Dietary Flavonoid and Subclass Intakes are not Associated with Markers of Bone Health in U.S. Adults Age 50+ Years.

BACKGROUND: Dietary flavonoid intakes have been associated with improved markers of bone health in Chinese and Scottish cohorts, but little data exist in middle aged to older adults in the United States. OBJECTIVES: The objective of our research was to assess if dietary flavonoid intakes are associated with bone mineral density (BMD), bone mineral content (BMC), and bone area of the lumbar spine and femoral neck in a nationally representative population of middle aged to older U.S. adults. We further sought to investigate if relationships of the main flavonoid subgroups (i.e., anthocyanins, flavan-3-ols, flavanones, flavones, flavonols, and isoflavones) exist, as a secondary objective. METHODS: Cross-sectional data from individuals aged 50+ years enrolled in the 2017-2018 National Health and Nutrition Examination Survey (NHANES) were used in our analyses (N = 2590). Weighted multivariate logistic regression models were used to investigate the relationship between quartiles of flavonoid intake and BMD, BMC, and bone area of the lumbar spine and femoral neck of participants. RESULTS: Mean age of participants was 63.4 ± 0.52 years and 64.1 ± 0.52 years for men and women, respectively. Average total flavonoid intake was 217 ± 19.4 mg/day and 306 ± 26.9 mg/day for men and women, respectively. Total flavonoid intakes were not significantly associated with BMD, BMC, or bone area of the femoral neck or lumbar spine in male or female participants. Flavonoid subclass intakes were also not consistently associated with improved markers of bone health. CONCLUSION: Although several limitations exist, this cross-sectional analysis of U.S. adults aged 50+ years provides contradictory evidence to the hypothesis that higher flavonoid and flavonoid subclass intakes beneficially impacts markers of bone health. Large prospective cohort investigations that better capture long-term dietary flavonoid intake and ascertain fractures the primary outcome, as well as randomized controlled trials, are needed to fully elucidate the effects flavonoids on bone health.

Xenohormetic Phytochemicals Inhibit Neovascularization in Microphysiological Models of Vasculogenesis and Tumor Angiogenesis.

Xenohormesis proposes that phytochemicals produced to combat stressors in the host plant exert biochemical effects in animal cells lacking cognate receptors. Xenohormetic phytochemicals such as flavonoids and phytoalexins modulate a range of human cell signaling mechanisms but functional correlations with human pathophysiology are lacking. Here, potent inhibitory effects of grapefruit-derived Naringenin (Nar) and soybean-derived Glyceollins (Gly) in human microphysiological models of bulk tissue vasculogenesis and tumor angiogenesis are reported. Despite this interference of vascular morphogenesis, Nar and Gly are not cytotoxic to endothelial cells and do not prevent cell cycle entry. The anti-vasculogenic effects of Glyceollin are significantly more potent in sex-matched female (XX) models. Nar and Gly do not decrease viability or expression of proangiogenic genes in triple negative breast cancer (TNBC) cell spheroids, suggesting that inhibition of sprouting angiogenesis by Nar and Gly in a MPS model of the (TNBC) microenvironment are mediated via direct effects in endothelial cells. The study supports further research of Naringenin and Glyceollin as health-promoting agents with special attention to mechanisms of action in vascular endothelial cells and the role of biological sex, which can improve the understanding of dietary nutrition and the pharmacology of phytochemical preparations.

Comparative analysis of macro- and micro-nutrients of Perilla frutescens var. crispa f. viridis microgreens and germinated seeds.

This study aimed to conduct a comparative analysis of germinated seeds and microgreens derived from Perilla frutescens var. crispa f. viridis, hypothesizing that microgreens would exhibit higher concentrations of nutrients and bioactive compounds compared to their precursors. Perilla frutescens was chosen for its popularity and wide use in Asian cuisine. A series of analytical methods was employed to quantify and qualify various components. The findings indicate that germinated seeds exhibit significantly higher quantities of lipids, proteins, sugars, free amino acids, and minerals, whereas microgreens possess significantly high concentration of vitamins and polyphenols. These results provide valuable insights into the nutritional differences between germinated seeds and microgreens, highlighting their distinct contributions to diet. Specifically, incorporating germinated seeds can enhance macronutrient intake, while microgreens can boost antioxidant intake. These findings can inform the development of targeted dietary recommendations, promoting the inclusion of both germinated seeds and microgreens to meet specific nutritional needs and improve health outcomes.

