Search

Diabetes mellitus (DM) is a complex metabolic disorder characterized by chronic hyperglycemia, with aldose reductase playing a critical role in the pathophysiology of diabetic complications. This study aimed to investigate the efficacy of flavonoid compounds as potential aldose reductase inhibitors using a combination of molecular docking and molecular dynamics (MD) simulations. The three-dimensional structures of representative flavonoid compounds were obtained from PubChem, minimized, and docked against aldose reductase using Discovery Studio’s CDocker module. The top 10 compounds Daidzein, Quercetin, Kaempferol, Butin, Genistein, Sterubin, Baicalein, Pulchellidin, Wogonin, and Biochanin_A were selected based on their lowest docking energy values for further analysis. Subsequent MD simulations over 100 ns revealed that Daidzein and Quercetin maintained the highest stability, forming multiple conventional hydrogen bonds and strong hydrophobic interactions, consistent with their favorable interaction energies and stable RMSD values. Comparative analysis of hydrogen bond interactions and RMSD profiles underscored the ligand stability. MMPBSA analysis further confirmed the significant binding affinities of Daidzein and Quercetin, highlighting their potential as aldose reductase inhibitors. This study highlights the potential of flavonoids as aldose reductase inhibitors, offering insights into their binding interactions and stability, which could contribute to developing novel therapeutics for DM complications.

Guanine-rich sequences of nucleic acids, including DNA and RNA, are known to fold into non-canonical structures named G-quadruplexes (G4s). Such arrangements of these macromolecular polymers are mainly located in telomeres and in promoter regions of oncogenes and, for this reason, they represent a potential target for compounds with therapeutic applications. In fact, the ligand-mediated stabilization of G4s inhibits telomerase and the activity of transcriptional machinery and counteracts cancer cell immortalization. Flavonoids, along with other classes of small molecules, have been previously tested for their ability to stabilize G4s, but the mechanism of their interaction has not been fully elucidated. In the current work, we report a multi-technique investigation on the binding of tosylated isoflavones obtained by the B-ring modification of compounds from Maclura pomifera to a telomeric DNA sequence. Our study demonstrates that such derivatization leads to compounds showing lower binding affinity but with an increased selectivity toward G4 with respect to double-stranded DNA. The binding mode to the macromolecular target G4 was studied by combining results from electrospray mass spectrometry binding studies, nuclear magnetic resonance experiments and computational simulations. Overall, our findings show that tosylation influences the selectivity toward the macromolecular target by affecting the interaction mode with the nucleic acid.

Cucumis sativus L. plants are subjected to stress during production, affecting their growth, development, and fruit quality due to abiotic factors. Thus, the aim of this research is to evaluate Pseudomonas paralactis, Sinorhizobium meliloti, and Acinetobacter radioresistens plant growth promoting rhizobacteria (PGPR) effect on C. sativus plants under three substrate moisture levels (100, 75, and 50%). A randomized complete block design (RCBD) was used with an A x B arrangement: (1) factor A (inoculant) with four levels; (2) PGPR and control (without bacterium); (3) factor B (substrate moisture content) with three levels. Plant height, root length, and fresh weight increased by inoculating PGPR (121%, 135%, and 134%, respectively); likewise, these variables increased with higher moisture content (177%, 204%, and 234%, respectively), while the effect of the interactions of the PGPR and the moisture content in the substrate showed statistical differences in plant height increasing of 197% and root length of 267%. On the other hand, the content of phenols, flavonoids, and antioxidant capacity was statistically different (p ≤ 0.05) in inoculated plants, with PGPR increasing by 117%, 126%, and 150% respectively. In the moisture content of the substrate, statistical differences were observed, with an increase in the flavonoid content (114%) and antioxidant capacity (116%). The assimilation of nitrogen was higher by 274% and phosphorus by 124% with the PGPR inoculation, the moisture content increased the nitrogen content in the plant (257%) and the phosphorus content in plant (135%), showing significant differences (p ≤ 0.05). However, the interaction of PGPR and moisture content only presented statistical differences in nitrogen assimilation. PGPR can be considered as an alternative to obtain vigorous cucumber seedlings.

Cardiovascular diseases (CVDs) are a global health problem. The mortality associated with them is one of the highest. Essentially, CVDs occur when the heart or blood vessels are damaged. Oxidative stress is an imbalance between the production of reactive oxygen species (free radicals) and antioxidant defenses. Increased production of reactive oxygen species can cause cardiac and vascular injuries, leading to CVDs. Antioxidant therapy has been shown to have beneficial effects on CVDs. Plants are a rich source of bioactive antioxidants on our planet. Several classes of these compounds have been identified. Among them, carotenoids and phenolic compounds are the most potent antioxidants. This review summarizes the role of some carotenoids (a/β-carotene, lycopene and lutein), polyphenols such as phenolic acids (caffeic, p-coumaric, ferulic and chlorogenic acids), flavonoids (quercetin, kaempferol and epigallocatechin gallate), and hydroxytyrosol in mitigating CVDs by studying their biological antioxidant mechanisms. Through detailed analysis, we aim to provide a deeper understanding of how these natural compounds can be integrated into cardiovascular health strategies to help reduce the overall burden of CVD.

Hyperlipidemia is a prevalent chronic metabolic disease that severely affects human health. Currently, commonly used clinical therapeutic drugs are prone to drug dependence and toxic side effects. Dietary intervention for treating chronic metabolic diseases has received widespread attention. Rosa sterilis is a characteristic fruit tree in China whose fruits are rich in flavonoids, which have been shown to have a therapeutic effect on hyperlipidemia; however, their exact molecular mechanism of action remains unclear. Therefore, this study aimed to investigate the therapeutic effects of R. sterilis total flavonoid extract (RS) on hyperlipidemia and its possible mechanisms. A hyperlipidemic zebrafish model was established using egg yolk powder and then treated with RS to observe changes in the integral optical density in the tail vessels. Network pharmacology and molecular docking were used to investigate the potential mechanism of action of RS for the treatment of hyperlipidemia. The results showed that RS exhibited favorable hypolipidemic effects on zebrafish in the concentration range of 3.0–30.0 μg/mL in a dose-dependent manner. Topological and molecular docking analyses identified HSP90AA1, PPARA, and MMP9 as key targets for hypolipidemic effects, which were exerted mainly through lipolytic regulation of adipocytes and lipids; pathway analysis revealed enrichment in atherosclerosis, chemical carcinogenic-receptor activation pathways in cancers, and proteoglycans in prostate cancer and other cancers. Mover, chinensinaphthol possessed higher content and better target binding ability, which suggested that chinensinaphthol might be an important component of RS with hypolipidemic active function. These findings provide a direction for further research on RS interventions for the treatment of hyperlipidemia.

Plants possess endless structural and chemical diversity, which is peerless with any synthetic library of small biomolecules, inspiring novel drug discovery. Plants are widely applied to encounter global health challenges such as antimicrobial resistance and diabetes. The objective of this work was to evaluate the antibacterial and antidiabetic potency of native plants grown in Cyprus. All plants were sequentially extracted with solvents of increasing polarity, namely hexane, acetone, methanol, and water. First, the phenolic and flavonoid contents of the extracts were assessed. Afterwards, the bacteriostatic and bactericidal potency of plant extracts were tested against a panel of six bacteria using the broth microdilution method, whereas the inhibitory effects on alpha-glucosidase and alpha-amylase enzymes were also determined with the employment of microplate assays. The results highlighted the superiority of Sarcopoterium spinosum as a potential enzyme inhibitor, while a knowledge base was also acquired for the inhibitory potential of all plants. Daucus carota, Ferula communis, and Tordylium.aegyptiacum displayed additionally outstanding bacteriostatic and bactericidal effects on Gram-positive bacteria at concentrations of 250 µg mL−1 and 500 µg mL−1. Overall, the present study describes the antibacterial and inhibitory activity against carbohydrate digestive enzymes of native plants grown in Cyprus delivering the first reports for many plant species.

