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Tecoma stans (L.) Kunth (Bignoniaceae), is popularly known as ipe-mirim, and used in traditional medicine for the treatment of diabetes and digestive problems. The aim of this work was to evaluate the antibacterial, antioxidant and synergistic potential of the ethanol extract and fractions from the T. stans flowers, and to determine their chemical composition. The hexane fraction (HEX) was analyzed by Gas Chromatography-Mass Spectrometry (GC-MS), and fatty acid esters and the phytosterols could be identified. The ethanol extract (EE), and dichloromethane (DCM), ethyl acetate (EA) and hydroethanol (HE) fractions were analyzed by liquid chromatography coupled to a diode array detector and mass spectrometer (LC-DAD-MS). Alkaloids (tecomine, tecostamine, and coumaroyl-spermidine analogs), O-glycosylated flavones and flavonols (O-glucuronyl O-methyl quercetin, O-hexosyl luteolin, and others), and phenylethanoid glycosides (dihydroxyphenyl ethyl O-caffeoyl O-deoxyhexosyl hexoside, hydroxyphenyl ethyl O-coumaroyl O-deoxyhexosyl hexoside, and others) were identified. The EE with DCM and EA fractions exhibited antioxidant effects, and had the highest levels of phenolic compounds. Regarding Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) tests, the EE, DCM and EA fractions showed potential results against Escherichia coli, E. coli EHEC and Enterococcus faecalis. The EE and DCM and EA fractions interacted synergistically with amoxicillin and tetracycline decreasing the MIC of antibiotics 2–5 fold when compared with the MIC of antibiotics used alone. These results provide a basis for additional studies aimed to evaluate the possibility of using extract or fractions from T. stans as natural sources of antioxidants and antibacterial agents of plant origin.

Cancer is one of the leading causes of death worldwide. A slight decline in mortality has been noted, but the currently available treatment options did not give an expected outcome and are associated with several side effects resulting a substantial economic burden. The advent of plant-based treatment is rising because of its ease of use, ready availability, cost-effectiveness, and low/no toxicity. In recent years, flavonoids with their diverse physico-biological properties have gained the scientific community's attention for the treatment of various forms of cancer. Different flavonoids, especially, flavonols (quercetin, kaempferol, fisetin, and isorhamnetin), flavanones (hesperidin and naringin), and anthocyanins, have shown potent anticancer activities affecting various signaling cascades. Among those, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/ mammalian target of rapamycin (mTOR) signaling pathway is widely known to play a significant role in different physio-cellular activities, which triggers malignant transformation and is considered a key target for anticancer compounds. This pathway plays a vital role in regulating the cell cycle, metabolism, survival, and proliferation. The flavonoids exhibit their anticancer activity via different molecular pathways, including PI3K/Akt/mTOR. In the current piece of paper, our focus is to underpin the action of the above-mentioned flavonoids against different cancers, mainly covering in-vitro data, through PI3K/Akt/mTOR targeting.

Corema album (L.) D. Don (Ericaceae) is an endemic bush that grows along the Atlantic littoral of the Iberian Peninsula. Its edible white berries (known as camarinas, camarinas, camarinhas, white crowberry, among other vernacular names) have been used in popular medicine as an antipyretic and are consumed in localised areas of Portugal and Spain as appetisers and in the preparation of juices and jams. The aim of the present review is to summarise the knowledge of the chemical composition and pharmacological studies performed with C. album fruit and extracts. These berries are rich in phenolic compounds, including phenolic acids, stilbenes, flavonols, flavanones, prenylated flavanone, flavanols, and anthocyanins. The total phenolic content of various extracts of the pulp of these berries has been positively correlated with their antioxidant capacity. In this respect, the treatment with acetone, ethyl acetate, and aqueous extracts of this fruit has protected HepG2 cells against chemically induced oxidative stress. The chemoprotective effect of these extracts is mediated by preventing reactive oxygen species formation, reduced glutathione depletion, antioxidant enzyme over-activity, and oxidative damage to proteins and lipids. Furthermore, the presence of pentacyclic triterpenes, such as ursolic and oleanolic acids, in C. album berries confers reflectance UV properties to this fruit and derived extracts. In short, existing studies suggest that the development of C. album crops should be considered as a promising opportunity to obtain these remarkable berries. Moreover, further experiments should also be designed to evaluate their in vivo effect and to ascertain the underlying mechanism of action.

Objective Carpobrotus edulis (L.) N.E.Br. is a succulent perennial plant native to South Africa and grows invasively in the Mediterranean basin. It is commonly used for the treatment of various diseases, including skin wound healing and regeneration, for which experimental validation is lacking. We therefore evaluated the skin healing properties by testing a C. edulis aqueous leaf extract (CAE) on cell cultures and in enzymatic assays. Methods Micro-morphological analysis of leaves was carried out using scanning electron microscopy and light microscopy. Phytochemical features and antioxidant activity of CAE were evaluated by reversed-phase liquid chromatography coupled with diode array detection and electrospray ion trap mass spectrometry (RP-LC-DAD-ESI-MS), and in vitro cell-free assays. Biological activities were evaluated using keratinocytes and fibroblasts, as well as elastase, collagenase, and hyaluronidase. Results CAE showed high carbohydrates (28.59% ± 0.68%), total phenols ([101.9 ± 6.0] g gallic acid equivalents/kg dry extract [DE]), and flavonoids ([545.9 ± 26.0] g rutin equivalents/kg DE). RP-LC-DAD-ESI-MS revealed the predominant presence of hydroxycinnamic acids (51.96%), followed by tannins (14.82%) and flavonols (11.32%). The extract was not cytotoxic, had a strong and dose-dependent antioxidant activity, and inhibited collagenase (> 90% at 500 µg/mL) and hyaluronidase (100% at 1000 µg/mL). In cell culture experiments, CAE increased wound closure and collagen production, which was consistent with its high polyphenol content. Conclusion Our data support the use of the C. edulis for skin care and the treatment of skin problems. Moreover, use of C. edulis for skin care purposes could be an eco-friendly solution to reduce its invasiveness in the environment.

Red Clapp's Favorite is the red mutation cultivar of the pear cultivar Clapp's Favorite. Fruit color is an important feature of pear fruits, with red skin generally attracting consumers. Anthocyanin, chlorophyll, and carotenoids are the most important pigments in the color formation of fruits. The red color of pear skin is mainly due to the concentration and composition of anthocyanin. Metabolomics is an emerging discipline that focuses on the qualitative and quantitative analysis of small metabolites with low molecular weight in biological cells and tissues. As an important part of systems biology, it is an effective means to solve many complex biological problems. Studies have analyzed pigment content, composition, and differentially expressed genes in the skin of green and red pears from various aspects. Anthocyanins are responsible for physiological activity on regulating pathways. The aim of this study was to discover differential metabolites in the skin of Clapp's Favorite and its red mutation cultivar Red Clapp's Favorite. The metabolic components were detected using high-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). Chromatographic experiments were performed on an HSS T3 column (100 mm×2.1 mm, 1.8 μm) by using a mobile phase consisting of 0.1% (v/v) formic acid in acetonitrile and water, and mass spectrometry was conducted in the positive and negative modes by electrospray ionization (ESI). Red Clapp's Favorite and Clapp's Favorite were collected from the pear germplasm resource nursery of Yantai Institute of Agricultural Sciences in Shandong. The data were analyzed by principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) as well as cluster analysis and heat map. The first two principal components exhibited 62.3% and 8% of the total variance in the positive and negative ion modes, respectively. PCA can generally reflect metabolite differences between the two groups of samples, and there are significant differences in metabolites between the two cultivars. The results showed that PLS-DA clearly distinguishes the two groups of samples, which can be used to analyze the subsequent difference in components. The compounds were identified based on data retrieved from the PMDB databases according to the accurate mass number, secondary fragment, and isotope distribution. The results showed that the metabolite content in the skin of Red Clapp's Favorite and Clapp's Favorite were significant. There were 83 different metabolites (P

Foam cell formation is an important event in atherosclerosis. Fisetin, a bioflavonoid, has been identified to possess anti-inflammatory, antilipidemic, and anticancerous properties; however, its role as a lipid homeostasis regulator in macrophages, specifically in the presence of metabolic stressors such as oxidized low-density lipoprotein (oxLDL) is not well understood. In this study, we have investigated the role of fisetin in preventing oxLDL-induced macrophage foam cell formation. U937-derived macrophages were stimulated with oxLDL with or without fisetin for varied time points, and various parameters were assessed including cell viability by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay; reactive oxygen species (ROS) by dichlorofluorescin diacetate assay; lipid accumulation by Oil Red O staining; and expression of NLR family pyrin domain containing 3 (NLRP3), sterol regulatory element-binding protein (SREBP)-1, and associated downstream proteins 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) and fatty acid synthase (FAS) by quantitative reverse transcription polymerase chain reaction (RT-qPCR) and immunoblotting. Functionality of FAS enzyme was determined using enzyme activity assay. Docking studies were performed to determine the in silico interaction between NLRP3 and fisetin. The results showed that fisetin up to the dose of 10 µM did not alter cell viability but at the same dose could decrease the accumulation of lipids in macrophages and prevented foam cell formation. Fisetin could also ameliorate and reduce oxLDL-induced upregulation of SREBP-1 and thereby the expression of its downstream lipid synthesis genes HMGCR and FAS and inhibited ROS-induced NLRP3 inflammasome activation. In conclusion, fisetin could inhibit foam cell formation by blocking oxLDL-induced ROS formation and subsequent NLRP3 activation, thereby inhibiting SREBP-1 and its downstream genes including FAS and HMGCR.

