Polyphenol-rich Foods Research Articles

A serving of blueberry (Vaccinium corymbosum) improves peripheral vascular function but not metabolic and functional markers in older subjects: A randomized, controlled, crossover study

Evidence suggests that polyphenol-rich foods like berries may help counteract aging-related disorders such as vascular dysfunction and arterial stiffness. However, few intervention studies have been conducted in older adults. This study aimed to assess whether the consumption of blueberries may improve vascular function in older subjects. A randomized, controlled, crossover trial was conducted in a group of 20 volunteers over 60 years old. Participants consumed either a blueberry mousse (250 g, providing 480 mg of anthocyanins – ACNs) or a control product (250 mL of sugared water), with treatments separated by at least 1-week. Reactive hyperemia index (RHI), augmentation index (AIx), blood pressure, and heart rate were measured at baseline and 2 h post-consumption. Blood samples were collected at baseline and after 1, 1.5, 2 and 4 h from the intake to evaluate ACN bioavailability, metabolic, and vascular markers. Sixteen subjects completed the trial (9 males, 7 females; mean age 69 ± 5 years). Blueberry consumption significantly increased RHI compared to control (mean difference + 0.42, 95 % CI: 0.01–0.082, p < 0.05). Maximum serum ACN concentration was observed at 2 h (20.3 ± 7.4 ng/mL). No association was found between RHI improvement and total serum ACNs, but a significant positive correlation was detected with delphinidin and cyanidin-3-glucoside (p < 0.01). No effects on AIx, blood pressure, or other markers were found. In conclusion, blueberries may improve peripheral vascular function in older adults, potentially due to increased ACN levels. Further studies are needed to corroborate these findings and elucidate the mechanisms involved.

Advances in Gouty Arthritis Management: Integration of Established Therapies, Emerging Treatments, and Lifestyle Interventions.

Gouty arthritis, a prevalent inflammatory condition characterized by the deposition of monosodium urate crystals within joints, often results in debilitating pain and inflammation. Conventional therapeutic approaches, including nonsteroidal anti-inflammatory drugs, corticosteroids, and urate-lowering agents such as allopurinol and febuxostat, often have limitations such as adverse effects, drug interactions, and suboptimal patient compliance. This review presents a comprehensive overview of both established and emerging therapeutic strategies, developed between 2019 and 2024, for gouty arthritis; the review focuses on their mechanisms of action, efficacy, and safety profiles. Novel therapeutic approaches include pharmaceutical plant additives (e.g., Citrullus colocynthis, Atractylodes lancea), anti-inflammatory agents such as canakinumab and ozone therapy, and complementary therapies such as warm ginger compresses, Qingpeng ointment, and various lifestyle modifications. These strategies offer promising alternatives to conventional treatments by targeting uric acid metabolism, inflammatory pathways, and crystal formation, potentially reducing reliance on standard medications and minimizing adverse effects. Although therapies such as canakinumab have demonstrated significant efficacy in reducing gout flares, others such as polyphenol-rich foods offer favorable safety profiles. Further research, including large-scale clinical trials, is warranted to validate these findings and integrate these strategies into clinical practice to improve patient outcomes and quality of life.

Metatranscriptomics-guided discovery and characterization of a polyphenol-metabolizing gut microbial enzyme.

Gut microbial catechol dehydroxylases are a largely uncharacterized family of metalloenzymes that potentially impact human health by metabolizing dietary polyphenols. Here, we use metatranscriptomics (MTX) to identify highly transcribed catechol-dehydroxylase-encoding genes in human gut microbiomes. We discover a prevalent, previously uncharacterized catechol dehydroxylase (Gp Hcdh) from Gordonibacter pamelaeae that dehydroxylates hydrocaffeic acid (HCA), an anti-inflammatory gut microbial metabolite derived from plant-based foods. Further analyses suggest that the activity of Gp Hcdh may reduce anti-inflammatory benefits of polyphenol-rich foods. Together, these results show the utility of combining MTX analysis and biochemical characterization for gut microbial enzyme discovery and reveal a potential link between host inflammation and a specific polyphenol-metabolizing gut microbial enzyme.