Polyphenols as Therapeutics in Respiratory Diseases: Moving from Preclinical Evidence to Potential Clinical Applications.

Respiratory diseases are the most common and severe health complication and a leading cause of death worldwide. Despite breakthroughs in diagnosis and treatment, few safe and effective therapeutics have been reported. Phytochemicals are gaining popularity due to their beneficial effects and low toxicity. Polyphenols are secondary metabolites with high molecular weights found at high levels in natural food sources such as fruits, vegetables, grains, and citrus seeds. Over recent decades, polyphenols and their beneficial effects on human health have been the subject of intense research, with notable successes in preventing major chronic non-communicable diseases. Many respiratory syndromes can be treated effectively with polyphenolic supplements, including acute lung damage, pulmonary fibrosis, asthma, pulmonary hypertension, and lung cancer. This review summarizes the role of polyphenols in respiratory conditions with sufficient experimental data, highlights polyphenols with beneficial effects for each, and identifies those with therapeutic potential and their underlying mechanisms. Moreover, clinical studies and future research opportunities in this area are discussed.

Fabrication, characterization, and bioactivity of self-assembled carrier-free colloidal dispersions from Citrus × Limon 'Rosso' essential oil and tea polyphenols.

Carrier-free nanodelivery systems are fully self-assembled from active ingredients through interactions, offering the advantages of green, safe, and large-scale manufacturing. To improve the dispersion of Citrus × limon 'Rosso' peel essential oil (CEO) in water and boost the biological activity of CEO and tea polyphenols (TP), self-assembled CEO-TP colloidal dispersions (CEO-TP Colloids) were fabricated through sonication without surfactants or carriers. The optimal CEO and TP concentrations in the CEO-TP Colloids were determined to be 10.0 and 20.0 mg/mL by particle size and stability analyzer, respectively. The CEO self-assembled with TP to form spherical nanoparticles through hydrophobic and hydrogen-bonding interactions, whereas the CEO in CEO-TP Colloids weakened TP intramolecular aggregation. Meanwhile, the CEO-TP Colloids showed synergistic effects with better antibacterial, cellular antioxidant, and anti-inflammatory activities than single components. This study opens up the possibility of carrier-free co-delivery of hydrophobic and hydrophilic active components developed into food-grade formulations with multiple bioactivities.

Structures, biosynthesis and biological activities of benastatins, anthrabenzoxocinones and fredericamycins.

The fast spread of antibiotic resistance results in the requirement for a constant introduction of new candidates. Pentangular polyphenols, a growing family of actinomycetes-derived aromatic type II polyketides, have attracted considerable attention due to their intriguing polycyclic systems and potent antimicrobial activity. Among them, benastatins, anthrabenzoxocinones (ABXs), and fredericamycins, display unique variations in their polycyclic frameworks, yet concurrently share structural commonalities within their substitutions. The present review summarizes advances in the isolation, spectroscopic characteristics, biosynthesis, and biological activities of pentangular polyphenols benastatins (1-16), ABXs (17-39), and fredericamycins (40-42) from actinomycetes. The information presented here thus prompts researchers to further explore and discover additional congeners within these three small classes of pentangular polyphenols.

Luteolin for neurodegenerative diseases: a review.

Neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Huntington's disease, and multiple sclerosis affect millions of people around the world. In addition to age, which is a key factor contributing to the development of all neurodegenerative diseases, genetic and environmental components are also important risk factors. Current methods of treating neurodegenerative diseases are mostly symptomatic and do not eliminate the cause of the disease. Many studies focus on searching for natural substances with neuroprotective properties that could be used as an adjuvant therapy in the inhibition of the neurodegeneration process. These compounds include flavonoids, such as luteolin, showing significant anti-inflammatory, antioxidant, and neuroprotective activity. Increasing evidence suggests that luteolin may confer protection against neurodegeneration. In this review, we summarize the scientific reports from preclinical in vitro and in vivo studies regarding the beneficial effects of luteolin in neurodegenerative diseases. Luteolin was studied most extensively in various models of Alzheimer's disease but there are also several reports showing its neuroprotective effects in models of Parkinson's disease. Though very limited, studies on possible protective effects of luteolin against Huntington's disease and multiple sclerosis are also discussed here. Overall, although preclinical studies show the potential benefits of luteolin in neurodegenerative disorders, clinical evidence on its therapeutic efficacy is still deficient.