Halophyte plants and seaweed are described in the literature as rich sources of antioxidant compounds that can be used in the pharmaceutical and food industries. In this work, we studied the antioxidant composition of five species of halophytic plants (Suaeda vera Forssk, Halimione portulacoides L., Inula crithmoides L., Salicornia ramosissima (Hook.f.) J. Woods and Sarcocornia perennis (Mill.) A.J.Scott) and three seaweeds (Gracilaria gracilis (Stackhouse) Steentoft, L.Irvine and Farnham, Fucus spiralis L. and Ulva rigida C. Agardh) collected in Sado Estuary, Portugal. In the case of the plants, different parts of the plant were also assessed. Various extraction procedures were also performed to understand which methods were most suitable for extracting the various antioxidant compounds. Therefore, the aim of this study was to characterize the antioxidant compounds in halophytes and seaweed using various methods (ABTS, DPPH and FRAP), as well as the phenolic (TPC) and flavonoid (TFC) contents in the different extracts obtained. The amount of soluble protein in each extract was also determined. The results show that methanolic extracts generally have a higher antioxidant capacity, while the highest soluble protein content was observed in aqueous extracts. The seaweed Fucus Spiralis showed the highest antioxidant content, while in halophytic plants the highest antioxidant content was detected in the leaves. In general, this work confirms the potential of halophytes and seaweed as sources of antioxidant compounds for use in the food and pharmaceutical industries.

Zika virus (ZIKV) is involved in the etiology of serious nervous system pathologies. Currently, there are no specific and effective vaccines or antiviral drugs to prevent the diseases caused by ZIKV. This study aimed to assess the activity of flavonoids present in crude hydroethanolic extract (CHE) and fractions obtained from B. holophylla leaves against ZIKV. O-glycosylated flavonoids were characterized by high-performance liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS/MS). The cytotoxic concentration and the effective concentration for 50% of the cells (CC50 and EC50, respectively) were determined, and the selectivity index (SI) was calculated. Molecular networks were constructed based on the chemical composition of the samples and global antiviral activity data using the Global Natural Products Social Molecular Networking (GNPS) platform. Protein–ligand docking was performed in the NS2B-NS3 protease, NS3 helicase, and NS5 methyltransferase of the ZIKV. CHE showed greater antiviral activity at a multiplicity of infection (MOI) of 1.0, with an EC50 of 11.93 µg/mL, SI = 13.38, and reduced cytopathic effects. Molecular networks indicated that O-glycosylated flavonoids are responsible for the activity against ZIKV, being quercetin-O-deoxyhexoside more selective and effective. Molecular docking confirmed the inhibitory activity of quercetin-O-deoxyhexoside, which showed an affinity for the tested targets, especially for NS2B-NS3 protease. The results showed that B. holophylla has flavonoids with potential for future therapeutic applications against ZIKV.

Distributed throughout the environment are various microorganisms such as bacteria, fungi, parasites, and viruses. Although many are part of the human microbiome, many are pathogenic and cause infections ranging from mild to severe. In recent years, the identification of multidrug-resistant microorganisms has become a serious public health problem. The resulting infections call into question the therapeutic capacity of health systems and lead to approximately 70,000 deaths annually worldwide. The progressive resistance to antibiotics and antifungals has been a major challenge for the medical and pharmaceutical community, requiring the search for new compounds with antimicrobial properties. Several studies have demonstrated the potential of natural and synthesized flavonoids, especially the dimers of these molecules. In this review are presented many examples of dimeric flavonoids that have demonstrated antimicrobial activity against viruses, like influenza and Human Immunodeficiency Virus (HIV), protozoal infections, such as Leishmaniasis and Malaria, fungal infections by Candida albicans and Cryptococcus neoformans, and bacterial infections caused, for example, by Staphylococcus aureus and Escherichia coli. In the pursuit to find potential safe agents for therapy in microbial infections, natural dimeric flavonoids are an option not only for the antimicrobial activity, but also for the low toxicity usually associated with these compounds when compared to classic antimicrobials.

At present, the occurrence of a large number of infectious and non-communicable diseases poses a serious threat to human health as well as to drug development for the treatment of these diseases. One of the most significant challenges is finding new drug candidates that are therapeutically effective and have few or no side effects. In this respect, the active compounds in medicinal plants, especially flavonoids, are potentially useful compounds with a wide range of pharmacological activities. They are naturally present in nature and valuable in the treatment of many infectious and non-communicable diseases. Flavonoids are divided into fourteen categories and are mainly derived from plant extraction, chemical synthesis and structural modification, and biosynthesis. The structural modification of flavonoids is an important way to discover new drugs, but biosynthesis is currently considered the most promising research direction with the potential to revolutionize the new production pipeline in the synthesis of flavonoids. However, relevant problems such as metabolic pathway analyses and cell synthesis protocols for flavonoids need to be addressed on an urgent basis. In the present review, new research techniques for assessing the biological activities of flavonoids and the mechanisms of their biological activities are elucidated and their modes of interaction with other drugs are described. Moreover, novel drug delivery systems, such as nanoparticles, bioparticles, colloidals, etc., are gradually becoming new means of addressing the issues of poor hydrophilicity, lipophilicity, poor chemical stability, and low bioavailability of flavonoids. The present review summarizes the latest research progress on flavonoids, existing problems with their therapeutic efficacy, and how these issues can be solved with the research on flavonoids.

Flavonoids share a common structural framework that serves as a hallmark indicative of their biological activity. In this study, we investigated the effects of two structurally similar flavonoids, fisetin and morin, through independent and combined in vitro assessments on embryonic mouse cells overexpressing the human 70 kDa heat shock protein (Hsp70) (Tg/Tg) and normal mouse fibroblast cell line (NIH/3T3). The primary objectives were to evaluate the biocompatibility and potential cytotoxicity of these flavonoids, along with assessing the cytoprotective role of Hsp70 in these cellular environments. To address these objectives, we conducted dose- and time-dependent cell survival tests. Additionally, we utilized flow cytometry to detect intracellular reactive oxygen species (ROS) production and to analyze apoptosis and the cell cycle. Throughout the experimental procedures, a notable observation was made: NIH/3T3 normal cells exhibited greater susceptibility compared to Tg/Tg cells when exposed to fisetin and morin. This difference in susceptibility is likely attributed to the robust cytoprotective effect of Hsp70 in Tg/Tg cells. Importantly, both cell lines demonstrated increased sensitivity to fisetin toxicity in comparison to morin, leading to significantly lower cell survival rates. These findings shed light on the differential responses of cell lines to flavonoid exposure, emphasizing the influence of Hsp70 and the distinct impact of fisetin and morin on cell viability.

Arthritis, a global health burden comprising osteoarthritis and rheumatoid arthritis, demands advanced therapeutic approaches. In this context, flavonoids, a diverse group of naturally occurring compounds abundant in fruits, vegetables, and medicinal plants, have emerged as promising candidates for mitigating the inflammatory processes associated with arthritic conditions. This review aims, first, to provide a comprehensive exploration of the potential of flavonoids, focusing on specific compounds such as quercetin, epigallocatechin-3-gallate (EGCG), apigenin, luteolin, fisetin, silibinin, kaempferol, naringenin, and myricetin. The second section of this review delves into the anti-arthritic activities of these flavonoids, drawing insights from clinical trials and scientific studies. Each flavonoid is scrutinized individually to elucidate its mechanisms of action and therapeutic efficacy in the context of both osteoarthritis and rheumatoid arthritis. The third section of this review highlights the challenges associated with harnessing flavonoids for anti-inflammatory purposes. Bioavailability limitations pose a significant hurdle, prompting the exploration of innovative strategies such as the use of nanoparticles as delivery vehicles. In response to these challenges, the fourth section focuses on the emerging field of flavonoid-based nanoparticles. This includes detailed discussions on quercetin, EGCG, fisetin, and naringenin-based nanoparticles, highlighting formulation strategies and preclinical evidence supporting their potential in arthritis management. The targeted delivery to inflammatory sites and the exploration of synergistic combinations with other compounds are also discussed as promising avenues to enhance the therapeutic impact of flavonoids. This review consolidates current knowledge on flavonoids and their nanoformulations as potential therapeutic interventions for osteoarthritis and rheumatoid arthritis. By addressing challenges and presenting future research directions, this review aims to contribute to the advancement of innovative and effective strategies for alleviating the global burden of arthritis.

