Search Results (99)

Estrogens are considered the most important risk factor for the development of breast cancer. Therefore, attempts are being made to reduce their level through diminished synthesis on one hand and to protect against the formation of DNA-damaging estrogen metabolites on the other. Cytochromes P450 (CYPs) play key roles in estrogen synthesis and catabolism, leading to potentially carcinogenic metabolites. CYP19 (aromatase) catalyzes the conversion of androgens to estrogens. The estrogen receptor-dependent pathway induces cell growth. CYP1 family enzymes, particularly CYP1B1, are involved in the redox cycling of estrogen metabolites and the subsequent estrogen–DNA adducts formation. Naturally occurring phytochemicals of different classes were shown to modulate the CYP expression and activity in cell-free systems or breast cancer cells. One of the most promising CYP19 inhibitors is chrysin (flavone), while stilbenes seem to be the most effective CYP1B1 inhibitors. In most cases, their effect is not specific. Therefore, different approaches are made to find the best candidate for the drug prototype of a new therapeutic or chemopreventive agent and to improve its pharmacokinetic parameters. This review presents and discusses the possible effects on major CYPs involved in estrogen metabolism by phytochemicals from the most investigated classes, namely flavonoids, stilbenes, and glucosinolates breakdown products. Full article

Polyphenols are structurally diverse plant metabolites that have attracted significant interest. Their compositions are versatile, depending on their structures, including the number of rings in the polyphenol composition. Based on these attributes, polyphenols can be classified as flavanols, anthocyanins, flavones, phenolic acids, stilbenes, and lignans. Polyphenols mainly possess inhibition of viral replication, interference with viral protein synthesis, and modulation of immune responses, providing significant antiviral effects against several viruses, including herpes simplex virus, hepatitis C virus, and influenza. They are crucial for medical compounds in diverse, versatile treatments, namely in diabetes, cardiovascular disorders, cancer, and neurodegenerative problems. Plants are the primary source of bioactive molecules, which are valued for their anti-inflammatory, antioxidant, anticancer, and antiviral activities. Especially, polyphenols are extracted as the most abundant bioactive compounds of plants. Moreover, viral infections are one of the major factors in illnesses and diseases, along with bacteria and fungi. Numerous in vitro and in vivo studies report antiviral activity against SARS-CoV-2, Mayaro virus, dengue virus, herpesvirus, and influenza A virus, though clinical validation remains limited. Additionally, inhibition of viral entry, interference with viral replication, modulation of host immune response, and direct virucidal effects were examined. Full article

Hormonomics represents an innovative approach to plant physiology and biochemistry. We utilized hormonomics to analyze the hormone profiles of three lily bulbs. The hormones specifically enriched in BiFeng7 lily show a strong response to secondary metabolism pathways, while the Diwanghuang lily profile was predominantly focused on growth. Physiological experiments demonstrated that Diwanghuang exhibited higher levels of primary nutrients, whereas BiFeng7 displayed a greater concentration of secondary metabolites and enhanced antioxidant capacity. Through untargeted metabolomic analysis, it was revealed that BiFeng7 highly enriched four flavonoid glycosides, two flavones, one flavan, one pyranoflavonoid, two isoflavonoid O-glycosides and one rotenoid. These findings provide valuable information for developing breeding strategies and cultivation practices aimed at achieving ornamental quality, nutritional value, or stress resilience outcomes. This research demonstrates the practical application of hormone profiling in plant evaluation and offers insights into the mechanisms underlying flavonoid synthesis in lilies, serving as a reference for breeding stress-resistant lily varieties. Full article

Flavonoids are a class of secondary metabolites synthesized by plants, characterized by a C6-C3-C6 carbon skeleton and derived from the phenylpropane metabolism pathway. They play crucial biological roles, not only in plant pigment production and responses to biotic and abiotic stresses but also in medicinal applications. Consequently, the biosynthesis and regulatory mechanisms of flavonoids have been a focal point in plant transcription and gene expression research. The biosynthetic pathways of flavonoids include branches such as isoflavones, flavones, flavonols, anthocyanins, and proanthocyanidins, with some pathways and key enzymes already well-characterized. Studies indicate that plant flavonoids are regulated by various factors, including transcription factors, non-coding endogenous small RNAs (miRNAs), and plant hormones. This review systematically summarizes the structure and classification of plant flavonoids, their biosynthetic and regulatory mechanisms, and the factors influencing flavonoid synthesis. By discussing the regulation of flavonoid-related gene expression in plants, this work provides valuable insights and a theoretical foundation for future research and applications of flavonoids. Full article

