Recent advances in dietary androgen receptor inhibitors.

As a nuclear transcription factor, the androgen receptor (AR) plays a crucial role not only in normal male sexual differentiation and growth of the prostate, but also in benign prostatic hyperplasia, prostatitis, and prostate cancer. Multiple population-based epidemiological studies demonstrated that prostate cancer risk was inversely associated with increased dietary intakes of green tea, soy products, tomato, and so forth. Therefore, this review aimed to summarize the structure and function of AR, and further illustrate the structural basis for antagonistic mechanisms of the currently clinically available antiandrogens. Due to the limitations of these antiandrogens, a series of natural AR inhibitors have been identified from edible plants such as fruits and vegetables, as well as folk medicines, health foods, and nutritional supplements. Hence, this review mainly focused on recent experimental, epidemiological, and clinical studies about natural AR inhibitors, particularly the association between dietary intake of natural antiandrogens and reduced risk of prostatic diseases. Since natural products offer multiple advantages over synthetic antiandrogens, this review may provide a comprehensive and updated overview of dietary-derived AR inhibitors, as well as their potential for the nutritional intervention against prostatic disorders.

Effects of Protein on Green Tea Quality in a Milk-Tea Model during Heat Treatment: Antioxidant Activity, Foaming Properties, and Unbound Small-molecule Metabolome.

Tea drinks/beverage has a long history and milk is often added to enhance its taste and nutritional value, whereas the interaction between the tea bioactive compounds with proteins has not been systematically investigated. In this study, a milk-tea model was prepared by mixing green tea solution with milk and then heated at 100°C for 15 min. The milk tea was then measured using biochemical assay, antioxidant detection kit, microscopy as well as HPLC-QTOF-MS/MS after ultrafiltration. The study found that as the concentration of milk protein increased in the milk-tea system, the total phenol-protein binding rate raised from 19.63% to 51.08%, which led to a decrease in free polyphenol content. This decrease of polyphenol was also revealed in the antioxidant capacity, including 2,2-diphenyl-1-picrylhydrazyl radical scavenging ability and ferric ion reducing antioxidant power, in a dose-dependent manner. Untargeted metabolomics results revealed that the majority of small-molecule compounds/polyphenols in tea, such as epigallocatechin gallate, (-)-epicatechin gallate, and Catechin 5,7,-di-O-gallate, bound to milk proteins and were removed by ultrafiltration after addition of milk and heat treatment. The SDS-PAGE and Native-PAGE results further indicated that small molecule compounds in tea formed covalent and non-covalent complexes by binding to milk proteins. All above results partially explained that milk proteins form conjugates with tea small-molecule compounds. Consistently, the particle size of the tea-milk system increased as the tea concentration increased, but the polymer dispersity index decreased, indicating a more uniform molecular weight distribution of the particles in the system. Addition of milk protein enhanced foam ability in the milk-tea system but reduced foam stability. In summary, our findings suggest that the proportion of milk added to tea infusion needs to be considered to maintain the quality of milk-tea from multiple perspectives, including stability, nutritional quality and antioxidant activity.

Target-based screening for natural products against Staphylococcus aureus biofilms.

As a notorious food-borne pathogen, Staphylococcus aureus can readily cause diseases in humans via contaminated food. Biofilm formation on various surfaces can increase the capacity of viable S. aureus cells for self-protection due to the stubborn structure of the biofilm matrix. Increased disease risk and economic losses caused by biofilm contamination in the food industry necessitate the urgent development of effective strategies for the inhibition and removal of S. aureus biofilms. Natural products have been extensively used as important sources of "eco-friendly" antibiofilm agents to avoid the side effects of conventional strategies on human health and the environment. This review discusses biofilm formation of S. aureus in food industries and focuses on providing an overview of potential promising target-oriented natural products and their mechanisms of S. aureus biofilm inhibition or removal. Hoping to provide valuable information of attractive research targets or potential undeveloped targets to screen potent natural anti-biofilm agents in food industries.

Dietary phytochemicals as modulators of human pregnane X receptor.