Pancreatic cancer is an extremely malignant digestive tract tumor. With the increase of chemotherapeutic resistance of pancreatic cancer, clinical treatment is in a dilemma. Hence, it is pivotal to design an effective drug for treating individuals with pancreatic cancer. Fisetin extracted from vegetables, as well as fruits was explored to possess antioxidant, anti-cancer, anti-inflammatory along with anti-microbial properties. Nonetheless, there is limited research focusing on the utility of fisetin as an inhibitor of pancreatic cancer. Similarly, the mechanism through which Fisetin dampens pancreatic cancer remains unknown. This research work systematically evaluated the possible anti-cancer influences of fisetin in pancreatic cancer, as well as explored its responsible molecular mechanism. Our data revealed that fisetin obviously dampens pancreatic cancer progress in vitro along with in vivo dose-dependently. Furthermore, we established that fisetin repressed pancreatic cancer via explicitly targeting PI3K/AKT/mTOR signaling cascade and not the JAK2 cascade. Our data clarified that fisetin is a prospective anti-cancer drug for pancreatic cancer, as well as indicated the distinct molecular target of fisetin.

An R2R3-MYB transcription factor, CmMYB9a, activates floral coloration in chrysanthemum by positively regulating CmCHS, CmDFR and CmFNS, but inhibiting the expression of CmFLS. Chrysanthemum is one of the most popular ornamental plants worldwide. Flavonoids, such as anthocyanins, flavones, and flavonols, are important secondary metabolites for coloration and are involved in many biological processes in plants, like petunia, snapdragon, Gerbera hybrida, as well as chrysanthemum. However, the metabolic regulation of flavonoids contributing to chrysanthemum floral coloration remains largely unexplored. Here, an R2R3-MYB transcription factor, CmMYB9a, was found to be involved in flavonoid biosynthesis. Phylogenetic analysis and amino acid sequence analysis suggested that CmMYB9a belonged to subgroup 7. Transient overexpression of CmMYB9a in flowers of chrysanthemum cultivar 'Anastasia Pink' upregulated the anthocyanin-related and flavone-related genes and downregulated CmFLS, which led to the accumulation of anthocyanins and flavones. We further demonstrated that CmMYB9a independently activates the expression of CmCHS, CmDFR and CmFNS, but inhibits the expression of CmFLS. Overexpression of CmMYB9a in tobacco resulted in increased anthocyanins and decreased flavonols in the petals by upregulating NtDFR and downregulating NtFLS. These results suggest that CmMYB9a facilitates metabolic flux into anthocyanin and flavone biosynthesis. Taken together, this study functionally characterizes the role of CmMYB9a in regulating the branched pathways of flavonoids in chrysanthemum flowers.

Introduction: Hymenosporum flavum (Hook.) F. Muell. is the sole species within the genus Hymenosporum is known for its antimicrobial activity. The current study aims to examine the prospective activity of H. flavum as a safe supporter of sorafenib (as a reference standard) against hepatocellular carcinoma (HCC). Methods: Isolation and identification of compounds were made by chromatographic and spectroscopic methods. A fingerprint for the plant extract was done using HPLC-MS/MS spectrometric analysis. The total plant extract was examined in vitro for HCC activity. The isolated flavonoids were examined for their cytotoxic activities using molecular docking studies against both RAF-1 and ERK-2, and the promising compounds were further examined in vitro using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Results: Two new flavonols were isolated from the leaf extract of H. flavum (Hook.) F. Muell., quercetin-3-O-(glucopyranosyl 1→2 ribopyranoside) (1) and kaempferol-3-O-(glucopyranosyl 1→2 ribopyranoside) (2), accompanying other six known flavonoids (3-8), and identified via spectroscopic analysis. Moreover, HPLC- PDA/MS/MS spectrometric analysis revealed the presence of seventy phenolic metabolites. The cytotoxic activity of the plant extract confirmed its potential action on HepG2 cells indicated by the production level of lactate dehydrogenase (LDH) upon treatment compared with the normal cells. The isolated flavonoids were examined for their cytotoxic activity using molecular docking studies against both RAF-1 and ERK-2 as proposed mechanisms of their anticancer activities. Furthermore, compounds 1 and 3, which showed the best in silico results, were further examined in vitro using qRT-PCR. They exhibited promising inhibitory activities against both RAF-1 and ERK-2 gene expression. Moreover, they showed promising cytotoxic activities indicated by the MTT assay. Also, both of them improved the efficiency of sorafenib in targeting both RAF-1 and ERK-2 pathways suggesting synergistic combinations. Conclusion: Our findings showed the potential cytotoxic activity of H. flavum extract on HepG2 cells. Some isolated compounds (1 & 3) exhibited promising inhibitory activities against both RAF-1 and ERK-2 gene expression giving a lead future study for these compounds to be used in pharmaceutical preparations either alone or in combination with sorafenib.

The results of studies of the content of polyphenolic compounds and their antioxidant activity in the Pontic hawthorn plant Crataegus pontica K.Koch., growing in the mountainous regions of the Tashkent region of the Republic of Uzbekistan are presented. The collection of raw materials took place in the spring at the beginning of October 2019 and at the end of April 2020. The conditions for the isolation of polyphenolic compounds were selected under various conditions. It was shown that the optimal content of polyphenols is extracted with 70% acetone, followed by fractionation of the aqueous residue with ethyl acetate and precipitation with hexane. It was shown that in the plants harvested in spring, the amount of polyphenols was 4.28%, and the collected volume was 2.6%, of the air-dry mass of the raw material. Chromatographic methods (BC and TLC) revealed that the composition of plant leaves collected in spring contains more polyphenols than those collected in autumn. This plant contains compounds belonging to the class of flavonols, phenolic acids and flavan-3-ols. Polyphenols were identified by rutin, quercetin, quercetin-3-O-β-galactoside, catechin, and gallic acid by BC and TLC methods. The antioxidant activity of the sum of polyphenolic compounds was studied in the model of lipid peroxidation (LPO) in rat liver mitochondria. It was found that polyphenols have a protective effect on mitochondria, a reduced damaging effect of Fe2+ / ascorbate and antioxidant activity depends on the concentration of the studied polyphenolic substances. The introduction of rutin into the incubation medium in 5 μM medium inhibits LPO processes by 32.0%, and at 10 μM – by 85.9% and in 20 μM – by 96.8%, compared with the control.

Myricetin (MYR) and dihydromyricetin (DHM) are classified as natural flavonoids. Both substances are known for their anti-inflammatory and antioxidant properties. In this study, an in vitro model of inflammation was demonstrated on monolayers of scratched fibroblasts or keratinocytes exposed to LPS from Pseudomonas aeruginosa for six hours. MYR and DHM were subsequently applied to the cells for 24 hours at sub toxic concentrations (5-15 µM). Inflammatory parameters were analysed in collected cell medium and lysate after the incubation period using the Enzyme-Linked ImmuneSorbent Assay (ELISA) and Western blot. Both flavonoids inhibit the production of pro-inflammatory cytokines (IL-6, IL-8) in LPS-stimulated skin cells as well as the decreased level of MMP-1 in fibroblasts. However, the application of MYR and DHM dose dependently increased the level of MMP-1 in keratinocytes. In our experiments, we focused on the anti-glycation activity of MYR and DHM, where the higher concentration of MYR seems to be more effective.

Polyphenolic substances kaempferol and quercetin are major flavonols found in plant foods, while caseins are major protein fractions in milk. In this study, the non-covalent interactions involved in the formation of caseinate–flavonol complexes as well as the resultant scavenging activities to three free radicals were assessed by multi-spectroscopic, molecular docking, and chemical assays. The results revealed that the binding of kaempferol/quercetin to caseinate was through a mode of energy transfer, resulting in fluorescence quenching of caseinate; meanwhile, both hydrophobic interaction and H-bonds were the forces involved in the resultant non-covalent caseinate–flavonol interactions. The results from UV-absorption and three-dimensional fluorescence spectra indicated that the two flavonols induced conformational change of caseinate. Moreover, quercetin with two hydroxyl groups at the carbon-4ʹ and -5ʹ positions of the B-ring exerted higher affinity to caseinate than kaempferol with one hydroxyl group at the carbon 4ʹ-position of the B-ring. In addition, the caseinate–quercetin complexes had higher scavenging activities against the DPPH, ABTS, and hydroxyl radicals than the caseinate–kaempferol complexes. In conclusion, both chemical structures and especially hydroxyl group numbers of flavonols are critical to the non-covalent casein–flavonol interactions and radical scavenging activities of the resultant complexes.

