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In genetically heterogeneous (UM-HET3) mice produced by the CByB6F1 × C3D2F1 cross, the Nrf2 activator astaxanthin (Asta) extended the median male lifespan by 12% (p = 0.003, log-rank test), while meclizine (Mec), an mTORC1 inhibitor, extended the male lifespan by 8% (p = 0.03). Asta was fed at 1840 ± 520 (9) ppm and Mec at 544 ± 48 (9) ppm, stated as mean ± SE (n) of independent diet preparations. Both were started at 12 months of age. The 90th percentile lifespan for both treatments was extended in absolute value by 6% in males, but neither was significant by the Wang-Allison test. Five other new agents were also tested as follows: fisetin, SG1002 (hydrogen sulfide donor), dimethyl fumarate, mycophenolic acid, and 4-phenylbutyrate. None of these increased lifespan significantly at the dose and method of administration tested in either sex. Amounts of dimethyl fumarate in the diet averaged 35% of the target dose, which may explain the absence of lifespan effects. Body weight was not significantly affected in males by any of the test agents. Late life weights were lower in females fed Asta and Mec, but lifespan was not significantly affected in these females. The male-specific lifespan benefits from Asta and Mec may provide insights into sex-specific aspects of aging.

Increasing aridity in the Mediterranean region will result in longer and recurrent drought. These changes could strongly modify plant defenses, endangering tree survival. We investigate the response of chemical defenses from central and specialized metabolism in Quercus pubescens Willd. to future Mediterranean drought using a long-term drought experiment in natura where trees have been submitted to amplified drought (~ –30% annual precipitation) since April 2012. We focused on leaf metabolites including chlorophylls and carotenoids (central metabolism) and flavonols (specialized metabolism). Measurements were performed in summer from 2016 to 2022. Amplified drought led to higher concentrations of total photosynthetic pigments over the 2016–2022 period. However, it also led to lower AZ/VAZ and flavonol concentrations. Additionally, chemical defenses of Q. pubescens responded to previous precipitation where low precipitation 1 year and/or 2 years preceding sampling was associated to low concentrations of VAZ, flavonol and high neoxanthin concentrations. Our study indicates that the decline of flavonol concentration under long-term drought is counterbalanced by a higher production of several central metabolites. Such results are potentially due to an adjustment in tree metabolism, highlighting the importance of performing long-term experimental studies in natura for assessing drought legacy effects and thus forest adaptation to climate change. [ABSTRACT FROM AUTHOR]

The present study is an evaluation of Centella asiatica ethanolic extract in terms of total phenolic content, total flavonoids, total flavonols, anthocyanin, antioxidants, and antibacterial activities. Centella asiatica plants were collected from Guilan province, Iran. High-performance liquid chromatography-Diode array detector analysis demonstrated that the ethanolic extract of C. asiatica contained phenolic substances such as sinapic acid, catechin, quercetin, p-coumaric acid, hesperidin, eugenol, and hesperetin. The predominant phenolic compound in the extract was hesperetin. The antibacterial activities of the extract were highly potent against S. aureus and B. cereus. These findings suggest that C. asiatica is rich in phenolic compounds and can be utilised for future cosmetic and pharmaceutical purposes. [ABSTRACT FROM AUTHOR]

To understand the effects and related potential mechanism of H2O2 on pigment metabolism in postharvest broccoli, an integrated analysis of transcriptome and metabolome was performed. Results suggested that 65 differentially expressed genes and 26 differentially accumulated metabolites involved in chlorophyll, carotenoid, and flavonoid metabolism were identified. H2O2 treatment delayed the decrease of chlorophyll content by upregulating the expressions of chlorophyll synthetic genes, thylakoid synthetic genes, and 15 light‐harvesting complex genes compared with the control and diphenylene iodonium treatments. H2O2 treatment decreased the accumulation of 11 flavonoids and 5 flavonols by downregulating the flavonoid synthetic genes. In addition, H2O2 treatment promoted carotenoid biosynthesis to eliminate reactive oxygen species in thylakoids, thereby protecting chlorophyll molecules from degradation. The inhibition of flavonoids and flavonols accumulation and chlorophyll decrease was the crucial reason for the delayed yellowing in H2O2 treatment. This study provides a new method and theoretical support for delaying the yellowing process in postharvest broccoli. [ABSTRACT FROM AUTHOR]

Summary: Reproduction in angiosperms relies on the precise growth of pollen tubes, facilitating the delivery of sperm cells to the ovule for double fertilization. LATERAL ORGAN BOUNDARIES DOMAIN10 (LBD10), a plant‐specific transcription factor, plays a pivotal role in Arabidopsis pollen development.Here, we uncovered LBD10's function in sustaining pollen tube growth and integrity.The lbd10 mutant exhibited elevated levels of reactive oxygen species (ROS) and hydrogen peroxide (H2O2) in both pollen grains and tubes, leading to compromised pollen tube growth. The inhibition of ROS synthesis and scavenging of excess ROS with an antioxidant treatment each alleviated these defects in lbd10. The lbd10 mutant displayed reduced flavonol accumulation in both pollen grains and tubes. All the altered phenotypes of lbd10 were complemented by expressing LBD10 under its native promoter. Exogenous application of flavonoids recused the defects in pollen tube growth and integrity in lbd10, along with reducing the excess levels of ROS and H2O2. LBD10 directly binds the promoters of key flavonol biosynthesis genes in chromatin and promotes reporter gene expression in Arabidopsis mesophyll protoplasts.Our findings indicate that LBD10 modulates ROS homeostasis by transcriptionally activating genes crucial for flavonol biosynthesis, thereby maintaining pollen tube growth and integrity. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Sulla coronaria is indigenous to the Mediterranean region. It is grown as fodder in southern Italy because it contains various secondary metabolites with beneficial activities on animals. Recently, its potential use in cosmeceutical treatments for skin problems was reported. In this scenario, to contribute to a possible cosmeceutical application, we characterized the phytochemical profile of Sulla coronaria flowers' hydroalcoholic extract by HPLC-DAD, Folin-Ciocalteu, Aluminum Chloride methods, DPPH assay, and, for the first time, we evaluated the antioxidant and anti-inflammatory activities on dermal fibroblasts. The phytochemical analysis confirmed the significant content of phenolic compounds (TPC 69.8 ± 0.6 mg GAE/g extract, TFC 15.07 mg CE/g extract) and the remarkable presence of rutin, quercetin, and isorhamnetin derivatives that give to the phytocomplex a good antioxidant activity as highlighted by the DPPH assay (IC50 of 8.04 ± 0.5 µg/mL). Through the reduction in NO• and ROS levels in human dermal fibroblasts, the biological tests demonstrated both the safety of the extract and its ability to counteract the inflammatory state generated by Interleukin-1β exposure. Our findings indicate that the antioxidant activities of the phytocomplex are strictly related to the anti-inflammatory action of the Sulla coronaria flowers extract, confirming that this plant could be a valuable source of bioactive molecules for cosmeceutical and nutraceutical applications. [ABSTRACT FROM AUTHOR]

Ready-to-eat fresh-cut apples deteriorate rapidly in visual quality due to browning, leading to consumer rejection and food waste. In addition, minimal processing induces tissue damage and releases organic substrates, which could accelerate microbial growth. The present study evaluated the impacts of alkaline and acidic electrolyzed water (AIEW and AEW) on natural microbial load and bioactive compounds on fresh-cut 'Granny Smith' apples. Minimally processed apples were dipped for 10 min in AEW and AIEW solutions (200 mg L−1), packed in PET containers with lids, and stored for 9 days at 2 °C. Overall, fresh-cut 'Granny Smith' apples treated with AEW significantly (p < 0.05) maintained higher total phenolics (99.4 ± 4.3 mg GAE L−1) and antioxidant capacity (79.5 ± 6.5 mg VitCE L−1) compared to the non-treated control samples (42.9 ± 5.1 mg GAE L−1, 31.9 ± 8.1 mg GAE L−1, respectively). Similarly, pretreatment with AIEW maintained the highest total flavonol content (55.71 ± 1.5 mg QE L−1) compared to the AEW-treated samples and control (p < 0.05). AEW pretreatment led to a 2 Log and a 1 Log decline in total aerobic mesophilic bacteria and yeasts and moulds, respectively. The best visual quality and highest visual score was maintained by AEW and followed by AIEW. This study further demonstrated the effectiveness of electrolyzed water treatments in minimizing browning and enhancing bioactive compounds in fresh-cut 'Granny Smith' apples. [ABSTRACT FROM AUTHOR]