As a promiscuous xenobiotic sensor, pregnane X receptor (PXR) plays a crucial role in drug metabolism. Since dietary phytochemicals exhibit the potential to modulate human PXR, this review aims to summarize the plant-derived PXR modulators, including agonists, partial agonists, and antagonists. The crystal structures of the apo and ligand-bound forms of PXR especially that of PXR complexed with binary mixtures are summarized, in order to provide the structural basis for PXR binding promiscuity and synergistic activation of PXR by composite ligands. Furthermore, this review summarizes the characterized agonists, partial agonists, and antagonists of human PXR from botanical source. Contrary to PXR agonists, there are only a few antagonists obtained from botanical source due to the promiscuity of PXR. It is worth noting that trans-resveratrol and a series of methylindoles have been identified as partial agonists of PXR, both in activating PXR function, but also inhibiting the effect of other PXR agonists. Since antagonizing PXR function plays a crucial role in the prevention of drug-drug interactions and improvement of therapeutic efficacy, further research is necessary to screen more plant-derived PXR antagonists in the future. In summary, this review may contribute to understanding the roles of phytochemicals in food-drug and herb-drug interactions.

Anti-biofilm activity of biochanin A against Staphylococcus aureus.

Biofilm-forming Staphylococcus aureus can easily accumulate on various food contact surfaces which induce cross-contamination and are difficult to eliminate in the food industry. This study aimed to evaluate the anti-biofilm effects of natural product biochanin A against S. aureus. Results showed that biochanin A effectively eradicated established S. aureus biofilms on different food-contact materials. Fluorescence microscopic analyses suggested that biochanin A disintegrated the established biofilms by dissociate extracellular polymeric substance (EPS) in matrix. In addition, biochanin A at the sub-MIC concentration also effectively inhibited the biofilm formation by regulating the expression of biofilm-related genes (icaA, srtA, eno) and suppressing the release of EPS in biofilm matrix. Molecular docking also demonstrated that biochanin A conducted strong interactions with biofilm-related proteins (Ica A, Sortase A, and Enolase). These findings demonstrated that biochanin A has the potential to be developed as a potent agent against S. aureus biofilm in food industries. KEY POINTS: • Anti-biofilm effect of biochanin A against S. aureus was revealed for the first time. • Biofilm of S. aureus on various food-contact surfaces were efficiently eradicated. • Biochanin A prevented S. aureus biofilm formation via reducing EPS production.

Selenium nanoparticles: Enhanced nutrition and beyond.

Selenium is a trace nutrient that has both nutritional and nutraceutical functions, whereas narrow nutritional range of selenium intake limits its use. Selenium nanoparticles (SeNPs) are less toxic and more bioavailable than traditional forms of selenium, suggesting that SeNPs have the potential to replace traditional selenium in food industries and/or biomedical fields. From the perspective of how SeNPs can be applied in health area, this review comprehensively discusses SeNPs in terms of its preparation, nutritional aspect, detoxification effect of heavy metals, nutraceutical functions and anti-pathogenic microorganism effects. By physical, chemical, or biological methods, inorganic selenium can be transformed into SeNPs which have increased stability and bioavailability as well as low toxicity. SeNPs are more effective than traditional selenium form in synthesizing selenoproteins like glutathione peroxidases. SeNPs can reshape the digestive system to facilitate digestion and absorption of nutrients. SeNPs have shown excellent potential to adjunctively treat cancer patients, enhance immune system, control diabetes, and prevent rheumatoid arthritis. Additionally, SeNPs have good microbial anti-pathogenic effects and can be used with other antimicrobial agents to fight against pathogenic bacteria, fungi, or viruses. Development of novel SeNPs with enhanced functions can greatly benefit the food-, nutraceutical-, and biomedical industries.

Formation and characterization of noncovalent ternary complexes based on whey protein concentrate, high methoxyl pectin, and phenolic acid.

