Chrysanthemi Flos (CF), as one of the important 'dual-use' plants, possesses great pharmacological research and development potential. This work aimed to find the pharmacodynamic material basis of CF in cardiovascular-protection by spectrum-effect relationship and component knock-out method. The fingerprint was established by ultra-high performance liquid chromatography and 25 peaks were picked out as common peaks. The common peaks were identified by ultra-performance liquid chromatography-quadrupole-orbitrap-mass spectrometry including twelve flavonoids, nine phenylpropanoids, three organic acids, and one nucleoside. The cardiovascular-protective effect of CF was determined by angiotensin II-induced injury model of human umbilical vein endothelial cells. Grey relation analysis, partial least squares regression analysis and Pearson's correlation analysis were performed to assess the relationship between the cardiovascular-protective effect and ingredients. Spectrum-effect relationship and component knock-out method revealed that P11 (luteolin-7-O-β-D-glucoside), P14 (3,4-O-dicaffeoylquinic acid), P16 (1,5-O-dicaffeoylquinic acid), and P17 (3,5-O-dicaffeoylquinic acid) were the pharmacological material basis for the cardiovascular-protective effect of CF. This work preliminarily elucidated the pharmacodynamic material basis of cardiovascular-protective effect of CF, which could be used to considerable methods and insight for the fundamental research of the pharmacodynamic material basis of Traditional Chinese Medicine.

This study evaluated Tripleurospermum inodorum extract for cytotoxic, anti-inflammatory, antioxidant, antimicrobial, and antibiofilm properties, alongside its phenolic profile, predicted pharmacological interactions and in vivo anti-inflammatory properties. The methanolic extract of T. inodorum was rich in apigenin derivatives, including apigenin-O-pentoside (5.234 mg/g) and apigenin-O-acetyl hexoside (4.929 mg/g), as identified using LC-DAD-ESI/MSⁿ. The extract demonstrated potent anti-inflammatory activity (IC₅₀ = 8.4 µg/mL) by inhibiting nitric oxide production in a RAW 264.7 macrophage model, a key mechanism in controlling inflammatory responses. Its cytotoxicity against NCI-H460 lung carcinoma cells (GI₅₀ = 62.9 µg/mL) suggests potential for targeting inflammation-driven carcinogenesis. Antioxidant activity, ranging from 204.4 (FRAP) to 442.2 (ABTS) mmol of gallic acid equivalents per 100 mg dry weight, highlights its role in mitigating oxidative stress-a critical driver of chronic inflammation. The extract also displayed moderate antimicrobial activity (MIC: 3-12 mg/mL) and strong antibiofilm potential (> 70% inhibition in a crystal violet assay), which are essential for managing infection-associated inflammation. Network pharmacology revealed that dominant phenolic compound act as aldose reductase inhibitors, targeting inflammatory pathways linked to metabolic stress. In vivo assessment using a xylene-induced ear edema model revealed a dose-dependent, biphasic anti-inflammatory effect, with lower doses (125 and 250 mg/kg) exhibiting greater efficacy compared to the highest dose (500 mg/kg), suggesting a hormetic response that emphasizes the importance of optimal dosing. These findings indicate that the methanolic extract of T. inodorum possesses a broad spectrum of bioactivities relevant to inflammation control and supports its further development as a source of novel anti-inflammatory therapeutics.

A common and serious side effect of diabetes is diabetic peripheral neuropathy (DPN), which is characterised by gradual nerve damage brought on by oxidative stress, chronic inflammation, and prolonged hyperglycemia. Studies identify NLRP3 inflammasome as a key mediator in the pathogenesis of DPN, connecting neuroinflammation and neuronal damage to metabolic failure. Because of their strong anti-inflammatory and antioxidant qualities, flavonoids, a broad class of naturally occurring polyphenols, have drawn interest as potential treatments for DPN. The various ways that flavonoids affect the NLRP3 inflammasome and their potential as a treatment for DPN are examined in this review. It has been demonstrated that flavonoids prevent NLRP3 activation, which lowers the release of pro-inflammatory cytokines including IL-1β and IL-18 and causes neuroinflammation. Flavonoids work mechanistically by reducing oxidative stress, altering important signalling pathways, and blocking the activities of NF-κB and caspase-1, which are both essential for the activation of the NLRP3 inflammasome. Preclinical research has shown that flavonoids have strong neuroprotective benefits, and few clinical evidence also points to the potential of flavonoids to improve nerve function and lessen neuropathic pain in diabetic patients. The current review emphasises how flavonoids may be used as a treatment strategy to target inflammation in DPN caused by the NLRP3 inflammasome. By targeting important inflammatory pathways, flavonoids provide a new way to slow the progression of this debilitating illness. Further investigation into the mechanisms, clinical translation, and novel drug delivery techniques could enhance the therapeutic efficacy of diabetic peripheral neuropathy.

Pomegranate peel is a by-product generated during the processing of pomegranate (Punica granatum L.) fruit, accounting for approximately 50% of the total mass of the fruit. Although pomegranate peel is usually regarded as waste, it is rich in various bioactive metabolites such as polyphenols, tannins, and flavonoids, demonstrating significant medicinal and nutritional value. In recent years, Pomegranate peel extract (PPE) has shown broad application prospects in the biomedical field due to its multiple effects, including antioxidant, anti-inflammatory, antibacterial, anti-apoptotic properties, and promotion of cell regeneration. This review consolidates the major bioactive metabolites of PPE and explores its applications in biomedical materials, including nanodrug carriers, hydrogels, and tissue engineering scaffolds. By synthesizing the existing literature, we delve into the potential value of PPE in biomedicine, the challenges currently encountered, and the future directions for research. The aim of this review is to provide a scientific basis for optimizing the utilization of PPE and to facilitate its broader application in the biomedical field.

