovial fibroblast (SF) in articular cartilage of RA patients is considered as the essential etiology. Traditional chemotherapeutic agents for RA treatment are imperfect for their high cost and unpredictable side-effects. L. ruthenicum anthocyanins (LRAC) is a natural product that of potential for therapeutic application against RA., Methods: LRAC was characterized by UPLC-MS/MS. Bioinformatics analyses based on network pharmacology were applied to predict the potential targets of LRAC, and to select DEGs (differentially expressed genes) caused by RA pathogenesis from GSE77298. Interactions between LRAC and the predicted targets were evaluated by molecular docking. Effects of LRAC on SFs from RA patients were examined by in vitro assays, which were analyzed by flow cytometry and western blotting (WB)., Results: LRAC was able to inhibit the abnormal proliferation and aggressive invasion of SFs from RA patients. LRAC was mainly constituted by petunidin (82.7%), with small amount of delphinidin (12.9%) and malvidin (4.4%) in terms of anthocyanidin. Bioinformatics analyses showed that in 3738 RA-related DEGs, 58 of them were collectively targeted by delphinidin, malvidin and delphinidin. AR, CDK2, CHEK1, HIF1A, CXCR4, MMP2 and MMP9, the seven hub genes constructed a central network mediating the signal transduction. Molecular docking confirmed the high affinities between the LRAC ligands and the protein receptors encoded by the hub genes. The in vitro assays validated that LRAC repressed the growth of RASF by cell cycle arresting and cell invasion paralyzing (c-Myc/p21/CDK2), initiating cell apoptosis (HIF-1α/CXCR4/Bax/Bcl-2), and inducing pyroptosis via ROS-dependent pathway (NOX4/ROS/NLRP3/IL-1β/Caspase-1)., Conclusion: LRAC can selectively inhibit the proliferation of RASFs, without side-effecting immunosuppression that usually occurred for RA treatment using MTX (methotrexate). These findings demonstrate the potential application of LRAC as a phytomedicine for RA treatment, and provide a valid approach for exploring natural remedies against autoimmune diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

This study was conducted to investigate the beneficial effect of purple sweet potato anthocyanins (PSPA) on growth performance, oxidative status, immune response, intestinal morphology, and intestinal flora homeostasis in heat-stressed Wenchang chickens. A total of 100 Wenchang chickens (50-day-old) were randomly assigned to 5 groups, including the thermoneutral environment (TN) group (26°C); high-temperature stressed (HS) group (33°C ± 1°C); low-dose PSPA treatment (L&#95;HS) group (8 mg/kg body weight, 33°C ± 1°C); medium-dose PSPA treatment (M&#95;HS) group and high-dose PSPA treatment (H&#95;HS) group (16 mg/kg and 32 mg/kg body weight, respectively, 33°C ± 1°C). The results showed that PSPA reversed the adverse effects of heat stress on growth performance, meat quality, and carcass characteristics. And the effect was associated with the concentration of PSPA partially. Heat stress increased the serum lipids of Wenchang chickens. LDL-C, TG, TC, and FFA in the serum were significantly decreased, and HDL-C and LPS in the serum were increased by PSPA treatment. The digestive enzymes in duodenal chyme were significantly (P < 0.05) increased by PSPA treatment. And PSPA treatment significantly (P < 0.05) enhanced the redox status by improving antioxidant parameters (GSH-Px and SOD) and decreasing the MDA level in the serum and liver. Moreover, the level of inflammatory cytokines was significantly (P < 0.05) regulated by PSPA treatment compared to the HS group. The villus length and goblet cell numbers after PSPA treatment were significantly higher than HS group. Furthermore, PSPA also played protection on the intestine structure by decreasing the level of D-LA and DAO. 16S rRNA sequencing revealed the microbial composition was altered by PSPA, and Acetanaerobacterium and Oscillibacter were dominant in the H&#95;HS group. Microbial functional prediction indicated that function pathways based on KEGG and metacyc database were regulated by PSPA, and intestinal flora correlated with metabolic function significantly. The spearman correlation analysis showed that Saccharibacteria and Clostridium&#95;IV correlated with the serum lipids, antioxidant, and inflammatory cytokines. Collectively, these findings suggest that PSPA has a positive effect against heat stress in poultry., (Copyright © 2023. Published by Elsevier Inc.)

The inhibition of carbohydrate digestion by plant bioactive compounds is a potential dietary strategy to counteract type 2 diabetes. Indeed, inhibition of α-amylase, a key enzyme that carries out the bulk of starch digestion, has been demonstrated for a range of bioactive compounds including anthocyanins; however, sample pigmentation often interferes with measurements, affecting colorimetric assay outcomes. Therefore, the present study compared the performance of a direct chromogenic assay, using 2-chloro-4 nitrophenyl α-D-maltotrioside (CNPG3) as a substrate, with the commonly used 3,5-dinitrosalicylic acid (DNS) assay. The direct chromogenic assay demonstrated a 5-10-fold higher sensitivity to determine α-amylase inhibition in various samples, including acarbose as a reference, pure anthocyanins, and anthocyanin-rich samples. The IC 50 values of acarbose presented as 37.6 μg/mL and 3.72 μg/mL for the DNS assay and the direct chromogenic assay, respectively, whereas purified anthocyanins from blackcurrant showed IC 50 values of 227.4 µg/mL and 35.0 µg/mL. The direct chromogenic assay is easy to perform, fast, reproducible, and suitable for high-throughput screening of pigmented α-amylase inhibitors., Competing Interests: The authors declare no conflicts of interest. The funders had no role in the design of this study; in the collection, analyses, or interpretation of data; in the writing of this manuscript; or in the decision to publish the results.

Anthocyanins are the major polyphenols in myrtle berries seeds aqueous extract (MBSAE). This study investigates the protective potentials of MBSAE against obesity lipotoxicity and inflammation induced by a high-fat diet (HFD). It also describes the underlying mechanisms involved in its protective effects, with special attention to myocardial reactive oxygen species (ROS) production. Male Wistar rats were fed HFD for 6 weeks to induce obesity. MBSAE (100 mg/kg, b.w., p.o .) was orally administered to HFD-fed rats. Anti-obesity effects were triggered by the inhibitory action of the MBSAE against the weights of the body, its relative heart and the total abdominal fat. Treatment with MBSAE also restored the lipid profile to baseline compared with the HFD rats and lowered also the white blood cells count, including neutrophils, lymphocytes, and basophils number as well as cytokines (tumor necrosis factor- α , interleukin [IL]-6, and IL-1 β ) levels in the rats serum, thus improving the tissue inflammatory status associated with obesity. Exposure of rats to HFD during 6 weeks induces a myocardial oxidative stress as assessed by deleterious effects on lipoperoxidation state, antioxidant enzyme (SOD, CAT, and GPx) activities as well as sulfhydryl groups and GSH rates. Of importance, our study shows also that HFD provokes a heart ROS (H 2 O 2 , OH • , and O 2 •- ) overload. Of interest, all these oxidative heart disturbances were clearly ended by MBSAE treatment. Therefore, consumption of MBSAE as a natural extract may be a potential therapeutic strategy to treat obesity-associated diseases.

Anthocyanins are potential bioactive compounds with less bioavailability due to instability in physicochemical and physiological harsh environments. This study synthesized a "nanolipo-fibersomes (NLFS)" using Lipoid® S75 and Nutriose® FB 06 (dextrinization of wheat starch) through a self-assembly technique with probe sonication. We aimed to encapsulate delphinidin-3-O-sambubioside (D3S) successfully and evaluate physicochemical and controlled release properties with improved antioxidant activity on palmitic acid (PA)-induced colonic cells (Caco-2 cells). D3S-loaded nanolipo-fibersomes (D3S-NLFS) were nanosized (<150 nm), spherical shaped, and homogenously dispersed in solution with promising encapsulation efficiency (~ 89.31 to 97.31 %). Particles formation was further verified by FTIR. NLFS were well-stable in thermal, storage, and gastrointestinal mimic environments. NLFS exhibited better-controlled release and mucoadhesive properties compared to nanoliposomes (NL). The NLFS showed better cellular uptake than NL, which was correlated to higher mucoadhesive properties. Furthermore, D3S-NLFS exhibited promising protective effects against PA-induced cytotoxicity, O 2 •- radicals generation, mitochondrial dysfunctions, and GSH depletion, while the free D3S was ineffective. Among D3S-loaded nanoparticles, D3S-NLFS 3 was the most efficient nanocarrier followed by D3S-NLFS 2, D3S-NLFS 1, and D3S-NL, respectively. The above data suggest that nanolipo-fibersomes can be considered as promising nanovesicles for improving colonic delivery of hydrophilic compounds with controlled release properties and greater antioxidant activity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The granary weevil (Sitophilus granarius L.) is a major primary pest of stored cereals throughout the world. Among the major classes of plant secondary metabolites, flavonoids can affect insect feeding behaviour and their growth rate. In this study, the susceptibility of an anthocyanin-rich purple durum wheat genotype (T1303) to the granary weevil was evaluated in comparison with two yellow durum (Ofanto) and bread (Mec) wheat varieties. The feeding response and food utilisation efficiency by adult insects was also investigated by calculating nutritional indices in whole flour disk bioassays. Different levels of susceptibility to granary weevil emerged among genotypes tested. The mean food consumption by an insect, F1 progeny, and female parental offspring calculated for the T1303 genotype were significantly lower than those of yellow kernel wheat varieties. Moreover, T1303 genotype induced deterrence in the adult insects as demonstrated by the positive values of the food deterrence index. Besides, relative grow rate and efficiency conversion of ingested food indices were negative for T1303 and positive for both yellow wheat varieties indicating respectively a decrease and an increase of insect body weight during the bioassays. Finally, a higher mortality rate was recorded for insects fed on T1303 flour disks compared to disks obtained from yellow wheat varieties. These results provide evidence for the antifeedant and toxic effects of anthocyanins present in the T1303 pericarp against the granary weevil. Overall, this study contributes new insights into the mechanisms of host acceptance and food utilization by S. granarius and would be useful to identify antifeedant flavonoids as well as to develop varietal resistance-based strategies against this pest., (© 2023. Springer Nature Limited.)