Protein-polysaccharide-polyphenol noncovalent ternary complexes possess unique physicochemical, structural, and functional properties. In the present study, ternary complexes based on whey protein concentrate (WPC; 2%, wt/vol) and high methoxyl pectin (HMP; 0.5%, wt/vol) complexes and 0.2 to 0.6% (wt/vol) chlorogenic acid (CA) or rosmarinic acid (RA) were formed and characterized at 3 pH values (4, 4.5, and 5). The pH conditions were decided according to phase diagram of WPC and HMP during acidification. Fluorescence quenching experiments indicated that WPC-HMP complexes bound RA stronger than CA and the binding constant increased with increasing pH for both phenolic acids. Particle size of ternary complexes decreased and absolute ζ-potential increased with pH values changing from 4 to 5, and RA influenced the particle size of WPC-HMP complexes greater than CA. The CA and RA in ternary complexes showed good stability against UV light with pH order of pH 5 > pH 4.5 > pH 4. Fourier-transform infrared spectroscopy spectra indicated the involvement of hydrogen bonding between WPC-HMP and CA or RA. Antibacterial tests showed that ternary complexes had good antibacterial activity against Staphylococcus aureus and Escherichia coli at concentrations of 6.2 mg/mL and the ability increased with decreasing pH values. All ternary complexes possessed strong scavenging radical capacities with median inhibitory concentration (IC50) values ranging from 2.71 ± 0.05 to 6.20 ± 0.41 µg/mL. Antioxidative ability of ternary complexes increased as pH went up and WPC-HMP-RA showed significantly higher antioxidative property compared with WPC-HMP-CA. Data may provide useful information for rational design of ternary complexes and applications of the formed complexes in food matrices such as beverages and emulsions.

Influence of ultrasound and enzymatic cross-linking on freeze-thaw stability and release properties of whey protein isolate hydrogel.

This study investigated the effect of ultrasound and enzymatic cross-linking on the freeze-thaw (FT) stability and release properties of whey protein isolate hydrogels. We evaluated the FT stability by the changes in the microstructure, riboflavin retention, syneresis, water holding capacity (WHC), and texture of gels subjected to 3 FT cycles. High-intensity ultrasound (HUS) and transglutaminase (TGase)-mediated cross-linking improved the FT stability of whey protein isolate hydrogels loaded with riboflavin (WPISAR), as demonstrated by a more uniform and denser porous structure, significantly higher riboflavin retention, WHC, and textural properties, and lower syneresis after 3 FT cycles than those of untreated hydrogels. Furthermore, HUS- and TGase-mediated cross-linking decreased protein erosion and swelling ratio of WPISAR in simulated gastrointestinal fluids (SGIF) and reduced the riboflavin release rate in SGIF both with and without the addition of digestive enzymes. After 3 FT cycles, faster riboflavin release occurred due to a more porous structure induced by ice crystal formation compared with their unfrozen counterparts as detected by confocal laser scanning microscopy. High-intensity ultrasound- and TGase-mediated cross-linking alleviated the FT-induced faster riboflavin release rate in SGIF. High-intensity ultrasound- and TGase-treated gel samples showed that both diffusion and network erosion were responsible for riboflavin release regardless of FT. These results suggest that HUS- and TGase-mediated cross-linking improved the FT stability of WPISAR with a high riboflavin retention, and might be a good candidate as a controlled-release vehicle for riboflavin delivery to overcome undesired FT processing.

Natural tyrosine kinase inhibitors acting on the epidermal growth factor receptor: Their relevance for cancer therapy.

Epidermal growth factor receptor (EGFR), also known as ErbB-1/HER-1, plays a key role in the regulation of the cell proliferation, migration, differentiation, and survival. Since the constitutive activation or overexpression of EGFR is nearly found in various cancers, the applications focused on EGFR are the most widely used in the clinical level, including the therapeutic drugs of targeting EGFR, monoclonal antibodies (mAbs) and tyrosine kinase inhibitors (TKIs).Over the past decades, the compounds from natural sources have been a productive source of novel drugs, especially in both discovery and development of anti-tumor drugs by targeting the EGFR pathways as the TKIs. This work presents a review of the compounds from natural sources as potential EGFR-TKIs involved in the regulation of cancer. Moreover, high-throughput drug screening of EGFR-TKIs from the natural compounds has also been summarized.

Natural and synthetic compounds as dissociated agonists of glucocorticoid receptor.

