Flavonol Glycosides Research Articles

Shining insights: Deciphering the biogenic synthesis of Ajuga bracteosa-mediated gold nanoparticles with advanced microscopy techniques.

In this study, gold nanoparticles (AuNPs) were bioreduced from Ajuga bracteosa, a medicinal herb known for its therapeutic properties against various diseases. Different fractions of the plant extract were used, including the methanolic fraction (ABMF), the n-hexane fraction (ABHF), the chloroform fraction (ABCF), and the aqueous extract for AuNPs synthesis. The characterization of AuNPs was performed using UV-Vis spectrophotometry, FT-IR, XRD, EDX, and TEM. UV-Vis spectroscopy confirmed the formation of AuNPs, with peaks observed at 555 nm. FT-IR analysis indicated strong capping of phytochemicals on the surface of AuNPs, which was supported by higher total phenolic contents (TPC) and total flavonoid contents (TFC) in AuNPs. XRD results showed high crystallinity and a smaller size distribution of AuNPs. TEM analysis revealed the spherical shape of AuNPs, with an average size of 29 ± 10 nm. The biologically synthesized AuNPs exhibited superior antibacterial, antioxidant, and cytotoxic activities compared to the plant extract fractions. The presence of active biomolecules in A. bracteosa, such as neoclerodan flavonol glycosides, diterpenoids, phytoecdysone, and iridoid glycosides, contributed to the enhanced biological activities of AuNPs. Overall, this research highlights the potential of A. bracteosa-derived AuNPs for various biomedical applications due to their remarkable therapeutic properties and effective capping by phytochemicals. RESEARCH HIGHLIGHTS: This research underscores the growing significance of herbal medicine in contemporary healthcare by exploring the therapeutic potential of Ajuga bracteosa and gold nanoparticles (AuNPs). The study highlights the notable efficacy of A. bracteosa leaf extracts and AuNPs in treating bacterial infections, demonstrating their bactericidal effects on a range of strains. The anti-inflammatory properties of plant extracts and nanoparticles are evidenced through paw edema method suggesting their applicability in managing inflammatory conditions. These findings position A. bracteosa and AuNPs as potential candidates for alternative and effective approaches to modern medication.

The Lipophilic Extract from Ginkgo biloba L. Leaves Promotes Glucose Uptake and Alleviates Palmitate-Induced Insulin Resistance in C2C12 Myotubes.

Ginkgo biloba L. (ginkgo) is a widely used medicinal plant around the world. Its leaves, which have been used as a traditional Chinese medicine, are rich in various bioactive components. However, most of the research and applications of ginkgo leaves have focused on terpene trilactones and flavonol glycosides, thereby overlooking the other active components. In this study, a lipophilic extract (GL) was isolated from ginkgo leaves. This extract is abundant in lipids and lipid-like molecules. Then, its effect and potential mechanism on glucose uptake and insulin resistance in C2C12 myotubes were investigated. The results showed that GL significantly enhanced the translocation of GLUT4 to the plasma membrane, which subsequently promoted glucose uptake. Meanwhile, it increased the phosphorylation of AMP-activated protein kinase (AMPK) and its downstream targets. Both knockdown of AMPK with siRNA and inhibition with AMPK inhibitor compound C reversed these effects. Additionally, GL ameliorated palmitate-induced insulin resistance by enhancing insulin-stimulated glucose uptake, increasing the phosphorylation of protein kinase B (PKB/AKT), and restoring the translocation of GLUT4 from the cytoplasm to the membrane. However, pretreatment with compound C abolished these beneficial effects of GL. In conclusion, GL enhances basal glucose uptake in C2C12 myotubes and improves insulin sensitivity in palmitate-induced insulin resistant myotubes through the AMPK pathway.