Flavonoids represent a class of natural plant secondary metabolites with multiple activities including antioxidant, antitumor, anti-inflammatory, and antimicrobial properties. However, due to their structural characteristics, they often exhibit low bioavailability in vivo. In this review, we focus on the in vivo study of flavonoids, particularly the effects of gut microbiome on flavonoids, including common modifications such as methylation, acetylation, and dehydroxylation, etc. These modifications aim to change the structural characteristics of the original substances to enhance absorption and bioavailability. In order to improve the bioavailability of flavonoids, we discuss two feasible methods, namely dosage form modification and chemical modification, and hope that these approaches will offer new insights into the application of flavonoids for human health. In this article, we also introduce the types, plant sources, and efficacy of flavonoids. In conclusion, this is a comprehensive review on how to improve the bioavailability of flavonoids.

Purple yam (Dioscorea alata L.) is a tuber widely distributed in the tropics and subtropics. We previously isolated several acylated anthocyanins from purple yam. In this study, purple yam extract was orally administered to rats and the absorption of the constituent anthocyanins was investigated. Acylated anthocyanins were detected in the plasma, confirming that they were absorbed into the body as their intact forms. The time required to reach the maximum anthocyanin concentration was 15 min, indicating rapid absorption into the blood. In addition, more than half of the total amount of anthocyanins excreted into the urine was excreted within the first 6 h after administration. To the best of our knowledge, this is the first report of the detection of characteristic acylated anthocyanins from purple yam in rat plasma and urine after oral administration.

(Poly)phenols are a wide and heterogeneous class of substances with several potential health benefits. Their role in neuroprotection and cognition is still questionable. This study's scope is to examine the possible association between total and individual (poly)phenol intake, major dietary sources, and the severity of multiple sclerosis (MS) in a cohort of MS patients. Participants' demographics, physical activity, smoking, and dietary information were collected, alongside clinical parameters including the Expanded Disability Status Score (EDSS), Multiple Sclerosis Severity Score (MSSS), MS phenotype, and current therapy. A validated 110-item food frequency questionnaire (FFQ) was used to assess participants' habits. The (poly)phenol content of foods was estimated using the Phenol-Explorer database. Data from 106 participants were analyzed. A high intake of vegetables was associated with a 4.6-fold higher probability of mild MS (95% CI: 1.49, 14.28), whereas no association was found for other food and beverage sources. Hydroxycinnamic acids were significantly related to MSSS (OR: 6.55, 95% CI: 2.15, 19.92). Although coffee intake differed significantly between patients with mild and severe MS (90.5 ± 53.9 vs. 59.4 ± 40.8 mL/d, respectively), linear regression analysis did not confirm an association with MSSS. A higher intake of hydroxycinnamic acids and vegetables may impact MS severity. Coffee's role remains unclear and needs to be further investigated.

Clostridium difficile is an opportunistic infection that can lead to antibiotic- associated diarrhea and toxic megacolon.

This systematic review study aimed to investigate polyphenols' antibacterial and antitoxin properties and their effects on reducing complications related to C. difficile Infections (CDI).

This systematic review was conducted following the PRISMA guideline 2020. Multiple databases, including Web of Science, PubMed, Cochrane Library, EMBASE, and Scopus, were searched thoroughly for existing literature. After considering the inclusion and exclusion criteria for the review, 18 articles were included. Data were collected and registered into an Excel file for further investigations and conclusions.

Polyphenols by reducing Reactive Oxygen Species (ROS) levels, increasing inflammatory factor Interleukin 10 (IL-10), reducing Nuclear Factor kappa B (NF-κB) and Tumour Necrosis Factor- α (TNF-α), IL-6, IL-1α, IL-1β, Granulocyte Colony-stimulating Factor (G-CSF), and Monocyte Chemoattractant Protein-1 (MCP-1) and Macrophage Inflammatory Protein-1 alpha (MIP-1α) levels, and regulating the expression of Bcl-2 and Bax, make the growth and replication conditions of C. difficile more difficult and prevent it from producing toxins. Furthermore, polyphenols can exhibit prebiotic properties, promoting the growth of beneficial Bifidobacterium and Lactobacillus species and consequently regulating gut microbiota, exerting antimicrobial activities against C. difficile. They also induce their beneficial effects by inhibiting the production of C. difficile TcdA and TcdB.

Polyphenols have been reported to inhibit C. difficile growth and toxin production by several mechanisms in preclinical studies. However, more clinical studies are needed to investigate their safety in humans.

Chicory, recognized as a functional food, is increasingly becoming the focus of research. This study aimed to investigate the in vitro impact of gastrointestinal digestion on the composition and bioactive properties of chicory decoction. Chicory flour, derived from the roots, was transformed into an aqueous decoction and was subjected to simulated in vitro human gastrointestinal digestion (SGID). For the first time, the influence of the digestive process on specific classes of bioactive molecules was tracked across different digestive compartments (oral, gastric, and intestinal) using a metabolomic approach. Concurrently, the antioxidant, anti-inflammatory, and intestinal hormone regulation effects were assessed before and after SGID. The findings revealed that specific transformations of chlorogenic acid (CGA) and sesquiterpene lactones (STL) during SGID enhanced antioxidant and anti-inflammatory properties post-digestion. Quantitative results demonstrated a significant increase in ROS scavenging capacity and metabolite activity.

Escherichia coli is the most common uropathogen in humans, dogs and cats. Dietary consumption of cranberry (Vaccinium macrocarpon) is known to be associated with a reduction in uropathogenic E. coli (UPEC) adhesion to human and canine urinary epithelial cell lines, but this has not been shown in cats.

Six neutered domestic cats, one male and five females, were randomly fed three diets successively, one containing 0.1% cranberry powder, one containing 0.3% cranberry powder, and one being the control without cranberry. Naturally emitted urine was collected on the last two days of each period of two weeks and used for bacterial growth. Adherence to Crandell-Rees feline kidney (CRFK) uroepithelial cells of the feline UPEC C571 strain (positive for the papC gene marker for P-fimbriae and the fimA marker for type 1 pili and negative for the gene of the alpha haemolysin cytotoxin hlyA, and additionally non-haemolytic in vitro on blood agar) was quantified after growth in urine samples.

Significant reductions in bacterial adherence to CRFK cells were observed for 60% of cats receiving 0.1% cranberry powder supplementation and for all cats receiving 0.3% cranberry powder supplementation, compared to the same animals consuming the control diet.