Main conclusions: The albino phenotype of Agave angustifolia Haw. accumulates higher levels of phenylalanine and phenylpropanoids, while the green phenotype has a greater concentration of phenolic compounds. The metabolic consequences of chlorophyll deficiency in plants continue to be a captivating field of research, especially in relation to production of metabolic compounds. This study conducts a thorough analysis of the metabolome in green (G), variegated (V), and albino (A) phenotypes of Agave angustifolia Haw. Specifically, it examines the differences in the accumulation of compounds related to the phenylpropanoid and flavonoid biosynthesis pathways. Methanol extracts of leaf and meristem tissues from the three phenotypes grown in vitro were analyzed using liquid chromatography coupled with quadrupole time-of-flight high-resolution mass spectrometry (UPLC-MS-QTOF) for untargeted metabolomics and triple quadrupole (QqQ) mass spectrometry for targeted metabolomic analyses. By employing these methods, we discovered notable differences in the levels of important metabolites such as L-phenylalanine, 4-hydroxyphenylpyruvic acid, and various flavonoids among the different phenotypes. The results of our study indicate that the A phenotype shows a significant increase in the levels of phenylalanine and phenylpropanoids in both leaf and meristem tissues. This is in contrast to a decrease in flavonoids, suggesting a metabolic reprogramming to compensate for the lack of chlorophyll. Significantly, compounds such as kaempferol-3-O-glucoside and rutin exhibited significant quantitative reduction in the A leaves, suggesting a subtle modification in the production of flavonols and potentially a changed mechanism for antioxidant protection. This study emphasizes the complex metabolic changes in A. angustifolia´s chlorophyll-deficient phenotypes, providing insight into the complex interplay between primary and secondary metabolism in response to chlorophyll deficiency. Our research not only enhances the comprehension of plant metabolism in albino phenotypes but also opens new avenues for exploring the biochemical and genetic basis of such adaptations, with potential biotechnological applications of these distinct plant variants. [ABSTRACT FROM AUTHOR]

Using “Lianjiu No.1”, “Yuntaihongjiu” and “Yuntaijinjiu” as research objects, the anthocyanin components and content of their leaves before and after color transformation were qualitatively and quantitatively analyzed using ultra-high performance liquid chromatographymass spectrometry technology.The results showed that a total of 14 anthocyanins were detected in leaves from three varieties, including malvidin, pelargonidin, delphinidin, peonidin, cyanidin 3-galactoside, isorhamnetin, cyanidin, cyanidin 3, 5-diglucoside, petunidin, quercetin, rutin, procyanidin B4, procyanidin B2 and kaempferol. Cyanidin 3-galactoside and rutin were the main anthocyanin components of three varieties. The cyanidin 3-galactoside was the main pigment component for the red colored leaves of “Yuntaihongjiu”; rutin was the main reason for the yellow colored leaves of “Yuntaijinjiu”. The main anthocyanins types in three varieties were rutins, cyanidins and others. After the color change of leaves, the content of cyanidins from high to low was in order of “Lianjiu No.1” > ”Yuntaihongjiu” > ”Yuntaijinjiu”. After the color change of leaves, the content of rutins from hight to low was in order of “Yuntaijinjiu” > “Lianjiu No.1” > “Yuntaihongjiu”. [ABSTRACT FROM AUTHOR]

The changes produced during the aging of wines in oak barrels are strongly dependent on the oak's geographical origin and aging time. This paper analyzes the effect of Quercus alba oak from four different geographical locations in four states in the USA, namely Missouri (Mo), Ohio (Oh), Kentucky (Kt), and Pennsylvania (Py), during 24 months of aging. Oak origin had a higher effect on the wine's aromatic composition than the polyphenolic one. Mo and Oh barrels enhanced coconut, spicy, and sweet notes for 12 months of aging, while Kt barrels achieved higher extraction of wood-related compounds at longer aging (24 months). Py wines showed the lowest contents of most volatile compounds at both aging times, as well as hydroxycinnamic acids, flavanols, anthocyanins, flavonols, stilbenes, and ellagitannins, attributed to their higher porosity. At 12 months of aging, Kt wines showed the highest content of ellagitannins, and Mo wines had the highest content of anthocyanins, but Oh wines had the highest concentrations at 24 months. In the sensory analysis, Kt wines were preferred at both aging times. Kt and Mo wines achieved the highest punctuations for the olfactory phase at 12 months of aging and Kt wines kept it after 24 months. These findings are essential for producers to achieve the sensory characteristics of their wines through strategic barrel aging. [ABSTRACT FROM AUTHOR]

The influence of the composition of the functional used for density functional theory computations on one structural parameter (a dihedral angle) and a spectroscopic parameter (absorption wavelength) is assessed in this study on the basis of two molecules (flavonols). In this kind of molecules, these two parameters should be correlated according to the nature of the electronic transition involved. However, it is shown herein that by varying the proportion of true exchange and correlation while building a functional, it is possible to obtain independently a large range of values for these parameters without any relation with the underlying real values. Therefore, it is concluded that the choice of a functional after a benchmark, especially using user‐defined functionals, should be carried out with great care to avoid such effects. [ABSTRACT FROM AUTHOR]

Fruit color substantially affects consumer preferences, with darker red strawberries being economically more valuable due to their higher anthocyanin content. However, the molecular basis for the dark red coloration remains unclear. Through screening of an ethyl methanesulfonate mutant library, we identified a rg418 mutant, that demonstrated anthocyanin accumulation during early fruit development stages. Furthermore, the ripening fruits of this mutant had higher anthocyanin content than wild-type (WT) fruits. An analysis of flavonoid content in WT and rg418 mutant fruits revealed substantial changes in metabolic fluxes, with the mutant exhibiting increased levels of anthocyanins and flavonols and decreased levels of proanthocyanidins. Bulked sergeant analysis sequencing indicated that the mutant gene was anthocyanidin reductase (ANR), a key gene in the proanthocyanidin synthesis pathway. Furthermore, transcriptome sequencing revealed the increased expression of MYB105 during the early development stage of mutant fruits, which promoted the expression of UFGT (UDP-glucose flavonoid 3-O-glucosyltransferase), a key gene involved in anthocyanin synthesis, thus substantially enhancing the anthocyanin content in the mutant fruits. Additionally, mutating ANR in a white-fruited strawberry variant (myb10 mutant) resulted in appealing pink-colored fruits, suggesting the diverse roles of ANR in fruit color regulation. Our study provides valuable theoretical insights for improving strawberry fruit color. [ABSTRACT FROM AUTHOR]

Carrier‐free nanodrugs that integrate chemodrugs and other therapeutic agents demonstrate good efficacy and minimized side effects, showing promise for combined therapy. However, a key challenge lies in enhancing the bioavailability and therapeutic potential of the nanodrugs through a controllable assembly process. Herein, a carrier‐free photothermal nanodrug (ZPQ NPs) is constructed through flavonol‐driven assembly with amine‐substituted perylene diimide for enhanced chemo‐photothermal combined cancer therapy. The flavonol, particularly quercetin, facilitates J‐aggregation of perylene diimide derivatives within the nanodrug and contributes to multiple improvements, including red‐shifted absorption, enhanced fluorescence intensity, improved photothermal conversion efficiency as well as excellent photostability. Moreover, the nanodrug also demonstrates enhanced cellular uptake and intracellular reactive oxygen species scavenging capability. The combination of quercetin and photothermal effect effectively kills cancer cells, as well as alleviates inflammation following photothermal therapy. Guided by in vivo fluorescence imaging, the application of ZPQ NPs results in complete tumor elimination and effectively inhibits tumor recurrence through chemo‐photothermal combined therapy. This work presents a straightforward strategy for constructing carrier‐free nanodrugs that exhibit simultaneous enhancements in both photophysical properties and biological activity. [ABSTRACT FROM AUTHOR]

Various seeds, including sea buckthorn (Hippophae rhamnoides L.) seeds, are sources of different bioactive compounds. They can show anti-inflammatory, hypoglycemic, anti-hyperlipidemic, antibacterial, antioxidant, or other biological properties in in vitro and in vivo models. Our preliminary in vitro results have demonstrated that the extracts from raw (no thermal processing) and roasted (thermally processed) sea buckthorn seeds have antioxidant potential and anticoagulant activity. However, it was unclear which compounds were responsible for these properties. Therefore, in continuation of our previous study, the extracts were fractionated by C18 chromatography. Phytochemical analysis of three fractions (a, b, and c) from raw sea buckthorn seeds and four fractions (d, e, f, and g) from roasted sea buckthorn seeds were performed. Several in vitro assays were also conducted to determine the antioxidant and procoagulant/anticoagulant potential of the fractions and two of their major constituents—isorhamnetin 3-O-β-glucoside7-O-α-rhamnoside and serotonin. LC–MS analyses showed that serotonin is the dominant constituent of fractions c and f, which was tentatively identified on the basis of its HRMS and UV spectra. Moreover, fractions c and f, as well as b and e, contained different B-type proanthocyanidins. Fractions b and e consisted mainly of numerous glycosides of kaempferol, quercetin, and isorhamnetin. The results of oxidative stress assays (measurements of protein carbonylation, lipid peroxidation, and thiol groups oxidation) showed that out of all the tested fractions, fraction g (isolated from roasted seeds and containing mainly dihexoses, and serotonin) demonstrated the strongest antioxidant properties. [ABSTRACT FROM AUTHOR]

