Due to the host immunological disease brought on by infection is sepsis, multiple organ dysfunction syndrome (MODS), which has a high morbidity and mortality rate, could be the result. With advances in pathogen detection technologies, breakthroughs in anti-infection drugs, and the creation of organ function support, the clinical diagnosis and treatment of sepsis have advanced significantly. Pathogen-induced abnormal immunological responses, which can range from excessive inflammation to immunosuppression, are recognized to play a significant role in the high death rate. Unfortunately, no medications that are specifically intended to treat sepsis have been licensed. In order to offer a theoretical foundation for the management of sepsis, we will now discuss current advancements in research on immunological responses in sepsis. The prognosis of sepsis patients may be improved by developing and optimizing a dynamic immune system treatment plan based on anti-infection therapy, fluid replacement, support for organ function, and timely application of immunomodulatory therapies

Lemon pectin extracted along with water-soluble flavonoids and other phytochemicals from citrus industry’s waste lemon peel via hydrodynamic cavitation in water, directly at pre-industrial scale and further isolated via freeze drying, shows exceptionally high antioxidant and non-cytotoxic activity. Preliminary investigation indicates also significant antimicrobial activity. These findings open the route to the development of new nutraceutical and healthcare application of a versatile biopolymer endowed with new functionality, rapidly and conveniently obtained from an abundant by-product of the agrofood industry.

Flavonoids are a class of polyphenolic secondary metabolites found in plants. Due to their ubiquity in our daily dietary intake and their major anti-oxidative, anti-inflammatory and anti-mutagenic activities, they have been a major focus of wide-ranging research for the past two decades. Mass spectrometry combined with liquid chromatography is one of the most popular techniques for the analysis of flavonoids. In this study, high-resolution accurate mass electrospray tandem mass spectrometry was used to study 30 flavonoids in both positive and negative ionisation modes. From the data obtained, common losses are summarised and compiled. Dominating neutral losses are tabulated. The radical loss of CH3. was observed in flavonoids containing methoxy groups and three diagnostic product ions were identified which could be useful in structural elucidation of unknown flavonoids and flavonoid metabolites. Energy breakdown graphs were utilised to dis-tinguish between three pairs of structural isomers, and to help rationalise proposed fragmentation pathways. Lastly, a competition of loss of CH3. and methane were reported for rhamnetin and isorhamnetin in the negative ion mode for the first time. Proposed fragmentation pathways were given to rationalise the differences in peak intensities for this competitive process.

Histone changes that are adjustable and transmitted without altering the DNA sequence are part of epigenetic control. In many disorders, most famously malignancy, abnormal genetic information is seen as a result of mismanagement of typical epigenetic mechanisms. A paradigm change in the diagnosis and treatment of cancer has been brought about by recent discoveries about the processes of epigenetic modifications, chromatin remodeling, and noncoding RNAs implicated in the changed expression patterns of tumor cells. There is a significant increase in the search for drugs that could alter the epigenetic environment altered by tumor cells and benefit from their therapeutic potential. Phytochemicals with a high concentration of naturally produced phenol molecules known as flavonoids can regulate genomic processes. Understanding the precise epigenetic alterations brought on by flavonoid-mediated mechanisms is necessary to develop combination therapy techniques and genomic therapies for cancer. This article aims to thoroughly examine the epigenetic modifications of flavonoids, including their anticancer properties.

The exogenous application of phenolic compounds is increasingly recognized as a valuable strategy for promoting growth and mitigating the adverse effects of abiotic stress. However, the biostimulant effect under optimal conditions have not been thoroughly explored. In this study, we investigated the impact of foliar application of flavonoids, specifically Crop Bio Life (CBL), on tomato plants grown under controlled conditions. Our study focused on determining growth parameters, such as cell size, and assessing the concentration of hormones. Principal component analysis (PCA) from all physiological variables were determined. Additionally, we utilized high-throughput mRNA sequencing technology and bioinformatic methodologies to robustly analyze the transcriptomes of tomato leaves regulated by flavonoids. The findings revealed that CBL primarily influenced cells enlargement, leading to increased growth. Furthermore, CBL-treated plants exhibited higher concentrations of the hormone zeatin but lower concentrations of IAA. Moreover, RNAseq analysis indicated that CBL-treated plants required increased mineral transport and water uptake, as evidenced by gene expression patterns. Genes related to pathways such as fatty acid degradation, phenylpropanoid biosynthesis, and ABC transporters showed regulatory mechanisms governing internal flavonoid biosynthesis, transport, and tissue concentration, ultimately resulting in higher flavonoid concentrations in tomato leaves.

Heavy metals toxicity is a grave environmental issue in contemporary times. Phytoremediation is economic, effective and ecofriendly approach to decontaminate and remediate metal contaminated areas. Phenolic and Flavonoid content are important abiotic stress markers. The individual and combined impacts of toxiferous metals Arsenic (As), Cadmium (Cd) and (Copper) Cu were employed in recent studies to investigate their effect on Total flavonoids content (TFC) and total phenolic content (TPC) in various parts of Hydrocotyle umbellata L. to explore the role of plant in abating metal contamination. Folin- ciocalteu and AlCl 3 methods were used for investigating TPC and TFC respectively. Two-way ANOVA and CART model were employed for statistical analysis. Highest TPC was examined in decreasing order as leaf & gt; stem & gt; root in case of all the metals. Whereas highest TFC was found in all plant parts when subjected to As toxicity, and the lowest TFC was found in stem of the plant in respect to Cu toxicity. There was significant effect on TPC on plant part when subjected to Cu and As stress, but so significance was observed in plant part in case of Cd and combined metal stress. Treatment concentration had no significant effect on TPC when subjected to unique impact of all the three metals but had significant effect in case of combined metal stress. Similarly, in case of TFC no significant effect was recorded in case of plant part in all the stress types. But treatment amount has significant impact on Cd and combined metal stress. Metal type has significant effect on TPC and TFC. Whereas plant part has significant impact on TPC but non-significant values were observed on TFC in this case. This study epitomizes TPC and TFC in plants as effective and viable tool to pertain their role in phytoremediation against metal contamination. Therefore H. umbellata L. can be exerted for successful assemblage and decontamination of Cd, Cu and As in different plant parts.

Leishmaniasis is a neglected tropical disease and affects more than 350 million people worldwide. However, there are no vaccines for humans, and current treatment is hampered due to its high cost, numerous side effects, and painful administration routes. Ending its epidemics by 2030 has become a United Nations goal, and the multitarget drug strategy emerges as a promising alternative. Flavonoids are an example of multitarget compounds and organic synthesis represents a tool to obtain high yields of these molecules. In our study, we synthesized 17 flavonoid analogs using a scalable, easy-to-reproduce, and inexpensive method. All compounds demonstrated an impressive inhibition capacity against rCPB2.8, rCPB3, and rH84Y, which are highly expressed in the amastigote stage, the target form of the parasite. Compounds 3c, f12a, and f12b stood out as effective against all isoforms and intermolecular interactions were investigated through a molecular modeling study. The compounds were highly potent against the parasite and demonstrated low cytotoxic action against mammalian cells. The results were pioneering, representing an advance in the investigation of the mechanisms behind the antileishmanial action of flavonoid derivatives. Furthermore, compounds have shown to be promising leads for the design of other cysteine protease inhibitors for the treatment of leishmaniasis diseases.

A brief technical and economic insight into producing the water-soluble yellow colorant limocitrol 3-O-6”-[3-hydroxyl-3-methylglutaryl)])-β-D-glucopyranoside from waste lemon peel via simple solid-liquid extraction in aqueous ethanol or via hydrodynamic cavitation of waste lemon peel in water, shows that the biocolorant can be obtained at affordable cost. Coupled to the simplicity and sustainability of the extraction processes suggested, the high chemical and physical stability of this polymethoxylated flavanol and the health benefits of citrus flavonoids, support industrialization of this new bioeconomy production.

Propolis is a bee product widely used as a dietary supplement and included in sweets or baby foods due to its well-known antioxidant and nutritional properties that are directly correlated with its phenolic composition. For this reason, this study analysed the total contents of flavones and flavonols, flavanones and dihydroflavonols, and the antioxidant capacity by using the methods of ABTS and linoleic acid/β-carotene in 99 samples of propolis from Spain and Chile. A rapid method was developed for quantifying these parameters in raw propolis using near infrared (NIR) spectroscopy with an optical fibre probe of remote reflectance applied directly to the ground up sample. The models developed allow the determination of the total of flavones and flavonols (0-183 mg rutin/ g propolis), of the total of flavanones and dihydroflavonols (9-109 mg pinocembrin/ g propolis extract), and the antioxidant capacity by the ABTS method (0-3212 nmolesTrolox/ mg of propolis) and of linoleic acid/β-carotene (22-86% inhibition). The NIR spectroscopy models were applied in external validation to different samples of the calibration group, which led to the conclusion that the methods developed provide significantly identical data to the initial chemical data of reference.

Celtis iguanaea is popularly used in the treatment of diabetes mellitus. However, thorough chemical and pharmacological investigations regarding its activity are lacking. In this study, we investigated the effects of the hydroalcoholic extract from C. iguanaea (CI) on markers of cardiovascular diseases and the glucose metabolism in cholesterol-fed rats. Therefore, hypercholesterolemic rats (1% cholesterol) were orally treated with CI (150, 300, or 600 mg/kg) or simvastatin (4 mg/kg) (n = 6) once a day for 30 days along with a hypercholesterolemic diet. A control group (C) was given saline solution. CI showed significant decreases in serum levels of total cholesterol, LDL-cholesterol, HMG-CoA-reductase, IL-1, IL-6, TNF-α, and IFN-γ when compared to group C (p ˂ 0.05). Hypoglycemic effects were observed along with a decrease of the activity of sucrase (CI 600), maltase (CI 150, CI 300), and an increase in muscle glycogen levels (CI 300). Antioxidant effects were observed in plasma, and the histopathological analysis showed a significant decrease in the liver fat area for CI compared to group C (p < 0.001). Our results suggest that the biological effects of CI could be related to the presence of flavonoids that possibly exert antioxidant, enzymatic inhibitory, and insulin-mimetic effects.