Silver nanoparticles, with various uses in pharmacy, cosmetics, sanitation, textiles, optoelectronics, photovoltaics, etc., that are provided by worldwide industrial production, estimated to hundreds of tons annually, are finally released in the environment impacting randomly the biosphere. An alternative synthesis approach could be implemented by replacing chemical reductants of silver with natural antioxidants ensuring production and utilization sustainability with focus on environmental pollution diminishing. We synthesized silver nanoparticles by using plant extracts, aiming to offer antimicrobial products with reduced impact on the environment through sustainable green-chemistry. Fresh extracts of lemon pulp, blueberry and blackberry fruits as well as of green tea dry leaves were the sources of the natural antioxidants able to ensure ionic silver reduction and silver nanoparticle formation in the form of colloidal suspensions. The four samples were characterized by UV–Vis spectrophotometry, scanning electron microscopy, dark field optical microscopy, X-ray diffractometry, dynamic light scattering, which evidenced specific fine granularity, plasmonic features, standard crystallinity, and good stability in water suspension. Antimicrobial activity was assayed using the agar diffusion method and the bacteria kill-time technique against Staphylococcus aureus and Escherichia coli. In both cases, all silver nanoparticles revealed their adequacy for the aimed purposes, the sample synthesized with green tea showing the best efficiency, which is in concordance with its highest contents of polyphenols, flavones and best total antioxidant activity. Various applications could be safely designed based on such silver nanoparticles for sustainable chemistry development. Full article

Chrysanthemum indicum L. is characterized by a high concentration of flavonoid compounds, which exert multifaceted influences on the organoleptic properties, chromatic stability, and therapeutic efficacy of capitulum-derived extracts. These components exhibit diverse biological activities, including heat-clearing, antibacterial, and hepatoprotective properties. A novel white C. indicum variant lacking linarin was recently identified, but its metabolic and transcriptional differences from traditional yellow varieties remain unclear. This study compared flavonoid metabolism in white mutant (BHYJ) and yellow (HJ06) varieties through integrated metabolomic and transcriptomic analyses. Metabolomics identified 491 flavonoids, revealing distinct accumulation patterns: BHYJ accumulated dihydroflavones/chalcones (eriodictyol, hesperetin-8-C-glucoside-3′-O-glucoside, naringenin chalcone), while HJ06 showed higher flavones/flavonols (linarin, rhoiflolin, vitexin, rutin, nicotiflorin). Transcriptomics identified 43 differentially expressed enzyme genes, with key regulators FNSII, F3′H, and F3H showing expression patterns correlating with metabolite profiles. Integrated analysis revealed metabolic divergence at the naringenin node: BHYJ produced less naringenin than HJ06 and preferentially channeled it toward eriodictyol synthesis rather than linarin production. This metabolic shift explains the reduced linarin accumulation in BHYJ. Experimental validation confirmed the coordinated expression patterns of key enzymes. These findings provide foundational insights into transcriptional regulation of flavonoid divergence in pigmented C. indicum varieties, establishing a framework for elucidating enzymatic control of flavonoid biosynthesis in capitulum development. Full article

Mineral nutrition is of vital importance in plant growth and secondary metabolites accumulation, and thereby in the nutritional value of plants. In Lonicera japonica, a preference to nitrate (NO₃⁻−N) in comparison to ammonium (NH₄⁺−N) was found in our previous study, which can be revealed from the rapid growth rate of L. japonica under NO₃⁻−N. This study assessed whether a preference for nitrogen sources could invoke metabolic reprogramming and interrelationships between factors. NO₃⁻−fed plants exhibited substantial enhancement of carbon stimulation, which was strongly and positively correlated with mesophyll conductance. As a result, the elevated carbon flux by NO₃⁻ supplement was shuttled to phenolic metabolites synthesis, including flavones and caffeoylquinic acids compounds. Notably, the stimulation was triggered by changes in the NO₃⁻ and C/N ratio and was mediated by the induction of several enzymes in the phenylpropanoid pathway. On the contrary, NH₄⁺ plants showed an increment in the content of nitrogen, carbohydrates, and amino acids (mainly a strong increase in citrulline and theanine). Within secondary metabolism, NH₄⁺ may involve active lignin metabolism, showing a dramatic increment in hydroxy−ferulic acid and lignin content. This work provides significant insights regarding the mechanisms of L. japonica in response to diverse nitrogen regimes and effective strategies of nitrogen fertilizer input for L. japonica. Full article