Dietary supplementation with cranberry may provide some degree of protection to cats against adhesion of UPEC to feline uroepithelial cells.

Numerous health benefits have been attributed in the last decades to the regular consumption of fruits, vegetables, herbs and spices, along with honey, in a balanced diet. In this context, the aim of the present review was to provide the literature with the most relevant studies focusing on the determination protocols of these polyphenols and other reducing agents in selected fruits (orange, lemon, grapefruit, prunus, apricot, peach, plum, sweet cherry), spices (oregano, cinnamon, clove, saffron, turmeric) and honey of different botanical origin (nectar or honeydew). In addition, the content and the extraction methods of these compounds, along with their metabolic pathway, have been critically evaluated and discussed. Results showed that all fruits, spices and honey exhibit a considerably high antioxidant activity, which is mainly owed to their phytochemical content. Therefore, a balanced diet consisting of the combination of the foods studied herein may comprise a shield against chronic and other pathophysiological disorders and may be achieved through consecutive educational programs for consumers at an international level.

Depression is a common mental illness that affects 5% of the adult population globally. The most common symptoms of depression are low mood, lack of pleasure from different activities, poor concentration, and reduced energy levels for an extended period, and it affects the emotions, behaviors, and overall well-being of an individual. The complex pathophysiology of depression presents challenges for current therapeutic options involving a biopsychosocial treatment plan. These treatments may have a delayed onset, low remission and response rates, and undesirable side effects. Researchers in nutrition and food science are increasingly addressing depression, which is a significant public health concern due to the association of depression with the increased incidence of cardiovascular diseases and premature mortality. Polyphenols present in our diet may significantly impact the prevention and treatment of depression. The primary mechanisms include reducing inflammation and oxidative stress, regulating monoamine neurotransmitter levels, and modulating the microbiota-gut-brain axis and hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis. This review summarizes recent advances in understanding the effects of dietary polyphenols on depression and explores the underlying mechanisms of these effects for the benefit of human health. It also highlights studies that are looking at clinical trials to help future researchers incorporate these substances into functional diets, nutritional supplements, or adjunctive therapy to prevent and treat depression.

Polyphenols are organic chemical compounds naturally present in plants, renowned for their anti-inflammatory, antioxidant, immunomodulatory, anticancer, and cardiovascular protective properties. Their bioactivity and bioavailability can vary widely depending on the methods of food processing and interactions with the gut microbiome. These factors can induce changes in polyphenols, affecting their ability to achieve their intended health benefits. Thus, it is essential to develop and apply food processing methods that optimize polyphenol content while maintaining their bioactivity and bioavailability. This review aims to explore how various food processing techniques affect the quantity, bioactivity, and bioavailability of polyphenols, as well as their interactions with the gut microbiome, which may ultimately determine their health effects.

Advances in the understanding of bioavailability and metabolism of bioactive compounds have been achieved primarily through targeted or semi-targeted metabolomics approaches using the hypothesis of potential metabolized compounds. The recent development of untargeted metabolomics approaches can present great advantages in this field, such as in the discovery of new metabolized compounds or to study the metabolism of compounds from multiple matrices simultaneously. Thus, this study proposes the use of an untargeted metabolomics strategy based on HPLC-ESI-QTOF-MS for the study of bioavailability and metabolism of bioactive compounds from different vegetal sources. Specifically, this study has been applied to plasma samples collected in an acute human intervention study using three matrices (Hibiscus sabdariffa, Silybum marianum and Theobroma cacao). This approach allowed the selection of those significant variables associated with exogenous metabolites derived from the consumption of bioactive compounds for their subsequent identification. As a result, 14, 25 and 3 potential metabolites associated with supplement intake were significantly detected in the plasma samples from volunteers who ingested the H. sabdariffa (HS), S. marianum (SM) and T. cacao (TC) extracts. Furthermore, Tmax values have been computed for each detected compound. The results highlight the potential of untargeted metabolomics for rapid and comprehensive analysis when working with a wide range of exogenous metabolites from different plant sources in biological samples.

Flavanones, a type of polyphenol, are found in substantial amounts in citrus fruits. When high- or moderate-dose orange juice consumption occurs, flavanones make up a significant portion of the total polyphenols in plasma. Disaccharide derivative narirutin, mainly dihydroxy flavanone, is found in citrus fruits. The substantial chemotherapeutic potential of narirutin has been amply demonstrated by numerous experimental studies. Consequently, the purpose of this study is to compile the research that has already been done showing narirutin to be a promising anticancer drug, with its mechanism of action being documented in treatment plans for various cancer forms. Narirutin functions in a variety of cancer cells by regulating several pathways that include cell cycle arrest, apoptosis, antiangiogenic, antimetastatic, and DNA repair. Narirutin has been shown to modify many molecular targets linked to the development of cancer, including drug transporters, cell cycle mediators, transcription factors, reactive oxygen species, reactive nitrogen species, and inflammatory cytokines. Taken together, these reviews offer important new information about narirutin's potential as a potent and promising drug candidate for use in medicines, functional foods, dietary supplements, nutraceuticals, and other products targeted at improving the treatment of cancer.

Evidence on the Mediterranean diet (MD) and age-related cognitive decline (CD) is still inconclusive partly due to self-reported dietary assessment. The aim of the current study is to develop an MD- metabolomic score (MDMS) and investigate its association with CD in community-dwelling older adults.

This study includes participants from the Three-City Study from the Bordeaux (n = 418) and Dijon (n = 422) cohorts who are free of dementia at baseline. Repeated measures of cognition over 12 years are collected. An MDMS is designed based on serum biomarkers related to MD key food groups and using a targeted metabolomics platform. Associations with CD are investigated through conditional logistic regression (matched on age, sex, and education level) in both sample sets. The MDMS is found to be inversely associated with CD (odds ratio [OR] [95% confidence interval (CI)] = 0.90 [0.80-1.00]; p = 0.048) in the Bordeaux (discovery) cohort. Results are comparable in the Dijon (validation) cohort, with a trend toward significance (OR [95% CI] = 0.91 [0.83-1.01]; p = 0.084).

A greater adherence to the MD, here assessed by a serum MDMS, is associated with lower odds of CD in older adults.