This study evaluates the potential therapeutic effects of anthocyanin-rich Prunus cerasus (sour cherry) extract (PCE) on atherosclerosis-associated cardiac dysfunction, described by the impairment of the NO-PKG (nitric oxide-protein kinase G) pathway and the antioxidant capacity. Initially, a rabbit model of atherosclerotic cardiovascular disease was established by administering a cholesterol-rich diet, enabling the examination of the impact of 9 g/kg PCE on the pre-existing compromised cardiovascular condition. After that, the animals were divided into four groups for 12 weeks: the (1) untreated control group; (2) PCE-administered healthy rabbits; (3) hypercholesterolemic (HC) group kept on an atherogenic diet; and (4) PCE-treated HC group. Dyslipidemia, impaired endothelial function, and signs of diastolic dysfunction were evident in hypercholesterolemic rabbits, accompanied by a reduced cardiac expression of eNOS (endothelial nitric oxide synthase), PKG, and SERCA2a (sarco/endoplasmic reticulum calcium ATPase 2a). Subsequent PCE treatment improved the lipid profile and the cardiac function. Additionally, PCE administration was associated with elevated myocardial levels of eNOS, PKG, and SERCA2a, while no significant changes in the vascular status were observed. Western blot analysis further revealed hypercholesterolemia-induced increase and PCE-associated reduction in heme oxygenase-1 expression. The observed effects of anthocyanins indicate their potential as a valuable addition to the treatment regimen for atherosclerosis-associated cardiac dysfunction.

Numerous studies have provided evidence that diets rich in anthocyanins show a broad spectrum of health benefits. Anthocyanins in nature are usually found in the form of glycosides. Their aglycone forms are called anthocyanidins. The chemical structure of anthocyanins is based on the flavylium cation, but they differ in the position and number of substituents. However, the bioactives and foods that contain them are frequently treated as a uniform group of compounds exhibiting the same biological activity, without paying attention to the structural differences between individual anthocyanidins. The aim of this study was to find out how structural differences impact the biological activity of the six most common dietary anthocyanidins, i.e., delphinidin (Dp), petunidin (Pt), cyanidin (Cd), malvidin (Mv), pelargonidin (Pg) and peonidin (Po). The study concentrated on redox-related phenomena and compared the following parameters: antioxidant activity (measured using various methods: spectrophotometric tests (ABTS, DPPH), ORAC assay and CAA test (cellular antioxidant activity)), the ability to inhibit growth of human colon cancer cells (HT29; determined using MTT assay), and the ability of studied compounds to protect DNA from oxidative damage (comet assay). Based on the obtained results, the relationship between the structure of studied anthocyanidins and their biological activity was assessed. The obtained results revealed that the number and position of the hydroxyl and methoxy groups in the anthocyanidin structure strongly influenced not only the color of anthocyanidins but most of all their antioxidant and biological activities.

Rice (Oryza L.) is an essential food for more than 50 percent of the world's population and is the world's second-largest grain crop. Pigmented rice comes in various colors, such as black, red, brown, and green. Anthocyanins, like cyanidin-3-O-glucoside and peonidin-3-O-glucoside, are the primary color pigments in colored rice, whereas proanthocyanidins and flavan-3-ol oligosaccharides, with catechins as the central synthesis unit, are found in brown rice. This review article's aim is to give information and a summary of rice activities, research methods, also mechanisms of action (Oryza L.). Intake of pigmented rice was already associated with a number of health benefits, including antioxidant activity, anticancer, antitumor, antidiabetic activity, and a reduced risk of cardiovascular disease. Rice contains several bioactive compounds, such as γ-oryzanol, phenolic acid, anthocyanins, proanthocyanidins, flavonoids, carotenoids, and phytosterols, which have been widely studied and shown to have several pharmacological activities. The use of current herbal compounds is rapidly increasing, including the practice of pharmacological disease prevention and treatment. Herbal remedies have entered the international market as a result of research into plant biopharmaceuticals and nutraceuticals. Through a variety of pharmacological activities, it is clear that Oryza L. is a popular herb. As a result, additional research on Oryza L. can be conducted to investigate more recent and comprehensive pharmacological effectiveness, to provide information and an overview of Rice (Oryza L.) activities, research methods, and mechanisms of action. Several natural substances are characterized by low water solubility, low stability, and sensitivity to light and oxygen, and the potential for poor absorption of the active substances requires modification of the formulation. To improve the effectiveness of pharmacologically active substances originating from natural ingredients, drug delivery systems that use lipid-based formulations can be considered innovations.

Due to the rising demand for supplements targeting cognitive enhancement and dry eye together with the health benefits of anthocyanins, we have developed a functional soup containing an anthocyanin-rich functional ingredient, or "Anthaplex," and assessed the effects on cognitive function and eye dryness together with the possible mechanisms. A total of 69 male and female health volunteers were randomized and divided into placebo, D2, and D4 groups. All subjects consumed 120 mL of placebo or functional soup containing "Anthaplex" either at 2 or 4 g per serving per day within 5 min in the morning for eight weeks. The cognitive function, working memory, dry eye, AChE, MAO, MAO-A, MAO-B, and GABA-T activities, BDNF, HAC, HDAC, and DNMT activities, pH, and amount of lactic acid-producing bacteria, particularly Lactobacillus and Bifidobacterium spp. in feces, were determined before intervention and after eight weeks of consumption. Subjects who consumed the "Anthaplex" soup had improved cognitive function, working memory, eye dryness, histone acetylation, ACh E suppression, and BDNF with increased Bifidobacterium spp. but decreased pH in feces. These data suggest that "Anthaplex" improves cognitive function and eye dryness via the modulations of the histone acetylation process, gut microbiome, and cholinergic function.

Sepsis, one of the most destructive diseases in the world, is a syndrome of systemic inflammatory response caused by the invasion of pathogenic microorganisms such as bacteria into the body. Malvidin is one of the most widespread anthocyanins, and its significant antioxidant and anti-inflammatory activities have been widely reported. However, the effect of Malvidin on sepsis and related complications is still unclear. The present study aimed to determine the mechanisms of Malvidin's potential protection from lipopolysaccharide (LPS)-induced spleen injury model of sepsis. In the LPS-induced mouse spleen injury model of sepsis, pretreatment with Malvidin was performed to assess morphological damage in spleen tissue and to detect the expression of mRNA levels of serum necrosis factor α, interleukin 1β and interleukin 6, and IL-10. Apoptosis was detected using the TUNEL technique, and the levels of oxidative stress-related oxidase and antioxidant enzymes were measured by kit to assess the effect of Malvidin on inflammation and oxidative stress associated with septic spleen injury. The results of this study indicated that Malvidin was be a potentially effective drug for the treatment of sepsis., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