Abiotic stress, especially drought stress poses a significant threat to the terrestrial plant growth, development, and productivity. Although mulberry have great genetic diversity and extensive stress tolerant traits in agroforestry systems, only a few reports offer preliminary insight into 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 up-regulated 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, form 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.

Prenylated flavonoids of Humulus lupulus L. have gained attention for their potential health benefits. In this study, Amber ALE and Russian Imperial Stout beers were prepared. In order to increase the content of prenylated flavonoids in beer, there was added ethanol extract of Polaris hops, they were dry hopping with Polaris hops or pure xanthohumol was added. In unfiltered beers, the highest total content of polyphenols (3.60 ± 0.32 g/L gallic acid) was determined on the eighth day of fermentation and maturation in Amber ALE beer without the addition of extract. The highest total antioxidant capacity was determined in Russian Imperial Stout beer with the addition of xanthohumol on the eighth day of fermentation and maturation (0.675 ± 0.008 mmol/L Trolox). This type of beer also had a high antioxidant efficiency (85.96 - 88.00%). Xanthohumol (2.05 mg/L) and isoxanthohumol (2.819 mg/L) were detectable only until the thirteenth day of fermentation and beer maturation. Therefore, the beers were filtered, and the ethanol extract of the Polaris was added to them for 24 hours. This procedure was used to prepare a functional beer of the Amber ALE type (15.210 ± 0.053 mg xanthohumol in 1 L and 0.922 ± 0.077 mg isoxanthohumol in 1 L) and a functional beer of the Russian Imperial Stout type (32.375 ± 0.032 mg xanthohumol in 1 L and 1.877 ± 0.043 mg isoxanthohumol in 1 L).

This study aimed to assess the variations in the nutritional attributes of thirteen Moringa oleifera cultivars. Leaves from six-month-old plants were harvested and tested for various nutritional attributes. There were significant (p ≤ 0.05) differences in the carbohydrates, energy, some of the sugars and fibre amongst the cultivars. The levels of moisture in the cultivars ranged from 7.10% to 8.20%. Additionally, there were significant (p ≤ 0.05) differences across the cultivars in microelements studied except for zinc (Zn). These data revealed that plants from different geographical provenances differed in their adapting to varied environments. In general, under the same cultivation, management and environmental conditions, the main reasons for these differences occurred in cultivars could be associated with the genetic background of each M. oleifera germplasm. However, the study cautions on the differences of nutritional properties, as some of the cultivars have been reported not to be pharmacological potent.

The role of plant growth-promoting rhizobacteria (PGPR) on enhancing tolerance of plants to abiotic stresses is well reported, but the effects of RGPRs on plants under salinity stress are not widely studied in the literature. Our study aimed to investigate the effect of Halomonas sp. and Azotobacter sp. on antioxidant activity, secondary metabolites, and biochemicals changes of purple basil under salinity stress conditions. The applied salt concentrations in this study were 50, 100, and 150 mM sodium chloride (NaCl). Salinity stress had a negative effect on plant growth parameters. Moreover, a reduction in some of the osmolytes and oxidative stress markers was observed. Inoculated plants ameliorated the oxidative damage by reducing the hydrogen peroxide (H2O2) contents and by increasing osmolytes (proline, total proteins, and soluble sugars), antioxidant enzymes activities (catalase, ascorbate peroxidase) and secondary metabolites (flavonoids). Overall, among treatments, plants inoculated with Azotobacter showed a better impact on physiological attributes to alleviate the adverse effects of 150 mM NaCl salinity stress on basil growth.

Pectin extracted via hydrodynamic cavitation in water only from waste lemon peel and further isolated via freeze drying displays significant antibacterial activity against Staphylococcus aureus, a Gram positive pathogen which easily contaminates food. The antibacterial effect of the new IntegroPectin is largely superior to that of commercial citrus pectin, opening the way to advanced applications of a new bioproduct now obtainable in large amounts and at low cost from citrus juice industry’s waste.

Environmental interventions and ecological adaptations harbor millions of valued substances and metabolites in plants which can be employed and commercialized for human benefits. Present study encompasses the untapped potential of pine needles of Indo-Himalayan region for the production of different metabolites and their pharmacological significance in terms of antioxidant and antimicrobial activity. Total phenolic and flavonoid content from the needles of ten pine species was quantified using three different solvent systems. Results revealed that out of 10 different selected Pinus species, Pinus taeda showed highest concentration of total phenolics, soluble-F phenolics and flavonoids content (approx.147.02 mg/g, 141.08 mg/g and 21.91mg/g respectively) as compared to other species. On the other hand P. greggii showed highest Bound-W phenolic content (approx.3.62mg/g). Among all the selected plant species, the needles of P.echinata exhibited the highest and P.thunbergii had the lowest ratio of total flavonoids to total phenolics. Most of these compounds were found to have effective antioxidant activities as well as antimicrobial activity, as estimated by oxygen radical absorbance capacity (ORAC) and disk diffusion test respectively.

Seaweeds are considered as one of the largest biomass producers in marine environment that is rich in bioactive metabolites and a source of natural ingredients for functional foods. The potential antioxidant activity and the potential inhibition of Caco2 cell proliferation, of crude extracts of: Chlorophyta (Ulva lactuca, and Codium tomentosum), Phaeophyta (Cystoseira crinita, Cystoseira stricta, and Sargassum vulgare), and Rhodophyta (Gelidium latifolium, Hypnea musciformis, and Jania rubens) collected from western Libyan coast were evaluated in vitro. The antioxidant activity was determined by reducing power and DPPH assays while cell proliferation, morphological changes and the cell cycle arrest were assessed by MTT, inverted light microscope and flow cytometry methods respectively. The polyphenols and flavonoids rich extracts showed remarkable reducing power and antiradical properties. After exposure of Caco2 cells to; various concentrations of extracts (50, 100,150 and 200 µg/mL) especially from brown algae for 72 h, significantly reduced cell proliferation. The antiproliferative effect of algae extracts was correlated with their polyphenol and flavonoid contents. Cell cycle analysis further showed that cells were arrested in G phases along with an increment in sub-diploidal cell population (sub-G) after extract application. These results imply that seaweeds which are rich in bioactive compounds may be in anticancer drug research programs. However, further investigations are essential to reveal the molecular mechanisms of the anticancer activities of these algae.

Since the use of antioxidants can potentially reduce the risk of chronic diseases related to oxidative stress, such as metabolic dysfunction-associated steatotic liver disease (MASLD), we analyzed the effects of aqueous infusions from natural sources with a high antioxidant capacity on a model of MASLD. We applied a central composite rotatable design to establish the extraction conditions for Citrus sinensis (orange) leaves with maximum antioxidant capacity. These conditions were then applied to Baccharis articulate (carqueja) leaves. This approach resulted in antioxidant capacities of 71.6 ± 2.2 % and 51.5 ± 1.3 % for orange and carqueja leaves, respectively. Only flavonoids were significantly higher in Baccharis articulata (0.44 ± 0.08 mg/mL) than in Citrus sinensis (0.14 ± 0.04 mg/mL), as confirmed by HPLC. We developed an in vitro MASLD model with human hepatic cells, specifically Hep-G2 cells. MASLD cells were treated with both infusions for 48 h. Our results demonstrate that only Baccharis articulata could inhibit lipid accumulation in the MASLD cells (1.11 ± 0.21 AU [infusion-treated MASLD cells] vs. 2.19 ± 0.32 AU [MASLD cells], p &lt; 0.05). We suggest that despite the different components of the infusions, the high concentration of flavonoids could be responsible for such activity.

The knowledge in chemical composition of propolis is crucial for understanding the characteristics of products of different origin, but also for quality control and regulatory purposes. To date, offical monographs or official analyses that allow to evaluate propolis in a proper way have not yet been released. This study focuses on the characterization of twenty-seven Italian propolis and the identification of chemical markers that define its geographical provenance. Total polyphenol (TP) and total flavonoid (TF) content, alongside the quantification of pinocembrin, chrysin, galangin, and caffeic acid phenethyl ester (CAPE), were identified as as potential markers. Additionally, DPPH assays was conducted to evaluate antiradicalic activity of propolis samples. Our findings demonstrated that TP, TF and pinocembrin differed in propolis of different origin, especially in samples from the islands. However, the quantification of the sum of chrysin and galangin and CAP provided a clear distinction of the geographical origin of the propolis samples. In contrast, the DPPH assay did not prove useful for this purpose, as most results were similar and, therefore, not significant. This study lays the groundwork for future research on propolis. These findings could contribute to the development of more refined methods for distinguishing propolis origins, enhancing the understanding, valuation and quality control of this natural product in various applications.