Flavonoids, including proanthocyanidins (PAs), anthocyanins and flavonols are essential secondary metabolites that contribute to the nutritional value and sensory quality of grape berry and red wine. Advances in molecular biology technology have led to substantial progress in understanding the regulation of flavonoid biosynthesis. The influence of terroir on grape berries and wine has garnered increasing attention, yet its comprehensive regulatory network remains underexplored. In terms of application, environmental factors such as water, light, and temperature are more easily regulated in grapevines compared to soil conditions. Therefore, we summarize their effects on flavonoid content and composition, constructing a network that links environmental factors, hormones, and metabolites to provide a deeper understanding of the underlying mechanisms. This review enriches the knowledge of the regulatory network mechanisms governing flavonoid responses to environmental factors in grapes. [ABSTRACT FROM AUTHOR]

Background: Camellia nitidissima is a rare, prized camellia species with golden-yellow flowers. It has a high ornamental, medicinal, and economic value. Previous studies have shown substantial flavonol accumulation in C. nitidissima petals during flower formation. However, the mechanisms underlying the golden flower formation in C. nitidissima remain largely unknown. Results: We performed an integrative analysis of the transcriptome, proteome, and metabolome of the petals at five flower developmental stages to construct the regulatory network underlying golden flower formation in C. nitidissima. Metabolome analysis revealed the presence of 323 flavonoids, and two flavonols, quercetin glycosides and kaempferol glycosides, were highly accumulated in the golden petals. Transcriptome and proteome sequencing suggested that the flavonol biosynthesis-related genes and proteins upregulated and the anthocyanin and proanthocyanidin biosynthesis-related genes and proteins downregulated in the golden petal stage. Further investigation revealed the involvement of MYBs and bHLHs in flavonoid biosynthesis. Expression analysis showed that flavonol synthase 2 (CnFLS2) was highly expressed in the petals, and its expression positively correlated with flavonol content at all flower developmental stages. Transient overexpression of CnFLS2 in the petals increased flavonol content. Furthermore, correlation analysis showed that the jasmonate (JA) pathways positively correlated with flavonol biosynthesis, and exogenous methyl jasmonate (MeJA) treatment promoted CnFLS2 expression and flavonol accumulation. Conclusions: Our findings showed that the JA-CnFLS2 module regulates flavonol biosynthesis during golden petal formation in C. nitidissima. [ABSTRACT FROM AUTHOR]

Copigmentation is a noncovalent interaction between anthocyanins and colourless copigments that stabilises the anthocyanin‐coloured forms by protecting them against water attack. Copigmentation can be responsible for almost half of the colour observed in young red wines. It has been reported that flavonols are the most effective wine copigments, but studies on the influence of the structure of these copigments on the magnitude of copigmentation are scarce. However, flavonol profiles change with grape variety and can condition the colour of the resulting wines. In addition, mannoproteins (MPs) have been reported to interact with flavonoids, which, consequently, might affect the flavonol‐anthocyanin interaction. The objective of the present study was to evaluate the ability of five grape flavonols (isorhamnetin, kaempferol, quercetin, syringetin, and myricetin 3‐O‐glucosides: I‐3‐glc, K‐3‐glc, Q‐3‐glc, S‐3‐glc, and My‐3‐glc) by conventional spectrophotometric measurements and CIELAB analysis to copigment with malvidin 3‐O‐glucoside (mv‐3‐glc) in the absence or presence of five different MPs (binary and ternary model systems). Among the tested flavonols, I‐3‐glc was the most effective copigment, whereas K‐3‐glc was the least one. S‐3‐glc and Q‐3‐glc showed intermediate effectiveness, but that of S‐3‐glc was closer to I‐3‐glc and that of Q‐3‐glc to K‐3‐glc. These results point out that the presence of methoxyl groups in the B‐ring of the flavonol increases copigmentation magnitude. The participation of My‐3‐glc in copigmentation interactions seemed to be hindered by its colloidal instability. Regarding the tested MPs, they did not provoke a direct copigmentation effect, but were able to modify the magnitude of the interaction between the flavonols and the anthocyanin and, in some cases, the colloidal behaviour of coloured aggregates formed over time. Finally, the results of the additional HPLC‐DAD analyses point to a greater protection of the anthocyanin against degradation in the model systems where the magnitude of copigmentation was greater. [ABSTRACT FROM AUTHOR]

Background/Objectives: Agriophyllum squarrosum (L.) Moq. (A. squarrosum), also known as sandrice, is an important medicinal plant widely distributed in dunes across all the deserts of China. Common garden trials have shown content variations in flavonoids among the ecotypes of sandrice, which correlated with temperature heterogeneity in situ. However, there have not been any environmental control experiments to further elucidate whether the accumulation of flavonoids was triggered by cold stress; Methods: This study conducted a four-day ambient 4 °C low-temperature treatment on three ecotypes along with an in situ annual mean temperature gradient (Dulan (DL), Aerxiang (AEX), and Dengkou (DK)); Results: Target metabolomics showed that 12 out of 14 flavonoids in sandrice were driven by cold stress. Among them, several flavonoids were significantly up-regulated, such as naringenin and naringenin chalcone in all three ecotypes; isorhamnetin, quercetin, dihydroquercetin, and kaempferol in DL and AEX; and astragalin in DK. They were accompanied by 19 structural genes of flavonoid synthesis and 33 transcription factors were markedly triggered by cold stress in sandrice. The upstream genes, AsqAEX006535−CHS, AsqAEX016074−C4H, and AsqAEX004011−4CL, were highly correlated with the enrichment of naringenin, which could be fine-tuned by AsqAEX015868−bHLH62, AsqAEX001711−MYB12, and AsqAEX002220−MYB1R1; Conclusions: This study sheds light on how desert plants like sandrice adapt to cold stress by relying on a unique flavonoid biosynthesis mechanism that regulating the accumulation of naringenin. It also supports the precise development of sandrice for the medicinal industry. Specifically, quercetin and isorhamnetin should be targeted for development in DL and AEX, while astragalin should be precisely developed in DK. [ABSTRACT FROM AUTHOR]

Although the petals of Rosa rugosa are rich in flavonoids and their bioactivity has a significant impact on human health, the flavonoid content decreases during flower development. In this study, R. rugosa 'Feng hua' was used to investigate the effects of the melatonin foliar spray on enhancing the quality of rose by focusing on major flavonoids. The results showed that the contents of total flavonoids in rose petals at the full bloom stage induced by melatonin obeyed a bell-shaped curve, with a maximum at 0.3 mM, indicating the concentration-dependent up-regulation of flavonoid biosynthesis. In the treatment with 0.3 mM melatonin, metabolomic analyses showed that the concentrations of ten main flavonoids were identified to be increased by melatonin induction, with high levels and increases observed in three flavonols and two anthocyanins. KEGG enrichment of transcriptomic analysis revealed a remarkable enrichment of DEGs in flavonoid and flavonol biosynthesis, such as Rr4CL, RrF3H, and RrANS. Furthermore, functional validation using virus-induced gene silencing technology demonstrated that Rr4CL3 is the crucial gene regulating flavonoid biosynthesis in response to the stimulant of melatonin. This study provides insights into the exogenous melatonin regulation mechanism of biosynthesis of flavonoids, thereby offering potential industrial applications. [ABSTRACT FROM AUTHOR]

Human intestinal bacteria are the primary producers of azo reductase, and the content of azo reductase is closely associated with various intestinal diseases, including ulcerative colitis (UC). The rapid detection of changes in azo reductase levels is crucial for diagnosing and promptly intervening in UC. In this study, a therapeutic agent, FAI, specifically targeting UC, was designed and synthesized. This agent was developed by linking the anti-inflammatory drug indomethacin to flavonols with antioxidant activity via an azo bond (off–on). Breakage of the azo bond breaks results in the release of both fluorophores and drugs, achieving targeted tracing and integrated treatment effects. In vivo and in vitro fluorescence imaging experiments were used to demonstrate the potential of FAI in the diagnosis of UC, together with synergistic therapeutic effects through the release of both fluorophores and anti-inflammatory agents. Therefore, this diagnostic agent shows promise as a potential tool for diagnosing and treating UC. [ABSTRACT FROM AUTHOR]