Polyphenols in foods: a potential strategy for preventing and managing the postprandial hyperglycemic response.

Type 2 diabetes mellitus (T2DM) is a significant health risk worldwide, and effective management strategies are needed. Polyphenols exhibit diverse biological functions, are abundant in various plants, and influence carbohydrate digestion and absorption. This review provides a comprehensive overview of clinical evidence regarding the relationship between dietary polyphenols and the postprandial hyperglycemic response. Human intervention studies have demonstrated the benefits of polyphenol-rich foods in improving glucose and insulin metabolism, underscoring their role in preventing T2DM. These findings highlight the potential of polyphenol-rich foods for managing hyperglycemia and mitigating T2DM risk and provide insight into effective dietary strategies for glycemic control and overall health.

PSIX-15 Elevated level of ATG12, an autophagy–associated gene, in canines with dermatological problems fed a polyphenol-rich food

PSIX-15 Elevated level of ATG12, an autophagy–associated gene, in canines with dermatological problems fed a polyphenol-rich food

Effects and medical application of plant-origin polyphenols: A narrative review

The impact of oxidative stress in the pathogenesis of various diseases is well known. Oxidative stress occurs when there is an imbalance between the production of reactive oxygen species (ROS) and the ability of a biological system to detoxify these reactive intermediates or repair the resulting damage. Polyphenols, a diverse group of compounds with antioxidant properties, help reduce damage by ROS. They are abundant in fruits, vegetables, tea, coffee, wine, and other plant-based foods. The mechanisms of their antioxidant activity are related to their ability to regulate cellular signaling pathways, metal chelation, and mitochondrial protection, while modulating antioxidant enzyme activity and exhibiting anti-inflammatory effects. Polyphenols can also reduce oxidative stress through ROS scavenging, direct neutralization, or enhancing antioxidant defenses within cells. It has been established that polyphenols derived from plant compounds do not harm the metabolism of normal cells, but are involved in modulating the metabolic pathways of diseased cells, which is related to their high redox sensitivity. Incorporating polyphenol-rich foods into the diet is beneficial for maintaining overall health and reducing the risk of oxidative stress-related diseases. Researchers are exploring the therapeutic potential of polyphenols as dietary supplements or functional foods in medical applications. This review discusses the origin, structure, benefits, and application of plant polyphenols in medicine and the food industry. Keywords: biologically active compounds, polyphenols, oxidative stress, antioxidant activity, functional food.

Food-breastmilk combinations alter the colonic microbiome of weaning infants: an in silico study.

The introduction of solid foods to infants, also known as weaning, is a critical point for the development of the complex microbial community inhabiting the human colon, impacting host physiology in infancy and later in life. This research investigated in silico the impact of food-breastmilk combinations on growth and metabolite production by colonic microbes of New Zealand weaning infants using the metagenome-scale metabolic model named Microbial Community. Eighty-nine foods were individually combined with breastmilk, and the 12 combinations with the strongest influence on the microbial production of short-chain fatty acids (SCFAs) and branched-chain fatty acids (BCFAs) were identified. Fiber-rich and polyphenol-rich foods, like pumpkin and blackcurrant, resulted in the greatest increase in predicted fluxes of total SCFAs and individual fluxes of propionate and acetate when combined, respectively, with breastmilk. Identified foods were further combined with other foods and breastmilk, resulting in 66 multiple food-breastmilk combinations. These combinations altered in silico the impact of individual foods on the microbial production of SCFAs and BCFAs, suggesting that the interaction between the dietary compounds composing a meal is the key factor influencing colonic microbes. Blackcurrant combined with other foods and breastmilk promoted the greatest increase in the production of acetate and total SCFAs, while pork combined with other foods and breastmilk decreased the production of total BCFAs.IMPORTANCELittle is known about the influence of complementary foods on the colonic microbiome of weaning infants. Traditional in vitro and in vivo microbiome methods are limited by their resource-consuming concerns. Modeling approaches represent a promising complementary tool to provide insights into the behavior of microbial communities. This study evaluated how foods combined with other foods and human milk affect the production of short-chain fatty acids and branched-chain fatty acids by colonic microbes of weaning infants using a rapid and inexpensive in silico approach. Foods and food combinations identified here are candidates for future experimental investigations, helping to fill a crucial knowledge gap in infant nutrition.