The characterization and quantification of phenolic compounds in bearberry leaves were performed using hyphenated ion mobility spectroscopy (IMS) and a quadrupole time-of-flight mass spectrometer. A higher identification confidence level was obtained by comparing the measured collision cross section (TWCCSN2) with predicted values using a machine learning algorithm. A total of 88 compounds were identified, including 14 arbutin derivatives, 33 hydrolyzable tannins, 6 flavanols, 26 flavonols, 9 saccharide derivatives, and glycosidic compounds. Those most reliably reproduced in all samples were quantified against respective standards. Arbutin (47-107 mg/g), 1,2,3,4,6-pentagalloylglucose (6.6-12.9 mg/g), and quercetin 3-galactoside/quercetin 3-glucoside (2.7-5.7 mg/g) were the most abundant phenolic components in the leaves. Quinic acid and ellagic acid were also detected at relatively high concentrations. The antioxidant activity of the most abundant compounds was evaluated. A critical view of the advantages and limitations of traveling wave IMS and CCS for the discovery of natural products is given.

Antioxidant activity (AA), total polyphenols content (TPC) and polyphenols profile (PP) were investigated during 10 days of postharvest ripening, in peels and pulps from fruits from three Carica papaya genotypes of different origin. Wild-genotype (WG) collected in Yucatan, Mexico (part of its center of origin) showed higher AA and TPC values than the commercial-genotype (CG). Likewise, PP analysis resulted in the identification and quantification of 4 families: phenolic acids, flavanols, dihydrochalcones and flavonols in both peels and pulps, as well as lignans, that were only found in fruit peels. Interestingly, fruits from WG also had higher contents than CG, in the following specific polyphenols: in peels; 5-O-Caffeoylquinic acid (chlorogenic acid) and kaempferol (both absent in CG), 4-Hydroxybenzoic acid 4-O-glucoside (3.8 times), quercetin 3-O-hexoside (3.5 times), 4-O-Caffeoylquinic acid (2.8 times), 5-O-Galloylquinic acid (2.7 times) and matairesinol (2.6 times). In pulps; 4-O-Caffeoylquinic acid (9.4 times), quercetin-3-O-rutinoside (rutin; 6.8 times), p-Coumaric acid 4-O-glucoside (p-coumaroyl hexoside; 2.5 times), p-Coumaroyl glycolic acid (2.5 times) and phloridzin (1.7 times). The superior capacity of wild native genotypes to accumulate more total polyphenols, to show higher antioxidant activity and to show even higher contents of some specific polyphenols known to have beneficial health effects (against chronic degenerative diseases such as cancer and cardiovascular diseases), might represent a good base for breeding programs aiming to obtain new varieties with superior nutraceutical properties.

Epidemiological studies have shown that higher intake of flavonoid is inversely associated with CHD risk. However, which flavonoid subclass could reduce CHD risk has remained controversial. The present meta-analysis of prospective cohort studies aimed to quantitatively assess the associations between flavonoid subclasses and CHD risk. A systematic literature search was implemented from PubMed and Web of Science databases up to March 2021, and eligible studies were identified. Multivariate-adjust relative risks (RR) with corresponding 95 % CI were pooled by using a random-effects model. A restricted cubic spline regression model was performed for non-linear dose–response analysis. A total of 19 independent prospective cohort studies with 894 471 participants and 34 707 events were included. The results showed that dietary intakes of anthocyanins (RR = 0·90; 95 % CI: 0·83, 0·98), proanthocyanidins (RR = 0·78; 95 % CI: 0·65, 0·94), flavonols (RR = 0·88; 95 % CI: 0·79, 0·98), flavones (RR = 0·94; 95 % CI: 0·89, 0·99) and isoflavones (RR = 0·90; 95 % CI: 0·83, 0·98) were negatively associated with CHD risk. Dose–response analysis showed that increment of 50 mg/d anthocyanins, 100 mg/d proanthocyanidins, 25 mg/d flavonols, 5 mg/d flavones and 0·5 mg/d isoflavones were associated with 5 % reduction in CHD risk, respectively. Sensitivity and subgroup analyses were used to further support these associations. The present results indicate that dietary intakes of fruits and vegetables abundant five flavonoid subclasses, namely anthocyanins, proanthocyanidins, flavonols, flavones and isoflavones, are associated with a lower risk of CHD.

Flavonoids confer a wide color range to plants, thus influencing the flower quality and commercial value of various ornamental plants. Flavones and flavonols are colorless pigments that are distinct from the colored anthocyanins. Flavones and flavonols are transformed from flavanones and dihydrokaempferol, which are catalyzed by flavone synthase (FNS) and flavonol synthase (FLS), respectively, and play important roles in regulating plant growth and development, and resistance to various stresses, in addition to coloration. However, few studies have been conducted on CmFNS and CmFLS genes in chrysanthemums. In this study, we isolated and identified CmFNS and CmFLS from Chrysanthemum morifolium. CmFNS and CmFLS were constitutively expressed at different levels in various C. morifolium organs, and in vitro catalytic activity of CmFNS and CmFLS was verified. CmFNS- and CmFLS-overexpressing tobacco plants exhibited phenotypes that accumulated more flavones and flavonols, respectively, but less anthocyanins. Moreover, the transcripts of CmFNS were negatively correlated with flower color, whereas CmFLS presented an opposite trend compared to CmFNS in five flower color cultivars with different anthocyanin levels. These findings suggest that CmFNS and CmFLS act as important regulators of flavone and flavonol biosynthesis, respectively, and dicate flower coloration in chrysanthemums.

Flavonoids have shown anti-hypertensive and anti-atherosclerotic properties: the impact of habitual flavonoid intake on vascular function, central haemodynamics and arterial stiffness may be important. We investigated the relationship between habitual flavonoid consumption and measures of central blood pressure and arterial stiffness. We performed cross-sectional analysis of 381 non-smoking healthy older adults (mean age 66·0 (sd 4·1) years; BMI, 26·4 (sd 4·41) kg/m2; 41 % male) recruited as part of the Australian Research Council Longevity Intervention study. Flavonoid intake (i.e. flavonols, flavones, flavanones, anthocyanins, isoflavones, flavan-3-ol monomers, proanthocyanidins, theaflavins/thearubigins and total consumption) was estimated from FFQ using the US Department of Agriculture food composition databases. Measures of central haemodynamics and arterial stiffness included systolic blood pressure (cSBP), diastolic blood pressure (cDBP), mean arterial pressure (cMAP) and augmentation index (cAIx). After adjusting for demographic and lifestyle confounders, each sd/d higher intake of anthocyanins ((sd 44·3) mg/d) was associated with significantly lower cDBP (−1·56 mmHg, 95 % CI −2·65, −0·48) and cMAP (−1·62 mmHg, 95 % CI −2·82, −0·41). Similarly, each sd/d higher intake of flavanones ((sd 19·5) mg/d) was associated with ~1 % lower cAIx (−0·93 %, 95 % CI −1·77, −0·09). These associations remained significant after additional adjustment for (1) a dietary quality score and (2) other major nutrients that may affect blood pressure or arterial stiffness (i.e. Na, K, Ca, Mg, n-3, total protein and fibre). This study suggests a possible benefit of dietary anthocyanin and flavanone intake on central haemodynamics and arterial stiffness; these findings require corroboration in further research.