Bergamot flavonoids have been shown to prevent metabolic syndrome, non-alcoholic fatty liver disease (NAFLD) and stimulate autophagy in animal models and patients. To investigate further the mechanism of polyphenol-dependent effects, we performed RT2-PCR array analysis on 168 metabolism, transport and autophagy-related genes expressed in rat livers exposed for 14 weeks to different diets: standard, cafeteria (CAF) and CAF diet supplemented with 50 mg/kg of Bergamot Polyphenol Fraction (BPF). CAF diet caused a strong upregulation of the gluconeogenesis pathway (Gck, Pck2) and a moderate (>1.7 fold) induction of genes regulating lipogenesis (Srebf1, Pparg, Xbp1), lipid and cholesterol transport or lipolysis (Fabp3, Apoa1, Lpl) and inflammation (Il6). However, only one -oxidation gene (Cpt1a) and a few autophagy genes were modulated in the CAF group compared to controls. While most of these transcripts were significantly modulated by BPF, we observed a particularly potent effect on lipogenesis genes, like Acly, Acaca, Fasn and Scd1, which were suppressed far below the mRNA levels of control livers as confirmed by alternative primers-based RT2-PCR analysis and western blotting. These effects were accompanied by downregulation of pro-inflammatory cytokines (Il6, Tnfa, and Il10) and diabetes-related genes. Few autophagy (Map1Lc3a, Dapk) and no -oxidation gene expression changes were observed, suggesting minor transcriptional effects on autophagy. In conclusion, chronic BPF supplementation efficiently prevents NAFLD by modulating hepatic energy metabolism and inflammation gene expression programs, with no effect on -oxidation, but profound suppression of de-novo lipogenesis.

Flavonoids are polyphenolic phytochemical compounds found in many plants, fruits, vegetables, and leaves. They have a multitude of medicinal applications due to their anti-inflammatory, anti-oxidative, anti-viral, and anti-carcinogenic properties. Furthermore, they also have neuroprotective and cardioprotective effects. Their biological properties depend on the chemical structure of flavonoids, their mechanism of action, and their bioavailability. The flavonoid’s beneficial effects have been proven for a variety of diseases. In the last few years, it is demonstrated that flavonoids’ effects are mediated by inhibiting the NF-κB (Nuclear Factor-κB) pathway. In this review, we have summarized the effects of some flavonoids on the most common diseases such as cancer, cardiovascular, and neurodegenerative human diseases. In particular, here we collected all recent studies describing plant-derived flavonoids’ protective and prevention role, by specifically focusing their action on the NF-κB signaling pathway.

One of the mechanisms used in the management and cure of atherosclerosis is reverse cholesterol transfer (RCT), which plays a vital role in the export of cholesterol from peripheral cells. Cholesterol efflux from macrophages in the subintima of the vessel wall is a critical part of RCT. ATP-binding cassette transporter A1 (ABCA1) and ATP-binding cassette transporter G1 (ABCG1) are involved in the transfer of cholesterol from arterial macrophages to extracellular high-density lipoprotein cholesterol (HDL). The HDL then transports esterified cholesterol to the liver for elimination. An important factor in the reverse cholesterol transport and excretion of extracellular cholesterol is HDL. Atherogenesis can be prevented by altering the processes of RCT and cholesterol efflux, and this might lead to novel treatment options for cardiovascular disease. Research of novel modifying variables for RCT and cholesterol efflux is necessary. A better understanding of RCT's molecular processes has been gained via research, allowing for the creation of new treatments that make use of RCT's potential for pharmacological improvement. The purpose of this review is to provoke discussion on the potential impact of selected flavonoids on cholesterol efflux on the progression of atherosclerosis (Fig. 1.).

Following the analysis of terpenes present in new lemon and grapefruit “IntegroPectin” pectins obtained via the hydrodynamic cavitation of industrial lemon and grapefruit processing waste, the HPLC-MS analysis of the flavonoid compounds reveals the presence of eriocitrin, naringin, hesperidin and kaempferol typical of the respective citrus fruits. The pectic fibers rich in rhamnogalacturonan-I “hairy” regions act as chemical sponges adsorbing and concentrating at their outer surface highly bioactive citrus flavonoids and terpenes. These findings, together with the unique molecular structure of these new whole citrus pectins, provide preliminary insight into the broad-scope and powerful biological activity of these biomaterials. Numerous new biomedical applications beyond prevention and treatment of microbial infections and neurodegenerative disease are anticipated.

Polyphenols have been shown to possess outstanding anti-obesity properties. In this study, the effect of blue honeysuckle berry extract (BHBE) with high polyphenol content on lipid accumulation in adipocytes and the underlying mechanism were investigated for the first time. Composition analysis demonstrated that flavonoids (mainly flavonols and anthocyanins) were the primary polyphenols in BHBE, which contributed to its biological functions. The results of Oil Red O staining combined with triglyceride (TG) content determination showed that BHBE exhibited an obvious inhibitory effect on intracellular lipid accumulation in a dose-dependent manner. BHBE also reduced the protein level of fatty acid synthase (FAS) and increased the phosphorylation level of acetyl-CoA carboxylase (ACC), indicating that lipogenesis was suppressed by BHBE treatment. Moreover, BHBE was found to significantly promote the phosphorylation of AMP-activated protein kinase (AMPK) and further reduce the expression of key transcription factors (PPARγ, C/EBPα, and SREBP-1c) that regulate lipogenesis. In addition, the expression of beige adipocyte markers (Tmem26 and Cd137) and uncoupling protein 1 (UCP1) was increased in BHBE-treated adipocytes. In summary, we consider that BHBE inhibits lipid accumulation in adipocytes by suppressing lipogenesis as well as by promoting beiging of adipocytes. These results support blue honeysuckle berry as a candidate functional food against obesity.

Silybum marianum (L.) Gaertn is a rich source of antioxidants and anti-inflammatory flavonolignans with great potential for use in pharmaceutical and cosmetic products. Its biotechnological production using in vitro culture system has been proposed. Chitosan is a well-known elicitor that strongly affects both secondary metabolites and biomass production by plants. The effect of chitosan on S. marianum cell suspension is not known yet. In the present study, suspension cultures of S marianum were exploited for their in vitro potency to produce bioactive flavonolignans in the presence of chitosan. Established cell suspension culture was maintained on the same hormonal media supplemented with 0.5 mg/L BAP (6-benzylaminopurine) and 1.0 mg/L NAA (α-naphthalene acetic acid) under photoperiod 16/8 h (light/dark) and exposed to various treatments of chitosan (ranging from 0.5 to 50.0 mg/L). The highest biomass production was observed for cell suspension treated with 5.0 mg/L chitosan, resulting in 123.3 g/L fresh weight (FW) and 17.7 g/L dry weight (DW) productions. Chitosan treatment resulted in an overall increase in the accumulation of flavonoids, phenolic compounds and silymarin. High accumulation levels of silybin B, silydianin and silybin A were recorded by HPLC analysis. The corresponding extracts displayed interesting antioxidant and anti-inflammatory capacities. In particular, high ABTS antioxidant activity (741.5 μM Trolox C equivalent antioxidant capacity) was recorded in extracts obtained in presence of 0.5 mg/L of chitosan. On the opposite, highest inhibitions of cyclooxygenase 2 (COX-2, 30.5 %), secretory phospholipase A2 (sPLA2, 33.9 %) and 15-lipoxygenase (15-LOX-2, 31.6 %) enzymes involved in inflammation process were measured in extracts obtained in presence of 5.0 mg/L of chitosan. Taken together, these results highlight the high potential of the chitosan elicitation of the S. marianum cell suspension for enhanced production of antioxidant and anti-inflammatory silymarin-rich extracts.

Computational studies suggest that hesperidin, a flavonoid abundant in citrus peel, binding the three main cellular receptors of SARS-CoV-2 virus can act in the prophylaxis and treatment of COVID-19. Herein we urge the uptake of hydrodynamic cavitation industrial-scale reactors based on the low cost, reliable Venturi tube for the extraction of citrus pectin rich in hesperidin (and in other bioflavonoids including naringing) by very fast processing of waste orange peel or waste lemon peel in water only. A device able to process up to 500 kg of waste peels per session, similar to the one lately deployed in Italy for hydrodynamic cavitation-assisted brewing, is capable to provide 36,000 doses of 1000 mg hesperidin per day.

COVID-19, a rapidly spreading new strain of coronavirus, has affected more than 150 countries and received worldwide attention. The lack of efficacious drugs or vaccines against SARS-CoV-2 has further worsened the situation. Thus, there is an urgent need to boost up research for the development of effective therapeutics and affordable diagnostic against COVID-19. The crystallized form of SARS-CoV-2 main protease (Mpro) was demonstrated by a Chinese researcher Liu et al. (2020) which is a novel therapeutic drug target. This study was conducted to evaluate the efficacy of medicinal plant-based bioactive compounds against COVID-19 Mpro by molecular docking study. Molecular docking investigations were performed by using Molegro Virtual Docker 7 to analyze the inhibition probability of these compounds against COVID-19. COVID-19 Mpro was docked with 80 flavonoid compounds and the binding energies were obtained from the docking of (PDB ID: 6LU7: Resolution 2.16 Å) with the native ligand. According to obtained results, hesperidin, rutin, diosmin, apiin, diacetylcurcumin, (E)-1-(2-Hydroxy-4-methoxyphenyl)-3-[3-[(E)-3-(2-hydroxy-4- methoxyphenyl)-3-oxoprop-1-enyl]phenyl]prop-2-en-1-one, and beta,beta'-(4-Methoxy-1,3- phenylene)bis(2'-hydroxy-4',6'-dimethoxyacrylophenone have been found as more effective on COVID-19 than nelfinavir. So, this study will pave a way for doing advanced experimental research to evaluate the real medicinal potential of these compounds to cure COVID-19.