Objectives: Previous preclinical evidence indicates a protective role of quercetin against inflammatory bowel disease (IBD). However, there is no evidence from human populations, resulting in knowledge gaps regarding the role of quercetin in the IBD development. We aimed to prospectively evaluate the associations between dietary quercetin intake and IBD in humans and in vivo animal models. Methods: We included 187 709 IBD-free participants from the UK Biobank. Dietary information was collected using validated 24-hour dietary recalls and the quercetin intake was estimated based on national nutrient databases. Incident IBD was ascertained via inpatient and primary care data. Cox proportional hazard models were used to estimate the multi-variable adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). Experiments were conducted in two chemical-induced (dextran sulfate sodium salt and trinitro-benzene-sulfonic acid) mouse models orally pretreated with quercetin (CAS number: 117-39-5) solution to evaluate the effects of quercetin at physiological levels. Results: After a mean follow-up of 9.7 years, we documented 863 incident IBD. Compared to participants with the lowest quintile intake of quercetin, those in the highest quintiles were associated with a lower risk of IBD (aHR 0.76, 95% CI 0.60-0.95; P-trend = 0.004) and ulcerative colitis (aHR 0.69, 95% CI 0.53-0.91; P-trend = 0.001), but not Crohn's disease (aHR 0.95, 95% CI 0.62-1.45; P-trend = 0.765). Mouse models showed that pretreatment with quercetin could attenuate the chemically induced colitis. Conclusions: Higher quercetin intake was associated with a lower risk of IBD, especially UC. The protective role of quercetin is promising in humans and warrants further investigation into downstream mechanisms.

Background: Pure bergamot juice exerts lipid lowering effects in dyslipidemic subjects. It is unknown whether bergamot-based beverages exert similar effects in healthy subjects. Aim: To assess the effects, if any, of a bergamot-based beverage (BBB, bergamot juice ≤25%) on lipid, metabolic and inflammatory biomarkers. Methods: Forty-five healthy subjects were randomised 1 : 1 to BBB intake (400 mL day-1) (55.5%) or control (44.5%) for 12 weeks. Anthropometric (waist circumference, body mass index (BMI)) and clinical (blood pressure) parameters, blood samples (glucose, glycated haemoglobin, insulinemia, lipid profile, liver and renal function, inflammatory biomarkers) and 24-h urine for the analysis of (poly)phenol metabolites were collected at the baseline and at 12 weeks. Intakes of energy, nutrients and food groups were assessed by a 7-day dietary record. Results: Both groups exhibited a time-related significant decrease in total cholesterol (p = 0.02), fasting plasma glucose (p = 0.016), insulin (p = 0.034), BMI (p < 0.001) and waist circumference (p = 0.04), but with no significant between-arm difference. The urinary profile of metabolites from the BBB-derived (poly)phenols well discriminated the two study groups, documenting good compliance in the intervention arm. Notably, urinary bergamot 3-hydroxy-3-methylglutaryl (HMG) -containing flavanones or derived HMG-containing metabolites were not detectable. BBB was well tolerated and no adverse events were recorded. Conclusion: This first randomized controlled trial of BBB consumption in healthy subjects showed no effects of BBB on the cardiometabolic risk profile. BBB consumption is a safe nutritional adjunct in the context of a well balanced diet.

Human serum albumin (HSA) is a serum protein that carries flavonoids in blood circulation. In this report, the binding selectivity and strength of interactions to HSA-binding sites (sites I or II) by flavonoids were evaluated using competition experiments and the specific fluorescent dyes, dansylamide and BD140. Most tested flavonoids bound site I preferentially, with the binding strength dependent on the mother structure in the order flavonol > flavone > flavanone > flavan 3-ols. Glycosylation or glucuronidation reduced the binding of quercetin to site I of HSA, whereas sulfation increased binding. Quercetin 7-sulfate showed the strongest binding and molecular docking simulations supported this observation. Prenylation at any position or glucuronidation and sulfation at the C-4' or C-7 position of quercetin facilitated stronger binding to site II. The binding affinity of flavonoids toward site I correlated with the partition coefficient value (logP), whereas no corresponding correlation was observed for site II.

Green bananas contain a substantial amount of resistant starch (RS), dietary fiber (DF), and phytochemicals, which exhibit potent antioxidant capabilities, primarily attributable to the abundance of polyphenols. The objective of this study was to assess the variations in the contents and bioaccessibility of RS, DF, and phenolic compounds in three types of Australian green bananas (Cavendish "Musa acuminata", Ladyfinger "Musa paradisiaca L.", and Ducasse "Musa balbisiana"), along with their antioxidant capacities, and the production of short-chain fatty acids (SCFAs) following in vitro simulated gastrointestinal digestion and colonic fermentation. The studied cultivars exhibited significant levels of RS, with Ladyfinger showing the greatest (49%). However, Ducasse bananas had the greatest DF concentration (38.73%). Greater TPC levels for Ladyfinger (2.32 mg GAE/g), as well as TFC and TTC (0.06 mg QE/g and 3.2 mg CE/g, respectively) in Cavendish, together with strong antioxidant capacities (DPPH, 0.89 mg TE/g in Cavendish), have been detected after both intestinal phase and colonic fermentation at 12 and 24 h. The bioaccessibility of most phenolic compounds from bananas was high after gastric and small intestinal digestion. Nevertheless, a significant proportion of kaempferol (31% in Cavendish) remained detectable in the residue after colonic fermentation. The greatest production of SCFAs in all banana cultivars was observed after 24 h of fermentation, except valeric acid, which exhibited the greatest output after 12 h of fermentation. In conclusion, the consumption of whole green bananas may have an advantageous effect on bowel health and offer antioxidant characteristics.