Mast cells (MCs) are immune cells that reside in tissues; particularly in the skin, and in the gastrointestinal and respiratory tracts. In recent years, there has been considerable interest in the Mas-Related G Protein-Coupled Receptor X2 (MRGPRX2), which is present on the surface of MCs and can be targeted by multiple exogenous and endogenous ligands. It is potentially implicated in non-IgE-mediated pseudoallergic reactions and inflammatory conditions such as asthma or atopic dermatitis. In this paper, we review natural products and herbal medicines that may potentially interact with MRGPRX2. They mainly belong to the classes of polyphenols, flavonoids, coumarins, and alkaloids. Representative compounds include rosmarinic acid, liquiritin from licorice extract, osthole, and sinomenine, respectively. While evidence-based medicine studies are still required, these compounds have shown diverse effects, such as antioxidant, analgesic, anti-inflammatory, or neuroprotective. However, despite potential beneficial effects, their use is also burdened with risks of fatal reactions such as anaphylaxis. The role of MRGPRX2 in these reactions is a subject of debate. This review explores the literature on xenobiotic compounds from herbal medicines that have been shown to act as MRGPRX2 ligands, and their potential clinical significance.

Plant extracts can be therapeutic alternatives for depression and anxiety. However, some plant-derived preparations can also be toxic. Moringa oleifera leaves are used in human nutrition due to their high nutritional value and antioxidant activity. This study investigated a saline extract from M. oleifera leaves (MoLE) for secondary metabolites, proteins, cytotoxicity, hemolytic activity, in vivo acute oral toxicity, and neurobehavioral effects. MoLE contains flavonoids (rutin and vitexin), lectin, and a trypsin inhibitor. It is neither cytotoxic nor hemolytic for human cells and did not present acute oral toxicity (2000 mg/kg) to mice. The elevated plus maze test showed that MoLE (500, 1000, and 2000 mg/kg, p.o.) significantly increased the number of entries as well as the time spent by mice in open arms, while it decreased the number of entries and the time spent in closed arms when compared to the control. MoLE (500, 1000, and 2000 mg/kg, p.o.) reduced immobility time of mice in the tail suspension and forced swimming tests, compared to the control. The anxiolytic-like effect of MoLE is possibly mediated by a GABA mimetic action once it is prevented by pre-treatment with flumazenil. The present study demonstrated that MoLE has antidepressant and anxiolytic effects in mice and is a promising herbal medicine.

The objective of this study was to determine the optimal conditions for the recovery of bioactive and antioxidant compounds in aqueous solutions of Cistus creticus leaves and then employ the optimal extract for the enrichment of yogurt samples. The optimal conditions were established by a response surface methodology and were determined to be a liquid-to-solid ratio of 48 mL/g at 76 °C for 41 min. The optimum extract yielded TPC 157.17 mg GAE/g dw and TFC 2.38 mg QE/g dw, while FRAP and DPPH values were 1258.52 and 933.67 μmol AAE/g dw, respectively. HPLC-DAD was utilized to identify and quantify specific polyphenols, like myricetin rhamnoside, in the extract. The optimal extract was then added to yogurt desserts during their preparation at three different concentrations to study how the physicochemical characteristics of the yogurt, as well as the antioxidant capacity added during enrichment, were affected. Statistical analysis of the results was carried out in order to obtain more valid data. It seems that the most suitable concentration for yogurt fortification was 0.1% w/v of the extract as, at this concentration, the yogurts exhibited higher antioxidant capacity, and their physicochemical characteristics were improved.

Origanum dictamnus L. (Lamiaceae), a local endemic plant of Crete (Greece), creates polysaccharide-containing subcuticular compartments presenting biological activity against phytopathogenic fungi, and, among others, significantly affects the fungal cell wall polysaccharides. This field study introduces a fertilization scheme for O. dictamnus, which was developed and refined to optimize the yield as well as critical herbal quality aspects. Five fertilization schemes were investigated, based on a polysaccharide-based Integrated Nutrient Management (INM), a mixture of conventional inorganic fertilizers (ChF) and two biostimulants (not algae) via foliar and soil application. Plant growth, together with leaf chlorophyll fluorescence and color (SPAD meter, DA meter, Chroma Meter) were determined. The leaf content of chlorophyll, three critical antioxidant compounds (carotenoids, flavonoids, phenols) and nutrients were also assessed. Considering all three antioxidants together, the enhanced efficiency, non-toxic, water-soluble, polysaccharide-based INM by foliar application was the most stimulatory scheme, playing an important role in plant growth and development. The present field study provides, for the first time, baseline fertilization data improving key herbal quality features in O. dictamnus and unravels the attainment of high antioxidant properties. The latter may be exploited in favor of its further utilization as a raw material for tea preparation, medicinal purposes, natural food flavoring and/or food preservative.

Consuming fruits and vegetables necessitates discarding the inedible parts, which raises issues such as waste management and contamination of the environment. Numerous studies have been conducted in recent years in an effort to identify alternatives that reduce the negative effects of food and agricultural waste. This study aims to investigate the polyphenol recovery and the antioxidant capacity of overripe banana peel through cloud point extraction (CPE), which is a green method. The optimal conditions of the CPE were three steps of CPE with 10% w/v lecithin, which was used as surfactant, pH 7, and a salt concentration of 15% at 45 °C for 20 min. The total polyphenol content (TPC) was determined to be 541.25 mg GAE/L, the total flavonoid content (TFC) was determined to be 226.38 mg RtE/L, and FRAP and DPPH assays were found to be 2.52 and 2.91 mmol AAE/L, respectively. According to the results, the antioxidant compounds from banana peels can effectively be extracted with the proposed CPE procedure. The as-prepared extracts can potentially be used as food additives to improve human well-being and even as feed additives for a similar purpose.

The design of biosourced and/or bioinspired photoinitiators is an active research field as it offers a unique opportunity to develop photoinitiating systems exhibiting better biocompatibility as well as reduced toxicity. In this field, flavonoids can be found in numerous fruits and vegetables so these structures can be of interest for developing, in the future, polymerization processes, offering a reduced environmental impact but also better biocompatibility of the polymers. In this review, the different flavonoids reported to date as photoinitiators of polymerization are presented. Over the years, different modifications of the flavonoid scaffold have been examined including the grafting of well-known chromophores, the preparation of Type II photoinitiators or the introduction of photocleavable groups enabling the generation of Type I photoinitiators. Different families of flavonoids have also been investigated, enabling to design of high-performance photoinitiating systems.

As a byproduct of corn processing, corn husk is usually burned or disposed of. To make a better use of corn husk, its bioactive components need to be further explored. In this work, the carotenoids and phenolics of the extracts from the corn grain and corn husk of 15 different yellow corn and 8 different waxy corn were identified and quantified, and their antioxidant activities were assessed. The results showed many considerable variations in carotenoid contents. Four types of carotenoids were observed only in both yellow corn and black waxy corn. The highest lutein and zeaxanthin contents were both observed in yellow corn husks. Lutein dominates in yellow corn, ranging from 494.5 μg/g dw to 2870.8 μg/g dw, which is followed by zeaxanthin, ranging from 63.0 μg/g dw to 360.2 μg/g dw, and finally β-cryptoxanthin and β-carotene. The total content of polyphenols (TPC) and flavonoids (TFC) of the husk from 13 yellow corn cultivars, as well as the TPC of husk from 8 waxy corn cultivars, were all higher than those of their corn grain, with the highest TPC found in waxy corn husk. Additionally, a total of 20 phenolic compounds were identified, and ferulic acid showed the highest content and reached 1101.9 µg/g dw in a waxy corn husk. The average antioxidant activity of a waxy corn husk was 25–65% higher than that of a yellow corn husk, and the highest values were observed in the husk of the waxy corn cultivar Huhong 1. These results suggested that corn husk is a rich source of lutein and phenolics and provided excellent cultivars as a reference for functional food products in agriculture and the food industry.

This study examined the levels of major flavonoids, nutritional components, total secondary metabolite contents, and antioxidant activities in 136 mung bean accessions and statistically analyzed the effect of seed weight difference on each. Vitexin and isovitexin were detected in all the mung bean accessions, with isovitexin being in a higher concentration regardless of seed weight difference. The contents of total protein and total starch were in the ranges of 22.01–28.96 and 32.62–49.03 g/100 g, respectively. Five fatty acids were detected by GC–FID analysis in all mung bean accessions, with linoleic acid being the most dominant (37.96–50.71 g/100 g). Total saponin content (TSC), total phenol content (TPC), DPPH• scavenging activity, ABTS•+ scavenging activity, and ferric reducing antioxidant power (FRAP) showed more than five-fold differences. Analysis of variance supported by multivariate analysis demonstrated that seed weight difference had a significant effect on total starch, all individual fatty acids except for stearic acid and oleic acid, TSC, and all antioxidant activities except for ABTS•+ scavenging activity. On the other hand, vitexin, isovitexin, total protein, total phenol, and total fatty acid contents remained unaffected by seed weight difference. Overall, this study showed the diversity of key flavonoids, nutritional components, total secondary metabolite contents, and antioxidant activities in mung bean genetic materials. Moreover, the study unveiled how seed weight affects the analyzed parameters in mung beans for the first time. These findings could maximize the use of mung beans in food industries and breeding programs as well as lead to more studies in metabolomics and genomics.