How Do Polyphenol-Rich Foods Prevent Oxidative Stress and Maintain Gut Health?

Inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis, involves chronic inflammatory disorders of the digestive tract. Oxidative stress, associated with increased reactive oxygen species generation, is a major risk factor for IBD pathogenesis. Industrialized lifestyles expose us to a variety of factors that contribute to deteriorating gut health, especially for IBD patients. Many alternative therapeutic strategies have been developed against oxidative stress along with conventional therapy to alleviate IBD pathogenesis. Polyphenol-rich foods have attracted growing interest from scientists due to their antioxidant properties. Polyphenols are natural compounds found in plants, fruits, vegetables, and nuts that exhibit antioxidant properties and protect the body from oxidative damage. This review presents an overview of polyphenol benefits and describes the different types of polyphenols. It also discusses polyphenols' role in inhibiting oxidative stress and fungal growth prevention. Overall, this review highlights how a healthy and balanced diet and avoiding the industrialized lifestyles of our modern society can minimize oxidative stress damage and protect against pathogen infections. It also highlights how polyphenol-rich foods play an important role in protecting against oxidative stress and fungal growth.

Polyphenols: potent protectors against chronic diseases

Polyphenols, abundant in plant-based foods like fruits, vegetables, tea, coffee, wine, and chocolate, offer significant health benefits. Known for their potent antioxidant properties, they combat oxidative stress by neutralising free radicals, crucial in preventing chronic noncommunicable diseases (NCDs) such as cancer, cardiovascular issues, obesity, and diabetes. Polyphenols also exhibit anti-inflammatory effects, modulating gene expression and reducing inflammation associated with NCDs. Their anticancer activities involve inhibiting cancer cell growth and promoting apoptosis through various pathways. They enhance cardiovascular health by improving endothelial function, lowering blood pressure, and inhibiting atherosclerosis. Additionally, polyphenols improve metabolic health by enhancing insulin sensitivity and regulating glucose metabolism, aiding in diabetes and obesity management. These bioactive compounds interact with cellular pathways and gut microbiota, highlighting their multifaceted mechanisms. Integrating polyphenol-rich foods into diets could significantly improve health outcomes and alleviate NCD burdens, advocating for their inclusion in public health strategies and further research to optimise their potential.

Effect of Microencapsulated Cocoa Polyphenols on Macro- and Microvascular Function after Eccentric Exercise

Background: Evidence has demonstrated that non-habitual exercise, such as eccentric exercise, can increase reactive oxygen species and induce endothelial dysfunction, which plays a central role in the development of cardiovascular disease. Polyphenol-rich foods, such as cocoa, have been widely investigated in vascular function due to their antioxidant effect. Aims: The goal of this study was to evaluate the impact of microencapsulated cocoa (MC) polyphenols in the flow-mediated dilation (FMD) response and forearm muscle oxygenation (StO2) parameters after an eccentric exercise. Methods: Thirteen physically active adults were enrolled in a randomized, double-blind, and crossover study. FMD and StO2 were evaluated before and after 24 h, 48 h, and 72 h of eccentric exercise and MC or placebo supplementation. Results: No significant difference in FMD response and StO2 parameters was observed after MC and placebo (p &gt; 0.05). Conclusions: A single dose of MC did not change FMD and muscle StO2 parameters after eccentric exercise in healthy individuals.