The objective in this work was the evaluation of the stability and content of bioactive compounds (total phenols and total flavonoids) and antioxidant activity of emulsions of ethanolic extracts of propolis obtained by ultrasound, during simulated in vitro digestion. The emulsions prepared with propolis extracts were evaluated on certain properties: their emulsion efficiency, stability (zeta potential, particle size, electrical conductivity), content of bioactive compound (total phenolics and total flavonoids), antioxidant activity and their behavior during simulated in vitro digestion. Based on the total phenol content, an emulsification efficiency of 87.8 ± 1.9% to 97.8 ± 3.8% was obtained. The particle size of the emulsions was 322.5 ± 15.33 nm to 463.9 ± 33.65 nm, with a zeta potential of -31.5 ± 0.66 mV to -28.2 ± 1.0 mV and electrical conductivity of 22.7 ± 1.96 µS/cm to 30.6 ± 0.91 µS/cm. These results indicate good emulsion stability. During simulated in vitro digestion, the content of bioactive compounds (total phenolics, total flavonoids) and antioxidant activity were affected during 77 days of storage at 4 °C. It was concluded that the emulsion process fulfills the function of protecting the bioactive compounds and therefore their biological activity.

Allergic rhinitis (AR) remains a major health problem worldwide. Compared with traditional oral drugs, nasal administration avoids first-pass metabolism and achieve faster and more effective efficacy. In this study, we used the ion crosslinking method to prepare quercetin-chitosan nasal adaptive nanomedicine (QCS) delivery system and evaluated in the treatment of allergic rhinitis mice models. The obtained positively charged nanoparticles with a particle size of 229.2 ± 0.2 nm have excellent characteristics in encapsulation efficiency (79.604%), drug loading rate (14.068%), drug release (673.068 μg) and stability(> 7 days). Excitingly, QCS treatment significantly reduced the number of sneezing and nasal rubbing events in AR mice, while reducing the levels of inflammatory factors such as immunoglobulin E (IgE), interleukin (IL)-17, tumor necrosis factor (TNF)-α, and (IL)-6 to alleviate AR symptoms. Hematoxylin-eosin (HE) staining also showed the damaged nasal mucosa was improved. These experimental results suggest that QCS can effectively suppress allergic inflammation in a mouse model and hold promise as a therapeutic option for allergic rhinitis.

The gradual emergence of new bacterial strains impervious to one or more antibiotics necessitates discovering and applying natural alternatives. Among natural products, various polyphenols exhibit antibacterial activity. However, polyphenols with biocompatible and potent antibacterial characteristics are limited due to low aqueous solubility and bioavailability; therefore, recent studies are considering new polyphenol formulations. Nanoformulations of polyphenols, especially metal nanoparticles, are currently being investigated for their potential antibacterial activity. Nanonization of such products increases their solubility and helps attain a high surface-to-volume ratio and, therefore, a higher reactivity of the nanonized products with better remedial potential than nonnanonized products. Polyphenolic compounds with catechol and pyrogallol moieties efficiently bond with many metal ions, especially Au and Ag. These synergistic effects exhibit antibacterial pro-oxidant ROS generation, membrane damage, and biofilm eradication. This review discusses various nano-delivery systems for considering polyphenols as antibacterial agents.

The health benefits of chestnut (Castanea sativa) shells (CSs) have been ascribed to phytochemicals, mainly phenolic compounds. Nevertheless, an exhaustive assessment of their intestinal absorption is vital considering a possible nutraceutical application. This study evaluated the bioactivity of CSs extract prepared by Supercritical Fluid Extraction and untargeted metabolomic profile upon in-vitro intestinal permeation across a Caco-2/HT29-MTX co-culture model. The results demonstrated the neuroprotective, hypoglycemic, and hypolipidemic properties of CSs extract by inhibition of acetylcholinesterase, α-amylase, and lipase activities. The untargeted metabolic profiling by LC-ESI-LTQ-Orbitrap-MS unveiled almost 60 % of lipids and 30 % of phenolic compounds, with 29 metabolic pathways indicated by enrichment analysis. Among phenolics, mostly phenolic acids, flavonoids, and coumarins permeated the intestinal barrier with most metabolites arising from phase I reactions (reduction, hydrolysis, and hydrogenation) and a minor fraction from phase II reactions (methylation). The permeation rates enhanced in the following order: ellagic acid < o-coumaric acid < p-coumaric acid < ferulaldehyde ≤ hydroxyferulic acid ≤ dihydroferulic acid < ferulic acid < trans-caffeic acid < trans-cinnamic acid < dihydrocaffeic acid, with better outcomes for 1000 µg/mL of extract concentration and after 4 h of permeation. Taken together, these findings sustained a considerable in-vitro intestinal absorption of phenolic compounds from CSs extract, enabling them to reach target sites and exert their biological effects.

For the potential health benefits and nutritional value, polyphenols are one of the secondary metabolites of plants that have received extensive research. It has anti-inflammatory and cytotoxicity-reducing properties in addition to a high antioxidant content. Macromolecular polyphenols and polysaccharides are biologically active natural polymers with antioxidant and anti-inflammatory potential. Arsenic is an ecologically toxic metalloid. Arsenic in drinking water is the most common way people come into contact with this metalloid. While arsenic is known to cause cancer, it is also used to treat acute promyelocytic leukemia (APL). The treatment's effectiveness is hampered by the adverse effects it can cause on the body. Oxidative stress, inflammation, and the inability to regulate cell death cause the most adverse effects. Polyphenols and other macromolecules like polysaccharides act as neuroprotectants by mitigating free radical damage, inhibiting nitric oxide (NO) production, lowering A42 fibril formation, boosting antioxidant levels, and controlling apoptosis and inflammation. To prevent the harmful effects of toxins, polyphenols and pectin lower oxidative stress, boost antioxidant levels, improve mitochondrial function, control apoptosis, and suppress inflammation. Therefore, it prevents damage to the heart, liver, kidneys, and reproductive system. This review aims to identify the effects of the polyphenols in conjugation with polysaccharides as an ameliorative strategy for arsenic-induced toxicity in various organs.