According to our previous study, fisetin (3,3',4',7-tetrahydroxyflavone), a bioactive phytochemical (flavonol), reportedly showed cardioprotection against ischemia-reperfusion injury (IRI) by reducing oxidative stress and inhibiting glycogen synthase kinase 3β (GSK3β) [1]. GSK3β is said to exert a non-mitochondrial mediated cardioprotection; therefore, distinct mechanisms of GSK3β on the regulatory effect of mitochondria need to be addressed. The two distinct mitochondrial subpopulations in the heart, namely interfibrillar mitochondria (IFM) and subsarcolemmal mitochondria (SSM), respond differently to disease states. The current study aimed to understand the effect of fisetin on the subpopulation-specific preservation of IFM and SSM while rendering cardioprotection against ischemia reperfusion (I/R). Rats were pre-treated with fisetin (20 mg/kg) intraperitoneally, and IRI was induced using Langendorff isolated heart perfusion technique. Hemodynamic parameters were recorded, and the cardiac injury was assessed using infarct size (IS), lactate dehydrogenase (LDH), and creatine kinase (CK) levels. Subpopulation-specific mitochondrial preservation was evaluated by electron transport chain (ETC), catalase, superoxide dismutase (SOD), and glutathione (GSH) activities. The bioavailability of fisetin in IFM and SSM was measured using the fluorescence method. The ability of fisetin to bind directly to the mitochondrial complex-1 and activating it through donating electrons to FMN was studied using molecular docking studies and further validated by in vitro rotenone sensitivity assay. Cardioprotective effects exhibited by fisetin were mainly mediated through IFM preservation. Mitochondrial bioavailability of fisetin is more in IFM than SSM in both ex vivo and in vitro conditions. Fisetin increased mitochondrial ATP production in I/R insult hearts by activating ETC complex 1. Inhibition of complex 1 prevents the ATP-producing capacity of fisetin. Our results provide evidence that fisetin plays a protective role in myocardial IRI, possibly by preserving the functional activities of IFM.

BACKGROUND: Antioxidants are natural ingredients that can block the oxidation process of free radicals that enter the body so that damage to body cells can be prevented. Kawista plants are one of the plants that have antioxidant activity. AIM: This article review aims to determine the compounds that have antioxidant activity found in Kawista plants, the method used in testing antioxidants on Kawista plants, and the IC50 value found in antioxidant testing on Kawista plants. METHODS: The method used in this study is the Population, Intervention, Control, and Outcome method through inclusion and exclusion criteria using the keywords “Antioxidant activity of Limonia acidissima,” “Antioxidant activity of Feronia limonia,” “Antioxidant activity of Kawista,” “Testing Antioxidants in L. acidissima,” and “L. acidissima” with databases used for literature searches. RESULTS: This review shows that Kawista plants have antioxidant activity of various compounds based on the test method used. CONCLUSION: Compounds in Kawista plants that have antioxidant activity are phenols, especially phenolic acids, flavonoids, flavonols, triterpenoids, saponins, tannins, terpenes, steroids, alkaloids, and glycosides. Kawista plant activity tested had IC50 with an average value of very strong (16.45 g/mL), strong (77.85 g/mL), moderate (135.02 g/mL), weak (196.67 g/mL), and very weak (751.89 g/mL).

Nitrogen regulation can effectively promote the improvement of berry components and the formation of flavor compounds in wine grapes. In order to understand the effects of foliar nitrogen spraying on grape quality and flavonoid substance, took Cabernet Sauvignon as the test subject, grape leaves were sprayed by ammonium sulfate, calcium ammonium nitrate, urea, phenylalanine, and glutamate during veraison, and clear water was used as the control. The results showed that spraying ammonium sulfate could improve the contents of soluble solids, anthocyanins, and total phenols of grape berries; spraying phenylalanine significantly increased the content of titratable acid and tannin and decreased the ratio of sugar to acid in grape berries; compared with the control group, spraying glutamate could significantly upregulate some flavonol monomers; spraying calcium ammonium nitrate can adjust the monomer content of some flavanols; urea spraying significantly increased the contents of most anthocyanins, flavanols, and flavonol and increased the contents of total anthocyanins, total flavanols, and total flavonol in grape skins, laying a foundation for the improvement of the nutritional value of grapes and wine in the future., In this experiment, ammonium sulfate, calcium ammonium nitrate, urea, phenylalanine and glutamic acid were sprayed on the leaves during veraison stage period of the grapes，spraying clean water on the leaves as a control. The results showed that spraying urea had a significant effect on the up‐regulation of most anthocyanins, flavanols and flavonol monomers, and increased the content of total anthocyanins, total flavanols, and total flavonols in grape skins.

Citrus fruits contain numerous antioxidative biomolecules including phenolic acids, flavonols, flavanones, polymethoxyflavones (PMFs), and their derivatives. Previous in vitro and in vivo studies thoroughly investigated the antioxidant and therapeutic potential of bioflavonoids extracted from different citrus varieties and fruit fractions. Major bioflavonoids such as hesperidin, naringin, naringenin, and PMFs, had restricted their incorporation into food and health products due to their poor solubility, chemical stability and bioavailability. Considering these limitations, modern encapsulation methodologies such as hydrogelation, liposomal interactions, emulsifications, and nanoparticles have been designed to shield bioflavonoids with improved target distribution for therapeutic enhancements. The size, durability, and binding efficiency of bioflavonoid-loaded encapsulates were acquired by the optimized chemical and instrumental parameters such as solubility, gelation, dispersion, extrusion, and drying. Bioflavonoid-enriched encapsulates have been also proven to be effective against cancer, inflammation, neurodegeneration, and various other illnesses. However, in the future, newer natural binding agents with higher binding capacity might accelerate the encapsulating potential, controlled release, and enhanced bioavailability of citrus bioflavonoids. Overall, these modern encapsulation systems are currently leading to a new era of diet-based medicine, as demand for citrus fruit-based nutritional supplements and edibles grows.

Color acquisition is one of the most distinctive features of fruit development and ripening processes. The color red is closely related to the accumulation of polyphenolic compounds, mainly anthocyanins, during sweet cherry fruit maturity. In non-climacteric fruit species like sweet cherry, the maturity process is mainly controlled by the phytohormone abscisic acid (ABA), though other hormones may also play a role. However, the coordinated stage-specific production of polyphenolic compounds and their relation with hormone content variations have not been studied in depth in sweet cherry fruits. To further understand the accumulation dynamics of these compounds (hormones and metabolites) during fruit development, two sweet cherry cultivars ("Lapins" and "Glenred") with contrasting maturity timing phenotypes were analyzed using targeted metabolic analysis. The ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) approach revealed that phenolic acids, flavonols, and flavan-3-ols accumulated mainly until the straw-yellow stage in the early-maturing cultivar, while accumulation was mainly at the green stage in the mid-maturing cultivar, suggesting a cultivar-dependent stage-specific production of secondary metabolites. In the mid-maturing cultivar, anthocyanins were detected only from the red stage onward, whereas detection began at the pink stage in the early-maturing cultivar. ABA negatively correlated (p-value < 0.05) with the flavonols and flavan-3-ols in both cultivars. ABA and anthocyanin content increased at the same time in the early-season cultivar. In contrast, anthocyanins accumulated and the pink color initiation started several days after the ABA increase in the mid-maturing cultivar. Differential accumulation patterns of GA4, a ripening antagonizing hormone, between the cultivars could explain this difference. These results showed that both red-colored cultivars presented different accumulation dynamics of phenolic compounds and plant hormones during fruit development, suggesting underlying differences in the sweet cherry fruit color evolution.

The natural flavonoids in foods of plant origin have been well-characterized due to their beneficial biological properties. However, the information regarding the flavonoid compounds in edible insects remains severely limited. In the present study, we used a metabolomics approach to identify the flavonoid compounds in the Chinese oak silkworm, Antheraea pernyi Guerin-Meneville (Lepidoptera: Saturniidae), an traditional edible insect. Our study identified over 200 flavonoid metabolites in the larval midgut of A. pernyi with LC-ESI-MS/MS system. These flavonoid metabolites come from eight subclasses, including flavones (1 0 3), flavonols (34), flavonoids (28), flavanones (20), polyphenols (19), isoflavones (9), anthocyanins (9), and proanthocyanidins (4). The relative content of the flavones is the most abundant, with a value of 36.74% of the total. The top five flavonoid components in A. pernyi are hyperoside, isoquercitroside, tricin 7-O-hexoside, hesperetin 5-O-glucoside and protocatechuic acid, accounting for 51.17% of the total flavonoids. Hyperoside is the most abundant flavonoid compound (18.07% of the total) in A. pernyi. Our findings indicated targeted metabolomics is a useful approach to identify flavonoids in edible insects which contain abundant flavonoids than we already knew.

Polygonatum verticillatum (L.) All. is an important medicinal herb that belongs to the family Asparagaceae. The rhizome of the species is used in Chyavanprash preparation and several other ayurvedic formulations. Numerous active constituents like saponins, alkaloids, phytohormones, flavonoids, antioxidants, lysine, serine, aspartic acid, diosgenin, β-sitosterol, etc. have been reported from this species. In this study, morphological, phytochemical, antioxidant and genetic variations of 11 distant populations of P. verticillatum were measured. Considerably (P

An antiplasmodial activity-guided isolation was carried out on the dichloromethane extract of Tithonia diversifolia dried leaves. A total of five germacranolide type sesquiterpene lactones and a new flavonol, 3,6-dihydroxy-2-(4′-hydroxyphenyl)-7-methoxy-4H-chromen-4-one, were isolated. The flavonol reported an IC50 above 6.00 µM against the chloroquine sensitive strain, NF54. The antimalarial activity of the Tithonia diversifolia dichloromethane leaf extract was attributed to orizabin and tagitinin C.