Exploring Bioactive Compounds in Underutilized Fruit Crops of Arid and Semi-Arid Regions: A Comprehensive Review

Exploring the bioactive compounds in underutilized fruit crops of arid regions reveals a wealth of phytochemicals, including polyphenols, vitamins, polyunsaturated fatty acids, amino acids, and carotenoids. These compounds exhibit significant health benefits, evidenced through both in vitro and in vivo studies, demonstrating antioxidant, anti-inflammatory, antimicrobial, hypolipidemic and neuroactive properties. This review delves into the bioactive compounds found in fruits of arid and semi-arid regions, highlighting their phytochemical compositions and their potential in preventing chronic diseases, thereby enhancing human health. Underutilized fruit crops, typically grown and consumed locally rather than being commercially cultivated or widely traded, offer several advantages. They are easier to grow, more resilient to climate change, and exceptionally rich in phytochemicals with medicinal properties. These fruits, such as Indian jujube, Indian gooseberry, bael, and tamarind, among others, are valuable for their high nutritional content and potential to meet the dietary needs of rural populations in arid regions. Local knowledge attests to their nutritional and medicinal benefits, necessitating rigorous study for conservation and nutritional characterization to broaden future food options and enhance functional and nutritional values. This review outlines the ethnobotany, medicinal and nutritional values, biodiversity conservation, and utilization strategies for significant underutilized fruit crops from arid and semi-arid regions. These fruits are rich in diverse phytochemical compounds like flavonoids, tannins, terpenoids, saponins, glycosides, and alkaloids, which are utilized to treat various health conditions in humans and livestock. Their extracts demonstrate a range of activities, including antipyretic, analgesic, anti-inflammatory, anticancer, antimicrobial, antiplasmodial and antinociceptive effects. Highlighting the current research on the nutritional profiling, chemical composition, and potential applications of these fruits, this chapter addresses the knowledge gap concerning the health benefits of consuming arid and semi-arid fruits. This is particularly relevant given the growing interest in "superfoods" and the need for evidence-based public health guidelines to inform consumers about the benefits of polyphenol-rich plant foods in preventing chronic diseases such as cardiovascular disease and cancer.

Towards understanding enhanced hypoglycemic activity of fermented bee pollen in insulin-resistant HepG2 cells by widely targeted metabolomics analysis

Fermentation with lactic acid bacteria normally improved hypoglycemic activity of polyphenol-rich foods, where the contributing phenolic compounds offers an attractive approach to understanding the underlying mechanism. In this study, the correlation between hypoglycemic activity and phenolic compounds of a lacto-fermented bee pollen was investigated. Hypoglycemic activity analysis showed that the fermented bee pollen was superior in promoting glucose consumption, glycogen synthesis, and activation of PI3K/AKT/GSK3β signaling pathway in IR-HepG2 cells in comparison to the unfermented one. Widely targeted metabolomics analysis revealed that the content of 10 phenolic compounds were significantly increased after fermentation. Among them, eight compounds have been reported with hypoglycemic activities. Most interestingly, methyl 2,4-dihydroxyphenylacetate (DPLM) and 2,6-dimethoxybenzaldehyde (DOBA) were newly identified with strong hypoglycemic activity. Functional characterization of DPLM and DOBA supported their contribution to hypoglycemic activity of fermented bee pollen. The new panel of polyphenolic compounds will further enrich our knowledge of hypoglycemic activity of fermented foods.

Effects of Polyphenol-Rich Foods on Lipids and Oxidative Stress Status in Patients with Hyperlipidemia: A Systematic Review of Randomized Controlled Trials.