Luteolin loaded zein nanoparticles (Lut-ZNP) were prepared by using sodium caseinate as an electrostatic stabilizer. The formulation of the nanoparticles was optimized. Lut-ZNP were spray-dried, and the physicochemical properties were characterized by SEM, XRD, FT-IR and DSC. Then, the bioavailability of luteolin in rats was determined. Under the formulation of luteolin, zein and sodium caseinate with mass ratio of 1:5:15, the particle size, ζ-potential, encapsulation efficiency and loading efficiency of Lut-ZNP were 171.8 nm, -49.05 mV, 85.85% and 3.15%, respectively. Luteolin existed in the nanoparticles with amorphous form. Lut-ZNP exhibited good redispersibility in water after drying. Compared with free luteolin, the solubility, stability and release of luteolin in Lut-ZNP were greatly improved. Besides, the fecal excretion of luteolin in rats was significantly reduced after oral administration of Lut-ZNP. In addition to native luteolin, its metabolites including sulfate, glucuronidate and methylated glucuronidate were found in rat plasma. Lut-ZNP significantly increased the plasma concentrations of luteolin and its metabolites, and the bioavailability of luteolin was enhanced by 2.92 times.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) represents a promising anticancer agent, as it selectively induces apoptosis in transformed cells without altering the cellular machinery of healthy cells. Unfortunately, the presence of TRAIL resistance mechanisms in a variety of cancer types represents a major hurdle, thus limiting the use of TRAIL as a single agent. Accumulating studies have shown that TRAIL-mediated apoptosis can be facilitated in resistant tumors by combined treatment with antitumor agents, ranging from synthetic molecules to natural products. Among the latter, flavonoids, the most prevalent polyphenols in plants, have shown remarkable competence in improving TRAIL-driven apoptosis in resistant cell lines as well as tumor-bearing mice with minimal side effects. Here, we summarize the molecular mechanisms, such as the upregulation of death receptor (DR)4 and DR5 and downregulation of key anti-apoptotic proteins [e.g., cellular FLICE-inhibitory protein (c-FLIP), X-linked inhibitor of apoptosis protein (XIAP), survivin], underlying the TRAIL-sensitizing properties of different classes of flavonoids (e.g., flavones, flavonols, isoflavones, chalcones, prenylflavonoids). Finally, we discuss limitations, mainly related to bioavailability issues, and future perspectives regarding the clinical use of flavonoids as adjuvant agents in TRAIL-based therapies.

Alzheimer's Disease (AD) is a progressive neurodegenerative disorder impairing cognition and memory in the elderly. This disorder has a complex etiology, including senile plaque and neurofibrillary tangle formation, neuroinflammation, oxidative stress, and damaged neuroplasticity. Current treatment options are limited, so alternative treatments such as herbal medicine could suppress symptoms while slowing cognitive decline. We followed PRISMA guidelines to identify potential herbal treatments, their associated medicinal phytochemicals, and the potential mechanisms of these treatments. Common herbs, including Ginkgo biloba, Camellia sinensis, Glycyrrhiza uralensis, Cyperus rotundus, and Buplerum falcatum, produced promising pre-clinical results. These herbs are rich in kaempferol and quercetin, flavonoids with a polyphenolic structure that facilitate multiple mechanisms of action. These mechanisms include the inhibition of Aβ plaque formation, a reduction in tau hyperphosphorylation, the suppression of oxidative stress, and the modulation of BDNF and PI3K/AKT pathways. Using pre-clinical findings from quercetin research and the comparatively limited data on kaempferol, we proposed that kaempferol ameliorates the neuroinflammatory state, maintains proper cellular function, and restores pro-neuroplastic signaling. In this review, we discuss the anti-AD mechanisms of quercetin and kaempferol and their limitations, and we suggest a potential alternative treatment for AD. Our findings lead us to conclude that a polyherbal kaempferol- and quercetin-rich cocktail could treat AD-related brain damage.

Cobalt intoxication can occur after its release from metal-based prostheses, which is generally clinically severe. Therefore, there is a need for the development of a cobalt chelator since there are currently no approved drugs for cobalt intoxication. As flavonoids are known for their metal chelating properties and safety, the screening of cobalt chelating properties was performed in a total of 23 flavonoids by our recently developed new spectrophotometric assay. Further assessment of positive or negative consequences of cobalt chelation was performed both in vitro and ex vivo. Six and thirteen flavonoids significantly chelated cobalt ions at pH 7.5 and 6.8, respectively. Baicalein demonstrated a significant activity even at pH 5.5; however, none of the flavonoids showed chelation at pH 4.5. In general, baicalein and 3-hydroxyflavone were the most active. They also mildly decreased the cobalt-triggered Fenton reaction, but baicalein toxicity toward red blood cells was strongly increased by the addition of cobalt. Quercetin, tested as an example of flavonoid unable to chelate cobalt ions significantly, stimulated both the cobalt-based Fenton reaction and the lysis of erythrocytes in the presence of cobalt. Therefore, 3-hydroxyflavone can serve as a potential template for the development of novel cobalt chelators.

Agastache rugosa, commonly known as Korean mint (KM), is a medicinal plant renowned for its potential health-promoting properties. However, the lack of bioavailability studies has hindered the acquisition of conclusive evidence. In this study, we investigated the bioavailability of six key polyphenols present in KM, including rosmarinic acid (RA), acacetin (AC), and four glycosides of AC. Utilizing UPLC-MS/MS, we analyzed their presence in human plasma and Caco-2 monolayers grown in permeable filter supports. Following single ingestion, we were able to detect RA, AC, and tilianin (TA) in the plasma. Consistent results were obtained for AC and TA but no transport was found for RA in a highly tight Caco-2 cell monolayer, indicating transport through the intercellular space for RA and transepithelial transport for AC and TA. Other AC glucosides with acetyl and/or malonyl groups were rarely found in the plasma. Interestingly, AC glucosides with only an acetyl group appeared at the basolateral side in Caco-2 monolayers, suggesting exclusive hydrolysis of malonyl glucosides in the colon. These findings highlight the high potential of RA, AC, and TA as bioactive compounds that may confer health benefits.