The green biomass of horticultural plants contains valuable secondary metabolites (SM) which can potentially be extracted and sold. When exposed to stress, plants accumulate higher amounts of these SMs, making the extraction and commercialization even more attractive. We evaluated the potential for accumulating of the flavones cynaroside and graveobioside A in leaves of two bell pepper cultivars (Mavras and Stayer) when exposed to salt stress (100 mM NaCl), UVA/B excitation (UVA 4-5 W/m²; UVB 10-14 W/m² for 3 hours per day) or a combination of both stressors. HPLC analyses proved the enhanced accumulation of both metabolites under stress conditions. Cynaroside accumulation is effectively triggered by high-UV stress, whereas graveobioside A contents increase under salt stress. Highest contents were observed in plants exposed to combined stress. Effects of stress on overall plant performance differed significantly between treatments, with least negative impact on aboveground biomass found for high-UV stressed plants. The usage of two non-destructive instruments (Dualex and Multiplex) allowed us to gain insights in ontogenetical effects at the leaf level and temporal development of SM contents over time. Indices provided by those devices correlate fairly with amounts detected via HPLC (Cynaroside: R2 = 0.46 – 0.66; Graveobioside A: R2 = 0.51 – 0.71). The concentrations of both metabolites tend to decrease at leaf level during the ontogenetical development even under stress conditions. High-UV stress is a promising tool for enriching plant leaves with valuable SM without major effects on plant biomass. All data is available online [1].

Flavonoids are major secondary metabolites in plants, which play important roles in maintaining the cellular redox balance in cells. Chalcone synthase (CHS) is the key enzyme in the flavonoids biosynthesis pathway, and has been proved to monitor the changes to drought stress tolerance. In this work, we overexpressed a CHS gene in tobacco (Nicotiana tabacum). The transgenic tobacco plants were more tolerant than the control plants to drought stress. The transcription levels of the key genes involved in the flavonoids pathway and the contents of seven flavonoids were also significantly raised in the transgenic tobacco plants. In addition, overexpression of the CHS gene lead to a lower concentration of the oxidative stress product malondialdehyde. Overall, the NtCHS gene studied in this work was considered as a candidate gene for genetic engineering to enhance drought tolerance of plants and improve response to oxidative stress.

In recent years, Atherosclerotic Cardiovascular Disease (ACVD), Obesity and Diabetes, have increase exponentially worldwide. In the present work, we evaluate the genoprotective effect of consuming a flavonoids-rich chocolate and the improvement in the biochemical parameters related to the prevention and treatment of cardiovascular risk and metabolic syndrome in young Mexican adults. A randomized, placebo-controlled, double-blind study was undertaken in the Autonomous University of Baja California. The treatments were a daily intake of 2 grams of dark chocolate containing 70% cooca or milk chocolate. Total phenolic compounds and flavonoids were evaluated in both chocolates. Anthropometrical and Biochemical parameters were measured in the 84 participants before and after the study. Buccal epithelial genotoxicity was also evaluated from the beginning to the end of the experiment in the participants. Result suggested that flavonoids of cocoa intake have protective effects against DNA damage, and Biochemical parameters (total cholesterol, triglycerides, and LDL-cholesterol level in blood) and anthropometrical parameters (waist circumference) were also improved after six months of daily intake of 2 grams of dark chocolate with a 70% of cocoa.

Organic fertilization is gaining importance as an alternative to chemical fertilization. However, the effects of organic products on crop quality need to be characterized, especially in those new products. Therefore, the effect of an enriched-biochar supplied with an organic fertilizer (Biochar) on yield and nutritional compounds of artichoke (Cynara cardunculus var scolymus) heads was analyzed and compared to inorganic conventional fertilization (Control). For that, number of fruits and their weights were determined together with nutritional properties of artichoke heads, as mineral content, fatty acids, content phenolic compounds and flavonoids. Results showed that biochar increased crop yield as registered by the higher number of marketable or commercial artichokes, as compared to the Control. Besides, biochar-treated plants presented significantly higher contents of Ca, Mg, and S, in the artichoke heads, but a decreased content of Co, Cu, and Zn. The fatty acids content in the Biochar-treated artichokes was also significantly higher, mainly because of the palmitic acid. On the contrary, the contents of phenolic compounds (e.g. flavonoids), were negatively and significantly affected by the Biochar application. In conclusion, the application of Biochar as soil amendment in combination with organic matter, for growing artichokes in the Semiarid Mediterranean area (e.g. Murcia Region) favoured an increasement in yield without comprising its nutritional composition. Further developments to establish protocols for extended use of Biochar in this agri-food production area are guaranteed.

The study covered the leaves of 25 varieties of highbush blueberry Vaccinium corymbosum L. Determinations were performed for phenolic acid (chlorogenic, neochlorogenic, cryptochlorogenic, 3,5-dicaffeoylquinic and 4,5-dicaffeoylquinic acids), flavonoid (catechin, rutin, isoquercetin), arbutin and hydroquinone content. The content of phenolic acids and flavonoids in the test material suggests that highbush blueberry leaves can be a potentially good material for dietary supplement production, although the relatively high arbutin content (exceeding 4% in the case of the Bonus, Chantiklee and Herbert varieties) limits this possibility to herbal medicinal products applied in case of health issues for a limited time, similar to other over-the-counter arbutin products (bearberry Arctostaphylos uva-ursi and lingonberry Vaccinium vitis-idaea leaves).

Oxygen based heterocyclic moieties hold an ample range of therapeutic activities. Heterocyclic molecules are nominated as vital components of an extensive array of structural motifs with both biological and pharmaceutical significance. The oxygen-based scaffolds act as anticancer candidates and are also present in numerous phytomolecules viz; irinotecan, camptothecin, topotecan, taxol, taxotere, podophylotoxin, etoposide, daunorubicin and teniposide. The architectural design of numerous structural motifs for amelioration of cancer has become progressively amplified in recent past years. Until now presently there is no strategic treatment which is so capable that can cure cancer from its roots. Henceforth, it is very indispensible to design novel anticancer structural motifs with least side effects. The oxygen containing heterocyclic scaffolds includes flavonoids, pyrans, xanthones and coumarins are of utmost importance in medical chemistry for the mitigation of cancer. This assemblage offers several recent developments as anticancer oxygen containing heterocyclic molecules all-round the globe and attracted the structural motifs of auspicious molecules, along with their mechanistic insights, IC50 values, structure–activity relationships, and molecular docking studies. The encouraging properties discovered by these oxygen-based scaffolds unconditionally engaging them at frontline in invention of potential drug candidates. Consequently, these probably will be of amazing attention to scientists working on the design and synthesis of antitumor candidates.

In the chronic phase of chikungunya virus (CHIKV) infection, excessive inflammation manifests as incapacitating joint pain and prolonged arthritis. Arthritis resulted from a large influx of infiltrating immune cells driven by pro-inflammatory cytokines and chemokines originating from the toll-like receptor (TLR)-mediated innate antiviral response. This study investigated fisetin's ability to modulate TLR-mediated antiviral responses against CHIKV in Huh7 cells. The CHIKV inhibitory potential of fisetin was assessed by plaque-forming unit assay, virus yield reduction assay, and bright-field microscopy (cytopathic effect, immunofluorescence). Fisetin’s modulatory potential on TLR-mediated antiviral response was evaluated by immunofluorescence assay (expression of TLR proteins), qRT-PCR (mRNA level of antiviral genes), human cytokine array, and immunoblotting of key transcription factors. The present study showed fisetin induced the expression of the antiviral genes at an early time-point by promoting the phosphorylation of IRF3 and IRF7. Fisetin reduced excessive inflammatory cytokine responses in CHIKV-infected Huh7 cells by impeding the over-phosphorylation of NF-κB. Fisetin also reduced CHIKV-induced cytopathic effects in CHIKV-infected Huh7 cells. Altogether, our study suggests that fisetin modulates TLR-mediated antiviral responses by affecting the CHIKV-induced inflammatory responses.

We have evaluated the antihypertensive effect of several flavonoid extracts in the spontaneous hypertensive rat model (SHR). Treatments were carried out for 6 and 12 weeks in two groups of SHR rats which received Apigenin, Lemon Extract, Grapefruit + Bitter Orange (GBO) extracts and Cocoa extract. Captopril was used as a positive control in the SHR group treated for 6 weeks (SHR6) and Diosmin was used as the industry reference in the SHR group treated for 12 weeks (SHR12). Captopril and GBO extracts significantly reduced the elevated blood pressure of the SHR6 animals, but none of the extracts was effective in the SHR12 group. Apigenin, LE, GBO and captopril also ameliorated nitric oxide-dependent and independent aortic vascular relaxation and elevated plasma and urinary excretion of nitrites, only in the SHR6 group. Kidney and urinary TBARS were also significantly reduced by GBO in the SHR6 rats. Apigenin also improved vascular relaxation in the SHR12 group and all the flavonoids studied reduced urinary TBARS excretion and proteinuria. Vascular abnormalities such as lumen/wall ratio in coronary arteries and thoracic aorta were moderately improved by these treatments in the SHR6 group. In conclusion, the flavonoids included in this study, especially apigenin, LE and GBO improved vascular vasodilatory function of young adult SHRs but only the GBO-treated rats benefited from a reduction in BP. These extracts may be used as functional food ingredients with a moderate therapeutic benefit, especially in the early phases of arterial hypertension.

The latest scientific literature outlines a resilient interconnection between cancer modulation and dietary polyphenols by sphingolipid-mediated mechanisms, usually correlated with a modification of their metabolism. We aim to extensively survey this relation to show how it could be advantageous in cancer treatment or prevention by nutrients. Polyphenols, chemically characterized by polyhydroxylated phenolic structure, are well known for their pervasive pharmacological properties: anti-inflammatory, antibiotic, antiseptic, antitumor, antiallergic, cardioprotective and others. Pervasive is also their distribution in food products especially in plant foods as vegetables, cereals, legumes, fruits, nuts and beverages as wine, cider, beer, tea, cocoa. Recently, sphingolipids have been correlated with cancer by a dysregulation of their rheostat emerging as mediator of cell proliferation in cancer and modulator of chemotherapeutics.