Hyperlipidemia has been demonstrated to be an autonomous predictor of numerous cardiovascular and cerebrovascular ailments, and research indicates that polyphenols have preventive and therapeutic effects on hyperlipidemia. Nevertheless, the impact of polyphenol-rich foods on blood lipids and oxidative stress status in patients with hyperlipidemia remains inconclusive. To examine the impact of polyphenol-rich foods on lipid levels and oxidative stress in individuals with hyperlipidemia. To retrieve papers published from the establishment of the database through October 9, 2023, eight databases were searched: the Chinese National Knowledge Infrastructure, the China Biomedical Literature Database, the Wanfang Database, the China Science and Technology Journal Database, PubMed, the Cochrane Library, Embase, and the Web of Science. The quality of include studies was assessed using the Cochrane Risk of Bias in Randomized Trials tool, v2. The study involved 13 surveys encompassing 640 patients diagnosed with hyperlipidemia. The scope of the food surveys included 12 commonly consumed food groups and medicinal and food homologous substances. All 13 studies reported the effects of polyphenol-rich foods on blood lipids, with significant improvements observed in blood lipid levels for 9 types of foods. Eight studies examined the impact on oxidative stress, and six foods demonstrated a significant reduction in oxidative stress levels. The observed effects were found to be influenced by factors such as dosage, duration of intervention, and gender. Foods abundant in polyphenols play a crucial role in the prevention and treatment of hyperlipidemia by counteracting oxidative stress and regulating metabolic disorders. The confirmation of certain positive effects by several studies notwithstanding, discrepancies in results arise from various factors, necessitating further large-scale, prospective, well-designed randomized controlled studies to address this issue.

Effectiveness of Moringa oleifera extract supplementation in increasing Glucagon-like peptide-1 (GLP-1) in prediabetic model

Prediabetes is a serious global health problem. The prevalence of prediabetes is estimated to be higher than that of diabetes mellitus (DM), and 5%-12.5% of prediabetic patients will develop DM. Epidemiological studies showed that consumption of polyphenol-rich foods impacts blood glucose control and improves insulin resistance. Moringa leaves contain high levels of flavonoids that are effective in glucose control. This study aimed to determine the effect of moringa leaf extract supplementation on increasing GLP-1 levels in prediabetes models. This study used a randomized controlled trial-post-test-only design. Twenty-five male Rattus norvegicus were divided into five groups, namely the normal group, the prediabetes group, and three intervention groups, each given moringa leaf extract at a dose of 75 mg/kgbb, 150 mg / kgbb and 225 mg / kgbb. After 4 weeks of intervention, a GLP-1 examination was conducted. Data analysis using the ANOVA test. There was a significant difference in GLP-1 levels in the intervention group compared to the prediabetes control group (p&lt;0.05). GLP-1 levels increased as the dose given increased. In the intervention group, the dose of 225 mg/kg bw showed the highest increase in GLP-1 levels, but there was no significant difference compared to the 150 mg/kg bw dose group. Moringa leaf extract supplementation is proven to increase GLP-1 in the Rattus norvegicus model. The effect gets better with increasing doses. Further development and testing related to this supplementation are needed so it can be used as a safe non-pharmacological treatment for prediabetes and DM patients.

Iron/zinc Alginates as Vehicles for Food Fortification with Enhanced Stability in Polyphenol-Rich Foods

Iron/zinc Alginates as Vehicles for Food Fortification with Enhanced Stability in Polyphenol-Rich Foods

A Comprehensive Analytical Review of Polyphenols: Evaluating Neuroprotection in Alzheimer's Disease.

Alzheimer's Disease (AD), a prevalent neurodegenerative disorder, is the primary cause of dementia. Despite significant advancements in neuroscience, a definitive cure or treatment for this debilitating disease remains elusive. A notable characteristic of AD is oxidative stress, which has been identified as a potential therapeutic target. Polyphenols, secondary metabolites of plant origin, have attracted attention due to their potent antioxidant properties. Epidemiological studies suggest a correlation between the consumption of polyphenol-rich foods and the prevention of chronic diseases, including neurodegenerative disorders, which underscores the potential of polyphenols as a therapeutic strategy in AD management. Hence, this comprehensive review focuses on the diverse roles of polyphenols in AD, with a particular emphasis on neuroprotective potential. Scopus, ScienceDirect, and Google Scholar were used as leading databases for study selection, from 2018 to late March 2024. Analytical chemistry serves as a crucial tool for characterizing polyphenols, with a nuanced exploration of their extraction methods from various sources, often employing chemometric techniques for a holistic interpretation of the advances in this field. Moreover, this review examines current in vitro and in vivo research, aiming to enhance the understanding of polyphenols' role in AD, and providing valuable insights for forthcoming approaches in this context.