In the absence of a recommendation for daily intake of phenolic compounds, to compare the intake of the main dietary polyphenols between populations is a really challenge. This study aimed to estimate the total dietary intake of polyphenols, classes and their food sources among Brazilian graduates and postgraduates. This was a cross-sectional study using baseline data from the Cohort of Universities of Minas Gerais (CUME project). Food consumption was assessed using a quantitative food frequency questionnaire with 144 food items. Polyphenol intake was estimated from the Phenol-Explorer and US Department of Agriculture database, and previous studies that evaluated the phenolic content of specific foods. A total of 4130 individuals of both sexes with a median age of 34 (18-86) years old were finally included. The median intake of total polyphenols adjusted for energy was 753.41 mg/day (interquartile range - IQR=461.80; p<0.001), and the most consumed classes were phenolic acids and flavonoids, with median intakes of 552.30 mg/d (IQR=429.78; p<0.001) and 154.70 mg/day (IQR=108.70; p<0.001), respectively. The main food sources of polyphenols were coffee, peanuts, beans, and fruits. A lower intake of total polyphenols and their classes was observed in a population with similar characteristics to those from developed countries. The results demonstrate the importance of disseminating nutritional information about foods, so that the consumption of natural foods is prioritized. New studies that evaluate the consumption of polyphenols and their impact on human health are recommended to establish a daily recommendation for the consumption of such compounds.

Fruits, vegetables, and other food items contain phytochemicals or secondary metabolites which may be considered non-essential nutrients but have medicinal importance. These dietary phytochemicals exhibit chemopreventive and therapeutic effects against numerous diseases. Polyphenols are secondary metabolites found in vegetables, fruits, and grains. These compounds exhibit several health benefits such as immune modulators, vasodilators, and antioxidants. This review focuses on recent studies on using dietary polyphenols to treat cardiovascular disorders, atherosclerosis, and vascular endothelium deficits. We focus on exploring the safety of highly effective polyphenols to ensure their maximum impact on cardiac abnormalities and discuss recent epidemiological evidence and intervention trials related to these properties. Kaempferol, quercetin, and resveratrol prevent oxidative stress by regulating proteins that induce oxidation in heart tissues. In addition, polyphenols modulate the tone of the endothelium of vessels by releasing nitric oxide (NO) and reducing low-density lipoprotein (LDL) oxidation to prevent atherosclerosis. In cardiomyocytes, polyphenols suppress the expression of inflammatory markers and inhibit the production of inflammation markers to exert an anti-inflammatory response. Consequently, heart diseases such as strokes, hypertension, heart failure, and ischemic heart disease could be prevented by dietary polyphenols.

The endothelium, as the guardian of vascular homeostasis, is closely related to the occurrence and development of cardiovascular diseases (CVDs). As an early marker of the development of a series of vascular diseases, endothelial dysfunction is often accompanied by oxidative stress and inflammatory response. Natural flavonoids in fruits, vegetables, and Chinese herbal medicines have been shown to induce and regulate endothelial cells and exert anti-inflammatory, anti-oxidative stress, and anti-aging effects in a large number of in vitro models and in vivo experiments so as to achieve the prevention and improvement of cardiovascular disease. Focusing on endothelial mediation, this paper introduces the signaling pathways involved in the improvement of endothelial dysfunction by common dietary and flavonoids in traditional Chinese medicine and describes them based on their metabolism in the human body and their relationship with the intestinal flora. The aim of this paper is to demonstrate the broad pharmacological activity and target development potential of flavonoids as food supplements and drug components in regulating endothelial function and thus in the prevention and treatment of cardiovascular diseases. This paper also introduces the application of some new nanoparticle carriers in order to improve their bioavailability in the human body and play a broader role in vascular protection.

Self-triggered micro-/milli-devices (STMDs), which are artificial devices capable of responding to the surrounding environment and transferring external energy into kinetic energy, thus realizing autonomous movement, have come to the forefront as a powerful tool in cargo delivery via gastrointestinal tract. Urgent needs have been raised to overview the development of this area.

We summarize the advancement of designing STMDs for delivery via gastrointestinal tract. We first give a brief overview on the opportunities and challenges of delivery via gastrointestinal tract involving gastric barriers and intestinal barriers. Then, emphasis is laid on the design and applications of STMDs for delivery via gastrointestinal tract. We focus on their morphological characteristics and function design, expounding their working mechanisms in the complex gastrointestinal tract.

Although with much progress in STMDs, there is still a huge gap between laboratory researches and clinical applications due to some limitations including latent digestive burden, sophisticated fabrication, unstable delivery, and so on. We give a discussion on the potential, challenges, and prospects of developing STMDs for delivery via gastrointestinal tract.

Carob is botanically called as Ceratonia siliqua and belongs to the Legumes family. The fruit is derived from hermaphrodite trees and hard in shape. The carob contains high sugar contents in pulp, fat in seed and minerals like potassium, calcium, and phosphorus are present in pods. Polyphenols and antioxidants are abundant in leaves and pods. It can be used for enhancing human health due to its high nutritional profile. Carob gum is used in the pharmaceutical industry in the form of pomades, anti-celiac ingredients, pills, and dental paste. The clinical carob can aid as an anti-cancer, anti-reflux, anti-diabetic, anti-diarrheal, anti-hyperlipidemia, anti-bacterial, anti-microbial, and anti-fungal. Nowadays, carob seeds are being used as an alternative to cocoa powder in food items whereas the leaves, pods, and seeds of carob are also historically used as food for animal feed. However, these parts of carob are available in markets with reasonable prices. Carob production, though with a rising contribution, contributes to the local economy. In this sense, we can incorporate knowledge on the chemical properties and the biological effect of carob fruits on human health. In this study, the supportive and health-promoting impacts of carob are discussed along with the clinical testing obtained from natural constituents of carob. In addition, further studies can be performed to extract and separate polyphenols and antioxidant potential for the development of functional that play a valuable role in pharmaceutical and food sectors.

Based on the use of quercetin for treating diabetes and H2 S for promoting wound healing, a series of three quercetin-linker-H2 S donor conjugates was designed, synthesized and characterized by 1 H-NMR, 13 C-NMR and MS. Meanwhile, in vitro evaluation of these compounds was also researched by IR-HepG2 treatment experiment, MTT assay, scratch test and tubule formation experiment. The three compounds could be used to treat insulin resistance induced by high glucose and promote the proliferation of human umbilical vein endothelial cells, wound healing, and the formation of tubules in vitro under a high-glucose environment. Our results illustrate that these compounds could be used to treat diabetes and promote wound healing at the same time. Furthermore, molecular docking study results of the compounds were consistent with the evaluated biological activity. In vivo research of compounds is underway.