Summary: Sea buckthorn (SB) is used in cuisines and herbal remedies due to its remarkable nutritional composition and health‐enhancing properties. The phenolic compounds present in SB plant include phenolic acids (gallic, p‐coumaric, protocatechuic and ferulic acids), flavonols (isorhamnetin, quercetin and kaempferol), flavan‐3‐ols and polymeric procyanidins. The highest content of these compounds was reported in branches and leaves than corresponding edible parts of the plant. The antioxidant properties of SB are related to content and composition of phenolic compounds in different plant parts. The studies reported SB flavonoids (isorhamnetin and quercetin) as main phenolic compounds with medicinal potential and health‐promoting effects. The present review summarises information available in recent studies on phenolic composition, phenolic content, flavonoid content, antioxidant activity and health‐promoting activities (anti‐oxidant, hepatoprotective, cardioprotective, anti‐inflammatory, anti‐diabetic and obesity management) of SB that can be used in curtailing various acute and chronic maladies. SB can be projected as a promising source of bioactive constituents with the potential to be used in healthy foods for beneficial effects on human health. [ABSTRACT FROM AUTHOR]

Wine pomace (WP) is a major byproduct generated during winemaking, and skin pomace (SKP) comprises one of the most valuable components of WP. Since SKP differs in composition and properties from seed pomace (SDP), precise knowledge of SKP will aid the wine industry in the development of novel, high-value products. The current review summarizes recent advances in research relating to SKP presents a comprehensive description of the generation, composition, and bioactive components, primarily focusing on the biological activities of SKP, including antioxidant, gastrointestinal health promotion, antibacterial, anti-inflammatory, anticancer, and metabolic disease alleviation properties. Currently, the separation and recovery of skins and seeds is an important trend in the wine industry for the disposal of winemaking byproducts. In comparison to SDP, SKP is rich in polyphenols including anthocyanins, flavonols, phenolic acids, stilbenes, and some proanthocyanidins, as well as dietary fiber (DF). These distinctive benefits afford SKP the opportunity for further development and application. Accordingly, the health-promoting mechanism and appropriate application of SKP will be further elucidated in terms of physiological activity, with the progress of biochemical technology and the deepening of related research. [ABSTRACT FROM AUTHOR]

The objective of the study was to determine the effect of vintage and cultivar on the total polyphenol content and the antioxidant activity of wines made from the white wine cultivar 'Solaris' and the red wine cultivar 'Zilga' (both with skin maceration). The second goal was to describe the polyphenolic profile of 'Solaris' wine and compare it with that of 'Zilga' wine. Spectrophotometric methods were employed to determine the total polyphenol content and the antioxidant activity. High-performance liquid chromatography (HPLC) was used to determine the polyphenol composition. The total polyphenol content and the antioxidant activity of 'Solaris' wine differed significantly from that of 'Zilga' wine in the experimental years from 2021 to 2023. Significant differences between the wines also occurred on average over the years, with a significantly higher total polyphenol content and antioxidant activity obtained for the red wine of 'Zilga'. However, both wines were similarly influenced by vintage over the three-year experimental period. The antioxidant activity showed a high correlation with the total polyphenol content. The polyphenolic profile of 'Solaris' wine differed notably from that of 'Zilga' wine. While 'Solaris' wine exhibited lower levels of phenolic acids and flavonols, the content of the flavanols was significantly higher, even double that of 'Zilga' wine. Among the flavanols, there was a remarkably high content of catechin and epicatechin. [ABSTRACT FROM AUTHOR]

Necrotic enteritis (NE) is a critical disease affecting broiler health, with Clostridium perfringens as its primary pathogen. Polygonum hydropiper compound extract (PHCE), formulated based on traditional Chinese veterinary principles, contains primarily flavonoids with antibacterial, anti-inflammatory, and antioxidant properties. However, PHCE's efficacy against Clostridium perfringens-induced NE and its underlying mechanism remain unclear. This study employed network pharmacology and molecular docking to predict PHCE's potential mechanisms in treating NE, followed by determining its minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against Clostridium perfringens (C. perf). Subsequently, the effects of various PHCE doses on intestinal damage, antioxidant capacity, and inflammatory factors in C. perf-infected broilers were assessed. Network pharmacology and molecular docking suggested that PHCE's therapeutic mechanism for NE involves the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome signaling pathway, with flavonoids such as quercetin, kaempferol, and isorhamnetin as key active components. PHCE exhibited an MIC of 3.13 mg/mL and an MBC of 12.5 mg/mL against C. perf. High PHCE doses effectively reduced intestinal damage scores in both the jejunum and ileum, accompanied by attenuated intestinal pathological changes. Additionally, the high dose significantly increased superoxide dismutase (SOD) levels while decreasing malondialdehyde (MDA), hydrogen peroxide (H2O2), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) in the jejunum and ileum (p < 0.01 or p < 0.05). PHCE also modulated the expression of caspase-1, IL-1β, gasdermin D (GSDMD), and NLRP3 mRNA, key components of the NLRP3 inflammasome signaling pathway, in both intestinal segments. These findings collectively indicate that PHCE protects against C. perf-induced oxidative stress and inflammatory damage in NE. By enhancing antioxidant capacity, PHCE likely reduces oxidative stress and inflammatory responses, subsequently modulating NLRP3 inflammasome signaling pathway key factor expression. Overall, this research provides valuable insights into the protective mechanism of the herbal compound PHCE and its potential benefits for avian health. [ABSTRACT FROM AUTHOR]

The composition of flavonols, proanthocyanidins, anthocyanins, triterpene compounds, and chlorogenic acid in small cranberry fruit samples collected in natural habitats in Lithuania and variation in the antioxidant capacity of cranberry fruit extracts was determined. This study showed that in the flavonol group, hyperoside and myricetin-3-O-galactoside predominated in cranberry fruit samples; in the anthocyanin group, the predominant compounds were cyanidin-3-O-galactoside, cyanidin-3-O-arabinoside, peonidin-3-O-galactoside, and peonidin-3-O-arabinoside, and in the group of triterpene compounds, ursolic acid was predominant. The highest total amounts of flavonols and anthocyanins were found in the samples collected in Čepkeliai State Strict Nature Reserve (2079.44 ± 102.99 μg/g and 6993.79 ± 350.22 μg/g, respectively). Cluster analysis of the chemical composition of small cranberry fruit samples revealed trends in the accumulation of bioactive compounds in cranberry fruit. Cranberry fruit samples collected in central Lithuania had higher levels of triterpene compounds. Statistical correlation analysis showed the strongest correlation between the quantitative composition of cyanidin-3-O-arabinoside and peonidin-3-O-arabinoside and the reducing capacity of the ethanolic extracts of the cranberry fruit samples assessed in vitro by the FRAP assay (r = 0.882, p < 0.01 and r = 0.805, p < 0.01, respectively). Summarizing the results, the geographical factor affects the variation of the quantitative composition of biologically active compounds in cranberry fruit samples. [ABSTRACT FROM AUTHOR]

Abstract Increasing aridity in the Mediterranean region will result in longer and recurrent drought. These changes could strongly modify plant defenses, endangering tree survival. We investigate the response of chemical defenses from central and specialized metabolism in Quercus pubescens Willd. to future Mediterranean drought using a long-term drought experiment in natura where trees have been submitted to amplified drought (~ –30% annual precipitation) since April 2012. We focused on leaf metabolites including chlorophylls and carotenoids (central metabolism) and flavonols (specialized metabolism). Measurements were performed in summer from 2016 to 2022. Amplified drought led to higher concentrations of total photosynthetic pigments over the 2016–2022 period. However, it also led to lower AZ/VAZ and flavonol concentrations. Additionally, chemical defenses of Q. pubescens responded to previous precipitation where low precipitation 1 year and/or 2 years preceding sampling was associated to low concentrations of VAZ, flavonol and high neoxanthin concentrations. Our study indicates that the decline of flavonol concentration under long-term drought is counterbalanced by a higher production of several central metabolites. Such results are potentially due to an adjustment in tree metabolism, highlighting the importance of performing long-term experimental studies in natura for assessing drought legacy effects and thus forest adaptation to climate change.