The gut microbiota metabolizes flavonoids, amino acids, dietary fiber, and other components of foods to produce a variety of gut microbiota-derived metabolites. Flavonoids are the largest group of polyphenols, and approximately 7000 flavonoids have been identified. A variety of phenolic acids are produced from flavonoids and amino acids through metabolic processes by the gut microbiota. Furthermore, these phenolic acids are easily absorbed. Phenolic acids generally represent phenolic compounds with one carboxylic acid group. Gut microbiota-derived phenolic acids have antiviral effects against several viruses, such as SARS-CoV-2 and influenza. Furthermore, phenolic acids influence the immune system by inhibiting the secretion of proinflammatory cytokines, such as interleukin-1β and tumor necrosis factor-α. In the nervous systems, phenolic acids may have protective effects against neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases. Moreover, phenolic acids can improve levels of blood glucose, cholesterols, and triglycerides. Phenolic acids also improve cardiovascular functions, such as blood pressure and atherosclerotic lesions. This review focuses on the current knowledge of the effects of phenolic acids produced from food-derived flavonoids and amino acids by the gut microbiota on health and disease.

This is the first study to report on high performance thin layer chromatography (HPTLC) generated spectrophotometric data to systematically capture flavonoid compounds using optimized derivatization with either AlCl3 or NaNO2-AlCl3-NaOH as visualisation reagents. While the traditional AlCl3 colorimetric method using UV–Vis analysis provides valuable insights into the presence of flavonoids and allows derivation of the total flavonoid content (TFC) of a sample, HPTLC fingerprints obtained after spraying with AlCl3 or NaNO2-AlCl3-NaOH enable the visualization of the various flavonoids present in a sample based on their respective absorption shifts, thus complementing the traditional TFC assay. In this study, 40 different flavonoids representing different classes (flavonols, flavanolols, flavan-3-ol, flavones, flavanones, and isoflavonoids) were analysed. Upon derivatization with AlCl3 most of the investigated flavonoids recorded bathochromic shifts, yielding characteristic λmax values between 370 and 420 nm, while spraying with NaNO2-AlCl3-NaOH triggered hyperchromic shifts, and thus an increase in absorbance intensity in flavonoids with particular substitution patterns. A few non-flavonoid components with structural similarities to flavonoids (e.g., rosmarinic acid, gallic acid, aspirin, salicylic acid) served as the negative control in this study to determine whether the derivatization reagents allowed exclusive detection of flavonoids. The method was then applied to the analysis of flavonoid containing supplements as well as red clover honey to demonstrate the method’s application in the analysis of natural products.

Ginkgo (Ginkgo biloba L.) is a widely recognized medicinal plant, often grown as an ornamental species in parks around the world. Its leaves change color from green in spring to yellow in autumn. In this study, we collected ginkgo leaves at seven developmental stages from May to November and measured chlorophylls, carotenoids, flavonoids, and antioxidant activity. The total polyphenol content showed a significant increase from May to November, rising from 15.15 ± 0.14 mg GAE g−1 dw to 45.18 ± 0.42 mg GAE g−1 dw. The total flavonoid content reached its peak in August at 5.87 ± 0.18 mg GAE g−1 dw. In contrast, the highest concentrations of total polyphenolic acids (4.13 ± 0.16 mg CAE g−1 dw) and antioxidant activity (306.95 ± 3.47 µmol TE g−1) were recorded in May. We specifically focused on a less-studied group of dimeric flavonoids or biflavonoids—3′,8″-biflavones. We identified five 3′,8″-biflavones (amentoflavone, bilobetin, ginkgetin, isoginkgetin, and sciadopitysin) throughout all developmental stages. Sciadopitysin was the most abundant biflavonoid, with its concentration rising from 614.71 ± 5.49 µg g−1 dw in May to 2642.82 ± 47.47 µg g−1 dw in November. Alongside sciadopitysin, the content of other biflavonoids (excluding amentoflavone) generally increased over the same period. This trend is further highlighted by the total biflavonoid content, which grew from 1448.97 ± 6.63 µg g−1 dw in May to 6071.67 ± 97.15 µg g−1 dw in November. We observed a negative correlation between biflavonoid and chlorophyll content, which may indicate their involvement in leaf senescence. However, this hypothesis warrants further investigation.

Eclipta prostrata (Asteraceae) is employed as a hemostatic agent in many traditional medicines, owing to its sulfated flavonoid content. In this study, we obtained crude drug samples from three provinces collected in different years and analyzed their sulfated flavonoid contents using liquid chromatography–mass spectrometry (LC–MS) for quality evaluation. Because sulfated flavonoids are unstable and difficult to isolate from extracts, this study first synthesized a variety of sulfated flavonoids and accumulated spectral data in order to identify the compounds in E. prostrata. The LC–MS analysis of six crude drug samples revealed the presence of luteolin 7-sulfate, apigenin 7-sulfate, diosmetin 7-sulfate, and diosmetin 3′-sulfate. The samples without luteolin 3′-sulfate featured high apigenin 7-sulfate content. Although the samples were collected from the same locality, their compositions differed depending on the year of collection. Further, they were classified according to three patterns: (1) samples with luteolin 7-sulfate as the main component, (2) samples with apigenin 7-sulfate as the main component, and (3) samples with relatively high diosmetin sulfate content. Luteolin 7-sulfate typically exhibits relatively high erythrocyte aggregation efficiency and fibrinogen aggregation rate. These results demonstrate that the analysis of sulfated flavonoids is beneficial for the quality evaluation of E. prostrata for hemostatic applications.

Polyphenols are responsible for wine colour and astringency, and, as antioxidants, they also have beneficial health properties. In this work, we developed a robust full-scan high-resolution mass spectrometry method for the quantification of 90 phenolic compounds in wine samples (either red, rosé, or white wine), using a UHPLC-OrbitrapTM system. With this method, we could conduct a detailed analysis of phenolic compounds in red, rosé, and white wines with great selectivity due to sub-ppm mass accuracy. Moreover, accessing the full-scan spectrum enabled us to monitor all the other compounds detected in the sample, facilitating the adaptability of this method to new phenolic compounds if needed.

Background: Cardiovascular diseases rank as the top global cause of mortality, particularly acute myocardial infarction (MI). MI arises from the blockage of a coronary artery, which disrupts blood flow and results in tissue death. Among therapeutic approaches, bioactives from medicinal plants emerge as promising for the development of new medicines. Objectives: This study explored the effects of naringenin (NAR 100 mg/kg), a flavonoid found in citrus fruits, in normotensive (NTR) and spontaneously hypertensive (SHR) rats, both subjected to isoproterenol (ISO 85 mg/kg)-induced MI. Results: Post-treatment assessments indicated that NAR reduced blood pressure and minimized clot formation, particularly notable in the SHR group, which helps mitigate damage related to hypertension and ISO exposure. Additionally, NAR effectively restored KCl-induced contractility in the aortas of both NTR and SHR groups. NAR treatment reduced reduced glutathione (GSH) and lipid hydroperoxides (LOOH) values and recovered the activity of the antioxidant enzymes catalase (CAT) and glutathione-s-transferase (GST) in NTR groups. Moreover, myocardial damage assessed through histological analyses was reduced in groups treated with NAR. Conclusions: The results highlight significant pathophysiological differences between the groups, suggesting that NAR has protective potential against ISO-induced cardiac damage, warranting further investigation into its protective effects and mechanisms.