Dietary flavanols are known for disease preventative properties but are often poorly absorbed. Gut microbiome flavanol metabolites are more bioavailable and may exert protective activities. Using metabolite mixtures extracted from the urine of rats supplemented with flavanols and treated with or without antibiotics, we investigated their effects on INS-1 832/13 β-cell glucose stimulated insulin secretion (GSIS) capacity. We measured insulin secretion under non-stimulatory (low) and stimulatory (high) glucose levels, insulin secretion fold induction, and total insulin content. We conducted treatment-level comparisons, individual-level dose responses, and a responder vs. non-responder predictive analysis of metabolite composition. While the first two analyses did not elucidate treatment effects, metabolites from 9 of the 28 animals demonstrated significant dose responses, regardless of treatment. Differentiation of responders vs. non-responder revealed that levels of native flavanols and valerolactones approached significance for predicting enhanced GSIS, regardless of treatment. Although treatment-level patterns were not discernable, we conclude that the high inter-individual variability shows that metabolite bioactivity on GSIS capacity is less related to flavanol supplementation or antibiotic treatment and may be more associated with the unique microbiome or metabolome of each animal. These findings suggest flavanol metabolite activities are individualized and point to the need for personalized nutrition practices.

The consumption of 100% fruit juices has not been associated with substantial detrimental outcomes in population studies and may even contribute to improving the cardiometabolic profile if included in a healthy balanced diet. The main contributors to such potential beneficial effects include vitamins, minerals, and likely the (poly)phenol content. This study aimed to investigate whether the (poly)phenols contained in 100% fruit juices may mediate their effects on cardiometabolic risk factors based on published randomized controlled trials (RCT).

A systematic search in PubMed/MEDLINE and Embase, updated till the end of October 2022, was carried out to identify RCT providing quantitative data on (poly)phenol content in 100% fruit juices and used as an intervention to improve cardiometabolic parameters such as blood lipids, glucose, and blood pressure. Meta-regression analysis was performed to calculate the effect of the intervention [expressed as standardized mean difference and 95% confidence intervals (CI)] using the (poly)phenol content as moderator.

A total of 39 articles on RCT investigating the effects of 100% fruit juices on cardiometabolic risk factors reporting data on total (poly)phenol and anthocyanin content were included in the analysis. Total (poly)phenol content was substantially unrelated to any outcome investigated. In contrast, each 100 mg per day increase in anthocyanins was related to 1.53 mg/dL decrease in total cholesterol (95% CI, -2.83, -0.22, p = 0.022) and 1.94 mg/dL decrease in LDL cholesterol (95% CI, -3.46, -0.42, p = 0.012). No other potential mediating effects of anthocyanins on blood triglycerides, glucose, systolic and diastolic pressure were found, while a lowering effect on HDL cholesterol after excluding one outlier study was observed.

In conclusion, the present study showed that anthocyanins may mediate the potential beneficial effects of some 100% fruit juices on some blood lipids. Increasing the content of anthocyanins through specific fruit varieties or plant breeding could enhance the health benefits of 100% fruit juices.

Kombucha is a functional beverage obtained through fermentation of sweetened Camellia sinensis infusion by a symbiotic culture of bacteria and yeasts that exerts many beneficial biological effects, mostly related to its antioxidant and anti-inflammatory effects. Alternative raw materials have been used to create new kombucha or kombucha-like products. Coffee is the most important food commodity worldwide and generates large amounts of by-products during harvest and post-harvest processing. The main coffee by-product is the dried fruit skin and pulp, popularly known as cascara. To date, no studies have evaluated the potential bioactivity of coffee cascara kombucha. In this study, we aimed to measure and compare the effects of infusions and kombuchas made with arabica coffee cascaras (n = 2) and black tea leaves (n = 1), fermented for 0, 3, 6, and 9 days on the intracellular production of Reactive Oxygen Species (ROS) and Nitric Oxide (NO) in model cells. Oxidative stress was induced in HK-2 cells with indoxyl sulfate (IS) and high glucose (G). Inflammation was induced with lipopolysaccharide (LPS) in RAW 264.7 macrophage. The contents of phenolic compounds, caffeine, and other physicochemical parameters were evaluated. To the best of our knowledge, this is the first study providing information on the bioactive profile and on the potential biological effects of coffee cascara kombucha. Fermentation caused the release of bound phenolic compounds from the infusions, especially total chlorogenic acids, with an average increase from 5.4 to 10.7 mg/100 mL (98%) and 2.6-3.4 mg/100 mL (30%) in coffee cascara and black tea kombucha, respectively, up to day 9. All evaluated beverages reduced (p < 0.0001) similarly the intracellular ROS (41% reduction, on average) and uric acid (10-55%) concentrations in HK-2 model cells, reversing the induced oxidative stress. All beverages also reduced (p < 0.0001, 81-90%) NO formation in LPS-induced macrophages, exhibiting an anti-inflammatory effect. These potential health benefits may be mostly attributed to polyphenols and caffeine, whose contents were comparable in all beverages. Coffee cascara showed similar potential to C. sinensis to produce healthy beverages and support sustainable coffee production.

Common neurological disorders, including neurodegenerative diseases, stroke, epilepsy, autism and psychiatric disorders, affect many people worldwide and threaten their lives and health by inducing movement disorders, behavioral disorders, or a combination of both. Oxidative stress and neuroinflammation play a central role in neuronal damage and neurological diseases induction and progression. In addition, protein homeostasis (proteostasis) impairment occurs in many neurodegenerative diseases, which plays a critical role in the progression of the pathology. Grape seed contains several flavonoids and non-flavonoids and exerts potent antioxidant and anti-inflammatory effects. In addition, polyphenols and flavanols can maintain cellular proteostasis. Since impaired proteostasis is closely involved in all amyloid diseases, particularly neurodegenerative diseases, grape seeds extract can be a valuable therapeutic agent. Therefore, this review discusses the protective and therapeutic mechanisms of grape seed against neurological disorders and, in the end, links GSE to microRNAs as future therapeutic developments.