The liver is a central target organ of heavy metals toxicity, and secondary metabolites of several plant species are suggested to attenuate lead (Pb)-induced hepatotoxicity through antioxidant and anti-inflammatory mechanisms. We used a systematic review framework to map the impact of plant extracts and bioactive secondary metabolites on immunological markers and liver redox metabolism in preclinical models of Pb exposure. This is a systematic review performed according to PRISMA guidelines. The structured research of publications was done through PubMed, Scopus, Web of Science, and Embase databases, selecting and analyzing 41 original studies included via the eligibility criteria. Evidence indicates that Pb-exposure increases reactive oxygen/nitrogen species (ROS/RNS) production by δ-aminolevulinic acid auto-oxidation, xanthine dehydrogenase, and xanthine oxidase upregulation. Pb exposure also inhibits antioxidant enzymes, potentiating ROS/NOS levels and reactive cell damage. Plant extracts rich in flavonoids, tannins, alkaloids, anthocyanins, and vitamins exerted hepatoprotective effects by chelating and decreasing Pb bioaccumulation. In addition, plant extracts reinforce exogenous and endogenous antioxidant defenses, attenuating liver oxidative stress and cell death. The lack of blinded evaluators and randomized experimental groups were the main sources of bias identified, which need to be controlled in toxicological studies aimed at identifying natural products applied to the prevention or treatment of Pb poisoning., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The relationship between anthocyanin intake and obesity-related inflammatory markers remains unclear in existing research. To investigate this, we hypothesized that anthocyanin supplementation could reduce plasma concentrations of inflammatory markers, including C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), vascular cell adhesion molecule-1, and other cytokines in obesity. We conducted a systematic search of PubMed, Web of Science, Scopus, SinoMed, and other related literature and identified 16 randomized controlled trials that met our inclusion criteria. Our findings showed that anthocyanin intake was significantly associated with a reduction in vascular cell adhesion molecule-1 mean plasma concentrations (-53.56 ng/mL; 95% confidence interval [CI], -82.10 to -25.03). We also observed a modest decrease in CRP (-0.27 ng/mL; 95% CI, -0.58 to 0.05), TNF-α (-0.20 ng/mL; 95% CI, -0.54 to 0.15), and IL-6 (-0.53 ng/mL; 95% CI, -1.16 to 0.10) mean plasma concentrations. Subgroup analysis revealed that anthocyanin intake tended to decrease CRP and IL-6 concentrations in overweight or dyslipidemic individuals. Additionally, the intervention duration subgroup analysis showed that anthocyanin supplementation had a stronger effect on plasma IL-6 and TNF-α in participants after 8 to 12 weeks of intervention. In conclusion, our meta-analysis indicated that anthocyanin supplementation can effectively reduce obesity-related inflammatory markers associated with chronic low-grade inflammation., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Blackcurrant press cake (BPC) is a source of anthocyanins, and this study evaluated the bioactivity and gut microbiota modulation of blackcurrant diets with or without 1,2 dimethylhydrazine (DMH)-induced colon carcinogenesis in rats. In colon cancer-induced rats (CRC), BPC at the highest dosages increased pro-inflammatory parameters and the expression of anti-apoptotic cytokines, accentuating colon cancer initiation by aberrant crypts and morphological changes. Fecal microbiome analysis showed that BPC altered the composition and function of the gut microbiome. This evidence suggests that high doses of BPC act as a pro-oxidant, accentuating the inflammatory environment and CRC progression., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Luciana Azevedo reports financial support was provided by Minas Gerais State Foundation of Support to the Research. Nora Pap reports financial support was provided by Natural Resources Institute Finland (Luke). Luciana Azevedo reports financial support was provided by National Council for Scientific and Technological Development., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Colorectal cancer (CRC) is the second most lethal and the third most diagnosed type of cancer worldwide. More than 75% of CRC cases are sporadic and lifestyle-related. Risk factors include diet, physical inactivity, genetics, smoking, alcohol, changes in the intestinal microbiota, and inflammation-related diseases such as obesity, diabetes, and inflammatory bowel diseases. The limits of conventional treatments (surgery, chemotherapy, radiotherapy), as demonstrated by the side effects and resistance of many CRC patients, are making professionals search for new chemopreventive alternatives. In this context, diets rich in fruits and vegetables or plant-based products, which contain high levels of phytochemicals, have been postulated as complementary therapeutic options. Anthocyanins, phenolic pigments responsible for the vivid colors of most red, purple, and blue fruits and vegetables, have been shown protective effects on CRC. Berries, grapes, Brazilian fruits, and vegetables such as black rice and purple sweet potato are examples of products rich in anthocyanins, which have been able to reduce cancer development by modulating signaling pathways associated with CRC. Therefore, this review has as main objective to present and discuss the potential preventive and therapeutic effects of anthocyanins present in fruits and vegetables, in plant extracts, or in their pure form on CRC, taking into account up-to-date experimental studies (2017-2023). Additionally, a highlight is given towards the mechanisms of action of anthocyanins on CRC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Natural pigments are important sources for the screening of bioactive lead compounds. This article reviewed the chemistry and therapeutic potentials of over 570 colored molecules from plants, fungi, bacteria, insects, algae, and marine sources. Moreover, related biological activities, advanced extraction, and identification approaches were reviewed. A variety of biological activities, including cytotoxicity against cancer cells, antioxidant, anti-inflammatory, wound healing, anti-microbial, antiviral, and anti-protozoal activities, have been reported for different pigments. Considering their structural backbone, they were classified as naphthoquinones, carotenoids, flavonoids, xanthones, anthocyanins, benzotropolones, alkaloids, terpenoids, isoprenoids, and non-isoprenoids. Alkaloid pigments were mostly isolated from bacteria and marine sources, while flavonoids were mostly found in plants and mushrooms. Colored quinones and xanthones were mostly extracted from plants and fungi, while colored polyketides and terpenoids are often found in marine sources and fungi. Carotenoids are mostly distributed among bacteria, followed by fungi and plants. The pigments isolated from insects have different structures, but among them, carotenoids and quinone/xanthone are the most important. Considering good manufacturing practices, the current permitted natural colorants are: Carotenoids (canthaxanthin, β-carotene, β-apo-8'-carotenal, annatto, astaxanthin) and their sources, lycopene, anthocyanins, betanin, chlorophyllins, spirulina extract, carmine and cochineal extract, henna, riboflavin, pyrogallol, logwood extract, guaiazulene, turmeric, and soy leghemoglobin., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Lycium ruthenicum Murr. (LR) has long been used as a unique nutritional and medicinal food to treat various diseases such as gouty arthritis. However, although recently the literature has focused on the protective roles of LR anthocyanins on gouty arthritis, there is no relevant research from a holistic perspective of lipid metabolism to study their anti-gout effects. In this study, a combined tissue lipidomics, network pharmacology, and molecular docking approach was performed to investigate the intervention mechanism of LR anthocyanins against a monosodium urate (MSU)-induced gout mouse model. 54 gout-related lipid markers were identified via lipidomic profiling of the mouse knee joint, including glycerophospholipids, sphingolipids, glycerolipids, and plasmalogens. Integrating with pathway analysis, network pharmacology, and molecular docking, the potential targets of LR anthocyanins for treating gouty arthritis were predicted, while pathways in cancer, prostate cancer, sphingolipid signaling, choline metabolism in cancer, arachidonic acid metabolism, and ovarian steroidogenesis were involved as shared critical pathways of lipidomic analysis and network pharmacology. Furthermore, the binding sites and patterns of 3 active components and 4 core targets with the lowest binding energies were explored. Western blotting was finally used to verify the expression levels of 4 core proteins: MMP2, MMP9, MAP2K1, and MAPK14. These results provide new insights into our understanding of gouty arthritis and the anti-gout mechanism of LR anthocyanins.

Computational methods were used to investigate six anthocyanidins exhibiting antidiabetic activity by inhibiting glucokinase regulatory protein (GKRP) activity. Density functional theory was used to optimise the geometry of anthocyanidins and calculate their quantum chemical properties. A blind docking method was employed to conduct a molecular docking study, which revealed that delphinidin (Del), cyanidin (Cya), and pelargonidin (Pel) as potential GKRP inhibitors with the lowest binding free energy of -8.7, -8.6, and -8.6 kcal/mol, corresponding to high binding affinity. The molecular dynamics study further verified the blind docking results by showing high GKRP-F1P complex stability and high binding affinity calculated through the MM/GBSA method, upon the binding of pelargonidin. The lower RMSF values of pivotal GK-interacting residues for GKRP-F1P-Pel compared to GKRP-F1P, as a positive control, indicating pelargonidin ability to maintain the inactive conformation of GKRP through the inhibition of GK binding. The key residues that control the binding of the F1P to GKRP and anthocyanidin to GKRP-F1P were also identified in this study. Altogether, pelargonidin is anthocyanidins-derived natural products that have the most potential to act as inhibitors of GKRP and as antidiabetic nutraceuticals., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Kenneth et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Black rice ( Oryza sativa L.) is a great source of anthocyanins and dietary fiber and possesses various health-promoting properties. The modulating effect of insoluble dietary fiber (IDF) from black rice on the fermentation of cyanidin-3- O -glucoside (Cy3G) in an in vitro human colonic model, together with the possible microbiota-mediated mechanisms, was investigated. The combined Cy3G and IDF fermentation can promote the biotransformation of Cy3G into phenolic compounds such as cyanidin and protocatechuic acid with stronger antioxidant activities and increase the total production of SCFAs during the fermentation of Cy3G. 16S rRNA sequencing analysis revealed that the addition of IDF modulated the microbiota structure and bloomed Bacteroidota and Prevotellaceae -related genera, which were positively correlated with metabolites of Cy3G, thus potentially regulating the microbial metabolism of Cy3G. The work is of great significance for elucidating the material basis of the health benefits of black rice.