Glucocorticoid receptor (GR) belongs to the superfamily of steroid hormone receptors. The dissociated or selective GR modulators (SEGRMs), preferring the transrepression rather than the transactivation, might exhibit anti-inflammatory activities with fewer side effects. This work presents a review of the molecular mechanism of GR involved in regulation of inflammation. As complementary or alternative therapeutic agents, the botanical compounds have been extensively used in the treatment of various diseases. Hence, this work reviews the botanical compounds as well as the synthetic compounds currently known to be potential SEGRMs. High-throughput virtual screening of SEGRMs from natural products has also been summarized.

Saponins as modulators of nuclear receptors.

As plant-derived natural products, saponins have been widely applied for the dietary modification of metabolic syndrome. However, the underlying mechanisms of their preventive and therapeutic effects are still largely unclear. Nuclear receptors have been identified as potential pharmaceutical targets for treating various types of metabolic disorders. With similar structure to endogenous hormones, several saponins may serve as selective ligands for nuclear receptors. Recently, a series of saponins are proved to exert their physiological activities through binding to nuclear receptors. This review summarizes the biological and pharmacological activities of typical saponins mediated by some of the most well described nuclear receptors, including the classical steroid hormone receptors (ER, GR, MR, and AR) and the adopted orphan receptors (PPAR, LXR, FXR, and PXR).

Facile detection of melamine by a FAM-aptamer-G-quadruplex construct.

The development of a novel method for melamine detection that uses a FAM-aptamer-G-quadruplex construct due to the efficient quenching ability of an aptamer-linked G-quadruplex is reported herein. The construct, which is labeled with the fluorescent dye 6-carboxyfluorescein (FAM), consists of two parts: a melamine-binding aptamer and a G-rich sequence that can form a G-quadruplex structure. Because of the specific recognition of melamine by the T-rich aptamer, this aptamer folds into a hairpin structure in the presence of melamine, which draws the G-quadruplex closer to the FAM fluorophore, leading to the quenching of the fluorescence of FAM. Thus, a highly sensitive and selective fluorescence strategy for assaying melamine was established. Under optimal conditions, the fluorescence quenching is proportional to the concentration of melamine within the range 10-90 nM, and the method has a detection limit of 6.32 nM. Further application of the method to plastic cup samples suggested that it permitted recoveries of between 97.15% ± 1.02 and 101.92% ± 2.07. The detected amounts of melamine spiked into the plastic cup samples and the corresponding amounts measured by HPLC were in good accordance, indicating that this fluorescent method is reliable and practical. Owing to its high sensitivity, excellent selectivity, and convenient procedure, this strategy represents a promising alternative method of melamine screening. Graphical abstract.

Estrogenicity of halogenated bisphenol A: in vitro and in silico investigations.

The binding interactions of bisphenol A (BPA) and its halogenated derivatives (halogenated BPAs) to human estrogen receptor α ligand binding domain (hERα-LBD) was investigated using a combined in vitro and in silico approach. First, the recombinant hERα-LBD was prepared as a soluble protein in Escherichia coli BL21(DE3)pLysS. A native fluorescent phytoestrogen, coumestrol, was employed as tracer for the fluorescence polarization assay. The results of the in vitro binding assay showed that bisphenol compounds could bind to hERα-LBD as the affinity ligands. All the tested halogenated BPAs exhibited weaker receptor binding than BPA, which might be explained by the steric effect of substituents. Molecular docking studies elucidated that the halogenated BPAs adopted different conformations in the flexible hydrophobic ligand binding pocket (LBP), which is mainly dependent on their distinct halogenation patterns. The compounds with halogen substituents on the phenolic rings and on the bridging alkyl moiety acted as agonists and antagonists for hERα, respectively. Interestingly, all the compounds in the agonist conformation of hERα formed a hydrogen bond with His524, while the compounds in the antagonist conformation formed a hydrogen bond with Thr347. These docking results suggested a pivotal role of His524/Thr347 in maintaining the hERα structure in the biologically active agonist/antagonist conformation. Comparison of the calculated binding energies vs. experimental binding affinities yielded a good correlation, which might be applicable for the structure-based design of novel bisphenol compounds with reduced toxicities and for environmental risk assessment. In addition, based on hERα-LBD as a recognition element, the proposed fluorescence polarization assay may offer an alternative to chromatographic techniques for the multi-residue determination of bisphenol compounds.

The Prebiotic Activity of Simulated Gastric and Intestinal Digesta of Polysaccharides from the Hericium erinaceus.