Apigenin and luteolin are products of the phenylpropanoid pathway, where apigenin serves as a substrate for the synthesis of luteolin. Apigenin and luteolin are highly bioactive flavones; therefore, in search of prospective biopesticides, the receptiveness of the polyphagous green peach aphid Myzus persicae (Sulzer) (Hemiptera: Aphididae) to apigenin and luteolin was studied. The flavones were applied as 0.1% ethanolic solutions to the host plant leaf surface, and aphid probing and feeding activities were monitored using the Electrical Penetration Graph (EPG) technique. The structural difference between apigenin and luteolin, which was the number of hydroxyl groups in the molecule, had an impact on the activity of these flavones. On apigenin-treated plants, the duration of the first probe was three times as short as on the control and five times as short as on the luteolin-treated plants; the duration of the time to the first ingestion phase within the successful probe was shorter than on the control and luteolin-treated plants; the mean duration of xylem sap ingestion bouts and the proportion of xylem phase in all probing activities were the highest; and the duration of salivation before phloem sap ingestion was the longest. Aphids’ response to luteolin-treated plants was less distinct as compared to apigenin-treated plants. Full article

Background/Objectives: Flavonoids are common ubiquitous components of plants and are consumed by humans and livestock in their diets. Many different activities have been proposed for a variety of flavonoids that play a role in the benefits of a plant-rich diet. On the downside, excessive exposure to some flavonoids comes with a risk of endocrine disruption. Our objective was to define the structural elements of flavones and selected other flavonoids required for endocrine-disrupting activities on each of four steroid receptors, estrogen, androgen, progesterone, and glucocorticoid receptors. Methods: This work presents a systematic screen for the hormone agonist or antagonist activity of a selected panel of flavonoids on estrogen, androgen, progesterone, and glucocorticoid receptors. The screen is focused on the positional requirements of hydroxyl substituents on the flavone backbone. Results: Each receptor exhibited a distinct pattern for structural requirements of the flavones to impact receptor signaling. The most active flavones exhibited antagonist activity on androgen and progesterone receptors with an IC₅₀ of 0.5 and 2 µM, respectively. Flavones only exhibited weak antagonism on glucocorticoid receptors. When active, flavones acted as estrogen receptor agonists. The findings were utilized to design and synthesize a novel flavone, 3-fluoro, 6,4′-dihydroxyflavone 14, that displays increased potency as an estrogen agonist (EC₅₀~30 nM). Modeling of the binding of this novel flavone predicts increased preference for ERα versus ERβ relative to the estrogenic phytoestrogen, genistein. Conclusions: The structural requirements for flavones to act as estrogen agonists and antagonists of other steroid receptors are defined. The synthesis of a novel flavone offers potential for topical applications where systemic estrogen activity is undesired. However, the results highlight the potential for endocrine disruption when certain flavones are consumed in quantity as supplements. Full article

Broussonetia papyrifera is a deciduous tree with significant economic and medicinal value. It demonstrates notable physiological adaptability to mining areas with severe manganese contamination and is a pioneering species in the field of ecological restoration. Flavonoids are vital secondary metabolites that improve plant resilience to environmental stresses. In the study presented herein, immature and mature fruits of B. papyrifera grown in normal and high manganese environments were used as the test materials. B. papyrifera fruit was subjected to transcriptome sequencing via high-throughput sequencing technology to analyze its flavonoid metabolic pathways and related genes. Transcriptome sequencing identified a total of 46,072 unigenes, with an average length of 1248 bp and a percentage of Q30 bases ranging from 92.45 to 93.17%. Furthermore, 31,792 unigenes (69% of the total) were annotated using eight databases, including the GO and KEGG. Analysis of KEGG metabolic pathways and flavonoid content trends in B. papyrifera fruits revealed four unigenes with strong links to the flavonoid biosynthesis pathway under manganese stress: flavone 3-hydroxylase, flavonoids 3′,5′-O-methyltransferase, chalcone synthase, and flavonol synthase. These unigenes may play important roles in regulating flavonoid synthesis in B. papyrifera fruits under manganese stress. This study lays the groundwork for functional gene research in B. papyrifera. Full article