Pelargonidin (PG), a derivative of anthocyanins, has anti-oxidant and anti-inflammatory properties. Herein, the protective effect and the mechanism of PG in counteract the osteoarthritis (OA) progression were needed to further evaluate. In the current study, C57BL/6 mice was induced by destabilization of medial meniscus (DMM) surgery to establish the OA model. Primary chondrocytes were acquired from the knee cartilage of newborn mice. Then, PG was administrated to OA mice and IL-1β-stimulated chondrocytes to evaluate its protective effects, respectively. Results uncovered that no conspicuous cytotoxic effects were observed when chondrocytes were treated with PG at a concentration lower than 40 μM for 24-72 h. Thus, 10 μM, 20 μM, and 40 μM PG were chosen for subsequent experiments in vitro. Then, we observed that 10, 20, and 40 μM PG reduced the levels of IL-6, TNF-α, COX-2 and iNOS in chondrocytes. In line, PG inhibited the IL-1β-induced ECM catabolism in chondrocytes, as evidenced by deepening toluidine blue staining, increased expression of Collagen II, and decreased expressions of ADAMTS5 and MMP13. Moreover, PG also reduced the IL-1β-stimulated p-p65 overexpression and nuclear translocation of p65 in chondrocytes. In vivo, Safranin O/Fast green and HE staining showed that articular cartilage surface morphology was basically smooth and complete after PG treatment for 8 weeks. Similarly, OARSI scores and MMP13 expression were apparently decreased, whereas Aggrecan expression was elevated in PG-treated mice 8 weeks after DMM surgery. In conclusion, PG can effectively ameliorate inflammatory reactions and cartilage degeneration via suppressing the NF-κB pathway, thereby restraining the OA progression., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Muscadine wine has a unique polyphenol profile consisting of anthocyanins, ellagic acids, and flavonols. This study aims to compare the prevention, treatment, and combined activity (P + T) of dealcoholized muscadine wine (DMW) on DSS-induced colitis in mice and its impact on the gut microbiome. Male C57BL/6 mice in the healthy and colitis group received an AIN-93M diet for 28 days. In the prevention, treatment, and P + T (prevention + treatment) groups, mice received an AIN-93M diet containing 2.79% (v/w) DMW on days 1-14, 15-28, and 1-28, respectively. Except for mice in the healthy group, all mice were given water with 2.5% (w/v) DSS on days 8-14 to induce colitis. DMW in all three receiving groups reduced myeloperoxidase activity, histology scores, and phosphorylation of Iκb-α in the colon. Colon shortening, serum IL-6, and colonic mRNA of TNF-α were blunted only in the P + T group. Gut permeability was reduced in the treatment and P + T groups. DMW in P + T group showed higher activity to increase microbiome evenness, modulate β-diversity, elevate the cecal content of SCFAs, and enrich SCFA-producing bacteria, including Lactobacillaceae , Lachnospiraceae, Ruminococcaceae , and Peptococcaceae . This was accompanied by a decrease in pathogenic Burkholderiaceae in mice. This study suggests that muscadine wine has partial preventive and therapeutic effects against inflammatory bowel disease. The combination of prevention and treatment using DMW showed better activities than either prevention or treatment.

In this study, pectin (PC)/chitosan nanofiber (ChNF) films containing a novel anthocyanin from sumac extract were successfully developed for freshness monitoring and shelf-life extension of shrimp. The physical, barrier, morphological, color, and antibacterial properties of biodegradable films were evaluated. The addition of sumac anthocyanins to the films caused intramolecular interactions (such as hydrogen bonds) in the film structure, as confirmed by using attenuated total reflectance Fourier transform infrared (ATR-FTIR) analysis, suggesting good compatibility of film ingredients. Also, intelligent films showed significant sensitivity to ammonia vapors and changed color from reddish to olive color at the first 5 min. Moreover, the results showed that PC/ChNF and PC/ChNF/sumac films have significant antibacterial activity against Gram-positive bacteria and Gram-negative bacteria. In addition to the good functional characteristics of the smart film, the resulting films showed acceptable physicomechanical properties. So, PC/ChNF/sumac smart film exhibited the strength = 60 MPa with the flexibility = 23.3 %. Likewise, water vapor barrier reduced from 2.5 (×10 -11  g. m/m 2 . s. Pa) to 2.3 (×10 -11  g. m/m 2 . s. Pa) after adding anthocyanin. The results of the application of intelligent film containing anthocyanins of sumac extract for shrimp freshness monitoring showed that the color of the intelligent film changed from reddish to greenish color after 48 h of storage, which shows the high potential of the produced film for monitoring the spoilage of seafood products., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest with this manuscript., (Copyright © 2023. Published by Elsevier B.V.)

Anthocyanins are colored polyphenolic compounds that belong to the flavonoids family and are largely present in many vegetables and fruits. They have been used in traditional medicine in many cultures for a long time. The most common and abundant anthocyanins are those presenting an O-glycosylation at C-3 (C ring) of the flavonoid skeleton to form -O-β-glucoside derivatives. The present comprehensive review summarized recent data on the anticancer properties of cyanidings along with natural sources, phytochemical data, traditional medical applications, molecular mechanisms and recent nanostrategies to increase the bioavailability and anticancer effects of cyanidins. For this analysis, in vitro, in vivo and clinical studies published up to the year 2022 were sourced from scientific databases and search engines such as PubMed/Medline, Google scholar, Web of Science, Scopus, Wiley and TRIP database. Cyanidins' antitumor properties are exerted during different stages of carcinogenesis and are based on a wide variety of biological activities. The data gathered and discussed in this review allows for affirming that cyanidins have relevant anticancer activity in vitro, in vivo and clinical studies. Future research should focus on studies that bring new data on improving the bioavailability of anthocyanins and on conducting detailed translational pharmacological studies to accurately establish the effective anticancer dose in humans as well as the correct route of administration., Competing Interests: Conflict of interest statement The authors declare that they have no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Anthocyanins are flavonoid compounds that are abundantly present in fruits and vegetables. These compounds contribute to the color of these foods and offer various health benefits to consumers due to their biological properties. There are more than 1000 types of anthocyanins in nature, all derived from 27 anthocyanidin aglycones that have different glycosylations and acylations. Malvidin is one of the most well-known anthocyanidins. Several studies, including those conducted on cell lines, animals, and humans, have suggested that malvidin and its glycosides possess anti-carcinogenic, diabetes-control, cardiovascular-disease-prevention, and brain-function-improvement properties. These health benefits are primarily attributed to their antioxidant and anti-inflammatory effects, which are influenced by the molecular mechanisms related to the expression and modulation of critical genes. In this article, we review the available information on the biological activity of malvidin and its glycosides concerning their health-promoting effects.

Background: Blueberry extract (BE) is rich in phenols, especially anthocyanins. Anthocyanins regulate the inflammatory response in mice and may be related to gut microbiota and bile acid receptors. The aim of the present study was to explore the effects of BE on the inflammatory response by regulating gut microbiota and bile acid receptors in mice administered Escherichia coli lipopolysaccharide (LPS)., Method: Thirty male KM mice were randomly divided into three groups: CON (control diet) group; LPS (LPS stimulation) group; and LPS + BE (LPS stimulation, 5% BE intervention) group., Results: our results showed that, compared with the LPS group, the addition of BE decreased the level of inflammatory factors in serum and tissues, inhibited the TLR4/MyD88 signaling pathway, protected the intestinal barrier and activated FXR/TGR5, which was related to gut microbiota (especially Akkermansia). The active component (e.g., cyanidin 3-O-glucoside, C3G) in BE may be an important factor in regulating gut microbiota., Conclusion: BE alleviated the inflammatory response mainly by activating bile acid receptor expression and regulating the gut microbiota; this effect may be related to the composition of bioactive substances in BE. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