Polycommunin A, a dihydrocinnamoyl bibenzyl isolated from the moss Polýtrichum commúne, and its antioxidant activity.

A novel polyphenolic compound named Polycommunin A (1) was discovered in the aerial part of the common haircap moss (Polýtrichum commune) widely spread in boreal and temperate climate zones. Aqueous ethanol and extraction of the plant material with further isolation of polyphenolic fraction and preparative HPLC separation allowed obtaining individual compound and identifying it as dimeric dihydrocinnamoyl bibenzyl by NMR spectroscopy and high-resolution tandem mass spectrometry. Polycommunin A demonstrated high in vitro antioxidant activity determined by FRAP and PCL assays and comparable to that of Trolox and Quercetin.

Potential antiplatelet agents with grape seed - backbone polyphenols: computational studies.

The study focused on grape seed-derived polyphenols for their antiplatelet, anti-inflammatory, and fibrinolytic properties through molecular docking and dynamics simulations. Compounds were evaluated for their effects on P2Y12, PTP1B, thromboxane A2, and other targets. Compounds 1 and 6 showed strong inhibitory potential on P2Y12. Compounds 2 and 7, plus epigallocatechin gallate, demonstrated effective inhibition on NF-KB and COX1. The compounds exhibited drug-like properties and potential for new thrombotic disease therapies. The research sheds light on the interactions between polyphenols and target proteins, paving the way for novel antiplatelet strategies.

Interactions of different polyphenols with wheat germ albumin and globulin: Alterations in the conformation and emulsification properties of proteins.

In this study, chlorogenic acid (CA), piceatannol (PIC), epigallocatechin-3-gallate (EGCG) and ferulic acid (FA) was selected to explore the influence of polyphenol on the structural properties of wheat germ albumin (WGA) and wheat germ globulin (WGG). The emulsifying properties of the emulsions prepared by WGA-EGCG complex were also evaluated. The results indicated that all polyphenols could significantly enhance the antioxidant capacity of WGA and WGG. In particular, EGCG increased the ratio of random coil in WGA and WGG, resulting in protein unfolding and shifting from an order to disorder structure. In addition, lipid oxidation and protein oxidation of the soybean oil emulsion was significantly slowed down by WGA-EGCG. The stability of the emulsions under various environmental stress and the storage time was significantly improved by WGA-EGCG. These findings can provide a reference for expanding the application of wheat germ protein in food industry.

Solid-state cultivation of multiple industrial strains of koji mold on different Thai unpolished rice cultivars: biotransformation of phenolic compounds and their effects on antioxidant activity.

Colored rice is abundant in polyphenols, and koji molds have potential for biotransformation. This study aimed to produce Thai-colored rice koji to study its polyphenolic biotransformation. Four industrial koji mold strains: Aspergillus oryzae 6001, A. oryzae 6020, A. sojae 7009, and A. luchuensis 8035, were cultivated on unpolished Thai-colored rice (Riceberry and Sangyod), unpolished Thai white rice (RD43), and polished Japanese white rice (Koshihikari). We discovered that koji molds grew on all the rice varieties. Methanol extracts of all rice kojis exhibited an approximately 2-fold or greater increase in total phenolic content and DPPH antioxidant activity compared to those of steamed rice. Moreover, quercetin, quercetin-3-O-glucoside, isorhamnetin-3-O-glucoside, ferulic acid, caffeic acid, protocatechuic acid, vanillic acid, (+)-catechin, and (-)-epicatechin content increased in Riceberry and Sangyod koji samples. Consequently, Aspergillus solid-state cultivation on unpolished Thai-colored rice exhibited higher functionalization than the cultivation of unpolished Thai white rice and polished Japanese white rice.