Baohuoside I inhibits virulence of multidrug-resistant Staphylococcus aureus by targeting the transcription Staphylococcus accessory regulator factor SarZ

BackgroundStaphylococcus aureus is a versatile pathogen that can cause a wide range of infections in humans. Biofilms play a crucial role in the pathogenicity of S. aureus and contribute to its ability to cause persistent and chronic infections. Baohuoside I has garnered increasing recognition as a natural flavonol glycoside with a wide spectrum of health-related activities. PurposeThe antibacterial and anti-biofilm properties of Baohuoside I have not been extensively investigated. Our study aimed to assess its inhibitory effects and the underlying mechanisms on biofilm formation and hemolytic capacity in S. aureus. Study Design/MethodsThe impact of Baohuoside I on the biofilm and virulence of S. aureus was evaluated through in vitro experiments and Galleria mellonella as an in vivo infection model. The mechanisms were explored by Drug affinity responsive target stability (DARTS) and validated in genetic knockout strain and through molecular biological experiments using DARTS, molecular docking, electrophoretic mobility shift assay (EMSA), and bio-layer interferometry (BLI). ResultsBaohuoside I significantly inhibits the formation of S. aureus biofilms and hemolytic activity at 6.25 µM. Proteomics analysis revealed that treatment with Baohuoside I led to a reduction in the expression of quorum-sensing system agr-regulated genes. DARTS analysis identified Staphylococcus accessory regulator factor (SarZ), a key regulator involved in the expression of virulence factors in S. aureus by acting as activator of the agr quorum-sensing system, was the direct target of Baohuoside I. Molecular docking, DARTS, BLI and EMSA assays collectively confirmed the direct binding of Baohuoside I to SarZ, inhibiting its binding to downstream promoters. Furthermore, it is found through site-directed protein mutagenesis that the Tyr27 and Phe117 residues are key for Baohuoside I binding to SarZ. Additionally, the knockout of SarZ significantly diminished the hemolytic ability of S. aureus, underscoring its crucial role as a pivotal regulator of virulence. Lastly, in vivo tests utilizing the G. mellonella infection model demonstrated the efficacy of Baohuoside I. ConclusionThis study provides valuable insights into the mechanism by which Baohuoside I inhibits the virulence of S. aureus through its interaction with SarZ. These findings highlight the significance of SarZ as an effective target against the virulence of S. aureus.

Integrated Full-Length Transcriptomics and Metabolomics Reveal Glycosyltransferase Involved in the Biosynthesis of Flavonol Glycosides in Laportea bulbifera.

Many species of the Urticaceae family are important cultivated fiber plants that are known for their economic and industrial values. However, their secondary metabolite profiles and associated biosynthetic mechanisms have not been well-studied. Using Laportea bulbifera as a model, we conducted widely targeted metabolomics, which revealed 523 secondary metabolites, including a unique accumulation of flavonol glycosides in bulblet. Through full-length transcriptomic and RNA-seq analyses, the related genes in the flavonoid biosynthesis pathway were identified. Finally, weighted gene correlation network analysis and functional characterization revealed four LbUGTs, including LbUGT78AE1, LbUGT72CT1, LbUGT71BX1, and LbUGT71BX2, can catalyze the glycosylation of flavonol aglycones (kaempferol, myricetin, gossypetin, and quercetagetin) using UDP-Gal and UDP-Glu as the sugar donors. LbUGT78AE1 and LbUGT72CT1 showed substrate promiscuity, whereas LbUGT71BX1 and LbUGT71BX2 exhibited different substrate and sugar donor selectivity. These results provide a genetic resource for studying Laportea in the Urticaceae family, as well as key enzymes responsible for the metabolism of valuable flavonoid glycosides.

Hyperoside Inhibits RNF8-mediated Nuclear Translocation of β-catenin to Repress PD-L1 Expression and Prostate Cancer.