Typha angustifolia L. (TA) pollen has been utilized as a traditional Chinese medicine for treating various internal and external traumas. Moreover, bioactive compounds possess diverse pharmacological activities. This study aims to evaluate the antiviral properties of TA based on its ability to generate bioenergy, capable of inhibiting viruses. TA pollens were extracted using water and ethanol solvents. These extracts were utilized to identify the phytochemical contents and correlate with the antioxidant activity via 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays. HPLC analysis was conducted to identify its electron-shuttling compositions. The bioenergy-generating characteristics were determined via microbial fuel cells. The water extract (TA-W) showed higher antioxidant activity due to a higher phenolic and flavonoid content compared to the ethanol extract (TA-E). Quercetin-3-O-(2G-α-L-rhamnosyl)-rutinoside, quercetin-3-O-neohesperidoside, and quercetin are the electron shuttles (ES) identified out of the 11 compounds. TA obtained a 1.39 ± 0.10 amplification factor of power generation that indicates potential bioenergy-generating and associated antiviral characteristic properties. The findings may provide a foundation for developing antiviral medications specifically designed to target virus-related diseases, while minimizing the risk of drug toxicity and reducing the costs of drug development.

The optimization of artificial pollination is crucial in breeding programs for allogamous plants. In maize, achieving a balance between the labor-intensive nature of controlled pollinations and the need for large-scale production of hybrid seeds, along with considerations of germinability and pollen production, determines the success of genetic improvement programs. Breeding programs in maize have resulted in a reduction in the number of tassel branches to increase light interception and plant density in production fields. However, despite this genetic improvement, the decreased pollen production per plant has raised critical concerns regarding pollination and subsequent ear filling, especially under adverse environmental conditions. The aim of this work was the analysis of factors that can contribute to increasing the efficiency of controlled pollination in maize. The data obtained showed that pollen diameter, flavonoid, and phenolic acid content do not influence the percentage of germination and therefore the efficiency of pollination. The quantity of pollen is a central factor in ensuring the efficiency of controlled pollinations, and the data obtained by comparing traditional varieties with modern hybrids of maize showed that an increase in pollen production is determined by the increase in branching of the male inflorescence. Furthermore, we propose the use of a “smart” pollination method to make this step in maize breeding programs easier and faster.

Quercetin is the most abundant flavonoid present in fruits and vegetables. For its antiproliferative, antiviral, anti-inflammatory and antioxidants activities, it is an active ingredient of several herbal remedies and is available as a nutraceutical. Experimental studies performed in vitro have demonstrated that quercetin inhibits growth and function in normal thyroid cells and may act as a thyroid disruptor. These effects have also been confirmed in vivo using rodent models. Some studies have reported the ability of quercetin to interfere with the metabolism of thyroid hormones, since it inhibits the 5′-deiodinase type 1 (D1) activity in the thyroid, as well as in the liver. Besides the effects on normal thyroid cells, several experiments performed in vitro have shown a potential therapeutic role of quercetin in thyroid cancer. Indeed, quercetin inhibits the growth, the adhesion and the migration of thyroid cancer cells, and it also has redifferentiation properties in some thyroid cancer cell lines. In conclusion, these data suggest that, although its effects can be of benefit in hyperthyroidism and thyroid cancer, caution is required in the use of high doses of quercetin due to its anti-thyroid properties. Further in vivo studies are certainly needed to confirm these hypotheses.

Processing sustainability and the concept of zero waste discharge are of great interest for many industries. Every year, fruit and vegetable processing industries generate huge amounts of by-products, which are often intended for animal feed or discarded as waste, posing a problem to both environmental and economic points of view. However, to minimize the waste burden, the valorization of these residues received increased interest. In fact, fruit and vegetable by-products are an excellent source of valuable compounds, such as proteins, dietary fibers, lipids, minerals, vitamins, phenolic acids, flavonoids, anthocyanins, carotenoids, and pigments, which can be recovered and reused, creating new business prospects from a circular economy perspective. Understanding the chemical characteristics of these materials is a key concern for their valorization and the identification of their most appropriate intended use. In this study, the phytochemical and functional properties of fruit and vegetable processing by-products (peel and pomace) were investigated. Samples of different plants (i.e., apple, black and orange carrot, cucumber, kumquat, mango, parsnip, peach, black plum) were analyzed using chemical analytical methods and characterized using Fourier Transform Mid-Infrared spectroscopy (FT-MIR). The results highlighted their high nutritional composition in terms of protein, lipids, fiber, and ash, as well as bioactive and antioxidant profiles. These characteristics make these residues suitable as natural ingredients for the development of high-added-value products in food, cosmetic, and pharmaceutical industries.

This study optimized the extraction conditions to maximize the recovery yields of quercetin and total flavonoids from red onion skin waste using sequential microwave/ultrasound-assisted extraction. Five effective factors of quercetin extraction yield were investigated using response surface methodology. The method was successfully performed under optimal 60 s microwave irradiation conditions followed by 15 min sonication at 70 °C with 70% (v/v, water) ethanol with a solvent-to-solid ratio of 30 mL/g. The variance analysis of the model for both quercetin (Y1) and total flavonoid (Y2) recovery from DOS demonstrated that ultrasound temperature (X2) was the most highly significant and influential factor, with a p-value of 1X2, X2X4, and X2X5—were identified as highly significant, further underscoring the critical role of ultrasound temperature in optimizing the extraction process for both quercetin and total flavonoids. The maximum recovery yields of quercetin and total flavonoids from red onion skin were 10.32% and 12.52%, respectively. The predicted values for quercetin (10.05%) and total flavonoids (12.72%) were very close to the experimental results. The recovery yields obtained from different extraction methods under the identical experimental conditions mentioned earlier were ultrasound/microwave-assisted extraction (7.66% quercetin and 10.18% total flavonoids), ultrasound-assisted extraction (5.36% quercetin and 8.34% total flavonoids), and microwave-assisted extraction (5.03% quercetin and 7.91% total flavonoids). The ANOVA confirmed highly significant regression models (p-values < 0.0001), with an insignificant lack of fit (p = 0.0515 for quercetin, p = 0.1276 for total flavonoids), demonstrating the robustness and reliability of the optimization. This study provides valuable insights for improving the extraction of bioactive compounds, which is critical for developing effective cancer treatments and advancing medical research. Additionally, the model shows potential for scaling up food processing applications to recover valuable products from red onion skin waste.

The natural sweetness, unique flavour, and potential health benefits of honey make it a desirable ingredient for ice cream that can increase its appeal for consumers. The aim of this study was to investigate the polyphenolic content and sensory properties of ice cream made using a variety of New Zealand honey (clover, bush, pōhutukawa, rewarewa, kamahi, and thyme honey). The major polyphenols in honey ice cream were quinic acid, pinocembrin, hydroxybenzoic acid, pinobanksin and chrysin. Thyme and clover honey ice cream had the highest concentration of polyphenols. Ice cream sweetened with sucrose, as well as pōhutukawa, rewarewa and kāmahi honey were the most liked ice cream in terms of overall liking.

Our previous study showed that magnetic field pretreatment promoted germination and phenolic enrichment in quinoa. In this study, we further investigated the effects of NaCl stress on the growth and phenolic synthesis of germinated quinoa after magnetic field pretreatment (MGQ). The results showed that NaCl stress inhibited the growth of MGQ, reduced the moisture content and weight of a single plant, but increased the fresh/dry weight. The higher the NaCl concentration, the more obvious the inhibition effect. In addition, NaCl stress inhibited the hydrolysis of MGQ starch, protein, and fat but increased the ash content. Moreover, lower concentrations (50 and 100 mM) of NaCl stress increased the content of MGQ flavonoids and other phenolic compounds. This was due to the fact that NaCl stress further increased the enzyme activities of PAL, C4H, 4CL, CHS, CHI, and CHR and up-regulated the gene expression of the above enzymes. NaCl stress at 50 and 100 mM increased the DPPH and ABTS scavenging capacity of MGQ and increased the activities of antioxidant enzymes, including SOD, POD, CAT, APX, and GSH-Px, further enhancing the antioxidant system. Furthermore, principal component analysis showed that NaCl stress at 100 mM had the greatest combined effect on MGQ. Taken together, NaCl stress inhibited the growth of MGQ, but appropriate concentrations of NaCl stress, especially 100 mM, helped to further increase the phenolic content of MGQ and enhance its antioxidant system.