Microbiome-based precision nutrition: Prebiotics, probiotics and postbiotics.

Microorganisms have been used in nutrition and medicine for thousands of years worldwide, long before humanity knew of their existence. It is now known that the gut microbiota plays a key role in regulating inflammatory, metabolic, immune and neurobiological processes. This text discusses the importance of microbiota-based precision nutrition in gut permeability, as well as the main advances and current limitations of traditional probiotics, new-generation probiotics, psychobiotic probiotics with an effect on emotional health, probiotic foods, prebiotics, and postbiotics such as short-chain fatty acids, neurotransmitters and vitamins. The aim is to provide a theoretical context built on current scientific evidence for the practical application of microbiota-based precision nutrition in specific health fields and in improving health, quality of life and physiological performance.

Rosemary (Rosmarinus officinalis L.) polyphenols and inflammatory bowel diseases: Major phytochemicals, functional properties, and health effects.

Major polyphenols in Rosmarinus officinalis L. primarily consist of phenolic acids, phenolic diterpenes, and flavonoids, all of which have pharmacological properties including anti-inflammatory and antibacterial characteristics. Numerous in vitro and animal studies have found that rosemary polyphenols have the potential to decrease the severity of intestinal inflammation. The beneficial effects of rosemary polyphenols were associated with anti-inflammatory properties, including improved gut barrier (increased mucus secretion and tight junction), increased antioxidant enzymes, inhibiting inflammatory pathways and cytokines (downregulation of NF-κB, NLRP3 inflammasomes, STAT3 and activation of Nrf2), and modulating gut microbiota community (increased core probiotics and SCFA-producing bacteria, and decreased potential pathogens) and metabolism (changes in SCFA and bile acid metabolites). This paper provides a better understanding of the anti-inflammatory properties of rosemary polyphenols and suggests that rosemary polyphenols might be employed as strong anti-inflammatory agents to prevent intestinal inflammation and lower the risk of inflammatory bowel disease and related diseases.

Structural, physicochemical, and digestive properties of enzymatic debranched rice starch modified by phenolic compounds with varying structures.

The physicochemical properties of starch and phenolic acid (PA) complexes largely depend on the effect of non-covalent interactions on the microstructure of starch. However, whether there are differences and commonalities in the interactions between various types of PAs and starch remains unclear. The physicochemical properties and digestive characteristics of the complexes were investigated by pre-gelatinization of 16 structurally different PAs and pullulanase-modified rice starches screened. FT-IR and XRD results revealed that PA complexed with debranched rice starch (DRS) through hydrogen bonding and hydrophobic interaction. Benzoic/phenylacetic acid with polyhydroxy groups could enter the helical cavities of the starch chains to promote the formation of V-shaped crystals, and cinnamic acid with p-hydroxyl structure acted between starch chains in a bridging manner, both of which increased the relative crystallinity of DRS, with DRS-ellagic acid increasing to 20.03 %. The digestion and hydrolysis results indicated that the acidification and methoxylation of PA synergistically decreased the enzyme activity leading to a decrease in the digestibility of the complexes, and the resistant starch content of the DRS-vanillic acid complexes increased from 28.27 % to 71.67 %. Therefore, the selection of structurally appropriate PAs can be used for the targeted preparation of starch-based foods and materials.

Method development with high-throughput enhanced matrix removal followed by UHPLC-QqQ-MS/MS for analysis of grape polyphenol metabolites in human urine.

Grape and grape derived products contain many bioactive phenolics which have a variety of impacts on health. Following oral ingestion, the phenolic compounds and their metabolites may be detectable in human urine. However, developing a reliable method for the analysis of phenolic compounds in urine is challenging. In this work, we developed and validated a new high-throughput, sensitive and reproducible analytical method for the simultaneous analysis of 31 grape phenolic compounds and metabolites using Oasis PRiME HLB cleanup for sample preparation combined with ultra-performance liquid chromatography with triple quadrupole tandem mass spectrometry (UHPLC-QqQ-MS/MS). Using this new method, the accuracy achieved was 69.3 % ∼ 134.9 % (except for six compounds), and the recovery achieved was 52.4 % ∼ 134.7 % (except for two very polar compounds). For each of the 31 target analytes, the value of intra-day precision was less than 14.3 %. The value of inter-day precision was slightly higher than intra-day precision, with a range of 0.7 % ∼ 19.1 %. We report for the first time on the effect of gender and BMI on the accuracy and recovery of human urine samples, and results from analysis of variance (ANOVA), and principal component analysis (PCA) indicated there was no difference in the value of accuracy and recovery between different gender or BMI (>30) using our purposed cleanup and UHPLC-QqQ-MS/MS method. Overall, this newly developed method could serve as a powerful tool for analyzing grape phenolic compounds and metabolites in human urine samples.