The present study assessed the impact of using irrigation water contaminated with Azithromycin (AZM) residues on the biomass and antioxidant compounds of purple corn; for this purpose, the plants were cultivated under ambient conditions, and the substrate used consisted of soil free from AZM residues, mixed with compost in a ratio of 1:1 (v/v). The experiment was completely randomized with four replications, with treatments of 0, 1, 10, and 100 μg/L of AZM. The results indicate that the presence of AZM in irrigation water at doses of 1 and 10 μg/L increases the weight of dry aboveground biomass, while at an amount of 100 μg/L, it decreases. Likewise, this study reveals that by increasing the concentration of AZM from 1 to 10 μg/L, total polyphenols and monomeric anthocyanins double, in contrast, with an increase to 100 μg/L, these decrease by 44 and 53%, respectively. It has been demonstrated that purple corn exposed to the antibiotic AZM at low doses has a notable antioxidant function in terms of DPPH and ORAC. The content of flavonols, phenolic acids, and flavanols increases by 57, 28, and 83%, respectively, when the AZM concentration is from 1 to 10 μg/L. However, with an increase to 100 μg/L, these compounds decrease by 17, 40, and 42%, respectively. On the other hand, stem length, root length, and dry weight of root biomass are not significantly affected by the presence of AZM in irrigation water. [ABSTRACT FROM AUTHOR]

SUMMARY: Flavonols are widely synthesized throughout the plant kingdom, playing essential roles in plant physiology and providing unique health benefits for humans. Their glycosylation plays significant role in improving their stability and solubility, thus their accumulation and function. However, the genes encoding the enzymes catalyze this glycosylation remain largely unknown in apple. This study utilized a combination of methods to identify genes encoding such enzymes. Initially, candidate genes were selected based on their potential to encode UDP‐dependent glycosyltransferases (UGTs) and their expression patterns in response to light induction. Subsequently, through testing the in vitro enzyme activity of the proteins produced in Escherichia coli cells, four candidates were confirmed to encode a flavonol 3‐O‐galactosyltransferase (UGT78T6), flavonol 3‐O‐glucosyltransferase (UGT78S1), flavonol 3‐O‐xylosyltransferase/arabinosyltransferase (UGT78T5), and flavonol 3‐O‐rhamnosyltransferase (UGT76AE22), respectively. Further validation of these genes' functions was conducted by modulating their expression levels in stably transformed apple plants. As anticipated, a positive correlation was observed between the expression levels of these genes and the content of specific flavonol glycosides corresponding to each gene. Moreover, overexpression of a flavonol synthase gene, MdFLS, resulted in increased flavonol glycoside content in apple roots and leaves. These findings provide valuable insights for breeding programs aimed at enriching apple flesh with flavonols and for identifying flavonol 3‐O‐glycosyltransferases of other plant species. [ABSTRACT FROM AUTHOR]

Flavonoids play an important role in forming wine grapes and wine quality characteristics. The flavonoids of three winter red wine grapes, Yeniang No. 2 (YN2), Marselan (Mar), and Guipu No. 6 (GP6), were analyzed by ultra-high-performance liquid chromatography–triple quadrupole mass spectrometry (UPLC-QQQ-MS). Furthermore, the flavonoids in GP6 grapevines using two types of training systems, namely, trellis (T) and espaliers (E), were also compared in this study. Overall, 196 flavonoid metabolites, including 96 flavones, 38 flavonols, 19 flavanones, 18 polyphenols, 15 anthocyanins, 7 isoflavones, and 3 proanthocyanidins, were identified. The flavonoid profiles were remarkably different among these three grape varieties, while they did not change much in the GP6 managed on trellis and espaliers. Grape varieties with different genetic backgrounds have their own unique flavonoid profiles. Compared with Mar-T, isoflavones and flavonols presented higher contents in GP6-T and YN2-T, which mainly contain glycitein, genistin, calycosin, kaempferide, isotrifoliin, and ayanin. The anthocyanin content was significantly higher in YN2-T than in the other two varieties. YN2 and GP6-T present a more stable color, with significantly more acetylated diglucosides and methylated anthocyanins in YN2-T and GP6-T than in Mar-T. Notably, GP6 had more varied flavonoids and the better characteristics to its flavonoid profile out of these three varieties, due to it containing a higher number of anthocyanins, flavone, and flavonols and the greatest number of different flavonoid metabolites (DFMs), with higher contents than YN2 and Mar. Compared with the trellis training system, the espaliers training system increased the content of flavonoids detected in GP6 grape berries; however, the composition of flavonoids strictly depends on the grape variety. [ABSTRACT FROM AUTHOR]

In plants, salicylic acid (SA) hydroxylation regulates SA homoeostasis, playing an essential role during plant development and response to pathogens. This reaction is catalysed by SA hydroxylase enzymes, which hydroxylate SA producing 2,3‐dihydroxybenzoic acid (2,3‐DHBA) and/or 2,5‐dihydroxybenzoic acid (2,5‐DHBA). Several SA hydroxylases have recently been identified and characterised from different plant species, but no such activity has yet been reported in maize. In this work, we describe the identification and characterisation of a new SA hydroxylase in maize plants. This enzyme, with high sequence similarity to previously described SA hydroxylases from Arabidopsis and rice, converts SA into 2,5‐DHBA; however, it has different kinetic properties to those of previously characterised enzymes, and it also catalysers the conversion of the flavonoid dihydroquercetin into quercetin in in vitro activity assays, suggesting that the maize enzyme may have different roles in vivo to those previously reported from other species. Despite this, ZmS5H can complement the pathogen resistance and the early senescence phenotypes of Arabidopsis s3h mutant plants. Finally, we characterised a maize mutant in the S5H gene (s5hMu) that has altered growth, senescence and increased resistance against Colletotrichum graminicola infection, showing not only alterations in SA and 2,5‐DHBA but also in flavonol levels. Together, the results presented here provide evidence that SA hydroxylases in different plant species have evolved to show differences in catalytic properties that may be important to fine tune SA levels and other phenolic compounds such as flavonols, to regulate different aspects of plant development and pathogen defence. Summary statement: Maize plants express an enzyme of the 2‐oxoglutarate‐dependent oxygenase family with unique kinetic properties, having salicylic acid hydroxylase activity but it can also convert flavonols from dihydroflavonols. Zm2‐ODD7 confers increased resistance against pathogens and regulates senescence. [ABSTRACT FROM AUTHOR]

Flavonoids are usually present in forms of glucosides in plants, which could be catabolized by β‐glucosidase (BGLU) to form their corresponding flavonoid aglycones. In this study, we isolated three abiotic‐responsive BGLU genes (MtBGLU17, MtBGLU21 and MtBGLU22) from Medicago truncatula, and found only the recombinant MtBGLU17 protein could catalyse the hydrolysis of flavonoid glycosides. The recombinant MtBGLU17 protein is active towards a variety of flavonoid glucosides, including glucosides of flavones (apigenin and luteolin), flavonols (kaempferol and quercetin), isoflavones (genistein and daidzein) and flavanone (naringenin). In particular, the recombinant MtBGLU17 protein preferentially hydrolyses flavonoid‐7‐O‐glucosides over their corresponding 3‐O‐glucosides. The content of luteoin‐7‐O‐glucoside was reduced in the MtBGLU17 overexpression plants but increased in the Tnt‐1 insertional mutant lines, whereas luteoin content was increased in the MtBGLU17 overexpression plants but reduced in the Tnt‐1 insertional mutant lines. Under drought and salt (NaCl) treatment, the MtBGLU17 overexpression lines showed relatively higher DPPH content, and higher CAT and SOD activity than the wild type control. These results indicated that overexpression lines of MtBGLU17 possess higher antioxidant activity and thus confer drought and salt tolerance, implying MtBGLU17 could be potentially used as a candidate gene to improve plant abiotic stress tolerance. Summary statement: MtBGLU17 gene from Medicago truncatula encodes a β‐glucosidase that is able to hydrolyse a variety of flavonoid glucosides. Both gain‐of‐function and loss‐of‐function studies in M. truncatula demonstrated that MtBGLU17 is involved in drought and salt tolerance by balancing the accumulation of flavonoid aglycones with ROS scavenging activity. [ABSTRACT FROM AUTHOR]

Summary: In the present study, the effect of microwave roasting on the total phenolic quantities, antioxidant activities, phenolic constituents, fatty acids and tocopherol amounts of the pistachio kernel and oil was revealed. The moisture, oil, total phenolic amounts and antioxidant capacity value of raw and roasted pistachio nuts were assessed as 31.13%, 28.58%, 34.79 mgGAE/100 g and 0.75%–3.18%, 56.91%, 18.80 mgGAE/100 g and 2.26%, respectively. The raw pistachio nut contains 1.90 gallic acid, 0.22 3,4‐dihydroxybenzoic acid, 0.87 (+)‐catechin, 0.15 1,2‐dihydroxybenzene, 0.15 rutin trihydrate, 0.16 resveratrol, 0.1 quercetin, 0.19 kaempferol and 0.24 mg/100 g isorhamnetin. In addition, microwave‐roasted nuts contained 0.75 gallic acid, 0.62 3,4‐dihydroxybenzoic acid, 0.83 (+)‐catechin, 0.47 1,2‐dihydroxybenzene, 0.21 syringic acid, 0.17 caffeic acid and 0.17 mg/100 g quercetin. The raw and roasted pistachio nut oils contained 74.12% and 71.16% oleic, 13.76% and 15.23% linoleic, 8.16% and 8.92% palmitic and 2.09% and 2.10% stearic acids, respectively. The oil samples of the raw and roasted kernels contained 8.15 and 0.00 α‐tocopherol, 63.78 and 7.60 β‐tocopherol, 8.72 and 7.40 ɣ‐tocopherol and 5.61 and 6.77 mg g−1 δ‐tocopherols, respectively. The total phenolic quantity of the pistachio kernel roasted by microwave decreased significantly. Phenolic compounds of the pistachio kernel showed partial differences depending on microwave heating. Differences were monitored in the fatty acid profiles of Pistachio kernel oils. β‐tocopherol quantity of the oil of the pistachio kernel heated by microwave significantly decreased. [ABSTRACT FROM AUTHOR]