The flavonoids play important roles in plant salt tolerance. Blueberries (Vaccinium spp.) are extremely sensitive to soil salt increases. Therefore, improving the salt resistance of blueberries by increasing the flavonoid content is crucial for the development of the blueberry industry. To explore the underlying molecular mechanism, we performed an integrated analysis of the metabolome and transcriptome of blueberry leaves under salt stress. We identified 525 differentially accumulated metabolites (DAMs) under salt stress vs. control treatment, primarily including members of the flavonoid class. We also identified 20,920 differentially expressed genes (DEGs) based on transcriptome data; of these, 568 differentially expressed transcription factors (TFs) were annotated, and bHLH123, OsHSP20, and HSP20 TFs might be responsible for blueberry leaf salt tolerance. DEGs involved in the flavonoid biosynthesis pathway were significantly enriched at almost all stages of salt stress. Salt treatment upregulated the expression of most flavonoid biosynthetic pathway genes and promoted the accumulation of flavonols, flavonol glycosides, flavans, proanthocyanidins, and anthocyanins. Correlation analysis suggested that 4-coumarate CoA ligases (4CL5 and 4CL1) play important roles in the accumulation of flavonols (quercetin and pinoquercetin) and flavan-3-ol (epicatechin and prodelphinidin C2) under salt stress, respectively. The flavonoid 3′5′-hydroxylases (F3′5′H) regulate anthocyanin (cyanidin 3-O-beta-D-sambubioside and delphinidin-3-O-glucoside chloride) biosynthesis, and leucoanthocyanidin reductases (LAR) are crucial for the biosynthesis of epicatechin and prodelphinidin C2 during salt stress. Taken together, it is one of the future breeding goals to cultivate salt-resistant blueberry varieties by increasing the expression of flavonoid biosynthetic genes, especially 4CL, F3′5′H, and LAR genes, to promote flavonoid content in blueberry leaves.

Moderate amounts of Se can promote crop growth, enhance stress resistance, increase yield, and improve nutritional quality. In the present study, kudzu seedlings were used as experimental materials, and their physiological indicators, antioxidant activity, nutritional components, and flavonoid content were measured after being treated with Na2SeO3 hydroponics. Transcriptome sequencing analysis was used to reveal the relevant genes involved in regulating the effects of exogenous Se on the content of Se-compounds and flavonoids in kudzu. The results indicated that treatment with 20 mg/L Na2SeO3 significantly increased stem and root lengths, dry and fresh weight, lateral root development, and chlorophyll b content. However, at higher concentrations (30–40 mg/L), lateral root abundance and chlorophyll levels decreased. Na2SeO3 treatment also augmented the antioxidant capacity and enhanced the content of major nutrients in kudzu seedlings. The total Se content in kudzu escalated with increasing Na2SeO3 concentration, with selenomethionine emerging as the primary organic-Se species. After treatment with Na2SeO3, the content of puerarin in both aboveground and underground parts decreased, while the content of total flavonoids increased. Daidzin increased in the roots. Differential expression gene analysis revealed that genes such as TRXB2, SYM, MMT1, and METE were involved in Se uptake and transformation in kudzu, while bZIP43 and WRKY47 played a role in flavonoid biosynthesis.

Around 450 species of blueberries of the genus Vaccinium are known, of which some have gained preferential breeding, such as the ‘Biloxi’ variety. Some little studied species, such as Vaccinium leucanthum Schltdl. located in Mexico, could be a potential source of bioactive compounds. In this study, the phenolic compounds (chlorogenic acid content, hyperoside, phenols, flavonoids, tannins and total anthocyanins content) as well as the potential biological activity (antioxidant, antimicrobial, xanthine oxidase converting enzyme inhibition and angiotensin I inhibition) of Vaccinium leucanthum Schltdl. were studied, making a comparison with the Biloxi variety, which is the most widely cultivated one. The extract of V. leucanthum showed the highest content of flavonoids (4.853 ± 0.341 mg QE/g DW), total anthocyanins (0.303 ± 0.008 mg CGE/g DW), petunidin-3-glucoside (6.92 ± 0.12 mg PGE/g DW), malvidin-3-glucoside (11.80 ± 0.10 mg MGE/g DW) and hyperoside (5.137 ± 0.100 mg HE/g DW). It should be noted that V. leucanthum showed the same total tannin content and the same efficacy in the inhibition of Angiotensin I-converting enzyme as ‘Biloxi’, as well as the same antibacterial effect against the enterobacteria Salmonella choleraesuis ATCC 12022, Escherichia coli ATCC 12792and Shigella flexneri ATCC 10708. These findings demonstrate that V. leucanthum extracts could be an important source of preservatives as well as nutraceutical compounds for use in foods and medicines.

Phytochemical investigation of Staehelina uniflosculosa Sibth. & Sm. resulted in the isolation of twenty-two natural products: eleven sesquiterpene lactones, artemorin (1), tamirin (2), tanachin (3), reynosin (4), baynol C (5), desacetyl-β-cyclopyrethrosin (6), 1β-hydroxy-4α-methoxy-5α,7α,6β-eudesm-11(13)-en-6,12-olide (7), 1β,4α,6α-trihydroxyeudesm-11-en-8α,12-olide (8), 1β-hydroxy-arbusculin A (9), methyl-1β,4α,6α-trihydroxy-5α,7αH-eudesm-11(13)-en-12-oate (10) and methyl-1β,6α,8α-trihydroxy-5α,7αH-eudesma-4(15),11(13)-dien-12-oate (11); one lignan, pinoresinol (12); one norisoprenoid, loliolide (13); six flavonoids (four genins and two glycosides), hispidulin (14), nepetin (15), jaceosidin (16), eriodictyol (17), eriodictyol-3′-O-β-D-glucoside (18) and eriodictyol-7-O-β-D-glucuronide (19); and three phenolic derivatives (one phenolic acid and two phenolic glucosides), protocatechuic acid (20), arbutin (21) and nebrodenside A (22). From the isolated compounds, only nepetin (15) has been reported previously from the Staehelina genus and, to the best of our knowledge, it is the first time that compound (18) has been identified in Asteraceae. A number of these substances were tested for (a) inhibition of lipoxygenase and acetylocholinesterase, (b) their antioxidant activity using the DPPH (1,1-Diphenyl-2-picrylhydrazyl) method or/and (c) inhibition of lipid peroxidation. The tested components exhibited low antioxidant activity with the exception of 5 and 22, while the effectiveness of these compounds in the inhibition of acetylocholinesterase is limited. Furthermore, Molinspiration, an online computer tool, was used to determine the bioactivity ratings of the isolated secondary metabolites. The compounds’ bioactivity ratings for potential therapeutic targets were very promising.

5,6-dihydroxyflavone (5,6-DHF), a flavonoid that possesses potential anti-inflammatory and antioxidant activities owing to its special catechol motif on the A ring. However, its function and mechanism of action against inflammation and cellular oxidative stress have not been elucidated. In the current study, 5,6-DHF was observed inhibiting lipopolysaccharide (LPS)-induced nitric oxide (NO) and cytoplasmic reactive oxygen species (ROS) production with the IC50 of 11.55 ± 0.64 μM and 0.8310 ± 0.633 μM in murine macrophages, respectively. Meanwhile, 5,6-DHF suppressed the overexpression of pro-inflammatory mediators such as proteins and cytokines and eradicated the accumulation of mitochondrial ROS (mtROS). The blockage of the activation of cell surface toll-like receptor 4 (TLR4), impediment of the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 from the mitogen-activated protein kinases (MAPK) pathway, Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) from the JAK-STAT pathway, and p65 from nuclear factor-κB (NF-κB) pathways were involved in the process of 5,6-DHF suppressing inflammation. Furthermore, 5,6-DHF acted as a cellular ROS scavenger and heme-oxygenase 1 (HO-1) inducer in relieving cellular oxidative stress. Importantly, 5,6-DHF exerted more potent anti-inflammatory activity than its close structural relatives, such as baicalein and chrysin. Overall, our findings pave the road for further research on 5,6-DHF in animal models.