Hyperoside is a flavonol glycoside isolated from Hypericum perforatum L. that has inhibitory effects on cancer cells; however, its effects on prostate cancer (PCa) remain unclear. Therefore, we studied the anti-PCa effects of hyperoside and its underlying mechanisms in vitro and in vivo. This study aimed to explore the mechanism of hyperoside in anti-PCa. 3-(4,5-Dimethyl-2-Thiazolyl)-2,5-Diphenyl Tetrazolium Bromide (MTT), transwell, and flow cytometry assays were used to detect PCa cell growth, invasion, and cell apoptosis. Immunoblot analysis, immunofluorescence, immunoprecipitation, and quantitative real-time PCR (qRT-PCR) were used to analyze the antitumor mechanism of hyperoside. Hyperoside inhibited PCa cell growth, invasion, and cell cycle and induced cell apoptosis. Furthermore, RING finger protein 8 (RNF8), an E3 ligase that assembles K63 polyubiquitination chains, was predicted to be a direct target of hyperoside and was downregulated by hyperoside. Downregulation of RNF8 by hyperoside impeded the nuclear translocation of β-catenin and disrupted the Wnt/β-catenin pathway, which reduced the expression of the target genes c-myc, cyclin D1, and programmed death ligand 1 (PD-L1). Decreased PD-L1 levels contributed to induced immunity in Jurkat cells in vitro. Finally, in vivo studies demonstrated that hyperoside significantly reduced tumor size, inhibited PD-L1 and RNF8 expression, and induced apoptosis in tumor tissues of a subcutaneous mouse model. Hyperoside exerts its anti-PCa effect by reducing RNF8 protein, inhibiting nuclear translocation of β-catenin, and disrupting the Wnt/β-catenin pathway, in turn reducing the expression of PD-L1 and improving Jurkat cell immunity.

The effects of rutin coat on the biodistribution and toxicities of iron oxide nanoparticles in rats

Rutin (Ru) is a flavonol glycoside, has significant scavenging characteristics against various reactive oxygen species, which exploits for widespread pharmacological activities such as anti-inflammatory and anti-allergic effects. This study aims to improve the bioavailability of iron oxide nanoparticles (IONPs) by coating them with Ru (Ru-IONPs). Considering this, IONPs and Ru-IONPs were prepared and characterized via various physical techniques. In addition, atomic absorption spectroscopy (AAS) has been used to assess the bio-distribution of the prepared formulation in vivo. Results revealed that the prepared IONPs and Ru-IONPs have a spherical shape with an average diameter of about 8 nm and 10 nm, respectively. Their surface potentials were found to be −19 ± 3.9 and −29.5 ± 5.4 mV, respectively. In vivo results revealed that single dose of IV administration of IONPs (16 mg/kg) elevated oxidative stress, indicated by the reduction of GSH in both heart and liver tissues, and increased their MDA contents. Also, IONPs administration resulted in hepatotoxicity characterized by a significant increase in ALT and AST levels in addition to cardiotoxicity characterized by a significant increase in CK-MB and LDH, in addition to the downregulation of heat shock protein 70 (HSP70) expression, while upregulation of TNF-α expression in both heart and liver tissues. Conversely, nearly all of these alterations were significantly ameliorated for animal groups administrated Ru-IONPs and the morphological injury’s counteraction in both heart and liver tissues. Therefore, we suggest that Ru could be used to alleviate the harmful effects and damages associated with IONPs administration due to its antioxidant, anti-inflammatory, and free radical scavenging properties.

Icariin regulates RANKL-induced osteoclast differentiation via the ERα/c-Src/RANK signaling

Osteoporosis (OP) is a common metabolic bone disease. Excessive osteoclastic activity significantly contributes to the development of OP. Icariin (ICA) is a flavonol glycoside derived from herbal plants and possesses curative effects on postmenopausal OP and bone fracture. This study aimed to investigate the effects of ICA on osteoclast differentiation induced by receptor activator of nuclear factor kappa B (RANK) ligand (RANKL) and the involvement of estrogen receptor α (ERα) and RANK signaling cascade in this process. RANKL was used to induce the differentiation of RAW264.7 cells to into osteoclasts. Small interfering RNA technique was used to knockdown ERα in cells. Cell counting kit-8 assay was performed to determine the cytotoxicity of ICA. The number of tartrate-resistant acid phosphatase (TRAP)-positive cells was quantified by TRAP staining. RANKL induced the differentiation of RAW264.7 cells into osteoclasts, while ICA abolished the pro-osteoporotic effect of RANKL. Moreover, ERα knockdown abolished the effects of ICA on RANKL-induced osteoclastogenesis. Further exploration revealed that ICA inhibited the phosphorylation of c-Src in osteoclasts via regulating ERα, while inactivation of c-Src reversed ERα knockdown-promoted osteoclastogenesis. Lastly, ICA inhibited the activation of the mitogen-activated protein kinase signaling pathway and downregulated the expressions of target osteoclastogenic proteins in RANKL-treated RAW 264.7 cells, while ERα knockdown almost completely diminished the effects of ICA. ICA inhibited RANKL-induced osteoclast differentiation via regulating the ERα/c-Src/RANK signaling. These findings elucidated a novel mechanism by which ICA exerts an anti-osteoporotic effect.