Background: Ziwan and Taoren (ZT) is a classic medicine pair in the formula of Mai Dong Di Shao Decoction, has been used to treat primary Sjogren's syndrome (pSS) for more than 20 years. But its action mechanism is still unknown. This study is aimed to reveal the potential mechanism of ZT treated pSS and discover its active compounds of ZT and therapeutic target for pSS. Methods: Firstly, the potential pathways of ZT for pSS treatment were predicted through network pharmacology and GO and KEGG enrichment analysis. Secondly, the inter-structural relationships between active compounds of ZT and target proteins were visualized using molecular docking techniques. Finally, efficacy and mechanism were conducted through in vivo experiments, such as water intake, spleen index, hematoxylin-eosin staining pathological changes, ELISA, Western Blot analysis, and immunofluorescence staining. Results: Nine active compounds were extracted from network pharmacology, including quercitrin, luteolin, kaempferol, β-sitosterol, isorhamnetin, galangin, hederagenin, diosmetin and gibberellin 7. Seven disease targets were identified: RELA, TP53, AKT1, interleukin (IL) 6, MAPK1, ESR1, IL10; with RELA being the most core target. KEGG and GO enrichment analysis indicated that ZT may act through the TLR/NF-κB/RELA inflammatory mechanism process. preliminary results of molecular docking showed that ZT's active compounds bind well to the RELA (p65) receptor. In vivo results demonstrated that a high dose of ZT significantly improved water intake and reduced lymphocytes infiltration in submandibular gland pathology in NOD mice. The expression content of AQP5 and vasoactive intestinal peptide in the submaxillary gland was significantly increased, while levels of inflammatory factors such as tumor necrosis factor-α, IL-6, and IL-1β along with protein expressions including toll-like receptor4, p-p65 and p-IKKα/β in NF-κB pathway were reduced. Conclusions: The ZT treatment exhibits a promising efficacy in mitigating dryness symptoms of pSS, potentially attributed to its capacity for suppressing the TLR/NF-κB inflammatory signaling pathway. [ABSTRACT FROM AUTHOR]

A number of studies have indicated the potential role of secondary metabolites, referred to as 'resistance factors', in plant defence against insect pests. Nevertheless, it remains unclear which metabolites serve as predictors of resistance in chrysanthemum cultivars against thrips. In the present study, the phenolic compounds of chrysanthemum leaves at different ontogenetic stages were analysed using high-performance liquid chromatography (HPLC). Furthermore, the relative epidermal flavonol contents in the leaves were quantified using the Dualex® Scientific 4 sensor, and the suitability of this non-destructive method for the rapid discrimination of resistance levels was evaluated. The results demonstrated that the most notable discrepancies in phenolic metabolite profiles were observed in the older leaves and the vegetative state of the chrysanthemum plants. Multiple discriminant analysis was conducted using HPLC-analysed metabolites to predict the importance of metabolites in resistant, susceptible, or highly susceptible plants in the vegetative stage. The results demonstrated that multiple metabolites, rather than a single metabolite, are responsible for thrips resistance in chrysanthemum. However, the relative flavonol content did not reflect the HPLC-analysed flavonoid glycosides or hydroxycinnamic acid derivatives, indicating that the Dualex® sensor is not a suitable device for determining resistance levels in chrysanthemums. Testing is required to extend and analyse the results in greater depth. [ABSTRACT FROM AUTHOR]

Pitaya flower, a medicinal and edible plant commonly used in tropical and subtropical regions, was the focus of this study, which compared the effects of hot-air drying (HAD) and vacuum drying (VD) on phytochemical profiles and biological activities of its four parts: calyx, petals, stamens, and pistils. Both drying methods significantly increased the total phenolic content (TPC) of pitaya flowers, with values ranging from 1.86 to 3.24 times higher than those of fresh samples. Twelve flavonoid compounds were identified in pitaya flowers, with the glycoside derivatives of three flavonols (kaempferol, isorhamnetin, and quercetin) being the most abundant. VD resulted in 1.15 times higher total flavonoid glycoside content than HAD, whereas in petals, HAD yielded a total flavonoid glycoside content 1.21 times higher than VD. Both HAD and VD effectively increased the antioxidant capacities of pitaya flowers, though the difference between the two methods was not significant. Additionally, both drying methods enhanced the antiproliferative activity of pitaya flowers, with HAD showing a more significant effect than VD. The present study emphasized the efficacy of drying methods for enhancing flavonoids in pitaya flowers and provided insights for functional products' innovation with different parts of pitaya flowers. [ABSTRACT FROM AUTHOR]

Objective: This study aims to investigate the molecular mechanisms of Huangqi {Astragalus) in the treatment of premature ovarian insufficiency (POI) using network pharmacology and molecular docking methods. Methods: The active compounds and target proteins of Huangqi were screened from the TCMSP database, while the disease target proteins associated with POI were obtained from the Genecards database. The Venny online tool was used to identify the overlapping genes between the two datasets. Cytoscape software was used to construct a gene regulatory network for the active ingredients of Huangqi. The protein-protein interaction (PPI) network and core genes were selected based on the STRING database and CytoNCA plug-in of Cytoscape. GO (gene ontology) enrichment and KEGG (Kyoto encyclopedia of genes and genomes) pathway enrichment analyses of the overlapping genes were performed using the DAVID database. Molecular docking techniques were used to further elucidate the molecular mechanisms underlying the therapeutic effects. Human ovarian granulosa-like tumor cells (KGN) underwent serum starvation (SS) treatment to induce POI cell models and then received quercetin treatment, and experimentally validated the network pharmacology prediction results by TUNEL staining and Western blotting assay. Results: The TCMSP database provided 32 active compounds and 552 target genes associated with Huangqi, while totally 730 disease target genes associated with POI were screened out from the disease database. Of these, 62 genes were found to be shared between the two datasets. The top 6 compounds based on degree values were quercetin, isorhamnetin, kaempferol, mairin, formononetin and astragaloside IV. The 10 core genes identified were ALB, INS, AKT1, ACTB, TP53, TNF, ESR1, CASP3, STAT3 and PTEN. These potential targets were mainly involved in regulating the JAK2/STAT3 and PI3K/Akt signaling pathway. Molecular docking results revealed strong binding interactions between the compounds and the key proteins STAT3 and Akt1 in the JAK-STAT and PI3K-Akt signalling pathways. The results of in vitro experiments revealed that quercetin could activate the JAK2/STAT3 pathway and inhibit cell apoptosis. Conclusions: Network pharmacology and molecular docking analysis showed that Astragalus could regulate the response of ovarian cells to estradiol, inhibit apoptosis and regulate the JAK-STAT and PI3K-Akt signalling pathways in the treatment of early onset ovarian dysfunction. [ABSTRACT FROM AUTHOR]

AbstractTraditional Chinese Medicine (TCM) formulations often contain a complex mixture of compounds, making it challenging to evaluate their quality. Buzhong Yiqi Oral Liquid (BYOL), a well-known TCM formulation, has been used to treat gastrointestinal diseases and fatigue for a long time. However, the effective substances for its therapeutic effects remain unclear. This study aimed to establish a novel quality control approach for BYOL using a multidimensional feature network to identify quality markers (Q-markers). The multidimensional characteristic network was constructed by a “Spider-Web” model, including the compatibility of ingredients, traceability of compounds from raw materials to the final product, effectiveness, measurability, and stability. Multivariate statistical analysis was applied to quantify the individual dimensions of the feature network, and candidate compounds were identified based on regression regions within the network. Using the multidimensional characteristic network, 12 components were identified as key Q-markers for BYOL, consisting of calycosin-7-O-β-D-glucoside, formononetin, astragaloside IV, liquiritin, quercetin, hesperidin, glycyrrhizic acid, isorhamnetin, liquiritin apioside, hesperidin, luteolin, and nobiletin. The identified Q-markers offered valuable insights for future research on medicinal substances and quality control of BYOL. [ABSTRACT FROM AUTHOR]