Anthocyanins are important components in the peel of red pears and contribute to the appearance of the fruit. Melatonin application is known to affect anthocyanin biosynthesis, but the effect of preharvest melatonin application on fruit coloration remains largely unknown. The objective of this study was to determine the effects of preharvest melatonin application on pigmentation, phenolic compounds, and the expression of related genes in Nanhong pear (Pyrus ussuriensis). The applications were performed during the pre-color-change period by spraying 50 or 200 µmol L−1 of melatonin on fruits. We found that treatment with melatonin had a significant effect on color development. The concentrations of anthocyanins and flavonols were enhanced by melatonin treatment, whereas hydroxycinnamate and flavanol concentrations were reduced. Quantitative real-time PCR analyses indicated that the transcription levels for most anthocyanin biosynthetic genes and anthocyanin-related transcription factors were induced by melatonin. Melatonin application also stimulated the expression of melatonin biosynthesis-related genes and consequently caused an increase in endogenous melatonin concentration. These results provide insights into melatonin-induced fruit coloration and will facilitate the application of exogenous melatonin in agriculture.

Macrolobium latifolium Vogel belongs to the Fabaceae family and ethnopharmacological investigations have shown that some species from this family have been popularly used for treatment of chronic diseases. M. latifolium is widely distributed in semi-arid Bahia (Brazil) but reports on its biological activity and chemical composition are absent. In this context, our aim was to evaluate the preliminary chemical constitution and biological activity of M. latifolium stem bark. Overall, ethyl acetate fraction of M. latifolium stem bark (EAFML) was the most effective in reducing DPPH• (2,2-diphenyl-1-picrylhydrazyl radical) and ABTS•+ (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid cation radical) radicals in vitro (IC50 = 8.4 and 4.6 μg/mL, respectively) and protecting H2O2-exposed Raw 264.7 macrophages against cell death. Similarly, EAFML enhanced the heme oxygenase activity of Raw 264.7 macrophages in concentration-dependent manner, suggesting the involvement of Nrf2 pathway. EAFML demonstrated the highest antibacterial activity on Staphylococcus aureus (MIC = MBC = 250 µg/mL), Staphylococcus epidermidis (MIC = 50 µg/mL and MBC = 100 µg/mL), Klebsiella pneumoniae (MIC = MBC = 100 µg/mL), and Proteus mirabilis (MIC = MBC = 100 µg/mL) when compared among other fractions. In addition, proliferation of HepG2 (human hepatocellular carcinoma), MCF7 (human breast carcinoma), and HCT116 (human colon carcinoma) tumor cells were significantly reduced by EAFML (IC50 = 26.4, 19.9, and 22.1 μg/mL, respectively), with no evidence of toxicity against non-tumor cells (MCR5, human fibroblast) and Raw 264.7 macrophages. Classical phytochemical assays and UPLC-MS/MS analysis revealed the presence of quercetin-type flavonols and oleanane-type triterpenoids in the EAFML, which may be related to its biological activities. In conclusion, this study demonstrated the variety of biological properties of M. latifolium stem bark, indicating its therapeutic potential as source of molecules for treatment of oxidative and infectious disorders, as well as cancer.

Mechanisms associated with the control of flower color in crape myrtle varieties have yet to be sufficiently elucidated, which has tended to hamper the use of modern molecular and genetic strategies in the breeding programs for this plant. The whole transcriptome of four L. indica varieties characterized by different flower colors (white, light purple, deep purplish pink, and strong red) was sequenced, and we performed bioinformatic, quantitative PCR, and co-expression analyses of R2R3 MYB transcription factor and anthocyanin/flavonol pathway genes. We obtained a total of 49,980 transcripts with full-length coding sequences. Both transcriptome and qPCR analyses revealed that anthocyanin/flavonol pathway genes were differentially expressed among the four different flowers types, with the expression of LiPAL, LiCHS, LiCHI, LiDFR, LiANS/LDOX, and LiUFGT being induced in colorful flowers, whereas that of LiF3´5´H, LiFLS, and LiLAR was found to be inhibited. Base on phylogenetic analysis, seven R2R3 MYB transcriptional factors were identified as putative regulators of flower color. The molecular characteristics and co-expression patterns indicated that these MYBs differentially modulate their target genes, with two probably acting as activators, three as repressors, and one contributing to the regulation of vacuolar pH. The findings of this study indicate that the anthocyanin biosynthesis is more active than the flavonol and proanthocyanin in the colorful flowers. These observations provide new genomic information on L. indica and contribute gene resources for the flower color-targeted breeding of crape myrtle.

Aqueous methanolic (20:80) crude extract of the outer peel of Allium ascalonicum (onions) was fractionated into anthocyanin (II), acidic (i.e., phenolic acids, Ia), neutral A (i.e., flavanols, Ib) and neutral B (i.e., flavonols, Ic) phenols using C-18 and hydrophilic-lipophilic balanced (HLB) Co-polymer cartridges. The fractions were analysed for total phenolic, total flavonoids, antibacterial activity, antioxidant potential and lipoxygenase (LOX) inhibition. The recovery of total phenols and bio functional activity in all fractions were found to be more in HLB. All fractions showed antimicrobial activity against tested strains with phenolic acids (Ia) being most active and flavanol (Ib) least active, while the highest free radical scavenging, reducing power and LOX inhibition was exhibited by flavonol (Ic) and least by flavanols (Ib). HPLC analysis revealed the presence of vanillic acid and quercetin in non-anthocyanin I and cyanidin in anthocyanin II.

Nowadays, due to the high cost of active substances extraction operations from medicinal plants, it is very important to determine the best harvest time and organ type for extraction in order to reduce costs. The peel essential oil (EO) of citrus fruits can be considered as valuable by-products of manufacturing process, or they can be considered as main products extracted from specific cultivars of citrus. The essential oil obtained from Grapefruit (Citrus × paradisi) peel, which is considered as waste, contains valuable compounds having many applications in various food, cosmetics and pharmaceutical industries. As regards phytochemicals content change in different stages of fruit development, an experiment was conducted to investigate the phytochemical responses in relation to EO (quantity and quality) and antioxidant compounds (total phenolic compounds, flavones and flavonols, total flavonoids, free radical scavenging activity and tannin content) of Grapefruit peel during flavedo color change stages [green stage (GS), yellowish green stage (YGS), yellow stage (YS), and pinkish yellow stage (PYS)]. Also, correlation coefficient between most important properties are studied. The results showed significant changes in grapefruit EO content and composition during different fruit maturation stages. Monoterpene hydrocarbons in EO were the most abundant components in all stages (93.87–96.80%), such that limonene identified as the major compound (90.92–93.98%). EO yield and content (0.126 ml in fruit, 0.43% v/w), limonene amount and antioxidant activity (62.81%) at the YS and YGS were higher than other stages, thus fruits at YS and YGS are the best harvest time for EO extraction from grapefruit peel.

Flavonoids are a broad group of bioactive compounds with anticarcinogenic effects on the prostate that have been scarcely evaluated in Latin American populations. Our objective was to evaluate the association between dietary patterns of flavonoid intake and prostate cancer (PC) in a population-based case–control study carried out in Mexico City. Based on a semi-quantitative FFQ with a frame reference of 3 years before diagnosis or interview, we used an updated database for estimating the daily intake (mg/d) of flavones, flavonols and flavanols for 395 confirmed incident PC cases and 797 population controls matched by age (± 5 years). Histological PC differentiation was evaluated using the Gleason score at diagnosis. Flavonoid dietary intake patterns (FDIP) were determined through principal component analysis, and their association with PC was estimated using logistic regression models. Three FDIP were identified: gallate pattern (GP) characterised by (–)-epicatechin-3-O-gallate, (–)-epigallocatechin-3-O-gallate and (+)-gallocatechin; luteolin pattern (LP) characterised by luteolin and (–)-epigallocatechin-3-O-gallate; and a mixed pattern (MP) that included (+)-catechin, (–)-epicatechin and quercetin. A higher GP (ORT3 v.T1 = 0·47; 95 % CI 0·33, 0·66) and LP intake (ORT3 v. T1 = 0·39; 95 % CI 0·27, 0·59) were associated with a decreased PC likelihood. In contrast, a higher MP intake (ORT3 v. T1 = 2·32; 95 % CI 1·67, 3·23) increased PC likelihood. The possible differential and synergistic anticarcinogenic role of flavonoid compounds in PC deserves further study.