This study investigates blackberry juice's effects on glucose metabolism, oxidative stress, inflammation, and endoplasmic reticulum stress (ER) in streptozotocin (STZ)-induced diabetic rats. Fifty Wistar rats were distributed to five groups randomly of ten rats each: Normal control, diabetic control, 9 mL/kg body weight (b.wt) blackberry juice only, blackberry juice plus diabetes, and 500 mg/kg b.wt metformin plus diabetes. A single intraperitoneal injection of 50 mg/kg b.wt STZ induced diabetes in the rats. This animal study continued for 56 days after the confirmation of diabetes. The levels of liver function and renal function, as well as insulin, glucose-6-phosphatase, glucokinase, and malondialdehyde (MDA) levels, and the activities of catalase (CAT) and superoxide dismutase (SOD), were determined. Additionally, interleukin-6 (IL-6) levels, tumor necrosis factor-alpha (TNF-α), and activated transcription factor 4 (ATF4) expressions were examined in the liver homogenate of rats. Furthermore, the liver tissues were utilized for histopathological examination. The results showed that blackberry juice prevented drastic loss of body weight and reduced food consumption in diabetic rats. Additionally, the levels of blood glucose, total protein, aspartate aminotransferase (AST), albumin, alanine aminotransferase (ALT), uric acid, creatinine, and urea improved after the administration of blackberry juice in diabetic rats. Blackberry juice significantly increased glucose metabolism and antioxidant status while reducing ER stress and inflammation in diabetic rats. Moreover, blackberry juice improved glucose metabolism by increasing insulin levels and improving the dysregulated activities of glucose-metabolizing enzymes. The microstructure of liver tissues in diabetic rats was also improved with blackberry juice treatment. Therefore, blackberry juice has the potential to alleviate diabetes in rats and could be considered as a functional food for people with diabetes., (© 2023. The Author(s).)

Type 2 diabetes (T2D) accounts for a global health problem. It is a complex disease as a result of the combination of environmental as well as genetic factors. Morbidity is still increasing across the world. One of the possibilities for the prevention and mitigation of the negative consequences of type 2 diabetes is a nutritional diet rich in bioactive compounds such as polyphenols. This review is focused on cyanidin-3-O-glucosidase (C3G), which belongs to the anthocyanins subclass, and its anti-diabetic properties. There are numerous pieces of evidence that C3G exerts positive effects on diabetic parameters, including in vitro and in vivo studies. It is involved in alleviating inflammation, reducing blood glucose, controlling postprandial hyperglycemia, and gene expression related to the development of T2D. C3G is one of the beneficial polyphenolic compounds that may help to overcome the public health problems associated with T2D.

Cyanidin is the most abundant anthocyanin found in red-purple plants and possesses anti-obesity properties. However, its mechanism of action in adipocytes remains unknown. The objective of this study was to elucidate how cyanidin inhibits adipocyte formation in 3T3-L1 preadipocytes. Cells were cultured in adipogenic differentiation medium supplemented with cyanidin and examined for adipogenesis, cell viability, and adipocyte gene expression using Oil Red O staining, MTT assay, and RT-qPCR. Real-time Ca 2+ imaging analysis was performed in living cells to elucidate cyanidin's mechanism of action. The results demonstrated that cyanidin (1-50 μM) supplementation to the adipogenic medium inhibited adipogenesis by downregulating adipogenic marker gene expression (PPARγ, C/EBPα, adiponectin, and aP2) without affecting cell viability after 4 days of treatment. Stimulation of cells with cyanidin (30-100 μM) increased intracellular Ca 2+ in a concentration dependent manner with peak calcium increases at 50 μM. Pretreatment of cells with the phospholipase C (PLC) inhibitor U73122, inositol triphosphate (IP 3 ) receptor blocker 2-APB, and depletion of endoplasmic reticulum Ca 2+ stores by thapsigargin abolished the Ca 2+ increases by cyanidin. These findings suggested that cyanidin inhibits adipocyte formation by activating the PLC-IP 3 pathway and intracellular Ca 2+ signaling. Our study is the first report describing the mechanism underlying the anti-obesity effect of cyanidin., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Hibiscus sabdariffa L. is a worldwide component for tea and beverages, being a natural source of anthocyanins, which are associated with cardiovascular activities. To investigate this relationship, we explored different methods of aqueous extraction on the anthocyanin content and antioxidant activity of H. sabdariffa L. calyx extract (HSCE). Pharmacological effects via platelet aggregation, calcium mobilization, cyclic nucleotide levels, vasodilator-stimulated phosphoprotein Ser157 and Ser239, and on the vasomotor response of aortic rings isolated from mice are studied herewith. We found that the application of ultrasonic turbolization, 20 min, combined with acidified water was significantly more effective in the extraction process, providing extracts with the highest levels of anthocyanins (8.73 and 9.63 mg/100 g) and higher antioxidant activity (6.66 and 6.78 μM trolox/g of sample). HSCE significantly inhibited (100-1000 μg/mL) arachidonic acid-induced platelet aggregation, reduced calcium mobilization, and increased cAMP and cGMP levels with VASPSer157 and VASPSer239 phosphorylation. Vasorelaxation reduction was confirmed by the aortic rings and endothelium assays treated with nitric oxide synthase inhibitors, soluble guanylyl cyclase (sGC) oxidizing agent, or Ca 2+ -activated K + channel inhibitor. The increasing of cGMP levels could be understood considering the sGC stimulation by HSCE compounds in the specific stimulus domain, which allows an understanding of the observed antiplatelet and vasorelaxant properties of H. sabdariffa L. calyx extract., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Proanthocyanidins (PA) are polyphenol compounds that are widely distributed in the bark, fruit core, skin, or seeds of various plants. Anthocyanidins are water-soluble natural pigments widely found in plants. They are all flavonoids, a major coloring substance in plants and fruits. In recent years, research into PA and anthocyanins has become increasingly popular because of their excellent anti-oxidation, scavenging of reactive oxygen free radicals and other physical and chemical activities, and their anti-cancer, vision protection, aging prevention, skin beauty pharmacological, and nutraceutical effects. Especially, recent systematic reviews and meta-analyses indicate their value, safety, and efficacy in the prevention, adjuvant therapy, and management of cardiometabolic disease. Here, we summarize their research progress from the aspects of chemical structure, biosynthetic pathways, distribution, extraction and separation, coloration, efficacy, and potential. The comparison between them might provide a reference for their development and efficient utilization. However, more large-sample-size randomized controlled trials and high-quality studies are needed to firmly establish their clinical efficacy., (© 2023 John Wiley & Sons Ltd.)

The growing rates of obesity worldwide call for intervention strategies to help control the pathophysiological consequences of weight gain. The use of natural foods and bioactive compounds has been suggested as such a strategy because of their recognized antioxidant and anti-inflammatory properties. For example, polyphenols, especially anthocyanins, are candidates for managing obesity and its related metabolic disorders. Obesity is well known for the presence of metainflammation, which has been labeled as an inflammatory activation that leads to a variety of metabolic disorders, usually related to increased oxidative stress. Considering this, anthocyanins may be promising natural compounds able to modulate several intracellular mechanisms, mitigating oxidative stress and metainflammation. A wide variety of foods and extracts rich in anthocyanins have become the focus of research in the field of obesity. Here, we bring together the current knowledge regarding the use of anthocyanins as an intervention tested in vitro, in vivo, and in clinical trials to modulate metainflammation. Most recent research applies a wide variety of extracts and natural sources of anthocyanins, in diverse experimental models, which represents a limitation of the research field. However, the literature is sufficiently consistent to establish that the in-depth molecular analysis of gut microbiota, insulin signaling, TLR4-triggered inflammation, and oxidative stress pathways reveals their modulation by anthocyanins. These targets are interconnected at the cellular level and interact with one another, leading to obesity-associated metainflammation. Thus, the positive findings with anthocyanins observed in preclinical models might directly relate to the positive outcomes in clinical studies. In summary and based on the entirety of the relevant literature, anthocyanins can mitigate obesity-related perturbations in gut microbiota, insulin resistance, oxidative stress and inflammation and therefore may contribute as a therapeutic tool in people living with obesity., Competing Interests: Author Declarations The authors declare no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Spodoptera littoralis is a highly polyphagous pest that attacks numerous important crops in the world and causes substantial economic losses to agricultural production. In the present study, the effects of different leafy vegetables, including Purslane, Chives, Parsley, Basil, Dill, Coriander, and Mint, were investigated on feeding responses and enzymatic activities of S. littoralis under laboratory conditions. Furthermore, the total contents of the three major secondary metabolites (phenolics, anthocyanins, and flavonoids) in the studied vegetables were determined. Our findings showed that the lowest and the highest approximate digestibility were on Basil and Purslane, respectively. The highest values of efficiency of conversion of ingested and digested food were achieved in larvae fed on Chives and Coriander, respectively, whereas the lowest values were recorded after feeding on Purslane. The highest and lowest relative growth rates were in larvae reared on Dill and Purslane, respectively. Furthermore, the highest amylolytic and proteolytic activities were in larvae fed with Coriander and Dill, respectively, while the lowest activities of these enzymes were on Purslane. In addition, correlation analysis revealed significant correlations between feeding characteristics and enzymatic activity of S . littoralis with biochemical compounds of the studied leafy vegetables. Our results suggest that Coriander is a suitable host, while Purslane displayed tolerance traits against S . littoralis , which can be used in sustainable management programs aiming to reduce chemical inputs.