Chenopodium album L. (CAL) has many bioactive compounds and pharmacological activities. Fermentation is the preferred modification method of releasing target bioactive. We prepared two crude polysaccharides: SLC (the polysaccharide from the unfermented stem and leaves of CAL) and FSLC (the polysaccharide from the fermented stem and leaves of CAL). In vitro antioxidant and composition of SLC and FSLC were compared, and the effects of FSLC on antioxidant activity in the IPEC-J2 cells model and development-promoting activity in the zebrafish model were evaluated. The results revealed that FSLC possesses stronger DPPH, hydroxyl radical scavenging, and reducing power than SLC. The levels of total polysaccharide, polyphenol, and flavonoid, as well as the molar ratio of glucuronic acid increased in FSLC. Compared with SLC, the relative contents of protocatechuic acid, protocatechualdehyde, gentisic acid, vanillic acid, p-coumaric acid, quercetin, ferulic acid methyl ester, hispidulin, diosmetin, cinnamic acid, isorhamnetin, syringic acid and kaempferol in FSLC increased. In IPEC-J2 cells, antioxidant enzyme activities and GSH levels were significantly increased, while the MDA level was reduced by treatment with 0.25 mg/mL FSLC. In the zebrafish model, treatment with 25 ~ 300 μg/mL of FSLC had no harmful impact on the morphology and viability of embryos at 12 ~72 hpf. At 48 and 60 hpf, treatment with 100 ~ 300 μg/mL FSLC increased the hatching rate of embryos. At 72hpf, treatment with 100 ~ 300 μg/mL FSLC could relieve morphological abnormalities caused by LPS in zebrafish and improve the hatching rate of embryos. Together, these results provide useful information on the potential for applying polysaccharides from the stems and leaves of CAL as natural feed additives to exert its antioxidant and development-promoting functions. [ABSTRACT FROM AUTHOR]

SUMMARY: Skin color is an important trait that determines the cosmetic appearance and quality of fruits. In cucumber, the skin color ranges from white to brown in mature fruits. However, the genetic basis for this important trait remains unclear. We conducted a genome‐wide association study of natural cucumber populations, along with map‐based cloning techniques, on an F2 population resulting from a cross between Pepino (with yellow‐brown fruit skin) and Zaoer‐N (with creamy fruit skin). We identified CsMYB60 as a candidate gene responsible for skin coloration in mature cucumber fruits. In cucumber accessions with white to pale yellow skin color, a premature stop mutation (C to T) was found in the second exon region of CsMYB60, whereas light yellow cucumber accessions exhibited splicing premature termination caused by an intronic mutator‐like element insertion in CsMYB60. Transgenic CsMYB60c cucumber plants displayed a yellow‐brown skin color by promoting accumulation of flavonoids, especially hyperoside, a yellow‐colored flavonol. CsMYB60c encodes a nuclear protein that primarily acts as a transcriptional activator through its C‐terminal activation motif. RNA sequencing and DNA affinity purification sequencing assays revealed that CsMYB60c promotes skin coloration by directly binding to the YYTACCTAMYT motif in the promoter regions of flavonoid biosynthetic genes, including CsF3′H, which encodes flavonoid 3′‐hydroxylase. The findings of our study not only offer insight into the function of CsMYB60 as dominantly controlling fruit coloration, but also highlight that intronic DNA mutations can have a similar phenotypic impact as exonic mutations, which may be valuable in future cucumber breeding programs. Significance Statement: Genome‐wide association study and map‐based cloning revealed that CsMYB60 regulates mature cucumber fruit skin coloring, which is promising for cucumber breeding. Two loss‐of‐function mutations of CsMYB60 provided color variations in the natural cucumber population. [ABSTRACT FROM AUTHOR]

Rhododendrons produce a variety of methoxyflavonoids, including rarely found 3-methoxyflavonoids and 5-methoxyflavonoids. It was thus suggested that they have a series of regiospecific flavonoid O-methyltransferases (FOMTs). The 18 Class II O-methyltransferase (OMT) genes were retrieved from the Rhododendron delavayi genome, designating them as RdOMTs. A comprehensive biochemical characterization of RdOMTs was performed to identify functional FOMTs. The FOMT activity of recombinant RdOMTs was assayed with flavonoid substrates of different subclasses. Among the examined RdOMTs, RdOMT3, RdOMT10, and RdOMT12 showed FOMT activity for diverse flavonoids. In particular, RdOMT3 consumed only flavonols as a substrate. Structural analyses of the methylated products demonstrated that RdOMT3, RdOMT10, and RdOMT12 catalyze regiospecific methylation of flavonoids at the 3'/5'-, 3-, and 4'-hydroxyl groups, respectively. Their broad substrate spectrum and different regiospecificity suggest that these RdOMTs contribute to the formation of complex methoxyflavonoids in R. delavayi. Bioconversion of flavonoids using E. coli harboring each RdOMT demonstrated that RdOMT3, RdOMT10, and RdOMT12 are useful tools for the biotechnological production of valuable methoxyflavonoids, including the rarely found 3-methoxyflavonoids. [ABSTRACT FROM AUTHOR]

The medicinal plant Abrus precatorius L. was traditionally used in the Siddha and Ayurvedic systems of medicine in India. The Indian center of origin holds a vast variability in its seed color. The objective of this study was to assess the total monomeric anthocyanin, flavonol, as well as the antioxidative potential, protein content and ash content among the accessions. A total of 99 accessions conserved in the Indian National Genebank were used in this study. The methods used for the estimation of total monomeric anthocyanin, flavonol, as well as the antioxidative potential, protein content and ash content were the pH differential method, Oomah method, Ferric Reducing Antioxidant Potential, Dumas method and gravimetric method, respectively. The completely black colored accession was recorded with highest total monomeric anthocyanin (51.95 mg/100 g of cyanidin 3-glucoside equivalent) and flavonol content (66.41 mg/g of quercetin equivalent). Red + black colored accessions have recorded the maximum value with respect to antioxidants (14.18 mg/g of gallic acid equivalent). The highest amount of protein content was found in a completely white colored accession (20.67%) and the maximum ash content was recorded in red + black colored accession (4.01%). The promising accessions identified can be used by pharmaceutical companies in drug development and in curing degenerative diseases. [ABSTRACT FROM AUTHOR]

Background: The beneficial properties of wine by-products include actions that help prevent and treat cardiovascular conditions such as hypertension, primarily due to their antioxidant effects. Novel pharmacotherapies are being developed to treat arterial hypertension, including investigations into natural products exhibiting biological activity, necessitating rigorous evaluation of their efficacy and safety. This study aimed to identify and quantify phenolic compounds in Syrah (Vitis vinifera) grapes grown in the Brazilian Cerrado and their presence in winemaking by-products. It also examined the effects of grape pomace on blood pressure. Methods: Fresh grapes, pomace, and lees, were subjected to spectrophotometric determination of total phenolic compounds, followed by identification and quantification using HPLC-DAD-ESI-MSn. Normotensive male rats (Wistar) and spontaneously hypertensive rats (SHR) received grape pomace-enriched (150 or 300 mg/kg/day, 14 days) or standard chow. Indirect arterial pressure was assessed, while vascular reactivity was evaluated in mesenteric resistance arteries. Results: Pomace samples exhibited higher total phenolic compound concentrations than grapes or lees. Seven derivatives of hydroxycinnamic acids and twenty-one flavonols were identified. Quercetin-3-glucoside and ethyl caffeate were the most abundant phenolic compounds. Grape pomace-enriched chow demonstrated a dose-dependent hypotensive effect in rats. Conclusion: the abundance of flavonols and hydroxycinnamic acids, combined with their hypotensive effects, underscores the therapeutic potential of fine wine-making by-products produced in the Brazilian Cerrado. [ABSTRACT FROM AUTHOR]

The repurposing of therapeutic and preventive strategies against Alzheimer's disease (AD) is progressing rapidly. Pancratium aegyptiacum has been found to possess considerable anticholinesterase potential attributed to its alkaloid contents. In this study, the potential anti‐Alzheimer's activity of isolated flavonoids from P. aegyptiacum was investigated through computational analysis, focusing on the flavonoids rather than their well‐known alkaloids. Molecular docking was performed against three crucial targets involved in the development of AD, and the isolated phytoconstituents were analysed against these targets. Pathway enrichment analyses were also established, additionally, ADMETlab and PASS web servers predicted the pharmacological properties and potential biological functions of the isolated flavonoids. The phytochemical analysis of P. aegyptiacum aerial parts revealed the isolation and identification of eleven flavonoids. They were identified as derivatives of kaempferol (Km), quercetin (Qn) and isorhamnetin (Is). Our investigation revealed that these phytoconstituents potentially act against AD, with several phytochemicals showing superior binding affinity against essential AD targets. The Kyoto Encyclopaedia of Genes and Reactome pathway enrichment database revealed that isolated phytochemicals may have a role in regulating the immune pathway directly correlated to AD. Additionally, these phytochemicals exhibited lower toxicity with pleiotropic biological activities, including dementia treatment and neurotrophic factor enhancement. [ABSTRACT FROM AUTHOR]