Exposure to heat in the male reproductive system can lead to transient periods of partial or complete infertility. The current study aimed to examine the beneficial effects of Fisetin against spermatogenic disorders in mice affected by long-term scrotal hyperthermia. For this purpose, hyperthermia was induced daily by exposure to the temperature of 43 °C for 20 min for 5 weeks. Except for the Healthy group, six other groups were exposed to heat stress: two treated groups including Preventive and Curative which received oral administration of fisetin (10 mg/kg/day) starting immediately before heat exposure and 15 consecutive days after the end of the heat exposure, respectively. And for each treated group, two groups including Positive Control (Pre/Cur+PC group) and vehicle (Pre/Cur+DMSO group) were considered. Our results showed that the testicular volume; the density of spermatogonia, primary spermatocyte, round spermatid, and Sertoli and Leydig cells; and sperm parameters, as well biochemical properties of the testis tissue, were remarkably higher in both Preventive and Curative groups compared to the other hyperthermia-induced groups and were highest in Preventive ones. Unlike the c-kit gene transcript which was significantly increased in the Fisetin treatment groups (specially the Preventive group), the expression of HSP72 and NF-kβ genes, Caspase3 protein, and DFI in sperm cells were significantly more decreased in Preventive and Curative groups compared to other hyperthermia-induced groups and were lowest in Preventive ones. Overall, Fisetin exerts preventive and curative effects against spermatogenic disorders induced by long-term scrotal hyperthermia.

The aggregation of α-synuclein is linked to neurological disorders, and of these, Parkinson's disease (PD) is among the most widely studied. In this background, we have investigated here the effects of three α, β-unsaturated carbonyl based plant metabolites, daidzein, fisetin and scopoletin on α-Syn aggregation. The ThT and light scattering kinetics studies establish that these compounds have ability to inhibit α-Syn fibrillation to different extents; this is confirmed by TEM studies. It is pertinent to note here that daidzein and scopoletin have been predicted to be able to cross the blood brain barrier. ANS binding assays demonstrate that the compounds interfere in the hydrophobic interactions. The tyrosine quenching, molecular docking and MD simulation studies showed that the compounds bind with α-Syn and provide structural rigidity which delays onset of structural transitions, which is confirmed by CD spectroscopy. The results obtained here throw light on the mechanisms underlying inhibition of α-Syn fibrillation by these compounds. Thus, the current work has significant therapeutic implications for identifying plant based potent therapeutic molecules for PD and other synucleinopathies, an area which needs extensive exploration.

We investigate the antioxidant activity and protective effects of the aqueous leaf extract of Pistacia lentiscus (AELPL) against ulcerative colitis induced by acetic acid infusion through the rectum in Wistar rats. Phytochemical analyses allowed the identification of numerous phenolic compounds in P. lentiscus leaves such as flavonoids (isoquercetin and luterolin), flavonols (catechin, rutin, and kaempferol), phenolic acids (ellagic and dicaffeoylquinic), and tanins. Acetic acid exposure induced macroscopic colonic mucosal lesions with hemorrhage, congestion, edema, and the development of an expected oxidative stress state revealed by an increase in lipoperoxidation and carbonylation of proteins and a decrease in sulfhydryl (SH) group levels and antioxidant enzyme activities such as superoxide dismutase, catalase, glutathione-S-peroxidase, and glutathione transferase, as well as an increase in the inflammatory cytokine, interleukin-6, in the colon and plasma. Administration of acetic acid also increased plasma and tissue levels of hydrogen peroxide and rates of iron and free calcium, whereas AELPL significantly and dose-dependently attenuated all the previous biochemical alterations and intracellular mediator perturbations. In conclusion, the AELPL exhibited a potent cytoprotective effect against acetic acid-induced colitis in rats, mainly through its antioxidant and anti-inflammatory activities.

This work was conducted to optimize an accelerated solvent extraction for ultra high performance liquid chromatography-mass spectrometry/mass spectrometry analysis of blueberry phenolic compounds. The conditions for accelerated solvent extraction were verified using response surface methodology to obtain the following optimized conditions: ethanol concentration (pH = 3), 48%; temperature, 50℃, and static cycle times, 3. Further, ultra high performance liquid chromatography with quadrupole Exactive Orbitrap mass spectrometry and ultra high performance liquid chromatography with triple-quadrupole tandem mass methods for determination of the detailed phenolic composition were developed and validated. Total of 81 phenolic compounds were identified by ultra high performance liquid chromatography with quadrupole Exactive Orbitrap mass spectrometry including 23 anthocyanins, 32 flavonols, 11 proanthocyanidins, 2 other flavonoids, and 13 phenolic acids. Fifty-one of these compounds have been simultaneously quantified by ultra high performance liquid chromatography with triple-quadrupole tandem mass including 31 anthocyanins, 8 flavonols, 6 proanthocyanidins, 2 other flavonoids, and 8 phenolic acids. Malvidin-dinhexoside has, for the first time, been detected in wild. Moreover, by verifying the protection on PC12 cells against oxidative damage, it was showed that the phenolic extracts (500 µg/mL) can improve significantly the viability (9.26-24.78%) of hydrogen peroxide-induced PC12 cells, activities of superoxide dismutase (34.59-37.90 U/mg) and glutathione peroxidase (6.87-14.42 mU/mg) and decrease the content of malonic dialdehyde (13.27-24.62 nmol/mg). Correlation analysis suggested that anthocyanins might contribute most to these activities.

The aim of the study was to compare the variability of the composition, chemical identity and content of biologically active phenolic compounds in the fruits and leaves of the blue honeysuckle (Lonicera subsection Caeruleae) plants of different environmental and geographic provenances, sampled from the introduction plantation station in the forest steppe zone near the Ob River (Novosibirsk, Russia). In extracts from the leaves 25 individual compounds representing various polyphenolic classes were identified using HPLC-MS technique; seven of the compounds were identified as hydroxycinnamic acids, five compounds were flavonols, and eight compounds represented flavones. The maximal number of individual compounds was present in samples of the Altai subspecies of the tetraploid species L. caerulea subsp. altaica, whereas the minimal number was detected in samples of L. boczkarnikowae, a diploid species from the Russian Far East (Primorsky region). The lowest total polyphenolics content (6,260 mg/100 g of air-dry phytomass) was found in samples of L. caeruleae subsp. pallasii, whereas the content in samples from other blue honeysuckle subspecies ranged within 11.620-14.030 mg/100 g of air-dry phytomass. High content of flavones in extracts from leaves, always exceeding the flavonol content, was found to be a characteristic feature of L. caerulea subsp. altaica. Among L. сaerulea subspecies, L. сaerulea subsp. pallasii was shown to have the largest ratio of flavonols to flavones. L. boczkarnikowae also had high content of flavonols, significantly exceeding the flavones content in the plants organs. The main component of anthocyanins was cyanidin-3-glucoside, accounting for up to 91%. The fruits of L. caerulea subsp. altaica, L. сaerulea subsp. venulosa and L. boczkarnikowae had the highest anthocyanin content, ranging 2.950–3.200 mg/100 g air-dry phytomass, whereas the fruits of L. сaerulea subsp. pallasii had the lowest one (1,573 mg/100g). Extracts from the leaves were found to have significantly higher polyphenolics content as compared to the ones from the fruits; thus the leaves can be recommended as a prospective medicinal source., Целью данной работы было сравнительное изучение изменчивости индивидуально-группового состава биологически активных фенольных соединений плодов и листьев образцов рода Lonicera подсекции Caeruleae разного эколого-географического происхождения в интродукционной популяции лесостепи Приобья (г. Новосибирск). Методом ВЭЖХ-МС анализа в составе экстрактов листьев определено 20 соединений, относящихся к разным классам полифенолов, из которых 7 компонентов – гидроксикоричные кислоты, 5 компонентов – флавонолы и 8 компонентов – флавоны. Максимальное число компонентов содержится в образцах алтайского подвида тетраплоидного вида – L. caerulea subsp. altaica, минимальное число компонентов – в L. boczkarnikowae (диплоидный вид из Приморского кр.). Образцы L. caeruleae subsp. pallasii отличались наименьшим суммарным содержанием полифенолов в листьях (6260мг/100 г воздушно-сухой массы). У остальных представителей голубых жимолостей уровень накопления полифенолов изменялся в пределах 11620-14030 мг/100 г. Характерной чертой L. caerulea subsp. altaica является высокая концентрация флавонов в экстрактах листьев, содержание флавонов в них всегда выше, чем содержание флавонолов. L. сaerulea subsp. pallasii выделяется среди подвидов L. caerulea наибольшим отношением между содержанием флавонолов и флавонов. L. boczkarnikowae также характеризуется высоким содержанием флавонолов, значительно превышающим концентрацию флавонов в органах растений. В качестве основного компонента антоцианов плодов голубых жимолостей идентифицирован цианидин-3-глюкозид (до 91%). Наибольшее количество антоцианов содержится в плодах L. caerulea subsp. altaica, L. сaerulea subsp. venulosa и L. boczkarnikowae (2950–3200 мг/100 г), а наименьшее в L. сaerulea subsp. pallasii (1573 мг/100 г). В экстрактах листьев содержание и количество компонентов полифенолов значительно выше, чем в плодах, что позволяет рекомендовать их как лекарственное сырье.