Advances in combinatorial synthesis and high-throughput screening methods have led to renewed interest in synthetic plant immunity activators as well as priming agents. 3,5-Dichloroanthranilic acid (3,5-DCAA) is a derivative of anthranilic acid that has shown potency in activating defence mechanisms in Arabidopsis and barley. Chemical biology, which is the interface of chemistry and biology, can make use of metabolomic approaches and tools to better understand molecular mechanisms operating in complex biological systems. Here we report on the untargeted metabolomic profiling of barley seedlings treated with 3,5-DCAA to gain deeper insights into the mechanism of action of this resistance inducer. Histochemical analysis revealed the production of reactive oxygen species in the leaves upon 3,5-DCAA infiltration. Subsequently, methanolic extracts from different time periods (12, 24, and 36 h post-treatment) were analysed by ultra-high-performance liquid chromatography hyphenated to a high-resolution mass spectrometer. Both unsupervised and supervised chemometric methods were used to reveal hidden patterns and highlight metabolite variables associated with the treatment. Based on the metabolites identified, both the phenylpropanoid and octadecanoid pathways appear to be main routes activated by 3,5-DCAA. Different classes of responsive metabolites were annotated with flavonoids, more specifically flavones, which were the most dominant. Given the limited understanding of this inducer, this study offers a metabolomic analysis of the response triggered by its foliar application in barley. This additional insight could help make informed decisions for the development of more effective strategies for crop protection and improvement, ultimately contributing to crop resilience and agricultural sustainability. Full article

Long-term use of the global non-selective herbicide glyphosate for weed control has caused resistance in weeds. Overproducing of the target of glyphosate 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) is one of the resistance mechanisms in weeds. However, few studies have measured the effects on tolerance levels and metabolite content in model plant species overexpressing EPSPS from weeds. We assessed the resistance levels of transgenic Arabidopsis thaliana overexpressing EPSPS from Eleusine indica, and its effects on metabolite content using the method of both quasi-targeted and targeted metabolomics. The results showed that the average resistance index of the transgenic lines was 4.7 and the exogenous E. indica EPSPS expression levels were 265.3- to 532.0-fold higher than those in the wild-type (WT) line. The EPSPS protein ranged from 148.5 to 286.2 μg g⁻¹, which was substantially higher than that in the WT line (9.1 μg g⁻¹). 103 metabolites associated with flavone and flavonol biosynthesis, the metabolism of aromatic amino acids, energy metabolism, and auxin synthesis were significantly higher in the transgenic glyphosate-resistant individuals (R) than in the WT individuals. The results of quantitative analysis show that pyruvate, sedoheptulose 7-phosphate, and gluconic acid amounts in R plants were 1.1-, 1.6- and 1.3-fold higher than those in WT plants, respectively. However, both citric and glyceric acid levels were 0.9-fold lower than those in WT plants. The abundance of other metabolites in the glycolytic and pentose phosphate pathways of central carbon metabolism was similar in the WT and transgenic plants. Glutamic acid was significantly more abundant in the transgenic line than in the WT plants. In contrast, asparagine, glutamine, and lysine were less abundant. However, the concentration of other amino acids did not change significantly. Overexpression of E. indica EPSPS in A. thaliana conferred a moderate level of tolerance to glyphosate. Metabolites associated with flavone and flavonol biosynthesis, the metabolism of aromatic amino acids, and energy metabolism were significantly increased. The results of this study will be useful for evaluating the characterisation and risk assessment of transgenic plants, including identification of unintended effects of the respective transgenic modifications. Full article