Impatiens balsamina, commonly known as balsam rose, is widely grown in India and China as an ornamental plant. The flowers of this plant have been reported as a rich source of polyphenols, especially flavonols. In China and some parts of India, this plant has been traditionally utilized for various clinical conditions, both wholly and partially. As this plant is a rich source of flavonols, the current study was carried out to investigate its antihyperlipidemic activity. The methanolic extract of Impatiens balsamina flowers was tested against dexamethasone-induced hyperlipidemia in male Wistar rats. 10 mg/kg body weight of dexamethasone was used to induce hyperlipidemia in rats combined with the co-treatment by utilizing the methanolic extract of Impatiens balsamina flowers of 200 mg/kg and 400 mg/kg orally for 8 d. Lipid parameters, glucose and oxidative stress markers were analyzed in serum and liver tissues, respectively. Dexamethasone treatment caused sustained elevation of serum lipid parameters, glucose levels and oxidative stress markers. Co-treatment with the methanolic extract of Impatiens balsamina significantly reduced the elevated serum lipid profile, glucose levels and oxidative stress markers in dose-dependent manner. Pronounced antihyperlipidemic activity of methanolic extract of Impatiens balsamina flowers was observed at the dose of 400 mg/kg. Histopathological studies of rats' liver also reflected the same. The present study provides strong evidence for the antihyperlipidemic activity of methanolic extract of Impatiens balsamina flowers without any observed side effects at the studied dosage. [ABSTRACT FROM AUTHOR]

Abiotic stress, especially drought stress, poses a significant threat to terrestrial plant growth, development, and productivity. Although mulberry has great genetic diversity and extensive stress-tolerant traits in agroforestry systems, only a few reports offer preliminary insight into the biochemical responses of mulberry leaves under drought conditions. In this study, we performed a comparative metabolomic and transcriptomic analysis on the "drooping mulberry" (Morus alba var. pendula Dippel) under PEG-6000-simulated drought stress. Our research revealed that drought stress significantly enhanced flavonoid accumulation and upregulated the expression of phenylpropanoid biosynthetic genes. Furthermore, the activities of superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) content were elevated. In vitro enzyme assays and fermentation tests indicated the involvement of flavonol synthase/flavanone 3-hydroxylase (XM_010098126.2) and anthocyanidin 3-O-glucosyltransferase 5 (XM_010101521.2) in the biosynthesis of flavonol aglycones and glycosides, respectively. The recombinant MaF3GT5 protein was found to recognize kaempferol, quercetin, and UDP-glucose as substrates but not 3-/7-O-glucosylated flavonols and UDP-rhamnose. MaF3GT5 is capable of forming 3-O- and 7-O-monoglucoside, but not di-O-glucosides, from kaempferol. This implies its role as a flavonol 3, 7-O-glucosyltransferase. The findings from this study provided insights into the biosynthesis of flavonoids and could have substantial implications for the future diversified utilization of mulberry. [ABSTRACT FROM AUTHOR]

Herein, a novel fluorescence probe Fla-DNP based on flavonol has been designed and synthesized for rapid, specific detection of H2S. With the addition of H2S, Fla-DNP triggered thiolysis and released Fla displaying the "turn-on" fluorescence response at 566 nm, which is consistent with the reaction site predicted by calculating Electrostatic potential and ADCH charges. As an easily available H2S probe, Fla-DNP has the advantages of high selectivity, anti-interference, low detection limit (0.834 μM), short response time (6 min), and large Stokes shift (124 nm). The sensing mechanism of H2S was determined by HRMS analysis and DFT calculation. Moreover, Fla-DNP processes a wide range of multiple applications, including the detection of H2S in environmental water samples with good recovery rates ranging from 89.6% to 102.0%, as well as tracking the production of H2S during food spoilage. Meanwhile, the probe exhibits superior biocompatibility and can not only be available used for H2S detection in living cells but be further designed as an H2S-activated CO photoreleaser, based on which it can be developed as a targeted anti-cancer drug. A novel fluorescence probe Fla-DNP was synthesized utilizing 4-dimethylaminobenzoxanthone fluorescent dye (Fla) as the fluorophore, 2, 4-dinitrobenzenether group (DNP) as the recognition group, which can rapidly respond to H2S with high selectivity, anti-interference, low detection limit (0.834 μM), short response time (6 min), and large Stokes shift (124 nm) characteristics. The practical applications of Fla-DNP were further explored in water, foodstuffs samples and living cells. It is reflected that Fla-DNP can not only track H2S in complex environment water, but also can detect H2S produced during foodstuffs spoilage to monitor food freshness. More importantly, Fla-DNP can be available used for H2S detection in living cells and utilize the properties of the photoinduced release of CO from flavonols to be designed as a bifunctional platform for H2S detection and CO release. It is demonstrated that H2S-activated CO photoreleaser Fla-DNP has promise for development as an anti-cancer drug. [ABSTRACT FROM AUTHOR]

The incidence of neurological disorders, particularly age-related neurodegenerative pathologies, exhibits an alarming upward trend, while current pharmacological interventions seldom achieve curative outcomes. Despite their diverse clinical presentations, neurological diseases often share a common pathological thread: the aberrant accumulation of misfolded proteins within the endoplasmic reticulum (ER). This phenomenon, known as ER stress, arises when the cell's intrinsic quality control mechanisms fail to cope with the protein-folding burden. Consequently, misfolded proteins accumulate in the ER lumen, triggering a cascade of cellular stress responses. Recognizing this challenge, researchers have intensified their efforts over the past two decades to explore natural compounds that could potentially slow or even reverse these devastating pathologies. Flavonoids constitute a vast and heterogeneous class of plant polyphenols, with over 10,000 identified from diverse natural sources such as wines, vegetables, medicinal plants, and organic products. Flavonoids are generally divided into six different subclasses: anthocyanidins, flavanones, flavones, flavonols, isoflavones, and flavonols. The diverse family of flavonoids, featuring a common phenolic ring backbone adorned with varying hydroxyl groups and additional modifications, exerts its antioxidant activity by inhibiting the formation of ROS, as evidenced by research. Also, studies suggest that polyphenols such as flavonoids can regulate ER stress through apoptosis and autophagy. By understanding these mechanisms, we can unlock the potential of flavonoids as novel therapeutic agents for neurodegenerative disorders. Therefore, this review critically examines the literature exploring the modulatory effects of flavonoids on various steps of the ER stress in neurological disorders. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether galangin (Gal) affects the proliferation, migration, invasion and apoptosis of osteosarcoma MG63 cells by regulating the cGAS/STING signaling pathway. Methods: Human osteosarcoma MG63 cells were cultured in vitro and treated with Gal at concentrations of 0, 5, 15, 25, 50, 100 and 200 μmol/L for 48 hours, and the effect of Gal on cell viability was detected by CCK-8 method. MG63 cells were divided into the control group (untreated cells), the Gal low concentration group (Gal-L group, treated with 50 μmol/L Gal), the Gal high concentration group (Gal-H group, treated with 100 μmol/L Gal), and the Gal-H+STING inhibitor group (Gal-H+H-151 group, treated with 100 μmol/L Gal+8 μmol/L H-151). EdU staining method, scratch healing test, Transwell chamber method and flow cytometry were used to detect cell proliferation, migration, invasion and apoptosis of cells in each group. Western blot was applied to detect the expression levels of cGAS and STING proteins in cells of each group. Results: Compared with the control group, the proliferation activity, migration, and invasion abilities of the cells in the Gal-L and Gal-H groups were significantly decreased (all P<0.05); the apoptosis rate and the expression levels of cGAS and STING proteins were significantly increased (all P<0.05). Compared with the Gal-H group, the proliferation activity, migration, and invasion abilities of the cells in the Gal-H+H-151 group were significantly increased (all P<0.05); the apoptosis rate and the expression levels of cGAS and STING proteins were significantly decreased (all P<0.05). Conclusion: Gal may inhibit the proliferation, migration and invasion and promote the apoptosis of osteosarcoma cells by activating the cGAS/STING signaling pathway. [ABSTRACT FROM AUTHOR]