1) Background: we have evaluated the antihypertensive effect of several flavonoid extracts in a rat model of arterial hypertension caused by chronic administration (6 weeks) of the nitric oxide synthesis inhibitor, L-NAME. 2) Methods: Sprague Dawley rats received L-NAME alone or L-NAME plus flavonoid-rich vegetal extracts (Lemon, Grapefruit + Bitter Orange, and Cocoa) or purified flavonoids (Apigenin and Diosmin) for 6 weeks. 3) Results: L-NAME treatment resulted in a marked elevation of blood pressure, and treatment with Apigenin, Lemon Extract, and Grapefruit + Bitter Orange extracts significantly reduced the elevated blood pressure of these animals. Apigenin and some of these flavonoids also ameliorated nitric oxide-dependent and independent aortic vasodilation and elevated nitrite urinary excretion. End-organ abnormalities such as cardiac infarcts, hyaline arteriopathy and fibrinoid necrosis in coronary arteries and aorta were improved by these treatments, reducing the end-organ vascular damage. 4) Conclusions: the flavonoids included in this study, specially apigenin, may be used as functional food ingredients with potential therapeutic benefit in arterial hypertension.

The defining characteristic of Alzheimer's disease (AD) is the aberrant deposition of pathogenic proteins, particularly a massive build-up of amyloid-β peptides, specifically in the brain. Amy-loid-β aggregation is neurotoxic and ultimately results in dysfunction of the nervous system. The present investigation aims to predict potential amyloid-β fibrils disaggregating molecules from plant sources through molecular modeling techniques, this appears to be a very promising and appealing treatment philosophy. Here, 500 flavonoids from various plants were considered, ini-tially undergoing ADME studies to screen molecules that could cross the blood-brain barrier. Later, potential Amyloid-β-disaggregating molecules were identified by molecular docking and dynamics (MD) simulation studies. Five molecules, prenylmethoxy flavonol (-7.3 kcal×mol-1), isopentenyl flavonol (-7.3 kcal×mol-1), 7,3'-Dihydroxyflavone (-7.2 kcal×mol-1), 7-Hydroxy-5-methyl-4'-methoxyflavone (-7.2 kcal×mol-1), 8-hydroxy-7-methoxyflavone (-7 kcal×mol-1) showed higher binding affinity score against Alzheimer's Aβ (1-42) fibrils, these are very close to the standard drug (Donepezil) (-7.90 kcal×mol-1). Further, the MD simulation studies established the intermolecular interaction and stability of the five selected ligands-Amyloid-β oligomer protein complexes. These results suggest that the chosen five flavonoid molecules could be used as possible agents to disaggregate amyloid-β fibrils; however, more in vitro and in vivo investigations are required to verify the therapeutic effectiveness.

Citrus fruits are extensively cultivated worldwide, with Italy and Spain being major producers. Southern Italy, particularly in Reggio Calabria, a typical citrus fruit is produced, namely, bergamot (Citrus bergamia Risso et Poiteau), known for its mysterious origins and exceptional quality essential oil protected by the EU's PDO designation. Despite historical challenges, bergamot has regained prominence for its nutraceutical potential, especially its flavonoid-rich juice, offering significant health benefits. However, little attention has been paid to understanding the qualitative and quantitative differences of bergamot juice in Calabrian production areas. For this reason, this work aims to investigate the quality characteristics of bergamot juice produced in different areas of Ca-labria sites. The results showed the best quality attributes of bergamot fruits harvested in the DPO area. In particular, higher levels of total soluble solids, stable acidity and higher juice were found. In addition, higher contents of ascorbic and citric acids, which are nutritionally valuable and tasteful, were found. The phenolic profile, characterized by the key compounds of bergamot, highlighted the better nutraceutical potential of the fruit grown in the DPO area.

Alzheimer's disease (AD) is a stealthy and progressive neurological disorder that is a leading cause of dementia in the global elderly population, imposing a significant burden on both the elderly and society. Currently, the condition is treated with medications that alleviate symptoms. Nonetheless, these drugs may not consistently produce the desired results and can cause serious side effects. Hence, there is a vigorous pursuit of alternative options to enhance the quality of life for patients. Ginkgo biloba (GB), an herb with historical use in traditional medicine, contains bioactive compounds such as terpenoids (Ginkgolides A, B, and C), polyphenols, organic acids, and flavonoids (quercetin, kaempferol, and isorhamnetin). These compounds are associated with anti-inflammatory, antioxidant, and neuroprotective properties, making them valuable for cognitive health. A systematic search across three databases using specific keywords GB in AD and dementia yielded 1702 documents, leading to the selection of 15 clinical trials for synthesis. In eleven studies, GB extract/EGb 761® was shown to improve cognitive function, neuropsychiatric symptoms, and functional abilities in both dementia types. In four studies, however, there were no significant differences between the GB-treated and placebo groups. Significant improvements were observed in scores obtained from the Mini-Mental State Examination (MMSE), Short Cognitive Performance Test (SKT), and Neuropsychiatric Inventory (NPI). While the majority of synthesized clinical trials show Ginkgo biloba has promising potential in these conditions, more research is needed to determine optimal dosages, effective delivery methods, and appropriate pharmaceutical formulations. Furthermore, a thorough assessment of adverse effects, exploration of long-term use implications, and investigation into potential drug interactions are critical aspects that must be carefully evaluated in future studies.

The critical enzyme Dihydrofolate Reductase-Thymidylate Synthase in Leishmania major (LmDHFR-TS) serves a dual-purpose role and is essential for DNA synthesis, a cornerstone of the parasite's reproductive processes. Consequently, the development of inhibitors against LmDHFR-TS is crucial for the creation of novel anti-Leishmania chemotherapies. In this study, we employed an in-house database containing 314 secondary metabolites derived from cinnamic acid that occurred in the Asteraceae family. We conducted a combined ligand/structure-based virtual screening to identify potential inhibitors against LmDHFR-TS. By consensus analysis of both approaches, we identified three compounds, i.e., lithospermic acid (237), diarctigenin (306), and isolappaol A (308), that exhibited a high probability of being inhibitors according to both approaches and were consequently classified as promising hits. Subsequently, we expanded the binding mode examination of these compounds within the active site of the test enzyme through molecular dynamics simulations, revealing a high degree of structural stability and minimal fluctuations in its tertiary structure. The in-silico predictions were then validated through in-vitro assays to examine the inhibitory capacity of the top-ranked naturally-occurring compounds against LmDHFR-TS recombinant protein. The test compounds effectively inhibited the enzyme with IC50 values ranging from 6.1 to 10.1 μM. In contrast, other common cinnamic acid derivatives (i.e., flavonoid glycosides) from the Asteraceae family, such as hesperidin, isovitexin 4′-O-glucoside, and rutin, exhibited low activity against this target. The selective index (SI) for all tested compounds was determined using HsDHFR, with moderate inhibitory effect. Among these hits, lignans 306 and 308 demonstrated the highest selectivity, displaying superior SI values compared to methotrexate, the reference inhibitor of DHFR-TS. Therefore, continued research into the anti-leishmanial potential of these C6C3-hybrid butyrolactone lignans may offer a brighter outlook for combating this neglected tropical disease.

The broad bean plant contains L-DOPA, a compound that is essential for patients with Parkin-son’s disease. However, little has been reported on other broad bean compounds that have bene-ficial effects on health. The objective was to evaluate plants of four Mexican broad bean varieties to determine the content and yield of total phenolic compounds (TPC), total flavonoids (TF), and L-DOPA, as well as to analyze the flavonoid profile and antioxidant (AA) and anti-inflammatory (AANTI) activity in vitro. Broad bean seeds were sown in the field and plants were harvested 20 days after emergence. The analyses were performed with visible UV spectrophotometry and HPLC. The variety José María produced the highest yield of TPC (9.30 g m-2), TF (8.08 g m-2) and L-DOPA (5.64 g m-2) per unit of area. The highest yields per plant were obtained with the Rojita variety: TPC (0.25 g plant-1), TF (0.21 g plant-1) and L-DOPA (0.17 g plant-1). This variety also had the highest antioxidant (CI50= 87.68 µg mL-¹) and anti-inflammatory (CI50= 74.40 mg mL-1) activi-ty, which was attributed to the L-DOPA compounds and to rutin and isoorientins, respectively. The flavonoid profile revealed the presence of rutin and isoorientins, which had not been previ-ously detected in the broad bean plant.

The emergence of drug resistant pathogenic bacteria is increasingly challenging conventional antibiotics. Plant derived flavonoids are considered as potential alternatives to antibiotics due to their antimicrobial properties. However, the mechanisms by which flavonoids modulate pathogenic microorganisms’ growth are not fully understood. In our previous studies we found that Rutin, a kind of flavonoids showed inhibition against Klebsiella pneumoniae strains. In order to better understand its inhibitory mechanism on strain growth, we used both Rutin and Luteolin as treatments to incubate K. pneumoniae ATCC700603 strain. After incubation for 4 hours, the homogenous and differential effects of two different flavonoids on the growth of K. pneumoniae were evaluated. The integrated metabolomic and transcriptomic analysis was performed. The expression levels of 5,483 genes and the contents of 882 metabolites were measured. The differentially expressed genes (DEGs) and metabolites (DEMs) were screened and analyzed. The correlation between DEGs and DEMs were also studied. Our results showed that Rutin could inhibit the strain growth by changing metabolic pathways and ABC transporters pathways. Our study also revealed FU841_RS17580 and FU841_RS19145 as functional genes that played vital roles in the strain growth.

Terminalia arjuna possesses significant cardio protective, antidiabetic and antioxidant properties as these properties are described in Ayurveda. In the present study, three flavonoids were isolated through the separation and chromatographic purification of the whole plant material of T. arjuna. Spectroscopic characterization identified one of them as a new flavonoid “Terminalone A (1)” and two known flavonoids i.e. 6-hydroxy-2-(4-hydroxyphenyl)-7-methoxy-4H-chromen-4-one (2) and 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4H-chromen-4-one (3). The bioactivity studies showed considerable antibacterial and antioxidant (DPPH was used as a scavenger) potential for all the three compounds 1-3 where the compound 1 showed strong antibacterial and antioxidant activity.