Changes in Chemical Composition of Red and Black Currant Fruits and Leaves During Berry Ripening

ABSTRACT The composition and variations of sugars, organic acids and phenolic compounds of red and black currant fruits and leaves were studied during the last four weeks of ripening. The results showed that sugar content increased during berry ripening in both species. In comparison, organic acids decreased in red currant, whereas no differences between sampling dates were observed in black currant. Forty-seven individual phenolic compounds, belonging to anthocyanins, flavonols, flavanols, hydroxycinnamic acid derivatives and flavanones were identified in red currant fruits and 52 in black currant fruits by HPLC-MS analysis. In black currant fruits, the major phenolic compounds were anthocyanins (81.51–85.15% of total phenolics), which increased during ripening until the last sampling date. In both red and black currant leaves, 47 phenolic compounds were identified. The content of phenolic compounds in red currant leaves was 1.31-fold to 1.90-fold higher compared to the content in black currant leaves. The most abundant phenolics in both currant leaves were flavonol glycosides, accounting for 58.5–67.9% of total phenolics, and their content was the highest at the end of berry ripening.

Valeriana officinalis (Valerian) – review

Valeriana officinalis L. s.l. is a perennial herbaceous plant belonging to the Valerianaceae family. It is widely distributed in Ukraine and around the world. The official medicinal raw material derived from Valeriana officinalis consists of the dried, whole, or fragmented underground parts of the plant, including the rhizome along with the roots and stolons. To meet the standards outlined in the European Pharmacopoeia, this raw material must be standardized based on its essential oil content (a minimum of 4 ml/kg in dried preparations) and sesquiterpenic acids (a minimum of 0.17 percent by weight, calculated as valeric acid, in dried preparations). The aim of the work was searching, systematizing, and generalizing information from the specialized literature on the chemical composition, biological activity and therapeutic use of Valeriana officinalis. Valeriana officinalis has sedative, mild analgesic, hypnotic, antispasmodic, carminative, and hypotensive effects. Historically, it was used for hysterical conditions, hyperexcitability, insomnia, hypochondria, migraine, spasms, intestinal colic, rheumatic pains, dysmenorrhea, and especially for conditions accompanied by nervous excitability. The main classes of biological substances identified in Valeriana officinalis are valepotriates, iridolactones, alkaloids, phenolic acids, sesquiterpenes, flavonoids, terpene coumarins, lignans, terpene and flavonol glycosides. It has not yet been established which components of Valeriana officinalis are responsible for its pharmacological effects. Current opinion is that the overall effect of valerian is due to several different groups of components and their different mechanisms of action. Therefore, the activity of different preparations of valerian will depend on their content and concentration of several types of components. Conclusions. Summarized and systematized original works related to pharmacognostic study, phytochemical analysis, and medicinal use of underground and aerial parts of various species of Valeriana genus. The analysis of the material shows that in recent years, scientists from all over the world have paid attention to the above-ground part of valerian and have chosen it as an object of in-depth study. This approach opens new possibilities for the use of the herb Valeriana officinalis in medicine.

Paper-based ligand fishing method for rapid screening and real-time capturing of α-glucosidase inhibitors from the Chinese herbs

Identifying medicinally relevant compounds from natural resources generally involves the tedious work of screening plants for the desired activity before capturing the bioactive molecules from them. In this work, we created a paper-based ligand fishing platform to vastly simplify the discovery process. This paper-based method exploits the enzymatic cascade reaction between α-glucosidase (GAA), glucose oxidase (GOx), and horseradish peroxidase (HRP), to simultaneously screen the plants and capture the GAA inhibitors from them. The designed test strip could capture ligands in tandem with screening the plants, and it features a very simply operation based on direct visual assessment. Multiple acylated flavonol glycosides from the leaves of Quercus variabilis Blume were newly found to possess GAA inhibitory activities, and they may be potential leads for new antidiabetic medications. Our study demonstrates the prospect of the newly discovered GAA ligands as potential bioactive ingredients as well as the utility of the paper-based ligand fishing method.