The calyxes of Hibiscus sabdariffa present multiple pharmacological effects primarily attributed to their high anthocyanin content; however, little is known about their phytoestrogenic effect. Ovarian hypofunction (OH) is a process characterized by the rapid detention of the production of ovarian hormones, which compromises reproductive and cognitive functions. Hormone replacement therapy (HRT) efficiently compensates for OH; nevertheless, questions have been raised on its secondary effects and safety. One of the alternatives to tackling OH involves using phytoestrogens such as anthocyanins for their structural similarity to natural estrogens. In a Wistar rat model of ovariectomy (OVX), we recently reported the beneficial properties of an anthocyanin-rich extract prepared from the calyces of H. sabdariffa (HSE) in hindering the adverse effects of OH on memory performance and highlighted a possible phytoestrogenic impact through the modulation of estrogen receptor (ER) expression. We now report that HSE and estradiol differentially affected the expression of ERα and ERβ. ERα was more sensitive to HSE; meanwhile, estradiol preferentially modulated ERβ. Thus, our study leads to further research on using H. sabdariffa as a nutrition-based alternative to HRT., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Since drought stress is one of the key risks for the future of agriculture, exploring the molecular mechanisms of photosynthetic responses to water deficit stress is, therefore, fundamental. By using chlorophyll fluorescence imaging analysis, we evaluated the responses of photosystem II (PSII) photochemistry in young and mature leaves of Arabidopsis thaliana Col-0 (cv Columbia-0) at the onset of water deficit stress (OnWDS) and under mild water deficit stress (MiWDS) and moderate water deficit stress (MoWDS). Moreover, we tried to illuminate the underlying mechanisms in the differential response of PSII in young and mature leaves to water deficit stress in the model plant A. thaliana . Water deficit stress induced a hormetic dose response of PSII function in both leaf types. A U-shaped biphasic response curve of the effective quantum yield of PSII photochemistry (Φ PSII ) in A. thaliana young and mature leaves was observed, with an inhibition at MiWDS that was followed by an increase in Φ PSII at MoWDS. Young leaves exhibited lower oxidative stress, evaluated by malondialdehyde (MDA), and higher levels of anthocyanin content compared to mature leaves under both MiWDS (+16%) and MoWDS (+20%). The higher Φ PSII of young leaves resulted in a decreased quantum yield of non-regulated energy loss in PSII (Φ NO ), under both MiWDS (-13%) and MoWDS (-19%), compared to mature leaves. Since Φ NO represents singlet-excited oxygen ( 1 O 2 ) generation, this decrease resulted in lower excess excitation energy at PSII, in young leaves under both MiWDS (-10%) and MoWDS (-23%), compared to mature leaves. The hormetic response of PSII function in both young and mature leaves is suggested to be triggered, under MiWDS, by the intensified reactive oxygen species (ROS) generation, which is considered to be beneficial for activating stress defense responses. This stress defense response that was induced at MiWDS triggered an acclimation response in A. thaliana young leaves and provided tolerance to PSII when water deficit stress became more severe (MoWDS). We concluded that the hormesis responses of PSII in A. thaliana under water deficit stress are regulated by the leaf developmental stage that modulates anthocyanin accumulation in a stress-dependent dose.

Cyanidin-3-O-glucoside (C3G), the most widely distributed anthocyanin (ACN) in edible fruits, has been proposed for several bioactivities, including anti-inflammatory, neuro-protective, antimicrobial, anti-viral, anti-thrombotic and epigenetic actions. However, habitual intake of ACNs and C3G may vary widely among populations, regions, and seasons, among individuals with different education and financial status. The main point of C3G absorption occurs in the small and large bowel. Therefore, it has been supposed that the treating properties of C3G might affect inflammatory bowel diseases (IBD), such as ulcerative colitis (UC) and Crohn's disease (CD). IBDs develop through complex inflammatory pathways and sometimes may be resistant to conventional treatment strategies. C3G presents antioxidative, anti-inflammatory, cytoprotective, and antimicrobial effects useful for IBD management. In particular, different studies have demonstrated that C3G inhibits NF-κB pathway activation. In addition, C3G activates the Nrf2 pathway. On the other hand, it modulates the expression of antioxidant enzymes and cytoprotective proteins, such as NAD(P)H, superoxide dismutase, heme-oxygenase (HO-1), thioredoxin, quinone reductase-oxide 1 (NQO1), catalase, glutathione S-transferase and glutathione peroxidase. Interferon I and II pathways are downregulated by C3G inhibiting interferon-mediating inflammatory cascades. Moreover, C3G reduces reactive species and pro-inflammatory cytokines, such as C reactive protein, interferon-γ, tumor necrosis factor-α, interleukin (IL)-5, IL-9, IL-10, IL-12p70, and IL-17A in UC and CD patients. Finally, C3G modulates gut microbiota by inducing an increase in beneficial gut bacteria and increasing microbial abundances, thus mitigating dysbiosis. Thus, C3G presents activities that may have potential therapeutic and protective actions against IBD. Still, in the future, clinical trials should be designed to investigate the bioavailability of C3G in IBD patients and the proper therapeutic doses through different sources, aiming to the standardization of the exact clinical outcome and efficacy of C3G.

Blueberries are rich in phenolic compounds including anthocyanins which are closely related to biological health functions. The purpose of this study was to investigate the antioxidant activity of blueberry anthocyanins extracted from 'Brightwell' rabbiteye blueberries in mice. After one week of adaptation, C57BL/6J healthy male mice were divided into different groups that were administered with 100, 400, or 800 mg/kg blueberry anthocyanin extract (BAE), and sacrificed at different time points (0.1, 0.5, 1, 2, 4, 8, or 12 h). The plasma, eyeball, intestine, liver, and adipose tissues were collected to compare their antioxidant activity, including total antioxidant capacity (T-AOC), superoxide dismutase (SOD) activity and glutathione-peroxidase (GSH-PX/GPX) content, and the oxidative stress marker malondialdehyde (MDA) level. The results showed that blueberry anthocyanins had positive concentration-dependent antioxidant activity in vivo. The greater the concentration of BAE, the higher the T-AOC value, but the lower the MDA level. The enzyme activity of SOD, the content of GSH-PX, and messenger RNA (mRNA) levels of Cu,Zn-SOD , Mn-SOD , and GPX all confirmed that BAE played an antioxidant role after digestion in mice by improving their antioxidant defense. The in vivo antioxidant activity of BAE indicated that blueberry anthocyanins could be developed into functional foods or nutraceuticals with the aim of preventing or treating oxidative stress-related diseases.

It is important to explore the effective approaches to prevent dry age-related macular degeneration (AMD). In this study, significantly decreased full-field electroretinograms wave amplitudes and disordered retina structures were detected in rat retinas of sodium iodate induced dry AMD model. Six a- and b-wave amplitudes and the antioxidant activities were significantly increased, and the outer nuclear layer thickness was significantly improved in the rat retinas treated with the combination of Lactobacillus fermentum NS9 (LF) and aronia anthocyanidin extract (AAE) compared with the model. The effects were much better than the treatment with AAE alone. The proteomics analysis showed the expressions of α-, β- and γ-crystallins were increased by 3-8 folds in AAE treated alone and by 6-11 folds in AAE + LF treatment compared with the model, which was further confirmed by immuno-blotting analysis. Analysis of gut microbial composition indicated that higher abundance of the genus Parasutterella and species P. excrementihominis was found in the AAE + LF treatment compared with the other groups. The results indicated that the combined treatment of AAE + LF is a potential way to prevent the retina degeneration which is significantly better than the AAE treated alone., (© 2023. The Author(s).)