Although nitrogen deficiency and sucrose are linked to anthocyanin synthesis, the potential role of sucrose in regulating anthocyanin biosynthesis under low nitrogen conditions (LN) in purple lettuce (Lactuca sativa L.) remains unclear. We found that adding exogenous sucrose enhanced anthocyanin biosynthesis but significantly inhibited lettuce growth at high concentrations. Optimal results were obtained using 1 mmol/L sucrose in a low-nitrogen nutrient solution (LN + T1). Chlorophyll fluorescence imaging indicated that the addition of exogenous sucrose induced mild stress. Meanwhile, the activities of antioxidant enzymes (SOD, CAT, and POD) and antioxidant capacity were both enhanced. The mild stress activated the antioxidant system, thereby promoting the accumulation of anthocyanins induced by exogenous sucrose. LN + T1 (low nitrogen nutrient solution supplemented with 1 mmol/L sucrose) up-regulated enzyme genes in the biosynthetic pathway of anthocyanins, including phenylalanine ammonia-lyase (PAL), chalcone synthase (CHS), dihydroflavonol reductase (DFR), flavanone 3-hydroxylase (F3H), flavonoid 3′-hydroxylase (F3′H), flavone synthase II (FNSII), and anthocyanidin synthase (ANS). Additionally, various transcription factors such as AP2/ERF, MYB, bHLH, C2H2, NAC, C2C2, HB, MADS, bZIP, and WRKY were found to be up-regulated. This study elucidates the regulatory mechanism of anthocyanin metabolism in response to the addition of exogenous sucrose under low nitrogen conditions and provides a nutrient solution formula to enhance anthocyanin content in modern, high-quality agricultural cultivation. Full article

Rhododendron simsii Planchon is an important ornamental species in the northern hemisphere. Flower color is an important objective of Rhododendron breeding programs. However, information on anthocyanin synthesis in R. simsii is limited. In this research, the regulatory mechanism of anthocyanin biosynthesis in R. simsii was performed through the integrated analysis of metabolome and RNA-seq. A total of 805 and 513 metabolites were screened by positive and negative ionization modes, respectively, In total, 79 flavonoids contained seven anthocyanidins, 42 flavanones, 10 flavans, 13 flavones, and seven flavonols. Methylated and glycosylated derivatives took up the most. Differentially accumulated metabolites were mainly involved in “flavone and flavonol biosynthesis”, “cyanoamino acid metabolism”, “pyrimidine metabolism”, and “phenylalanine metabolism” pathways. For flavonoid biosynthesis, different expression of shikimate O-hydroxycinnamoyltransferase, caffeoyl-CoA O-methyltransferase, flavonoid 3′-monooxygenase, flavonol synthase, dihydroflavonol 4-reductase/flavanone 4-reductase, F3′5′H, chalcone synthase, leucoanthocyanidin reductase, and 5-O-(4-coumaroyl)-D-quinate 3′-monooxygenase genes ultimately led to different accumulations of quercetin, myricetin, cyanidin, and eriodictyol. In flavone and flavonol biosynthesis pathway, differential expression of F3′5′H, flavonoid 3′-monooxygenase and flavonol-3-O-glucoside/galactoside glucosyltransferase genes led to the differential accumulation of quercetin, isovitexin, and laricitrin. This research will provide a biochemical basis for further modification of flower color and genetic breeding in R. simsii and related Rhododendron species. Full article

The light plays a key role in regulating anthocyanin biosynthesis in plants. However, the molecular basis of anthocyanin synthesis in grape skins irradiated at night with supplemental white light (W), red light (R), blue light (B), and blue light for 3 h, 6 h, 9 h, and 12 h (B3, B6, B9, and B12) is not known. In the present study, the total anthocyanin content in grape skins was significant under different light (DL) and blue-light time (DT) treatments, and the best result was obtained with B9. Analysis of RNA-seq data determined that the key genes in the anthocyanin synthesis pathway, PAL, CHS, DFR, GT, CFIP, VIT_14s0068g00920, VIT_06s0009g02860, and VIT_06s0004g08150, were significantly up-regulated under night-time supplemental light treatments, which led to the significant expression of the phenylpropanoid biosynthesis, phenylalanine metabolism, flavonoid biosynthesis, flavone and flavonol biosynthesis, and the anthocyanin biosynthesis pathway, which were significantly expressed, promoting the accumulation of anthocyanin. The B caused significant expression of PAL (VIT_08s0040g01710), CFIP (VIT_13s0067g03820, VIT_13s0067g02870) and DFR (VIT_18s0001g12800), which may be one of the reasons for the better effect of B compared to W anthocyanin enrichment in grape skins. The DT treatment resulted in significant expression of GT (VIT_11s0052g01600), Peroxidase, VIT_09s0018g01190, and VIT_11s0037g00570. In addition, many TFs such as bHLH, MYB, ERF, WRKY, C2H2, MYB-related, and NAC were found to be involved in the synthesis of anthocyanins under light regulation. These results provide new insights into plants’ nocturnal supplemental-light regulation of anthocyanin accumulation. Full article