PHYTOCHEMICALS AND PHARMACOLOGICAL PROPERTIES OF CLITOREA TERNATEA: A REVIEW

Clitoria ternatea refers an herb (annual twining) found in India, Philippines, Madagascar & China. It belongs to family- Fabaceae. The present review was based on the description, phytochemicals, and pharmacological properties of Clitorea ternatea. The literature survey was done thorough PubMed, Scopus and Google Scholar. The root was utilized in induction of abortion in the past, and the paste is often used to treat abdominal inflammations, sore-throats & mucus problems. According to the results of the initial phytochemical screening, the plant included proteins, alkaloids, antharaquinone, anthocyanins, cardiac glycosides, phenols, tannins, phlobatannin, carbohydrates, saponins, triterpenoids, phenols, flavonoids, flavonol glycosides, and volatile oils in addition to steroids.

Holistic quality evaluation method of Epimedii Folium based on NIR spectroscopy and chemometrics.

There are some problems in the quality control of Epimedii Folium (leaves of Epimedium brevicornum Maxim.), such as the mixed use of Epimedii Folium from different harvesting periods and regions, incomplete quality evaluation, and time-consuming analysis methods. Near-infrared (NIR) spectroscopy was conducted to establish a rapid overall quality evaluation method for Epimedii Folium. Quantitative models of the total solid, moisture, total flavonoid, and flavonol glycoside (Epimedin A, Epimedin B, Epimedin C, Icariin) contents of Epimedii Folium were established by partial least squares regression (PLSR). The root mean square error (RMSE) and correlation coefficient (R) were used to evaluate the performance of models. The qualitative models of Epimedii Folium from different geographic origins and harvest periods were established based on K-nearest neighbor (KNN), back-propagation neural network (BPNN), and random forest (RF). Accuracy and Kappa values were used to evaluate the performance of models. A new multivariable signal conversion strategy was proposed, which combines NIR spectroscopy with the PLSR model to predict the absorbance values of retention time points in the high-performance liquid chromatography (HPLC) fingerprint to obtain the predicted HPLC fingerprint. The Pearson correlation coefficient and cosine coefficient were used to evaluate the similarity between real and predicted HPLC fingerprints. Qualitative models, quantitative models, and the similarity between real and predicted HPLC fingerprints are satisfactory. The method serves as a fast and green analytical quality evaluation method of Epimedii Folium and can replace traditional methods to achieve the overall quality evaluation of Epimedii Folium.

Metabolome and Transcriptome Analysis Provide Insights into Flower Bud Color Variation in the Adaptation to UV-B Radiation of Litchi

Flower color variations have increasingly been recognized as playing an important role in the adaptation to UV-B radiation; however, the underlying mechanism is poorly understood in perennial fruit trees. Litchi is an important fruit tree, and extremely early maturing (EEM) and middle-to-late-maturing (MLM) cultivars that originated from regions with high and low UV-B radiation have dark brown and light yellow flower buds, respectively, while their hybrid early-maturing (EM) cultivars have an intermediate brown flower bud. This study comprehensively analyzed the metabolome and transcriptome of flower buds of litchi EEM, EM and MLM cultivars to explore the mechanism underlying flower color variation during the adaptation to UV-B radiation for the first time. Metabolomic analysis identified 72 flavonoids in litchi flower buds, among which a higher accumulation of flavonol glycosides was responsible for darker flower buds of EEM cultivars. And transcriptome analysis revealed key structural genes, including LcCHI, LcFLS and seven UGTs, together with two transcription factors (LcMYB12 and LcMYB111), which could be directly up-regulated by UV-B radiation, playing critical roles in regulating the differential accumulation of flavonol glycosides. These results provide new insights into the molecular mechanism underlying adaptation to UV-B radiation and provide a genetic basis for future breeding of stress-tolerant cultivars of litchi.