Lettuce (Lactuca sativa) is commonly produced in vertical farms. The levels of nutritionally important phytochemicals such as beta-carotene (precursor to vitamin A) are generally low in lettuce. In this study, we investigated the benefits of variable lighting strategy (i.e., varying the light quality during production) on maintaining plant growth and increasing the biosynthesis of beta-carotene and anthocyanin. We tested two variable lighting methods, using green and red romaine lettuce, namely (i) providing growth lighting (supports vegetative growth) initially (21 days) followed by a high percentage of blue light (supports biosynthesis of phytochemicals) at final stages (10 days) and (ii) providing a high percentage of blue light initially followed by growth lighting at final stages. Our results indicate that the variable lighting method with initial growth lighting and high percentage of blue at final stages can maintain vegetative growth and enhance phytochemicals such as beta-carotene in green romaine lettuce while both variable lighting methods were not effective in red romaine lettuce. In green romaine lettuce, we did not observe a significant reduction in shoot dry weight but there was an increase in beta-carotene (35.7%) in the variable compared to the fixed lighting method with growth lighting for the entire duration. The physiological bases for differences in vegetative growth and synthesis of beta-carotene and anthocyanin in the variable and fixed lighting methods are discussed., Competing Interests: We declare that no competing interests exist for this submission., (Copyright: © 2023 Kong, Nemali. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The aim of the present study was to analyze the effects of cocoa flavanols and red berry anthocyanins on cardiovascular biomarkers, such as homocysteine, angiotensin-converting enzyme (ACE), nitric oxide (NO), flow-mediated vasodilation (FMD), blood pressure and lipid profile. Additionally, we aimed to ascertain their possible interactions with microbiota related metabolites, such as secondary bile acids (SBA), short-chain fatty acids (SCFA) and trimethylamine N-oxide (TMAO). A randomized, parallel-group study, single-blind for the research team, was performed on 60 healthy volunteers between the ages of 45 and 85, who consumed 2.5 g/day of cocoa powder (9.59 mg/day of total flavanols), 5 g/day of a red berry mixture (13.9 mg/day of total anthocyanins) or 7.5 g/day of a combination of both for 12 weeks. The group that had consumed cocoa showed a significant reduction in TMAO ( p = 0.03) and uric acid ( p = 0.01) levels in serum, accompanied by an increase in FMD values ( p = 0.03) and total polyphenols. corrected by creatinine ( p = 0.03) after the intervention. These latter values negatively correlated with the TMAO concentration (R = -0.57, p = 0.02). Additionally, we observed an increase in carbohydrate fermentation in the groups that had consumed cocoa ( p = 0.04) and red berries ( p = 0.04) between the beginning and the end of the intervention. This increase in carbohydrate fermentation was correlated with lower levels of TC/HDL ratio ( p = 0.01), systolic ( p = 0.01) and diastolic blood pressure ( p = 0.01). In conclusion, our study showed a positive modulation of microbiota metabolism after a regular intake of cocoa flavanols and red berry anthocyanins that led to an improvement in cardiovascular function, especially in the group that consumed cocoa.

Type II diabetes mellitus and its related complications are growing public health problems. Many natural products present in our diet, including polyphenols, can be used in treating and managing type II diabetes mellitus and different diseases, owing to their numerous biological properties. Anthocyanins, flavonols, stilbenes, curcuminoids, hesperidin, hesperetin, naringenin, and phenolic acids are common polyphenols found in blueberries, chokeberries, sea-buckthorn, mulberries, turmeric, citrus fruits, and cereals. These compounds exhibit antidiabetic effects through different pathways. Accordingly, this review presents an overview of the most recent developments in using food polyphenols for managing and treating type II diabetes mellitus, along with various mechanisms. In addition, the present work summarizes the literature about the anti-diabetic effect of food polyphenols and evaluates their potential as complementary or alternative medicines to treat type II diabetes mellitus. Results obtained from this survey show that anthocyanins, flavonols, stilbenes, curcuminoids, and phenolic acids can manage diabetes mellitus by protecting pancreatic β-cells against glucose toxicity, promoting β-cell proliferation, reducing β-cell apoptosis, and inhibiting α-glucosidases or α-amylase. In addition, these phenolic compounds exhibit antioxidant anti-inflammatory activities, modulate carbohydrate and lipid metabolism, optimize oxidative stress, reduce insulin resistance, and stimulate the pancreas to secrete insulin. They also activate insulin signaling and inhibit digestive enzymes, regulate intestinal microbiota, improve adipose tissue metabolism, inhibit glucose absorption, and inhibit the formation of advanced glycation end products. However, insufficient data are available on the effective mechanisms necessary to manage diabetes.

A low-density polyethylene (LDPE) film reinforced with cellulose nanocrystals (CNCs) with an encapsulated bioactive formulation (cinnamon essential oil + silver nanoparticles) was developed for preservation of fresh strawberries. Antimicrobial activity of the active LDPE films was tested against Escherichia coli O157:H7, Salmonella typhimurium, Aspergillus niger, and Penicillium chrysogenum by agar volatilization assay. The optimal condition of the films showed ≥75% inhibitory capacity against the tested microbes. Strawberries were stored with different types of films: Group 1 (control): (LDPE + CNCs + Glycerol), Group 2: (LDPE + CNCs + Glycerol + AGPPH silver nanoparticles), Group 3: (LDPE + CNCs + Glycerol + cinnamon), Group 4: (LDPE + CNCs + Glycerol + active formulation), and Group 5: (LDPE + CNCs + Glycerol + active formulation + 0.5 kGy γ-radiation) at 4°C for 12 days. Weight loss (WL) (%), decay (%), firmness (N), color, and total phenolics and anthocyanin content of the strawberries were measured. Results showed that the most effective LDPE-nanocomposite film for reducing the microbial growth was LDPE + CNCs + Glycerol + active formulation film (Group 4). When combined with γ-irradiation (0.5 kGy), the LDPE + CNCs + Glycerol + active formulation (Group 5) significantly reduced both decay and WL by 94%, as compared to the control samples after 12 days of storage. Total phenols (from 952 to 1711 mg/kg) and anthocyanin content (from 185 to 287 mg/kg) increased with storage time under the different treatments. The mechanical properties, water vapor permeability (WVP), and surface color of the films were also tested. Though the WVP of the films were not influenced by the types of antimicrobial agents, they did significantly (p ≤ 0.05) change color and mechanical properties of the films. Therefore, combined treatment of active film and γ-irradiation has potential as an alternative method for extending the shelf-life of storage strawberries while maintaining fruit quality. PRACTICAL APPLICATION: Bioactive Low-density polyethylene (LDPE) nanocomposite film was developed in the study by incorporating active formulation (essential oil and silver nanoparticle) to extend the shelf life of stored strawberries. The bioactive LDPE-based nanocomposite film along with γ-irradiation could be used to preserve fruits for long-term storage by controlling the growth of foodborne pathogenic bacteria and spoilage fungi., (© 2023 Institute of Food Technologists. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Obesity is associated with an imbalance of micro-and macro-nutrients, gut dysbiosis, and a "leaky" gut phenomenon. Polyphenols, such as curcumin, resveratrol, and anthocyanins may alleviate the systemic effects of obesity, potentially by improving gut microbiota, intestinal barrier integrity (IBI), and zinc homeostasis. The essential micronutrient zinc plays a crucial role in the regulation of enzymatic processes, including inflammation, maintenance of the microbial ecology, and intestinal barrier integrity. In this review, we focus on IBI- which prevents intestinal lipopolysaccharide (LPS) leakage - as a critical player in polyphenol-mediated protective effects against obesity-associated white adipose tissue (WAT) inflammation. This occurs through mechanisms that block the movement of the bacterial endotoxin LPS across the gut barrier. Available research suggests that polyphenols reduce WAT and systemic inflammation via crosstalk with inflammatory NF-κB, the mammalian target of rapamycin (mTOR) signaling and zinc homeostasis., Competing Interests: Declaration of competing interest T. I., K. A.-S., L. R., N. S.-L., O. P., M. Z.-M., N. S. K., and N. M.-M., declare no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

We studied the effect of an anthocyanin-containing complex from the fruits of S. aucuparia L. on doxorubicin-induced genotoxicity in bone marrow cells of C57BL/6 mice. The complex reduced the genotoxic effect doxorubicin in metaphase plates of bone marrow cells in 24, 48 h, and 10 days after the administration of the cytostatic. The mean number of single fragments and the fraction of cells with gaps and aberrant metaphases also decreased., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature.)

Obesity in the United States continues to worsen. Anthocyanin-rich fruits and vegetables provide a pragmatic dietary approach to slow its metabolic complications. Given American diet patterns, foods with high anthocyanin content could address dose-response challenges. The study objective was to determine the effect of 100% elderberry juice on measures of indirect calorimetry (IC) and insulin sensitivity/glucose tolerance in a placebo-controlled, randomized, crossover pilot study. Overweight and obese adults were randomized to a 5-week study which included 2 1-week periods of twice-daily elderberry juice (EBJ) or sugar-matched placebo consumption separated by a 3-week washout period. Following each 1-week test period, IC and insulin sensitivity/glucose tolerance was measured with a 3 h meal tolerance test (MTT). Treatment differences were tested with linear mixed modeling. A total of 22 prospective study volunteers (18 F/4 M) attended recruitment meetings, and 9 were analyzed for treatment differences. EBJ was well tolerated and compliance was 99.6%. A total of 6 IC measures (intervals) were created, which coincided with 10-20 min gaseous samplings in-between MTT blood samplings. Average CHO oxidation was significantly higher during the MTT after 1-week EBJ consumption (3.38 vs. 2.88 g per interval, EBJ vs. placebo, p = 0.0113). Conversely, average fat oxidation was significantly higher during the MTT after 1-week placebo consumption (1.17 vs. 1.47 g per interval, EBJ vs. placebo, p = 0.0189). This was in-line with a significantly lower average respiratory quotient after placebo treatment (0.87 vs. 0.84, EBJ vs. placebo, p = 0.0114). Energy expenditure was not different. There was no difference in serum glucose or insulin response between treatments. This pilot study of free-living volunteers describes significant change in IC but not insulin sensitivity with an EBJ intervention. Controlled feeding and increased sample size will help determine the utility of EBJ on these outcomes.