Cordia dichotoma Forst. (F. Boraginaceae) has been traditionally used for the management of a variety of human ailments. In our earlier work, the antidiabetic activity of methanolic bark extract of C. dichotoma (MECD) has been reported. In this paper, two flavonoid molecules were isolated (by column chromatography) and identified (by IR, NMR and Mass spectroscopy/spectrometry) from the MECD with an aim to investigate their antidiabetic effectiveness. Molecular docking and ADMET studies were carried out using AutoDock Vina software and Swiss ADME online tool, respectively. The isolated flavonoids were identified as 3,5,7,3’,4’-tetrahydroxy-4-methoxyflavanone-3-O-L-rhamnopyranoside and 5,7,3’-trihydroxy-4-methoxyflavanone-7-O-L-rhamnopyranoside (quercitrin). Docking and ADMET studies revealed the promising binding affinity of flavonoid molecules for human lysosomal alpha-glucosidase and human pancreatic alpha-amylase with acceptable ADMET properties. Based on computational studies, our study reports the antidiabetic potential of the isolated flavonoids with predictive pharmacokinetics profile.

Guava is a vital fruit worldwide, especially in Pakistan, and due to its nutritional value famous in each age group. Due to a very short shelf life, the marketing and export of this fruit faced severe constraints. Therefore, in the current study, edible coating of chitosan (0, 0.5, 1.0, 1.5, and 2.0%) was evaluated on postharvest shelf life when guava fruits were stored (room temperature and 4 °C temperatures) for 12 days. The chitosan treated coating fruits have shown reduced total sugars and malondialdehyde levels compared to untreated control samples. However, a significant difference (p ≤ 0.05) in total sugar and malondialdehyde levels exists between samples stored in m compared to refrigerated temperature (4 °C). The chitosan-coated samples have shown a greater amount of vitamin C, quercetin, rutin, and total phenolic contents than control samples. However, these nutritional parameters' levels were significantly different (p ≤ 0.05) in samples stored at room than samples stored at refrigerated temperature. However, the levels of crude fiber, potassium, and sodium were found statistically nonsignificant (p ≥0.05) in control versus chitosan treated coating treatments. The findings have documented that the coatings of 1.5 and 2.0% were most effective for extension in shelf life and maintaining the nutritional attributes of guava fruit.

The Cannabis plant (Cannabis sativa L.) produces an estimated 545 chemical compounds of different biogenetic classes. In addition to economic value, many of these phytochemicals have medicinal and physiological activity. The plant is most popularly known for its two most prominent and most studied secondary metabolites— Δ9-Tetrahydrocannabinol (Δ9-THC) and Cannabidiol (CBD). Both Δ9-THC and CBD have a wide therapeutic window across many ailments and form part of a class of secondary metabolites called cannabinoids—of which approximately over 104 exist. This review will focus on non-cannabinoid metabolites of Cannabis sativa that also have therapeutic potential, some of which share medicinal properties similar to those of cannabinoids. The most notable of these non-cannabinoid phytochemicals are flavonoids and terpenes. We will also discuss future directions in cannabis research and development of cannabis-based pharmaceuticals. Caflanone, a flavonoid molecule with selective activity against the human viruses including the coronavirus SARS-COV2, and certain cancers, is one of the most promising non-cannabinoid molecules that is being advanced into clinical trials. As validated by thousands of years of the use of cannabis for medicinal purposes, vast anecdotal evidence abounds on the medicinal benefits of the plant. These benefits are attributed to the many phytochemicals in this plant, including non-cannabinoids. The most promising non-cannabinoids with potential to alleviate global disease burdens are discussed.

Secondary phenolic metabolites are defined as valuable natural products synthesized by different organisms that are not essential for growth and development. These compounds play an essential role in plant defense mechanisms, and an important role in the pharmaceutical, cosmetics, food, and agricultural industries. Despite the vast chemical diversity of natural compounds, their content in plants is very low, in consequence, it eliminates the possibility of the production of these interesting secondary metabolites from plants. Therefore, microorganisms are widely used as cell factories by industrial biotechnology to the production of different non-native compounds. Among microorganisms commonly used in biotechnological applications, yeasts are prominent host for the diverse secondary metabolite biosynthetic pathways. Saccharomyces cerevisiae is often regarded as the better host organism for the heterologous production of phenolics compounds, especially if the expression of different plant genes is necessary.

An endemic pear species spreads in one region of western Georgia, Adjara, called Khechechuri. Pears are dietary source of bioactive components such as polyphenols and triterpenic acid. In addition to its gastronomic value, the aim of the article was to examine and compare phenolic compounds, flavonoids, catechins, phenolic acids, and antioxidant activities in five species of Khechechuri collected from various regions in Adjara region: Adjaristskali, Merisi, Dandalo, Shuakhevi, and Khulo. Five fruit parts, the skin, edible pulp, the whole pear (skin + pulp), juice and the pomace were analyzed and the results were compared. Our study revealed that the amount of total phenolic content found in the skin of West Georgian pear types was as much as 4650 mg/kg. Also, the pear pomace showed significant amount of total phenolic content in all species of Khechechuri. In addition, in all species of Khechechuri pears, flavonoids were found, except in the fruit juice.

Multiple sclerosis (MS) is an immune-mediated disease characterized by inflammation, demyelination, and neurodegeneration within the central nervous system. Brain plasticity, the brain's ability to adapt its structure and function, plays a crucial role in mitigating MS's impact. This paper explores the potential benefits of lifestyle changes and nutraceuticals on brain plasticity in MS patients. Lifestyle modifications, including physical activity and dietary adjustments, can enhance brain plasticity by upregulating neurotrophic factors, promoting synaptogenesis, and reducing oxidative stress. Nutraceuticals, such as vitamin D, omega-3 fatty acids, and antioxidants like alpha-lipoic acid, have shown promise in supporting brain health through anti-inflammatory and neuroprotective mechanisms. Regular physical activity has been linked to increased levels of brain-derived neurotrophic factor (BDNF) and improved cognitive function. Dietary interventions, including caloric restriction and the intake of polyphenols, can also positively influence brain plasticity. Integrating these lifestyle changes and nutraceuticals into the management of MS could provide a complementary approach to traditional therapies, potentially improving neurological outcomes and enhancing the quality of life for MS patients.

The legume-rhizobia symbiosis is one of the most important plant-microbe interactions in sustainable agriculture due to its ability to provide much needed N to cropping systems. This interaction is mediated by the mutual recognition of signaling molecules from the two partners, namely legumes and rhizobia. With legumes, these molecules are in the form of flavonoids and anthocyanins, which are responsible for the pigmentation of plants parts, such as seeds, flowers, fruits and even leaves. Seed coat pigmentation in legumes is a dominant factor influencing gene expression relating to N2 fixation, and may be responsible for the different N2-fixing abilities observed among legume genotypes under field conditions in African soils. Cowpea, Kersting’s bean and Bambara groundnut landraces with black seed coat color are reported to release higher concentrations of nod-gene-inducing flavonoids and anthocyanins when compared to the Red and Cream landraces, hence the black seed coat pigmentation is considered a biomarker for enhanced nodulation and N2 fixation. Cowpea, Bambara groundnut and Kersting’s bean with differing seed coat colors are known to attract different native soil rhizobia, confirmable by PCR-RFLP analysis of bacterial DNA from root nodules of these legumes. Even when seeds of the same legume with diverse seed coat colors were planted together in one hole, the nodulating bradyrhizobia clustered differently in the PCR-RFLP dendrograms. In one study, Kersting’s groundnut, Bambara groundnut and cowpea with differing seed coat colors were selectively nodulated by different bradyrhizobial species. Multilocus sequence analysis showed that different Bradyrhizobium species nodulated the Kersting's bean based on seed coat color. Phylogenetic analysis also placed the bradyrhizobial isolates in close proximity to different Bradyrhizobium species such as B. vignae 7-2T, B. subterraneum 58 2-1T, B. kavangense 14-3T, B. liaoningense 2281 (USDA 3622)T, B. yuanmingense LMG 21827T, B. huanghuaihaiense CCBAU 23303T, B. pachyrhizi PAC48T, and a reference type strain of B. elkanii according to seed coat color. Using 16S rDNA amplicon sequencing, we also found significant selective influences of seed coat pigmentation on microbial community structure in the rhizosphere of five Kersting’s groundnut landraces. For example, the rhizosphere of Belane Mottled landrace was dominated by Proteobacteria, while Bacteroidetes dominated the rhizospheres of the other landraces. With legumes, seed coat pigmentation therefore plays a dominant role in the selection of the bacterial symbiotic partner.

Flavonoids are widely recognized as natural polydrugs, given their anti-inflammatory, antioxidant, sedative and antineoplastic activities. Recently, different studies have shown that flavonoid have the potential to inhibit BET bromodomains. Previous reports suggest that flavonoids are putative inhibitors of the ZA channel due to their orientation and interactions with P86, V87, L92, L94 and N140. Herein, a comprehensive characterization of the binding mode of the biflavonoid amentoflavone and fisetin is discussed. To this end, both compounds were docked with BRD4 using four docking programs. Results were post-processed with protein-ligand interaction fingerprints. To gain further insights into the binding mode of the two natural products, docking results were further analyzed with molecular dynamics. Results showed that amentoflavone makes numerous contacts in the ZA channel, as previously described for flavonoids and kinase inhibitors. It was also found that amentoflavone can potentially make contacts with non-canonical residues for BET inhibition. Most of these contacts were not observed with fisetin. Based on these results, amentoflavone was tested for BRD4 inhibition, showing activity in the micromolar range. This work may serve as basis for scaffold optimization and further characterization of flavonoids as BET inhibitors.