Hericium erinaceus (HE) is a well-known edible and medicinal fungus widely grown in Asian countries. Polysaccharides from the Hericium erinaceus (HEP) are major biological macromolecules. It has been reported that HEP has multiple biological activities, such as antioxidant activity, immunomodulatory effects, anti-inflammatory effect, anti-chronic gastritis activity, and so on. In the current study, we investigated the biological property of HEP during gastrointestinal digestion. The results indicated that both simulated gastric and small intestinal digesta of HEP has better stimulation of probiotics growth than HEP alone, especially for Lactobacillus plantarum BG112. The prebiotic activity was the strongest when HEP was treated by simulated gastric juice for 2 h and by simulated small intestinal juice for 4 h. The molecular weight (Mw) of HEP decreased from 1.68 × 106 Da and 2.32 × 104 Da to 529.3 ± 7.2 Da, as digestion time increased. Meanwhile, the reducing sugar content was significantly increased from 0.610 ± 0.007 to 22.698 ± 0.752 mg/ml, suggesting that the decrease of Mw was likely due to the breakdown of glycosidic bonds. Considerable mannose and galactopyranose were released throughout the gastrointestinal digestion period, indicating that the gastrointestinal digestion resulted in production of free monosaccharides. After fermentation of L. plantarum BG112, the Mw of HEP was decreased and short chain fatty acids (SCFAs) including acetic acid, isovaleric acid, lactic acid, and butyric acid were produced. We speculated that the release of free monosaccharides during gastrointestinal digestion and utilization of HEP, by the probiotics, contributed to the prebiotic activity of HEP's gastric and intestinal digesta. These results unveiled some mechanisms on the close relationship between the structure and bioactivity of polysaccharides, during digestion.

In vitro and in silico assessment of the structure-dependent binding of bisphenol analogues to glucocorticoid receptor.

Widespread use of bisphenol A (BPA) and other bisphenol analogues has attracted increasing attention for their potential adverse effects. As environmental endocrine-disrupting compounds (EDCs), bisphenols (BPs) may activate a variety of nuclear receptors, including glucocorticoid receptor (GR). In this work, the binding of 11 BPs to GR was investigated by fluorescence polarization (FP) assay in combination with molecular dynamics simulations. The human glucocorticoid receptor was prepared as a soluble recombinant protein. A fluorescein-labeled dexamethasone derivative (Dex-fl) was employed as tracer. Competitive displacement of Dex-fl from GR by BPs showed that the binding affinities of bisphenol analogues were largely dependent on their characteristic functional groups. In order to further understand the relationship between BPs structures and their GR-mediated activities, molecular docking was utilized to explore the binding modes at the atomic level. The results confirmed that structural variations of bisphenol analogues contributed to different interactions of BPs with GR, potentially causing distinct toxic effects. Comparison of the calculated binding energies vs. experimental binding affinities yielded a good correlation (R 2 = 0.8266), which might be helpful for the design of environmentally benign materials with reduced toxicities. In addition, the established FP assay based on GR exhibited the potential to offer an alternative to traditional methods for the detection of bisphenols.

Microencapsulation of Lactobacillus acidophilus NCFM using polymerized whey proteins as wall material.

Survivability of probiotics in foods is essential for developing functional food containing probiotics. We investigated polymerized whey protein (PWP)-based microencapsulation process which is developed for protecting probiotics like Lactobacillus acidophilus NCFM and compared with the method using sodium alginate (SA). The entrapment rate was 89.3 ± 4.8% using PWP, while it was 73.2 ± 1.4% for SA. The microencapsulated NCFM by PWP and SA were separately subjected to digestion juices and post-fermentation storage of fermented cows' and goats' milk using the encapsulated culture. The log viable count of NCFM in PWP-based microencapsulation was 4.56, compared with that of 4.26 in SA-based ones and 3.13 for free culture. Compared with using SA as wall material, PWP was more effective in protecting probiotic. Microencapsulation of L. acidophilus NCFM using PWP as wall material can be exploited in the development of fermented dairy products with better survivability of probiotic organism.

Effect of Ganoderma lucidum water extract on flavor volatiles and quality characteristics of set-type yogurt.