Variability and determinants of secondary metabolite profiles in cranberry (Vaccinium macrocarpon) from Wisconsin and New Jersey

A comprehensive analysis was conducted on 112 fruit samples harvested in 2019 from six different cultivars of cranberry (Vaccinium macrocarpon Ait.). These cranberry crops were cultivated in both New Jersey and Wisconsin, under the management of diverse growers. The six cultivars investigated include Stevens (ST), Crimson Queen (CQ), Demoranville (DM), Mullica Queen (MQ), Welker (WE), and Haines (HA). This study delved into the variability and determinants of secondary metabolite profiles in cranberry. Fuzzy chromatograph mass spectrometry (FCMS) and ultra-high performance liquid chromatography high-resolution accurate-mass multistage mass spectrometry (UHPLC-HRAM-MSn) were used for analysis. Factorial multivariate analysis of variance (MANOVA)-principal component analysis (PCA) was employed to assess six experimental factors, including cultivar, cranberry growing state, grower, harvest times, and both analytical and biological replicates. The most substantial influence on the overall variability was observed with respect to cultivars and cultivation states. Specifically, the factor “cultivar” contributed 16.3 % to the total variance in the polar chemical profile, while the factor “state” contributed 31.5 %. Similarly, in the less polar chemical profile, the contributions were 29.0 % for “cultivar” and 22.3 % for “state” to the total variance. Consequently, the primary objective of this study was to examine the variations in the relative contents of secondary metabolite among cranberries cultivated in New Jersey and Wisconsin. The findings revealed that geographic factors exerted a significant effect on the levels of certain organic acids, flavonol glycosides, and iridoids even within the same cranberry cultivar.

The application of untargeted metabolomics coupled with chemometrics for the analysis of agitation effects on the sensory profiles of matcha tea

In the study, the effects of agitating parameters (different agitating rates and time) on the aroma and taste profiles of matcha tea were systematically investigated by the combination of untargeted metabolomics and chemometrics. The aroma profiles of matcha tea agitated at low rates (500 rpm) and for 30 s were more richness than that agitated with other parameters by sensory analysis and gas chromatography-ion mobility spectrometry. The key aroma compounds contributed to the sensory differences of matcha tea agitated at different rates and time were analyzed by gas chromatography-mass spectrometry and partial least square-discriminate analysis (PLS-DA), which were further verified by the triangle test. Thereinto, 2,4-decadienal associated with the sweet, brown and seaweed aroma significantly affected the aroma profiles of matcha tea with different agitating rates and time. The levels of bitterness and astringency were also higher in matcha tea with low agitating rates and time by sensory evaluation, which were attributed to the variations of phenolic compounds. Flavonol glycosides, gallic acid and (−)-gallocatechin were determined the key compound to the taste differences of matcha tea with different agitating parameters by the analysis of PLS-DA based on the results of high performance liquid chromatography and the sensory verification. And flavonol glycosides were mainly contributed to the bitterness and astringency, and gallic acid and (−)-gallocatechin influenced the umami and sweetness of matcha tea. Consequently, agitation has the potential to affect the sensory profiles of matcha tea by changing aroma and taste substances.

Isolation of two flavonol glycosides from <i>Rosa rugosa</i> pollen and their anti-inflammatory effect in lipopolysaccharide-stimulated macrophages

Isolation of two flavonol glycosides from <i>Rosa rugosa</i> pollen and their anti-inflammatory effect in lipopolysaccharide-stimulated macrophages

Portable paper-based probe for on-site ratiometric fluorescence determination of total flavonol glycosides in plant extract using smartphone imaging.