In this study, four previously undescribed flavonoids, named epimesatines P (1), Q (2), R (3), and S (4), were isolated from the aerial parts of Epimedium sagittatum Maxim. Their structures and absolute configurations were confirmed via spectroscopic analyses, quantum chemical electronic circular dichroism (ECD) calculations, Mo2(OAc)4–induced ECD, and Rh2(OCOCF3)4–induced ECD experiments. Epimesatines Q and R were characterized by the presence of furan rings. A cytotoxicity assay demonstrated that epimesatines P–S exhibited significant inhibitory effects on the viability of MCF-7 human breast cancer cells, with IC50 values ranging from 1.27 to 50.3 μM. Notably, epimesatines Q and R exhibited superior efficacy against MCF-7 cells compared to epimesatines P and S, suggesting that the presence of furan rings may enhance their activity against MCF-7 cells. Specifically, epimesatine Q displayed a more potent inhibitory effect at 1.27 μM compared to a positive control, docetaxel, which had an IC50 of 2.13 μM, highlighting its potential as a therapeutic agent for breast cancer. Importantly, none of the tested compounds exhibited obvious toxicity toward MCF-10A human breast epithelial cells. Furthermore, compounds 1, 3, and 4 were found to significantly inhibit the expression of sphingosine kinase 1 (Sphk1) in MCF-7 cells.

As an important member of innate immunity, macrophages show remarkable plasticity and heterogeneity, and play an important role in immune regulation, tissue development, homeostasis of the internal environment and injury repair. However, the excessive activation of macrophages is closely related to the occurrence and development of many diseases. The prenylated flavonoid structure is one of the characteristic structures isolated from Sophora flavescens, with anti-inflammatory, anti-tumor, anti-allergy and other effects. In this study, the effects of (2R)-3β,7,4′-trihydroxy-5-methoxy-8-prenylflavanone (TMP), a prenylated dihydroflavonol, on the polarization and phagocytosis of macrophages were systematically studied. In LPS-induced M1-type macrophages, TMP dose-dependently inhibited the expression of COX-2, iNOS and the secretion of NO, IL-1β, IL-6 and IL-18, showing an inhibitory effect on M1 polarization. Further experiments revealed that it was related to the inhibition of TLR4-related AKT/mTOR, MAPK and NF-κB signaling pathways; in IL-4-induced M2-type macrophages, TMP down-regulated the expression of M2-related Arg1, IL-10, TGF-β, CD206 and CD163, as well as the phosphorylation levels of AKT1 and STAT6. For macrophages in a physiological state, it was very important for cells to return from a stress state to a phenotypic stability in the M0 state. These results indicated that TMP negatively regulated the M1/M2 polarization of macrophages, and made them tend to M0 homeostasis, which might provide new theoretical and data support for explaining the anti-inflammatory immunoregulatory activity of Sophora flavescens.

Deep eutectic solvents (DESs) have attracted attention from researchers as novel compounds for extracting active substances because of their negligible toxicity, polarity, and ability to be tailored depending on the experiment. In this review, we discuss deep eutectic solvents as a promising medium for the extraction of adaptogenic compounds. In comparison to traditional methods, extraction with the use of DESs is a great alternative to the excessive usage of harmful organic solvents. It can be conducted in mild conditions, and DESs can be designed with different precursors, enhancing their versatility. Adaptogenic herbs have a long medicinal history, especially in Eastern Asia. They exhibit unique properties through the active compounds in their structures, including saponins, flavonoids, polysaccharides, and alkaloids. Therefore, they demonstrate a wide range of pharmaceutical effects, such as anti-inflammatory, antibacterial, and anticancer abilities. Since ancient times, many different adaptogenic herbs have been discovered and are well known, including Panax ginseng, Scutellaria baicalensis, and Schisandra chinensis. Active compounds can be extracted using standard methods, such as hydrolyzation, maceration, and conventional reflux extraction. However, due to the limitations of classical processing technologies, there has been a need to develop new and eco-friendly methods. We focus on the types of solvents, extraction efficiency, properties, and applications of the obtained active compounds. This review highlights the potential of DESs as eco-friendly alternatives for extracting bioactive compounds.

In this study, we achieved the biosynthesis of novel 7–8 nm iron-oxide nanoparticles in the presence of different concentrations (5 to 50% w/v) of commercial white quinoa extract. Initially, quinoa extract was prepared at various concentrations by a purification route. The biosynthesis optimization was systematically monitored by X-ray diffraction, and the Rietveld quantitative analysis showed the presence of goethite (5 to 10 wt.%) and maghemite phases. The first phase disappeared upon increasing the organic loading (40 and 50% w/v). The organic loading was corroborated by thermogravimetric measurements, and it increased with quinoa extract concentration. Its use reduces the amount of precipitation agent at high quinoa extract concentrations with the formation of magnetic nanoparticles with hard ferrimagnetic character (42 and 11 emu g−1). The enrichment of hydroxyl groups and the negative zeta potential above pH = 7 were corroborated by a reduction in the point of zero charge in all the samples. For alkaline values, the zeta potential values were above the stability range, indicating highly stable chemical species. The evidence of hydroxyl and amide functionalization was qualitatively observed using infrared analysis, which showed that the carboxyl (quercetin/kaempferol), amide I, and amide III chemical groups are retained after biosynthesis. The resultant biosynthesized samples can find applications in environmental remediation due to the affinity of the chemical agents present on the particle surfaces and easy-to-handle them magnetically.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is considered the main cause of nosocomial and community-associated infections. Because of antimicrobial resistance, MRSA infections are difficult or impossible to treat, leading to high mortality rates and significant economic and societal costs. In view of the MRSA challenge to public health all over the world, the identification of new and effective anti-MRSA agents is a high medical priority. Objectives: A new series of tricyclic flavonoids with a methyl substituent on ring A of the flavonoid skeleton was synthesized to assess their antimicrobial properties. Methods: The structures of novel synthetic tricyclic flavonoids and their 3-dithiocarbamic flavanones were proven by X-ray structural analyses. Minimum inhibitory concentration (MIC) and minimum bactericidal/fungicidal concentration (MBC/MFC) were used to evaluate antimicrobial activity. Growth kinetic and time–kill assays were employed to confirm the antibacterial effectiveness. The mechanism of action was investigated using fluorescence microscopy. Results: Our results show that the tricyclic flavonoids exhibited important antibacterial and antifungal activities, with MIC and MBC values as low as 1.95 µg/mL and 3.90 µg/mL recorded for compound 5e against a multidrug-resistant MRSA strain. Flavonoid 5e induced a more important bacteriostatic effect compared with chloramphenicol, inhibiting the bacterial growth for up to 24 h at concentrations equivalent to 2 × MIC. Also, 5e exhibited a significant bactericidal activity, with no viable cells evidenced after 6 h of incubation in the presence of MBC and a total kill effect recorded up to 24 h. The anti-MRSA activity may be explained by the cell membrane impairment induced by 5e. Conclusions: All the data support the idea that flavonoid 5e is a reliable candidate to develop effective anti-MRSA agents, but further studies are necessary.

Climate change, through increased aridity, threatens ecosystems, including Morocco’s endemic Argania Spinosa L. Skeels. This study assesses the impact of aridity on argan trees by analyzing morphological, ecophysiological, and biochemical parameters across various regions and comparing them with historical data. Significant variations were observed in leaf area, leaf length, chlorophyll content, relative water content, polyphenols, flavonoids, soluble sugars, and antioxidant activity, while leaf width ratio and chlorophyll ratio remained stable. Tioughza exhibited the largest leaf area (136.07 mm2), the highest chlorophyll content (436.76 mg/m2), and superior water retention (52.27%). Conversely, Ezzaouite showed the smallest leaf area (85.76 mm2) and lowest water content (37.68%). Increased aridity has intensified these differences, revealing the argan tree’s vulnerability to climate change. The findings underscore the need for targeted conservation efforts, including reforestation, strengthened legislation, and enhanced genetic research, to sustain this vital species.

In this study, the extraction, purification and metabolic enzyme inhibition potential of Selaginella doederleinii were investigated. In order to extract the total biflavonoids from S. doederleinii (SDTBs), the optimum extraction process was obtained by optimizing the ultrasonic extraction parameters using response-surface methodology. This resulted in a total biflavonoid content of 22.26 ± 0.35 mg/g. Purification of the S. doederleinii extract was carried out using octadecylsilane (ODS), and the transfer rate of the SDTBs was 82.12 ± 3.48% under the optimum purification conditions. We determined the effect of the SDTBs on α-glucosidase (AG), α-amylase and xanthine oxidase (XOD) and found that the SDTBs had an extremely potent inhibitory effect on AG, with an IC50 value of 57.46 μg/mL, which was much lower than that of the positive control. Meanwhile, they also showed significant inhibition of XOD and α-amylase, with IC50 values of 289.67 μg/mL and 50.85 μg/mL, respectively. In addition, molecular docking studies were carried out to understand the nature of the action of the biflavonoids on AG and XOD. The results showed that robustaflavone had the lowest binding energy to AG (−11.33 kcal/mol) and XOD (−10.21 kcal/mol), while, on the other hand, amentoflavone showed a good binding affinity to AG (−10.40 kcal/mol) and XOD (−9.962 kcal/mol). Moreover, molecular dynamics simulations verified the above results.