Studies have shown that targeting xanthine oxidase (XO) can be a feasible treatment for fructose-induced hyperuricemia and hyperglycemia. This study aimed to evaluate the dual regulatory effects and molecular mechanisms of diacylated anthocyanins from purple sweet potato (diacylated AF-PSPs) on hyperglycemia and hyperuricemia induced by a high-fructose/high-fat diet. The body weight, organ index, serum biochemical indexes, and liver antioxidant indexes of mice were measured, and the kidneys were observed in pathological sections. The relative expression levels of messenger RNAs (mRNAs) of fructose metabolism pathway enzymes in kidney were detected by fluorescent real-time quantitative polymerase chain (qPCR) reaction technique, and the expression of renal transporter protein and inflammatory factor pathway protein was determined by immunohistochemistry (IHC) technique. Results showed that diacylated AF-PSPs alleviated hyperuricemia in mice, and that this effect might be related to the regulation of liver XO activity, lipid accumulation, and relevant renal transporters. Diacylated AF-PSPs reduced body weight and relieved lipid metabolism disorder, liver lipid accumulation, and liver oxidative stress, thereby enhancing insulin utilization and sensitivity, lowering blood sugar, and reducing hyperglycemia in mice. Also, diacylated AF-PSPs restored mRNA levels related to renal fructose metabolism, and reduced kidney injury and inflammation. This study provided experimental evidence for the mechanisms of dual regulation of blood glucose and uric acid (UA) by diacylated AF-PSPs and their utilization as functional foods in the management of metabolic syndrome.

In the present study, an attempt was made to investigate the in vitro antioxidant, anticancer, and antibacterial activities of Delonix regia , then in vivo evaluate its safety as a natural colorant and sweetener in beverages compared to synthetic colorant and sweetener in rats, then serve the beverages for sensory evaluation. Delonix regia flowers had high protein, polysaccharide, Ca, Na, Mg, K, and Fe contents. The Delonix regia pigment extract (DRPE) polysaccharides were separated and purified by gel permeation chromatography on Sephacryl S-200, characterized by rich polysaccharides (13.6 g/L). The HPLC sugar profile detected the monosaccharides in the extracted polysaccharides, composed of mannose, galactose, glucose, arabinose, and gluconic acid, and the structure of saccharides was confirmed by FTIR, which showed three active groups: carbonyl, hydrocarbon, and hydroxyl. On the other hand, the red pigment constituents of DRPE were detected by HPLC; the main compounds were delphinidin and cyanidin at 15 µg/mL. The DRPE contained a considerable amount (26.33 mg/g) of anthocyanins, phenolic compounds (64.7 mg/g), and flavonoids (10.30 mg/g), thus influencing the antioxidant activity of the DRPE, which scavenged 92% of DPPH free radicals. Additionally, it inhibited the population of pathogenic bacteria, including Staphylococcus aureus , Listeria monocyogenes , Salmonella typhimurum , and Pseudomonas aeruginosa, in the range of 30-90 μg/mL, in addition to inhibiting 85% of pancreatic cancer cell lines. On the in vivo level, the rats that were delivered a diet containing DRPE showed regular liver markers (AST, ALP, and ALT); kidney markers (urea and creatinine); high TP, TA, and GSH; and low MDA, while rats treated with synthetic dye and aspartame showed higher liver and kidney markers; lowered TP, TA, and GSH; and high MDA. After proving the safety of DRPE, it can be safely added to strawberry beverages. Significant sensorial traits, enhanced red color, and taste characterize the strawberry beverages supplemented with DRPE. The lightness and redness of strawberries were enhanced, and the color change ΔE values in DRPE-supplemented beverages ranged from 1.1 to 1.35 compared to 1.69 in controls, indicating the preservative role of DRPE on color. So, including DRPE in food formulation as a natural colorant and sweetener is recommended for preserving health and the environment.

Context: Increased free fatty acids (FFAs) levels, typical in obesity condition, can contribute to systemic lipotoxicity and inflammation adversely influencing Inflammatory Bowel Disease development and progression. Anthocyanins possess health promoting properties mainly associated to the induction of Nrf2-regulated cytoprotective proteins., Objective: Using a novel experimental model, we evaluated the in vitro intracellular mechanisms involved in FFAs modulation of intestinal epithelial lipotoxicity and the protective effects of cyanidin-3-O-glucoside (C3G) in Caco-2 cells., Results: Caco-2 exposed to palmitic acid (PA) in the serosal (basolateral) side showed a combined state of epithelial inflammation, inducing NF-κB pathway and downstream cytokines, that was reverted by C3G apical pre-treatment. In addition, PA altered intracellular redox status and induced reactive oxygen species that were reduced by C3G via the redox-sensitive Nrf2 signalling., Discussion and Conclusion: Results suggest that anti-inflammatory properties of anthocyanins, mediated by Nrf2, could represent an interesting tool for intestinal inflammatory disorders.

Flavonoids are a major group of phytoestrogens associated with physiological effects, and ecological and social impacts. Although the estrogenic activity of flavonoids was reported by researchers in the fields of medical, environmental and food studies, their molecular mechanisms of action have not been comprehensively reviewed. The estrogenic activity of the respective classes of flavonoids, anthocyanidins/anthocyanins, 2-arylbenzofurans/3-arylcoumarins/α-methyldeoxybenzoins, aurones/chalcones/dihydrochalcones, coumaronochromones, coumestans, flavans/flavan-3-ols/flavan-4-ols, flavanones/dihydroflavonols, flavones/flavonols, homoisoflavonoids, isoflavans, isoflavanones, isoflavenes, isoflavones, neoflavonoids, oligoflavonoids, pterocarpans/pterocarpenes, and rotenone/rotenoids, was summarized through a comprehensive literature search, and their structure-activity relationship, biological activities, signaling pathways, and applications were discussed. Although the respective classes of flavonoids contained at least one chemical mimicking estrogen, the mechanisms varied, such as those with estrogenic, anti-estrogenic, non-estrogenic, and biphasic activities, and additional activities through crosstalk/bypassing, which exert biological activities through cell signaling pathways. Such mechanistic variations of estrogen action are not limited to flavonoids and are observed among other broad categories of chemicals, thus this group of chemicals can be termed as the "estrogenome". This review article focuses on the connection of estrogen action mainly between the outer and the inner environments, which represent variations of chemicals and biological activities/signaling pathways, respectively, and form the basis to understand their applications. The applications of chemicals will markedly progress due to emerging technologies, such as artificial intelligence for precision medicine, which is also true of the study of the estrogenome including estrogenic flavonoids., Competing Interests: Declaration of competing interests The authors declare that there are no conflicts of interest., (Copyright © 2022 The Author. Published by Elsevier Inc. All rights reserved.)

Berries and other anthocyanin-rich foods have demonstrated anti-obesity effects in rodents and humans. However, the bioactive components of these foods and their mechanisms of action are unclear. We conducted an intervention study with overweight and obese adults to isolate the effects of different berry components on bioenergetics. Subjects consumed whole mixed berries (high anthocyanin, high fiber), pressed berry juice (high anthocyanin, low fiber), berry-flavored gelatin (low anthocyanin, low fiber), or fiber-enriched gelatin (low anthocyanin, high fiber) for one week prior to a meal challenge with the same treatment food as the pre-feed period. Peripheral blood mononuclear cells were collected 2 h after the meal challenge, and cellular respiration was assessed via high-resolution respirometry. The high-anthocyanin, low-fiber treatment (berry juice) and the low-anthocyanin, high-fiber treatment (fiber-enriched gelatin) had opposite effects on cellular respiration. In the fasted state, berry juice resulted in the highest oxygen-consumption rate (OCR), while fiber-enriched gelatin resulted in the highest OCR in the fed state. Differences were observed in multiple respiration states (basal, state 3, state 4, uncoupled), with the greatest differences being between the pressed berry juice and the fiber-enriched gelatin. Different components of berries, specifically anthocyanins/flavonoids and fiber, appear to have differential effects on cellular respiration.