Brown algal bioactive molecules: a new frontier in oral cancer treatment.

Researchers are exploring brown algae as a source of potential treatments for Oral Squamous Cell Carcinoma (OSCC), a prevalent and aggressive form of oral cancer. Brown algae are rich in bioactive compounds, including polyphenols, carotenoids, fatty acids, and polysaccharides, which show promise in inhibiting cancer cell growth and inducing apoptosis. These compounds work through various mechanisms such as cell cycle arrest, apoptotic cell death, and inhibition of angiogenesis. Fucoxanthin and fucoidan, found in brown algae, have shown significant anti-OSCC properties by targeting specific pathways involved in cancer progression. Additionally, celecoxibloaded chitosan-fucoidan nanoparticles demonstrate potential in multiple pathways for OSCC treatment. Challenges in translating these findings into clinical applications include the need for further preclinical studies, efficient extraction methods, and clinical trials for safety and efficacy assessment. Despite challenges, brown algal compounds offer a promising avenue for developing novel and effective OSCC therapies, drawing from the ancient wisdom of the sea.

Microencapsulation of highly concentrated polyphenolic compounds from purple corn pericarp by spray-drying with various biomacromolecules.

Colored corn pericarp contains unusually high amounts of industrially valuable phytochemicals, such as anthocyanins, flavanols, flavonoids, and phenolic acids. Polyphenols were extracted in an aqueous solution and spray-dried to produce microencapsulates using four carrier materials, namely, maltodextrin (MD), gum arabic (GA), methylcellulose (MC), and skim milk powder (SMP) at three concentrations (1, 2, and 3 %, respectively). The encapsulates were evaluated for their polyphenolic contents using spectrophotometric techniques and HPLC analyses, and their antioxidant properties were evaluated using four different assays. The physicochemical properties of encapsulates were analyzed by measuring the zeta potential (ZP), particle size distribution, water solubility index (WSI), water absorption index (WAI), and color parameters. Structural and thermal properties were evaluated using Fourier transform infrared spectroscopy (FTIR), optical profilometry, and differential scanning calorimetry (DSC) analyses. Comparative analysis of structural characteristics, particle size distribution, zeta potential, WSI, WAI, and aw of the samples confirmed the successful formulation of encapsulates. The microencapsulates embedded with 1 % concentrations of MD, MC, GA, or SMP retained polyphenolic compounds and exhibited noteworthy antioxidant properties. The samples encapsulated with GA or MD (1 %) demonstrated superior physicochemical, color, and thermal properties. Comprehensive metabolomic analysis confirmed the presence of 38 phytochemicals in extracts validating the spray-drying process.

Investigating the chemo-preventive role of noscapine in lung carcinoma via therapeutic targeting of human aurora kinase B.

Lung carcinoma is the major contributor to global cancer incidence and one of the leading causes of cancer-related mortality worldwide. Irregularities in signal transduction events, genetic alterations, and mutated regulatory genes trigger cancer development and progression. Selective targeting of molecular modulators has substantially revolutionized cancer treatment strategies with improvised efficacy. The aurora kinase B (AURKB) is a critical component of the chromosomal passenger complex and is primarily involved in lung cancer pathogenesis. Since AURKB is an important therapeutic target, the design and development of its potential inhibitors are attractive strategies. In this study, noscapine was selected and validated as a possible inhibitor of AURKB using integrated computational, spectroscopic, and cell-based assays. Molecular docking analysis showed noscapine occupies the substrate-binding pocket of AURKB with strong binding affinity. Subsequently, MD simulation studies confirmed the formation of a stable AURKB-noscapine complex with non-significant alteration in various trajectories, including RMSD, RMSF, Rg, and SASA. These findings were further experimentally validated through fluorescence binding studies. In addition, dose-dependent noscapine treatment significantly attenuated recombinant AURKB activity with an IC50 value of 26.6 µM. Cell viability studies conducted on A549 cells and HEK293 cells revealed significant cytotoxic features of noscapine on A549 cells. Furthermore, Annexin-PI staining validated that noscapine triggered apoptosis in lung cancer cells, possibly via an intrinsic pathway. Our findings indicate that noscapine-based AURKB inhibition can be implicated as a potential therapeutic strategy in lung cancer treatment and can also provide a novel scaffold for developing next-generation AURKB-specific inhibitors.