The purpose of the present study is survey of extraction conditions and exploring antioxidant potential of the non-traditional for the Bulgarian ethno-medicine wild herb Cistus incanus widespread in Strandja Mountain. The influence of the extraction time (0–500 min) and solvent composition (0–50% ethanol in water) on the polyphenols, flavonoids yields and on antioxidant capacity of the extracts of leaves, stalks (wood parts) and buds mixture were studied. The antioxidant capacity (AOC) was evaluated by use of scavenging assays of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals. Total polyphenol and flavonoid contents were quantified using UV–vis spectrometry. Optimal yield of desired components has been obtained with 30% ethanol in water solvent at 390^th min extraction time. In addition, the influence of the seasonality (winter and summer Cistus incanus), and of the different areal parts - hard-coated seeds; buds, and mixture of leaves and stalks of the wild plant on the presence of polyphenols, flavonoids and AOC were investigated. Present work revealed the high values of the polyphenols, flavonoids, the high AOC not only in the summer leaves, but also found in the winter leaves, hard-coated seeds, buds and stalks. Based on the obtained results the Cistus incanus from Strandja mountain could be a new excellent source of natural antioxidants in food and pharmaceutical industries.

The metabolomics of Newhall navel oranges with geographical indication (GI) was measured by LC-MS/MS from three areas Ganzhou, Fengjie, and Zigui in China. Orthogonal partial least squares-discriminant analysis was performed for samples classification and important metabolites identification. This approach identified the best markers (i.e. tricarboxylic acid, amino acids, and phenolics) of the geographical origin able to discriminated Fengjie, Ganzhou, and Zigui organge samples. The results showed that peeled-samples from Zigui were richest and those from Fengjie lowest in all of the top ten most important markers. In whole samples, the highest levels of seven important markers occurred in those from Zigui, and the other three important markers appeared the highest levels in those from Ganzhou. According to the variation of the best markers, and the highest value of titratable acidity in those from Zigui, the samples planted in Ganzhou have the best balance between taste and nutrition. This work confirms the approach of metabolomics combined with OPLS-DA is an effective way for origin tracing and overall quality evaluation.

It seems that natural compounds with bioactivity are the food constituents, present in the diets, that may provide protective effects on health due to their biochemical effects. The main benefits appear to be decline in oxidative stress and inflammation that are crucial in the pathogenesis of obesity, diabetes and metabolic syndrome. Apart from anti-inflammatory activity, these molecules also possess antifungal, and anti-infective preventative effects. Further evidence indicate that these bioactive molecules are the constituents, which are known to increase function of the foods. This review aims to emphasize that plant based diet is rich in phytochemicals such as antioxidants, vitamins, minerals, polyphenolics and flavonoids, amino acids and fatty acids, that are able to cause benefits via these compounds. These bioactive molecules can target mechanisms of oxidative stress and inflammation that are crucial in the management of metabolic syndrome. These antioxidant compounds appear to be essential component of plant based diets and are crucial for healthiness. Most investigators have proposed that bioactive compounds act as nutraceuticals which are able to regulate certain patho-physiological mechanisms responsible for metabolic diseases. The bioactive compoundspresent in the plant based diets are primary and secondary metabolites of nutritive and non-nutritive natural components generating health benefits by preventing or managing chronic disease or its symptoms. The bioactive compounds are known for their beneficial effects to health. Despite their small quantity in the diets, these bioactive compounds may trigger certain mechanisms that may cause alteration with improvement in health. It seems that most of the bioactive compounds co-existing in the plant-based diets, may be extremely healthful. However, if they are taken in excess, they can cause toxic effects. There is an urgent need to evaluate each bioactive compound to establish a beneficial quantity and a threshold of toxicity, while treating metabolic syndrome.

Phenolic compounds, present in plants, provide substantial health advantages, such as antioxidant and anti-inflammatory properties, which enhance cardiovascular and cognitive well-being. Australia is enriched with a wide range of plants with phytopharmacological potential, which needs to be fully elucidated. In this context, we analyzed leaves of aniseed myrtle (Syzygium anisatum), lemon myrtle (Backhousia citriodora), and cinnamon myrtle (Backhousia myrtifolia) for their complex phytochemical profile and antioxidant potential. LC-ESI-QTOF-MS/MS was applied for screening and characterizing these Australian myrtles’ phenolic compounds and the structure-function relation of phenolic compounds. This study identified 145 and quantified/semi-quantified 27 phenolic compounds in these Australian myrtles. Furthermore, phenolic contents (total phenolic content (TPC), total condensed tannins (TCT), and total flavonoids (TFC)) and antioxidant potential of phenolic extracts from the leaves of Australian myrtles were quantified. Aniseed myrtle was quantified with the highest TPC (52.49 ± 3.55 mg GAE/g) and total antioxidant potential than other selected myrtles. Catechin, epicatechin, isovitexin, cinnamic acid, and quercetin were quantified as Australian myrtles' most abundant phenolic compounds. Moreover, chemometric analysis further validated the results. This study provides a new insight into the novel potent bioactive phenolic compounds from Australian myrtles that could be potentially useful for functional, nutraceutical, and therapeutic applications.

The antimicrobial quantitative structure–activity relationship of plant flavonoids against Gram-positive bacteria was established in our previous works, and the cell membrane was confirmed as a major site of action. To investigate whether plant flavonoids have similar antibacterial effects and mechanisms against both Gram-negative and Gram-positive bacteria, here, the minimum inhibitory concentrations (MICs) of 37 plant flavonoids against Escherichia coli were determined using the microdilution broth method, and then the correlation between their lipophilic parameter ACD/LogP or LogD_7.40 value and their MIC was analyzed. Simultaneously, the correlation between the ACD/LogP or LogD_7.40 value and the MIC of 46 plant flavonoids reported in literature against E. coli was also analyzed. Both sets of results showed that there is a significant correlation between the LogP value and the MIC of plant flavonoids against Gram-negative bacteria. However, it is difficult to effectively predict the MIC of plant flavonoids against Gram-negative bacteria from their lipophilic parameters. By comparing two regression curves derived from plant flavonoids against Gram-negative and Gram-positive bacteria, it was further discovered that the antibacterial activities of most plant flavonoids against Gram-negative bacteria are stronger than those against Gram-positive bacteria when their LogP values are less than about 3.0, but the opposite is true when their LogP values are more than about 3.6. Moreover, this comparison also suggests that unlike mainly acting on the cell membrane of Gram-positive bacteria, plant flavonoids have multiple mechanisms against Gram-negative species, while the cell membrane is also an important action site among them. Combined with the correlation analyses between the enzyme inhibitory activity and the LogP value of the reported flavonoids, it was further suggested that DNA gyrase is another important target of plant flavonoids against Gram-negative bacteria.

Culinary herbs and spices are widely used in daily diets. Pakistan flora is enriched with phytochemicals due to a diverse range of land. Phytochemicals, including volatile and non-volatile compounds, have captured much interest due to their numerous health advantages and significance in daily diet. The present study aimed to conduct in-depth metabolomic profiling of Pakistani-grown fenugreek leaves (Trigonella foenum-graecum), fennel seeds (Foeniculum vulgare), mint leaves (Mentha royleana), coriander seeds (Coriandrum sativum) and basil leaves (Ocimum basilicum) by using liquid chromatography–mass spectrometry (LC-MS/MS) and gas chromatography–mass spectrometry (GC-MS). The first study was conducted to optimize extraction using different solvents (methanol, ethanol, chloroform, acetone, and water). Total phenolic content (TPC), total flavonoid content (TFC), and total condensed tannins (TCT) were quantified along with the antioxidant and anti-diabetic activities. The highest TPC (125.42 ± 10.89 mg GAE/g) and the highest antioxidant and anti-diabetic potential were quantified in mint. Seventy-one phytochemical metabolites were identified using LC-MS/MS, while forty-nine volatile constituents were identified using the GC-MS. A positive correlation was identified between phenolic contents and their biological activities. Furthermore, molecular docking helped to find drug molecules with more excellent anti-diabetic activity based on their binding affinities. This study suggests that selected medicinal herbs from Pakistan have significant nutraceutical and phytopharmaceutical potential. This study could further help in drug discovery.

Mast cells play a critical role in allergies and inflammation via secretion of numerous vasoactive, pro-inflammatory and neuro-sensitizing mediators. Secretion may utilize different modes that involve the cytoskeleton, but our understanding of the molecular mechanisms regulating secretion is still not well understood. We previously showed that the ability of the so called mast cell “stabilizer” disodium cromoglycate (cromolyn) to inhibit secretion from rat mast cells closely paralleled the phosphorylation of a 78 kDa protein, and subsequently showed this protein to be moesin, a member of the Ezrin/Radixin/Moesin (ERM) family of proteins, which are involved in linking cell surface-initiated signaling to the actin cytoskeleton. Unlike phosphorylation on the C-terminus Thr558 associated with activation of ERMs, including secretion from macrophages and platelets, we showed that phosphorylation of moesin during inhibition of secretion was on the N-terminal Ser56/74 and Thr66 residues. This phosphorylation pattern could lock moesin in its inactive state and remain inaccessible to bind to the Soluble NSF attachment protein receptors (SNAREs) and synaptosomal associated proteins (SNAPs). Using Confocal microscopic imaging, we showed moesin to colocalize with actin and cluster around secretory granules during inhibition of secretion, In conclusion, the phosphorylation pattern and localization of moesin may be important in the regulation of mast cell secretion and could be targeted for the development of effective inhibitors of secretion from mast cells.