This study investigated the effects of several concentrations of Ganoderma lucidum water extract (GLWE) (0, 0.5, 1.0, and 1.5 %) on set-type yogurt's flavor volatiles as well as the physicochemical, textural, and antioxidant activities of the yogurt during storage. The HS-SPME-GC-MS investigation found that adding GLWE increased the amount of flavor volatiles in yogurt, which improved the quality of flavor volatiles produced by the yogurt. The yogurt's water holding capacity, syneresis, color, and texture all showed optimum values at a 0.5 % GLWE concentration, and its total number of flavor volatiles reached 43. To sum up, the incorporation of GLWE at a 0.5 % concentration promotes the development of superior flavor volatiles in yogurt and enhances its qualitative attributes in contrast to the control group.

Physicochemical and digestive properties of corn starch nanoparticles incorporated different polyphenols.

The corn starch nanoparticles were prepared by incorporating three kinds of polyphenols, including quercetin, proanthocyanidins and tannin acid. The physicochemical and digestive properties of corn starch nanoparticles were researched. The quercetin showed a higher complexation index than proanthocyanidins and tannin acid when they complexed with corn starch. The mean size of corn starch quercetin, proanthocyanidins and tannin acid were 168.5 nm, 179.1 nm and 188.6 nm, respectively. XRD results indicated that all the corn starch-polyphenols complex showed V-type crystalline structure, the crystallinity of corn starch-quercetin complex was 19.31 %, which showed more formation of amylose-quercetin single helical formed than the other two starch-polyphenol complexes. In vitro digestion revealed that polyphenols could resist digestion and quercetin increased the content of resistant starch from 23.32 % to 35.24 % and polyphenols can form complexes with starch through hydrophobic interactions or hydrogen bonding. This study indicated the hydrophobic polyphenols had a more significant effect on the digestibility of corn starch. And the cell toxicity assessments demonstrated that all nanoparticles were nontoxic and biocompatible.

Hydroxyl group-induced enhancement of antioxidant activity of resveratrol over pterostilbene by binding to lactoferrin.

The reduced antioxidant capacity of trans-resveratrol (Res) than the second generation of Res, namely pterostilbene (Pte), severely prohibits its in-depth intriguing radical-scavenging applications in food formulations. Herein, a unique chemical structure-dependent strategy was proposed to specifically enhance the radical scavenging activity of Res over Pte, relying on the two more hydroxyl groups on the A-benzene ring of Res, thus facilitating its binding with lactoferrin (LF) to form stable complexes through more hydrogen bonds. We prepared LF-Res and LF-Pte complexes, revealed their binding mechanisms by multispectral analysis and molecular docking/dynamics simulations, further evaluated their antioxidant properties via ABTS and DPPH assays and a model of inhibiting apple browning, eventually elucidated their structure-binding-property relationships. This contribution offers a new approach to restore the antioxidant capability of Res, also paves the way to precisely regulate the fascinating bioactivities of hydrophobic compounds by protein-binding in a chemical structure-, especially hydroxyl group-dependent manner.

Comparison of interactions between alpha-lactalbumin and three protopanaxadiol ginsenosides: Impacts on the structure and antitumor properties.

In this research, interactions between α-lactalbumin (ALA) and three protopanaxadiol ginsenosides [20(S)-Rg3, 20(S)-Rh2, and 20(S)-PPD] were compared to explore the effects of similar ligand on structure and cytotoxicity of ALA. Multi-spectroscopy revealed the binding between ALA and ginsenoside changed the conformation of ALA, which related to different structures and solubility of ligands. Scanning electron microscope illustrated that all ALA-ginsenoside complexes exhibited denser structures via hydrophobic interactions. Additionally, the cytotoxic experiments confirmed that the cytotoxicity of ginsenoside was enhanced after binding with ALA. Molecular docking showed all three ginsenosides were bound to the sulcus depression region of ALA via hydrogen bonding and hydrophobic interaction. Furthermore, molecular dynamics simulation elucidated the precise binding sites and pertinent system properties. Among all three composite systems, 20(S)-Rh2 had optimal binding affinity. These findings enhanced understanding of the synergistic utilization of ALA and ginsenosides as functional ingredients in food, medicine, and cosmetics.