Maternal supplementation with docosahexaenoic acid does not cause constriction of fetal ductus arteriosus: randomized controlled trial.

Docosahexaenoic acid (DHA) is recommended routinely in pregnancy to promote fetal development. DHA has anti-inflammatory activity, but its effects on the fetal heart and circulation are unknown. This study aimed to investigate whether maternal DHA supplementation in the third trimester affects maternal prostaglandin levels and fetal ductus arteriosus flow dynamics. This was a double-blind randomized controlled trial with parallel groups conducted between 2018 and 2021. Pregnant women aged over 18 years with a normal fetus at 27-28 weeks' gestation showing no cardiac/extracardiac anomalies or ductal constriction were eligible for the trial. Women consuming substances with a known inhibitory effect on prostaglandin metabolism, such as non-steroidal anti-inflammatory drugs and polyphenol-rich foods, were excluded. The intervention group received oral supplementation of omega-3 with 450 mg/day of DHA for 8 weeks and the placebo group received capsules of soy lecithin for 8 weeks. Anthropometric measurements, assessment of polyphenol and omega-3 consumption, fetal morphological ultrasound examination, fetal Doppler echocardiographic examination and blood sample collection were performed at the start of the study and the latter two were repeated at follow-up. Prostaglandin E2 (PGE2) level and echocardiographic parameters were compared between the intervention and placebo groups and between baseline and follow-up. A total of 24 participants were included in each group. After 8 weeks, there were no significant differences between the intervention and placebo groups in maternal serum PGE2 level or Doppler echocardiographic parameters of ductal flow. No case of ductus arteriosus constriction was observed. The expected intragroup changes in cardiac morphology, as a result of advancing gestation, were present. Maternal DHA supplementation in the third trimester at a clinically recommended dose did not result in inhibition of PGE2 or constriction of the ductus arteriosus. These findings should be confirmed in postmarket surveillance studies with larger patient numbers in order to test the full safety profile of DHA and provide robust clinical reassurance. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Excessive maternal iced-tea intake-reversible cause of premature ductus arteriosus constriction

Premature ductus arteriosus constriction is a rare entity associated with high neonatal morbidity and mortality. Most cases are idiopathic, with the major known cause being maternal use of nonsteroidal anti-inflammatory drugs. Polyphenol-rich foods have been proven to have a deleterious fetal hemodynamic effect that can lead to premature ductal constriction. We report a case of a neonate diagnosed with premature ductal arteriosus closure, whose only risk factor was an excessive maternal intake of commercial iced-tea during pregnancy. The authors aim to raise awareness to the impact of polyphenol-rich food consumption on ductus arteriosus, since maternal dietary advice can have a major preventive role. Furthermore, a timely diagnosis and intervention can prevent significant morbidity and mortality.

Mechanisms underlying the effect of walnut pellicle extracts and its four representative polyphenols on in vitro digestion of walnut protein isolate