Study of the effects of pasteurization and selected microbial starters on functional traits of fermented table olives.

Table olives are one of the most known fruit consumed as fermented food, being a fundamental component of the Mediterranean diet. Their production and consumption continue to increase globally and represent an important economic source for the producing countries. One of the most stimulating challenges for the future is the modernization of olive fermentation process. Besides the demand for more reproducible and safer production methods that could be able to reduce product losses and potential risks, producers and consumers are increasingly attracted by the final product characteristics and properties on human health. In this study, the contribution of microbial starters to table olives was fully described in terms of specific enzymatic and microbiological profiles, nutrient components, fermentation-derived compounds, and content of bioactive compounds. The use of microbial starters from different sources was tested considering their technological features and potential ability to improve the functional traits of fermented black table olives. For each fermentation assay, the effects of controlled temperature (kept at 20 °C constantly) versus not controlled environmental conditions (oscillating between 7 and 17 °C), as well as the consequences of the pasteurization treatment were tested on the final products. Starter-driven fermentation strategies seemed to increase both total phenolic content and total antioxidant activity. Herein, among all the tested microbial starters, we provide data indicating that two bacterial strains (Leuconostoc mesenteroides KT 5-1 and Lactiplantibacillus plantarum BC T3-35), and two yeast strains (Saccharomyces cerevisiae 10A and Debaryomyces hansenii A15-44) were the better ones related to enzyme activities, total phenolic content and antioxidant activity. We also demonstrated that the fermentation of black table olives under not controlled environmental temperature conditions was more promising than the controlled level of 20 °C constantly in terms of technological and functional properties considered in this study. Moreover, we confirmed that the pasteurization process had a role in enhancing the levels of antioxidant compounds.

Selenium-Mediated (-)-Epigallocatechin-3-Gallate Dynamics via Flavanone-3-Hydroxylase Regulation of Flavonoid Biosynthesis in Fu Tea (Camellia sinensis (L.) O. Kuntze).

Tea (Camellia sinensis (L.) O. Kuntze) is a highly selenium enrichment capacity plant; high selenium concentration contributes to the occurrence of oxidative stress and protein misfolding in tea plants, whereas flavonoids can chelate heavy metals to protect plants from oxidative stress caused by metal exposure. Nevertheless, the role of catechins in flavonoid synthesis and nutrient metabolism under selenium stress remains unidentified. Combining Word2vec and HNSW utilizing UHPLC-Q-Orbitrap HRMS-MS/MS to implement rapid matching annotation of the structural information on metabolites in Fu tea, we found that selenium-mediated changes in catechins in Fu tea were mainly associated with flavonoid biosynthesis pathways. The results demonstrated that selenium treatment increased benign selenol analogues (glutathioselenol) in tea and identified the novel selenopeptide PRSeMW (m/z 636.22571, Pro-Arg-SeMet-Trp) in selenium-enriched Fu tea samples to enhance the health benefits of tea. The selenium levels were negatively correlated with N5-ethyl-l-glutamine (11.63 to 4.26 mg kg-1) and (-)-epigallocatechin (13.26 to 11.19 mg kg-1), increasing the accumulation of tea polyphenols ((-)-catechin gallate, (-)-epigallocatechin 3-gallate, and (+)-gallocatechin), and decreasing the level of caffeine. These discoveries provide new insights into the mechanism of tea polyphenol-mediated transformation of selenium in Fu tea and theoretical support for the quality assessment of selenium-enriched tea.