Flavonoids are secondary metabolites that are widely distributed in plants with numerous biological functions. This study focused on Liquidambar formosana, a tree species rich in flavonoids that are used for ornamental and medicinal purposes. To better understand the chemical processes leading to seasonal variation in leaf color in L. formosana ‘Nanlinhong,’ we selected four colors of leaves in three seasons from the same individual trees, bright red in early spring, red in middle spring, green in summer, and dark red in autumn. The three-year-old trees of this variety were grown in the greenhouse under natural light with day and night temperatures from 30 to 23 ℃, and fully expanded leaves from the top of each individual were employed in flavonoid analyses. The results showed that the total flavonoid content was highest in spring, while anthocyanidin content was highest in autumn leaves. A total of 148 flavonoid metabolites were found using the Ultra-Performance Liquid Chromatography–Electrospray Ionization–Tandem Mass Spectrometry (UPLC-ESI–MS/MS) method; the compounds comprised 58 flavones, 33 flavonols, 18 flavanones, 16 polyphenols, 15 anthocyanins, six isoflavones, and two proanthocyanins. Through clustering analysis, a total of 122 types of metabolites were found in spring with higher expression levels, and 104 metabolites were found in autumn, indicating that flavonoids were more predominant in spring. To date, only 23 flavonoid compounds had been identified in this tree species, but the present study revealed 100 new compounds. In addition, our findings provide strong support for a differentiated use of L. formosana ‘‘s leaves from different seasons in targeting a wide range of medical conditions.

Flavonoids are a group of phenolic secondary metabolites in plants that have important physiological, ecological and economic value. In this study, using the desert plant Artemisia sphaerocephala Krasch. as the sample material, the content and components of the total flavonoids in its seeds at seven different developmental stages were determined. In addition, the genes involved in flavonoid metabolism were identified by full-length transcriptome sequencing (third-generation sequencing technology based on PacBio RS II). Their expression levels were analysed by RNA-seq short reading sequencing, to reveal the patterns and regulation mechanisms of flavonoid accumulation during seed development. The key results were as follows: the content of total flavonoids in mature seeds was 15.05 mg g−1, including five subclasses: flavonols, chalcones, flavones, flavanones and proanthocyanidins, among which flavonols accounted for 45.78%. The period of rapid accumulation of flavonoids was 40–70 d following anthesis. The high expression of phenylalanine ammonia-lyase (PAL), 4-coumarate-CoA ligase (4CL) and UDP-glucose:flavonoids 3-o-glucosyltransferase (UF3GT) promoted the accumulation of total flavonoids, while the high expression of flavonoids 3′-hydroxylase (F3′H) and flavonols synthase (FLS) made flavanols the main component. Transcription factors such as the MYB-bHLH-WDR (MBW) complex and Selenium-binding protein (SBP) directly regulated the structural genes of flavonoid metabolism, while C2H2-type zinc finger (C2H2), Zinc-finger transcription factor (GATA), Dehydration-responsive element binding (DREB), Global Transcription factor Group E protein (GTE), Trihelix DNA-binding factors (Trihelix) and Phytochrome-interacting factor (PIF) indirectly promoted the synthesis of flavonoids through hormones such as brassinoidsteroids (BRs) and abscisic acid (ABA). These results provided valuable resources for the application of related genes in genetics and breeding.

Active composite films were developed by incorporating different concentration of dihydromyricetin (DMY) into konjac glucomannan (KGM)/gellan gum (GG) matrix. Physicochemical, mechanical, released behaviour, antioxidant and antimicrobial properties of composite films were investigated. The results from the Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) indicated that DMY which well-dispersed in the KGM/GG matrix interacted with matrix through hydrogen bonds. The obtained films presented predominant thermostability, good water resistance property, excellent ultraviolet light barrier ability and sustained controlled release behaviour. In particular, the incorporation of DMY remarkably enhanced the antioxidant and antimicrobial activities of the films. Overall, the fabricated KGM/GG-DMY composite films have a promising application in the fields of food packaging.

Background Emerging drug-resistant strains of Candida albicans have led to the recurrence of fungal disease, rendering conventional drug therapies ineffective. Although in vitro studies on flavonoids as novel antifungal products have shown promising results, there is currently limited information regarding their in vivo effects. The aim of this review is to evaluate in vivo studies on the antifungal activity of flavonoids against C. albicans, as novel therapeutic agents. In this regard, we conducted broad searches of PubMed, Web of Science, and Embase covering the years 2009–2020. Highlight Flavonoids represent new natural therapeutic compounds to treat oral candidiasis. Among subclasses of flavonoids, flavonols and chalcones appear to have the most significant antifungal activities. Oral administration of Canthin-6-one, a flavonol, has the potential to damage fungal cell membrane while having minimal toxic effects on mice. Similarly, topical oral application of lichochalcone-A, a chalcone, reduces oral candidiasis in mice. There appears to be structural similarities in the hydroxyl residues among compounds within the same subclass of flavonoids, which may contribute to antibiofilm activity. Oral topical application of flavonoids shows low toxicity and has clinical relevance as potential novel antifungal treatments. Conclusion Flavonoids are a group of natural products exhibiting antifungal activity. The subclasses flavonols and chalcones appear to have the most significant in vivo antifungal activity against C. albicans infections in mouse models. Specifically, quercetin (flavonol) has been applied via vaginal gavage in a murine vulvovaginal candidiasis model, whereas lichochalcone-A (chalcone) has shown topical oral application in C. albicans-inoculated mice. Both compounds show efficacy in fungal elimination via biofilm inhibition for their respective subclasses. The translational significance of these in vivo studies should be examined in clinical trials of selected potent compounds for the treatment of oral candidiasis. Further studies are necessary to elucidate the specific mechanisms of flavonoids as antifungal agents.

Background: Lotus maritimus L. (Fabaceae) is a perennial herb species with yellow flowers, growing in Europe, Asia, Middle East and Maghreb. Some flavones and flavonols have been identified in their leaves and flowers. Their leaf extract was used as a cellulolytic and antiaging cosmetic ingredient. Objective: The aim of this work was to perform antioxidant, anti-tyrosinase and anti-elastase properties of L. maritimus aerial parts and their chemical profile. Methods: A 13C NMR-based dereplication method combined with a bio-guided purification was used for metabolite identification. Chemical structures were determined by NMR and ESI-MS spectroscopic methods. The antioxidant properties of the fractions and purified compounds were measured using CUPRAC, DPPH and hydroxyl radical scavenging assays. Their inhibitory activities against the fungal tyrosinase and human neutrophil elastase enzymes were also evaluated. Results: EtOAc and n-BF fractions were characterized as the most active parts. Twenty-two compounds were identified from these fractions by using a 13C NMR-based dereplication method. This process was completed by the purification of minor compounds in the n-BuOH fraction. Eight known compounds were isolated, including many mono-glycosylated flavonoids with variable substitutions on the B-ring, allowing structure-activity relationships. Conclusion: Twenty-two compounds, including phenolic acids, flavonoids and glycoside derivatives, were firstly described in L. maritimus. Three quercetin and myricetin-type flavonoids exhibited good antioxidant activities and all flavonoids tested have moderate effects on elastase inhibition.

Oxidative stress that damages cellular components affects various organs including the brain. It is thus believed to play an active role in neurodegenerative diseases, wherein the intrinsic antioxidant enzymes metabolize toxic intermediates. For therapeutic purpose, instead of antioxidant enzymes, small organic compounds as antioxidants may be more effective. Here, reducing power and electrochemical behavior of some flavanols, flavanonols, flavones, flavonols and O-methylated flavonols have been estimated and confirmed by the calculated bond dissociation energy. Compared to other classes, flavonols exhibited increased reducing power that decreased with methylation of the oxygen atom in the B-ring. Gossypetin emerged as the most effective of these flavonols. Generally, compounds with two hydroxyl groups in two consecutive positions of the phenyl ring and an enolic group in the C-ring with more preference for the hydroxyl group in the ortho position with respect to each other in the catechol moiety showed major activity. 5 position of the A-ring showed the least effect on the activity. The present understanding therefore may be applied for identifying compounds to be used as scaffold for designing potent antioxidants.