Walnut pellicle extracts (WPE) is rich in phenolic acids. The effects of WPE and its monomeric phenolics (ellagic acid (EA), (+)-catechin (CA), chlorogenic acid (CLA), and epigallocatechin gallate (EGCG)) on in vitro digestion of walnut protein isolate (WPI) were studied. The underlying mechanisms on WPI enzymatic digestion through WPE and pure phenolic compounds with digestive enzymes (pepsin and trypsin) therein using Michaelis-Menten kinetics, fluorescence quenching, molecules docking, and surface plasmon resonance (SPR). The in vitro digestibility of WPI decreased significantly by the addition of WPE. WPE had the strong inhibitory effect on WPI digestion and pepsin and trypsin activities. The effects of polyphenols on WPI digestibility were mainly manifested in the interaction between polyphenols and digestive enzymes. SPR as well as fluorescence quenching indicated that WPE bound to pepsin and trypsin was the strongest. Among the four phenolic compounds abundant in the tested WPE, EGCG inhibited pepsin and trypsin more strongly than the other three compounds. SPR showed that EGCG was bound more tightly to pepsin and trypsin than CLA, CA, and EA. In vitro WPI digestion was strongly inhibited by WPE, mainly due to its high content of EGCG, CLA, CA, and EA causing strong inhibition of pepsin and trypsin. The study investigated the influence of plant protein by phenolic acids in the human digestive system and providing a theoretical basis for the processing and manufacturing of polyphenol-rich nut-based functional foods.

Polyphenols from hickory nut reduce the occurrence of atherosclerosis in mice by improving intestinal microbiota and inhibiting trimethylamine N-oxide production

BackgroundTrimethylamine N-oxide (TMAO), a metabolite produced by intestinal microbiota through metabolizing phosphatidylcholine, choline, l-carnitine and betaine in the diet, has been implicated in the pathogenesis of atherosclerosis (AS). Concurrently, dietary polyphenols have garnered attention for their potential to ameliorate obesity, diabetes and atherosclerosis primarily by modulating the intestinal microbial structure. Hickory (Carya cathayensis) nut, a polyphenol-rich food product favored for its palatability, emerges as a candidate for exploration. Hypothesis/PurposeThe relationship between polyphenol of hickory nut and atherosclerosis prevention will be firstly clarified, providing theoretical basis for the discovery of natural products counteracting TMAO-induced AS process in hickory nut. Study Design and MethodsEmploying Enzyme-linked Immunosorbent Assay (ELISA) and histological examination of aortic samples, the effects of total polyphenol extract on obesity index, inflammatory index and pathological changes of atherosclerosis in C57BL/6 J mice fed with high-fat and high choline diet were evaluated. Further, the composition, abundance, and function of mouse gut microbiota were analyzed through 16srDNA sequencing. Concurrently, the levels of TMAO and the expression of key enzymes (CutC and FMO3) involved in its synthesis are quantified using ELISA, Western Blot and Real-Time Quantitative PCR (RT-qPCR). Additionally, targeted metabolomic profiling of the hickory nut polyphenol extract was conducted, accompanied by molecular docking simulations to predict interactions between candidate polyphenols and the CutC/FMO3 using Autodock Vina. Finally, the docking prediction were verified by microscale thermophoresis (MST) . ResultsPolyphenol extracts of hickory nut improved the index of obesity and inflammation, and alleviated the pathological changes of atherosclerosis in C57BL/6 J mice fed with high-fat and high-choline diet. Meanwhile, these polyphenol extracts also changed the composition and function of intestinal microbiota, and increased the abundance of microorganisms in mice. Notably, the abundance of intestinal microbiota endowed with CutC gene was significantly reduced, coherent with expression of CutC catalyzing TMA production. Moreover, polyphenol extracts also decreased the expression of FMO3 in the liver, contributing to the reduction of TMAO levels in serum. Furthermore, metabonomic profile analysis of these polyphenol extracts identified 647 kinds of polyphenols. Molecular docking predication further demonstrated that Casuariin and Cinnamtannin B2 had the most potential inhibition on the enzymatic activities of CutC or FMO3, respectively.Notably, MST analysis corroborated the potential for direct interaction between CutC enzyme and available polyphenols such as Corilagin, (-)-Gallocatechin gallate and Epigallocatechin gallate. ConclusionHickory polyphenol extract can mitigate HFD-induced AS by regulating intestinal microflora in murine models. In addition, TMA-FMO3-TMAO pathway may play a key role in this process. This research unveils, for the inaugural time, the complex interaction between hickory nut-derived polyphenols and gut microbial, providing novel insights into the role of dietary polyphenols in AS prevention.