A smartphone-assisted, paper-based ratio fluorescence probe is presented for the rapid, low-cost and on-site quantification of total flavonol glycosides in Ginkgo biloba extracts (GBE). The Al3+/Eu-MOF/paper-based probe utilizes lanthanide metal-organic framework (Ln-MOF) nanoparticles immobilized on Whatman filter paper along with Al3+ for detecting flavonols, which are the hydrolyzed products of flavonol glycosides. The color change of the paper-based fluorescence image from red to orange depends on the concentration of the target analyte in the sample solution. The smartphone equipped with a red, green, blue (RGB) color detector measured the fluorescence signal intensity on the paper substrate after adding flavonol. The analytical variables affecting the performance of the probe, including the addition sequence of the aluminum nitrate solution, its concentration, that of the Ln-MOF solution, the drying time of the paper probe, the reaction time and the sensitivity parameters of the mobile phone camera (ISO), were optimized. Under optimal conditions, the Al3+/Eu-MOF/paper-based probe has good linear response in the concentration range 7 ~ 80µg mL- 1 and a lower detection limit of 2.07µg mL- 1. The results obtained with the paper-based ratio fluorescence probe and smartphone combination were validated by comparing them with high-performance liquid chromatography (HPLC) measurements. This study provides a potential strategy for fabricating Al3+/Eu-MOF/paper-based probe used for total flavonol glycosides determination.

Hyperoside induces cell cycle arrest and suppresses tumorigenesis in bladder cancer through the interaction of EGFR-Ras and Fas signaling pathways.

Hyperoside is a natural flavonol glycoside widely found in plants and has been reported to have a variety of pharmacological effects, including anticancer abilities. In this study, we demonstrated for the first time that hyperoside inhibited the proliferation of bladder cancer cells in vitro and in vivo. Moreover, hyperoside could not only induce cell cycle arrest, but also induce apoptosis of a few bladder cancer cells. Quantitative proteomics, bioinformatics analysis and Western blotting confirmed that hyperoside induced the overexpression of EGFR, Ras and Fas proteins, which affects a variety of synergistic and antagonistic downstream signaling pathways, including MAPKs and Akt, ultimately contributing to its anticancer effects in bladder cancer cells. This study reveals that hyperoside could be a promising therapeutic strategy for the prevention of bladder cancer.

Determination of Total Flavonol Glycosides in ZhuangGuGuanJieWan Fluidextract Based on Near-Infrared Spectroscopy and Chemometrics

Determination of Total Flavonol Glycosides in ZhuangGuGuanJieWan Fluidextract Based on Near-Infrared Spectroscopy and Chemometrics

Comparative metabolomics analysis of unique yellow hawthorn (Crataegus pinnatifida) and red-skinned cultivars reveals a different polyphenol biosynthesis flux and antioxidative and antidiabetic potential

Abstract Objectives This paper aims to investigate the polyphenol metabolite variation and bioactivities of different-colored hawthorn berries (Crataegus pinnatifida). Materials and Methods Comparative metabolomics analysis between peel and flesh of yellow hawthorn 'Jinruyi' (JRY) and red-skinned ones was carried out by UPLC-MS/MS. Antioxidant activities and α-glucosidase inhibition capacity were also tested among different colored hawthorn samples. Results A total of 453 polyphenols was characterized, among which phenolic acids and flavonoids were abundant, and were closely relevant to the antioxidant capacity of hawthorn fruits. Polyphenol profile showed accession-specific accumulation in peel or flesh of different colored hawthorn. The unique yellow hawthorn was found to have few anthocyanins but showed enhanced flux to synthesize flavones and flavonols, especially flavone C-glycosides and acylated flavonol glycosides. The specific acylation decoration included acetylation, p-coumaroylation, and malonylation. In addition, yellow hawthorn showed excellent α-glucosidase inhibitory effect, which might be associated with the high concentration of 8 polyphenols including 5 phenolic acids, 2 flavone C-glycosides, and an acylated flavonol glycoside, namely, quercetin-7-O-(6ʹʹ-malonyl)glucoside. Such acylated flavonol showed the strongest correlation with the inhibition effect of hawthorn fruits on α-glucosidase, and was predicted to have the lowest binding energy with the enzyme according to molecular docking analysis, indicating its great potential as a strong α-glucosidase inhibitor and an important antidiabetic ingredient in yellow hawthorn. Conclusions The acylated flavonol glycosides and C-glycosyl flavones might be chemotaxonomic markers differentiating varieties and bioactivities of yellow hawthorn from the traditional red-skinned ones. These findings complement the existing knowledge on the metabolite composition and nutritional properties of hawthorn fruits.