Cognitive deficits are the core feature of schizophrenia and effective treatment strategies are still missing. Previous studies have reported that fisetin promotes long-term potentiation (LTP) and cognitive function in normal rodents and other model animals of neurological diseases. The aim of the present study was to assess the effect of fisetin on synaptic plasticity and cognitive deficits caused by a brief disruption of N-methyl-D-aspartate receptors (NMDARs) with dizocilpine (MK-801) during early development in rats. The cognitive performance was examined by the Morris water maze task and a fear conditioning test. Hippocampal synaptic plasticity was investigated by field potential recording. The expression of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) and cognition-related proteins were measured by Western blotting. We found that intraperitoneal administration of fisetin rescued hippocampus-dependent spatial and contextual fear memory in MK-801 rats. In parallel with these behavioral results, fisetin treatment in MK-801 rats reversed the impairment of hippocampal LTP. At the molecular level, fisetin treatment selectively increased the phosphorylation and surface expression of AMPA receptor subunit 1 (GluA1) in MK-801-treated rats. Moreover, fisetin restored the phosphorylation levels of calcium-calmodulin-dependent kinaseII (CaMKII), cAMP response element-binding protein (CREB) and the extracellular signal-regulated kinase (ERK1/2) in MK-801-treated rats. Collectively, our findings demonstrate that fisetin treatment can reverse the deficits of hippocampal synaptic plasticity and memory in a male rat model of schizophrenia by restoring the phosphorylation and surface expression of AMPAR GluA1 subunit, suggesting fisetin as a promising therapeutic candidate for schizophrenia-associated cognitive deficits.

Context Hepatic encephalopathy (HE) is a complex neuropsychiatric disease caused by liver failure. Dihydromyricetin (DMY) is a traditional medicine used to treat liver injury. Objective To investigate the effects of dihydromyricetin (DMY) on hepatic encephalopathy associated with acute hepatic failure mice models established by thioacetamide (TAA) exposure. Materials and methods Female BALB/c mouse were randomly divided into control, DMY, TAA, and TAA + DMY groups (n = 8). The first two groups were intraperitoneally injected with saline or 5 mg/kg DMY, respectively. The last two groups were injected with 600 mg/kg TAA to establish HE models, and then the mice in the last group were treated with 5 mg/kg DMY. Neurological and cognition functions were evaluated 24 and 48 h after injection. Mice were sacrificed after which livers and brains were obtained for immunoblot and histopathological analysis, while blood was collected for the analysis of liver enzymes. Results In the TAA + DMY group, ALT and AST decreased to 145.31 ± 12.88 U/L and 309.51 ± 25.92 U/L, respectively, whereas ammonia and TBIL decreased to 415.67 ± 41.91 μmol/L and 3.31 ± 0.35 μmol/L, respectively. Moreover, MDA decreased to 10.74 ± 3.97 nmol/g, while SOD and GST increased to 398.69 ± 231.30 U/g and 41.37 ± 21.84 U/g, respectively. The neurological score decreased to 2.87 ± 0.63, and the number of GFAP-positive cells decreased to 41.10 ± 1.66. Furthermore, the protein levels of TNF-α, IL-6, and GABAA in the cortex decreased. Conclusions We speculate that DMY can serve as a novel treatment for HE.

Water deficit is the main reason for sugar yield losses in semi-arid areas. Triazole derivatives may mitigate the harmful impacts of water stress. Therefore, this study aimed to assess the effect of tebuconazole (TEB) application on antioxidants, root quality traits, and sugar yield under drought stress conditions. The treatments included three levels of irrigation set according to crop evapotranspiration (ETC): 100%, 75%, and 50% ETC, as well as three levels of TEB (0, 25, and 50 mg L−1). While significantly increasing antioxidant and alpha-amino-nitrogen (α-amino-N) contents, limited irrigation decreased total chlorophyll content, net photosynthesis rate, leaf relative water content, the weight of roots, and sugar yield. In contrast, TEB treatment resulted in a marked rise in all biological and physiological traits as well as enzymatic antioxidants. Our findings indicated that the decline in α-amino-N content might be linked to increased NR activity in response to the TEB application. Our results also showed that the stress-ameliorating role of TEB cannot be associated with the increase of flavonols (quercetin and rutin). Overall, the results demonstrated that TEB has a high potential for ameliorating the negative impacts of limited irrigation.

In this study, we carried out an exhaustive characterization of the polyphenol profile of strawberry, raspberry, blueberry, and blackberry decoctions; as well as the extractable (EPP) and hydrolysable (HPP) polyphenolic and proanthocyanidin profile of the residues obtained during berries decoctions (decoction by-products) by UPLC-ESI-Q-ToF MS. A greater variety of polyphenols was identified in the EPP fraction of the berry decoction by-products as compared to the decoctions, which were rich in several ellagitannins, flavonols, hydroxybenzoic acids, and anthocyanins. Ellagic acid was identified as the major polyphenol after acid hydrolysis in all berry decoction by-products, followed by hydroxybenzoic acid, which was found bound to the matrix by glycosidic, ether and ester bonds. Regarding proanthocyanidins, procyanidin, prodelphinidin, and propelargonidin dimers were identified in the strawberry, raspberry, and blackberry decoction by-products by MALDI-ToF MS. The results obtained from this study demonstrates that berries decoctions are rich in polyphenols; however, berry decoction by-products were richer in polyphenols with a great variety of extractable and non-extractable polyphenols.

Pulmonary fibrosis is a common pulmonary interstitial disease of pathogenesis without effective drugs for treatment. Therefore, discovering new and effective drugs is urgently needed. In the present study, we prepared a novel compound named acetyl oxygen benzoate engeletin ester (AOBEE), investigated its effect on experimental pulmonary fibrosis, and proposed a long non-coding RNA (lncRNA)-mediated mechanism of its action. Bleomycin-induced pulmonary fibrosis in mice exhibited that AOBEE improved forced vital capacity (FVC) and alveolar structure and inhibited α-SMA, vimentin, and collagen expression. TGFβ1-stimulated fibroblast L929 cells showed that AOBEE reduced these fibrotic proteins expression and inhibited the activated-fibroblast proliferation and migration. Whole transcriptome sequencing was performed to screen out lncRNA-lnc865 and lnc556 with high expression under bleomycin treatment, but AOBEE caused a considerable decrease in lnc865 and lnc556. Mechanistic study elucidated that AOBEE alleviated pulmonary fibrosis through lnc865- and lnc556-mediated mechanism, in which both lnc865 and lnc556 sponged miR-29b-2-5p to target signal transducer and activator of transcription 3 (STAT3). Further signal pathway inhibitors and the Cignal Finder 45-pathway reporter array illustrated that the up- and downstream pathways were TGFβ1-smad2/3 and p38MAPK, and Krüppel-like factor 4 (KLF4), respectively. In conclusion, AOBEE promoted KLF4 degradation leading to the attenuation of pulmonary fibrosis by inhibiting TGFβ1-smad/p38MAPK-lnc865/lnc556-miR-29b-2-5p-STAT3 signal pathway. We hope this work will provide valuable information to design new drugs and therapeutic targets of lncRNAs for pulmonary fibrosis treatment.

The plant family Caryophyllaceae, commonly known as the pink family, is divided into 3 subfamilies and contains over 80 genera with more than 2600 species that are widely distributed in temperate climate zones. Plants belonging to this family produce a variety of secondary metabolites important in an ecological context; however, some of these metabolites also show health-promoting activities. The most important classes of phytochemicals include saponins, phytoecdysteroids, other sterols, flavonoids, lignans, other polyphenols, essential oils, andN-containing compounds such as vitamins, alkaloids or cyclopeptides. Flavonoids are polyphenolic compounds that remain one of the most extensively studied constituents of the Caryophyllaceae family. Numerous structurally diverse aglycones, including flavones, flavonols, flavonones (dihydroflavones), flavonols, isoflavones, and theirO- orC-glycosides, exhibit multiple interesting biological and pharmacological activities, such as antioxidant, anti-inflammatory, anti-oedemic, antimicrobial, and immunomodulatory effects. Thus, this review analysed the flavonoid composition of 26 different genera and more than 120 species of Caryophyllaceae for the first time.

Tea is an important beverage source of dietary polyphenols and well known for containing phenolic structure diversity. A series of phenylpropanoid-substituted catechins, flavonols, flavan-3-hexoside, and proanthocyanidin are present in different herbs with various biological activities, inspiring our exploration of phenylpropanoid-substituted ester type of catechins (PSECs) due to the enrichment of galloylated catechins in tea. In this study, we used a guiding-screening-location-isolation integrated route including creating a hypothesized PSEC dataset, MS/MS data acquiring, construction of molecular networks, and traditional column chromatography and preliminarily identified 14 PSECs by MS/MS spectrum. Two of these PSECs were further purified and elucidated by NMR and CD spectra. Further MS detection in tea products and fresh leaves suggests that the production of the two new compounds was enhanced during tea processing. The synthesis mechanism was proposed to obtain these types of components for further investigation on their roles in human health protection. This study provides an example for the exploration of new functional ingredients from food sources guided by MS/MS data-based networking, and also new insights into the reaction mechanism to form new catechin conjugates among polyphenols in green tea.