(1) Background: Improving feed efficiency and the vitality of the reproductive system in the late stage of the egg-laying period is of great significance for prolonging the egg-laying cycle and improving egg quality. In the present study, a new flavonoid, which was extracted from kudzu leaf, was chosen to investigate its effects on the productive performance and egg quality of late-laying hens. (2) Methods: A total of 360 500-day-old Hy-Line Brown layer hens were randomly divided into a control treatment group (no KLF supplementation), and groups that received 0.2%, 0.4%, 0.6%, 0.8%, and 1.0% KLF supplement treatments. Each treatment contained 6 replicates, with 10 hens in each replicate. Productive performance metrics, including the daily egg production, egg weight, the number of deformed eggs, egg quality, egg density, egg shape index, eggshell strength, yolk color, and the Haugh unit, were meticulously recorded for each replicate. Furthermore, microbial communities and hypothalamus gene expressions were investigated based on the results of the productive performance and egg quality. (3) Results: KLF supplementation significantly decreased the deformity rate while significantly increasing the eggshell strength in the finishing phase afterward (p < 0.05). Specifically, hens supplemented with 0.6% KLF possessed the lowest deformed egg rate. KLF supplementation significantly increased the relative abundances of Bifidobacterium sp., Blautia sp., Lactococcus sp., and Lactobacillus sp., while significantly decreasing Parasutterella sp. and Escherichia-Shigella sp. (p < 0.05). Furthermore, the interactive analysis showed the hypothalamus gene expression mainly interacted with probiotics, such as Bifidobacterium sp. and Lactobacillus sp., through ribosome biogenesis, nucleocytoplasmic transport, and cAMP signaling pathways. (4) Conclusions: The findings of the present study indicate that KLF supplementation significantly proliferated probiotics, such as Bifidobacterium and Lactobacillus, which may have further interacted with hypothalamus genes, thus decreasing the deformity rate while increasing eggshell strength in the finishing phase.

Type 2 diabetes mellitus (T2DM) remains a significant global health issue, marked by insulin resistance and disrupted glucose metabolism. AMP-activated protein kinase (AMPK) serves as a key regulator of cellular energy balance, playing a crucial role in enhancing insulin sensitivity, promoting glucose uptake, and reducing glucose production in the liver. Recently, there has been growing interest in plant-derived flavonoids as natural activators of AMPK, offering a promising complementary approach to conventional diabetes treatments. This review delves into ten flavonoids identified as AMPK activators, including baicalein, dihydromyricetin, bavachin, 7-O-MA, derrone, and alpinumisoflavone. Their activation mechanisms are explored, which include both direct binding to the AMPK complex and indirect pathways involving upstream signaling. Through molecular docking studies, the binding affinities and interaction profiles of these flavonoids with AMPK are assessed, revealing varying levels of activation potential. Notably, baicalein and dihydromyricetin showed strong binding to the α1 subunit of AMPK, indicating high potential for robust activation. Additionally, this review provides a thorough analysis of the pharmacokinetic properties and drug-likeness of these flavonoids using the SwissADME tool, focusing on aspects such as ADME (Absorption, Distribution, Metabolism, and Excretion). While the overall profiles of these compounds are promising, issues like solubility and possible drug–drug interactions are areas that need further refinement. In summary, plant-derived flavonoids emerge as a promising avenue for developing new natural therapies for T2DM. Moving forward, research should aim at optimizing these compounds for clinical application, elucidating their specific mechanisms of AMPK activation, and confirming their efficacy in T2DM treatment. This review highlights the potential of flavonoids as safer and more holistic alternatives or adjuncts to current diabetes therapies.

(1) Background: The non-enzymatic glycation of proteins is a significant contributor to the formation of advanced glycation end products (AGEs) and intermediates that are responsible for diabetic complications. It is imperative to explore effective inhibitors to prevent protein glycation. (2) Methods: This study aimed to investigate the inhibitory potential of various aqueous ethanol extracts of poplar-type propolis on AGEs and oxidative modifications in bovine serum albumin (BSA)-glucose and BSA-methylglyoxal models. (3) Results: The results revealed that these propolis extracts exhibited significant effectiveness in inhibiting the formation of total AGEs, pentosidine, and Nε-carboxymethyllysine (CML). Furthermore, the investigation discovered that these propolis extracts can effectively inhibit oxidative modification, based on measuring the levels of carbonyl and thiol groups and analyzing tryptophan fluorescence quenching. Notably, 75% ethanol extracts of propolis (EEP) exhibited the highest inhibitory activity, surpassing the chemical inhibitor aminoguanidine (AG). (4) Conclusions: The remarkable anti-glycation potency of aqueous ethanol extracts of poplar-type propolis can be attributed to their elevated contents of phenolic compounds, especially abundant flavonoids, which inhibit the formation of AGEs by scavenging free radicals, decreasing the levels of reactive oxygen species (ROS), and capturing reactive carbonyl species (RCS) in the protein glycation process. Our results indicate that poplar-type propolis may be a potential AGE inhibitor and could be used to develop functional foods and nutraceuticals to prevent diabetic complications.

To reveal the effect of sucrose concentration on the production of secondary metabolites, a metabolome and transcriptome joint analysis was carried out using callus induced from grape variety Mio Red cambial meristematic cells. We identified 559 metabolites—mainly flavonoids, phenolic acids, and stilbenoids—as differential content metabolites (fold change ≥2 or ≤0.5) in at least one pairwise comparison of treatments with 7.5, 15, or 30 g/L sucrose in the growing media for 15 or 30 days (d). Resveratrol, viniferin, and amurensin contents were highest at 15 d of subculture; piceid, ampelopsin, and pterostilbene had higher contents at 30 d. A transcriptome analysis identified 1310 and 498 (at 15 d) and 1696 and 2211 (at 30 d) differentially expressed genes (DEGs; log2(fold change) ≥ 1, p < 0.05) in 7.5 vs. 15 g/L and 15 vs. 30 g/L sucrose treatments, respectively. In phenylpropane and isoflavone pathways, DEGs encoding cinnamic acid 4-hydroxylase, chalcone synthase, chalcone isomerase, and flavanone 3-hydroxylase were more highly expressed at 15 d than at 30 d, while other DEGs showed different regulation patterns corresponding to sucrose concentrations and cultivation times. For all three sucrose concentrations, the stilbene synthase (STS) gene exhibited significantly higher expression at 15 vs. 30 d, while two resveratrol O-methyltransferase (ROMT) genes related to pterostilbene synthesis showed significantly higher expression at 30 vs. 15 d. In addition, a total of 481 DEGs were annotated as transcription factors in pairwise comparisons; an integrative analysis suggested MYB59, WRKY20, and MADS8 as potential regulators responding to sucrose levels in flavonoid and stilbene biosynthesis in grape callus. Our results provide valuable information for high-efficiency production of flavonoids and stilbenes using grape callus.

Flavonoids constitute a class of polyphenolic secondary metabolites synthesised mainly by plants and possessing anticancer, antioxidant, anti-inflammatory, and antiviral properties. Common buckwheat (F. esculentum Moench) is a dicotyledonous plant rich in different classes of flavonoids (e.g., rutin) and other phenolic compounds. Lipochitooligosaccharides (LCOs), i.e., rhizobial Nod factors and important signalling molecules for the initiation of symbiosis with legumes, are very effective mitogens that stimulate cell division in plant meristems and the production of secondary metabolites. They can also act in this way in non-legume plants. It has been shown that rhizobial Nod factors noticeably improve plant growth. Rhizobial Nod factors influence the production of flavonoids in common buckwheat grown in greenhouse conditions. The amount of rutin and isoorientin in leaves and flowers has been shown to increase in a statistically significant way after application of Nod factors to buckwheat seeds. The presence of rhizobial Nod factors has no influence on the flavonoid content in stems and roots.