Citrus flavonoids are well-known for beneficial effects at the cardiovascular and cardio-metabolic level, but often the encouraging in vitro results are not confirmed by in vivo approaches; also clinical trials are inconsistent. The limited bioavailability of them can be, at least in part, the reason of these discrepancies. Therefore many efforts were performed towards the improvement of their bioavailability. Hydrodynamic cavitation methods were successfully applied to the extraction of byproducts of the Citrus fruits industry, showing high process yields and affording stable phytocomplexes, known as IntegroPectin, endowed with great amounts of bioactive compounds and high water solubility. Cardioprotective effects of grapefruit IntegroPectin were evaluated by an ex vivo ischemia/reperfusion protocol. A further pharmacological characterization was carried out to assess the involvement of mitochondrial potassium channels. Grapefruit IntegroPectin, where naringin represented 98% of flavonoids, showed anti-ischemic cardioprotective activity, better than pure naringenin (the bioactive aglycone of naringin). On cardiac isolated mitochondria, this extract confirmed that naringenin/naringin were involved in the activation of mitochondrial potassium channels. The hydrodynamic cavitation-based extraction confirmed a valuable opportunity for the exploitation of Citrus fruits waste, with the end product presenting high levels of Citrus flavonoids and an improved bioaccessibility that enhances its nutraceutical and economic value.

Cereal crops, such as oats and barley, possess a number of valuable properties that meet the requirements for functional diet components. This review summarized the available information about bioactive compounds of oat and barley grain. The results of studying the structure and physicochemical properties of the cell wall polysaccharides of barley and oat are presented. The main components of the flavonoids formation pathway are shown and data, concerning anthocyanins biosynthesis in various barley tissues, are discussed. Moreover, we analyzed the available information about structural and regulatory genes of anthocyanin biosynthesis in Hordeum vulgare L. genome, including β-glucan biosynthesis genes in Avena sativa L species. However, there is not enough knowledge about genes responsible for biosynthesis of β-glucans and corresponding enzymes and plant polyphenols. The review also covers contemporary studies about collections of oat and barley genetic resources held by VIR. This review intended to provide information on the processes of biosynthesis of biologically active compounds in cereals that will promote further researches devoted to transcription factors controlling expression of structural genes and their role in other physiological processes in higher plants. Found achievements will allow breeders to create new highly productive varieties with the desirable properties.

Neurodegenerative disorders such as Parkinson’s disease (PD), Alzheimer’s disease (AD), Amyloidal lateral sclerosis (ALS), and Huntington disease (HD) are the most concerned disorders due to the lack of effective therapeutics and dramatic rise in affected cases. Although these disorders have diverse clinical manifestations, yet they all share a common cellular stress response. These cellular stress responses including neuroinflammation, oxidative stress, proteotoxicity, and ER-stress, which combats with stress conditions, but the overwhelming cellular stress response induces cell damage. Small molecules such as flavonoids could reduce cellular stress and have gained much attention in recent years. Evidence has shown the potential use of flavonoids in several ways such as antioxidants, anti-inflammatory, and anti-apoptotic, yet their mechanism is still elusive. This review provides an insight into the mechanistic ways of flavonoids against cellular stress response that prevent the pathogenesis of neurodegenerative disorders.

Silybum marianum L. is a well-known medicinal herb, primarily used in liver protection. Light strongly affects several physiological processes along with secondary metabolites biosynthesis in plants. Herein, S. marianum was exploited for in vitro potential under different light regimes in the presence of melatonin. The optimum callogenic response occurred in combination of 1.0 mg/L α-naphthalene acetic acid and 0.5 mg/L 6-Benzylaminopurine under photoperiod. Continuous light associated with melatonin treatment increased total flavonoid content (TFC), total phenolic content (TPC) and antioxidant potential, followed by photoperiod and dark treatments. The increased level of melatonin has a synergistic effect on biomass accumulation under continuous light and photoperiod, while adverse effect was observed under dark condition. More detailed phytochemical analysis showed maximum total silymarin content (11.92 mg/g DW) when placed under continuous light + 1.0 mg/L melatonin. Individually, the level of silybins (A and B), silydianin, isolsilychristin and silychristin was found highest under continuous light. Anti-inflammatory activities were also studied and highest percent inhibition was recorded against 15-LOX for cultures cultivated under continuous light (42.33%). The current study helps to better understand the influence of melatonin and different light regimes on silymarin production as well as antioxidant and anti-inflammatory activities in S. marianum callus extracts.

A multi-tool analytical practice was used for characterization of 16^th century carpet manufactured in Cairo. Mild extraction method with hydrofluoric acid enabled isolation of intact flavonoids and their glycosides, anthraquinones, tannins and indigoids from fibre samples. High-performance liquid chromatography coupled to spectroscopic and mass spectrometric detectors was used for identification of natural dyes present in the historical samples. Weld, young fustic and brazilwood were identified as the dye sources in yellow thread samples. Red fibres have been colored with lac dye, whereas green fibre shades were obtained with indigo and weld. Tannin-containing plant material in combination with indigo and weld were used to obtain brown hue of thread. Four uncommon and thus-far unknown dye components were also found in the historical samples. These compounds probably represent unique fingerprint of dyed threads from this region. Scanning electron microscopy with energy-dispersive X-ray detector (SEM-EDS) and Fourier transformation infrared spectroscopy (FT-IR) were used for identification and characterization of substrates and mordants present in the historical carpet. Carbon and oxygen were detected in large quantities as a part of the wool protein. The presence of aluminum, iron and calcium indicated their usage as mordants. FT-IR analysis showed bands characteristic to woolen fibres and SEM micrographs definite structure of wool.

Decoctions, macerations and fumigations of the stem bark and wood of Terminalia brownii Fresen. are used in traditional medicine for fungal infections and as pesticides on field crops and in traditional granaries in Sudan. In addition, T. brownii is commonly used for protecting wooden houses and furniture. Therefore, using agar disc diffusion and macrodilution methods, eight extracts of various polarities from the stem wood and bark were screened for their growth inhibitory effects against filamentous fungi commonly causing fruit, vegetable and grain decay, as well as infections in the immunocompromised host. Ethyl acetate extracts of the stem wood and bark gave the best antifungal activities, with MIC values of 250 µg/ml against Nattrassia mangiferae and Fusarium verticillioides, and 500 µg/ml against Aspergillus niger and Aspergillus flavus. Aqueous extracts gave almost as potent effects as the ethyl acetate extracts against the Aspergillus and Fusarium strains, and were slightly more active than the ethyl acetate extracts against Nattrassia mangiferae. Thin layer chromatography, RP-HPLC-DAD and tandem mass spectrometry (LC-MS/MS), were employed to identify the chemical constituents in the ethyl acetate fractions of the stem bark and wood. The stem bark and wood were found to have a similar qualitative composition of polyphenols and triterpenoids, but differed quantitatively from each other. The stilbene derivatives, cis- (3) and trans- (4) resveratrol-3-O-β-galloylglucoside, were identified for the first time in T. brownii. Moreover, methyl-(S)-flavogallonate (5), quercetin-7-β-O-di-glucoside (8), quercetin-7-O-galloyl-glucoside (10), naringenin-4`-methoxy-7-pyranoside (7), 5,6-dihydroxy-3`,4`,7-tri-methoxy flavone (12), gallagic acid dilactone (terminalin) (6), a corilagin derivative (9) and two oleanane type triterpenoids (1) and (2) were characterized. Our results justify the traditional uses of macerations and decoctions of T. brownii stem wood and bark for crop and wood protection and demonstrate that standardized extracts could have uses for the eco-friendly control of plant pathogenic fungi in African agroforestry systems. Likewise, our results justify the traditional uses of these preparations for the treatment of skin infections caused by filamentous fungi.

Zingiber officinale rhizome is widely cultivated in the central region of Sudan (Gezira) and data on the biological properties of this variety grown in the Sudan climate is scarce. The study aims to comprehensively analyze the antibacterial, antioxidant, phytochemical, and GC-MS properties of Zingiber officinale (Ginger rhizome) to explore its potential applications. The in vitro antibacterial assessment of the aqueous extract of the Sudanese ginger revealed moderate activity against Staphylococcus aureus, Salmonella typhi, Pseudomonas aeruginosa, Escherichia coli , and Klebsiella pneumonia, as resulted from the disc-diffusion which ranged between 12.87±0.11 mm to 14.5±0.12 mm at 30 µg/disc. The minimum inhibition concentration ranged between 6.25 to 25 µg/ml, the MBC were between 25 and 50 µg/ml, and the MBC/MIC exhibited its bactericidal effect against all tested bacteria. The phytochemical screening revealed the presence of various chemical constituents such as saponins, flavonoids, glycosides, alkaloids, steroids, terpenoids, and absence of tannins in the Sudanese ginger rhizome. Furthermore, the GC-MS study of ginger rhizome identified 22 chemical compounds with retention times ranging from 7.564 to 17.023 minutes. The identification of 22 chemical compounds through GC-MS analysis further underscores the prospect of harnessing ginger rhizome for the development of novel medications. The computational analyses showed that ginger compounds bind the 1JIJ and 2QZW with high binding affinities, which reach –9.5 kcal/mol. Ginger compounds also established promising molecular interactions with some key residues, that satisfactorily explain the in vitro results and support the pharmacokinetic and experimental findings. This study lays the groundwork for future research and pharmaceutical exploration aimed at harnessing the beneficial properties of ginger rhizome for medicinal and therapeutic purposes, particularly its antimicrobial potential.

Anthocyanins are well known as colorants of flowers, but many other invisible functions might have been more important during the evolution of complex biosynthesis networks in plants. The number of anthocyanin decorating enzymes, the subtle control of structural genes by numerous transcription factors, and routes of intracellular anthocyanin transport are reviewed here. Various ecological functions of anthocyanins hold the key to understanding evolutionary trajectories that lead to the success of these pigments. Proposed functions include carbon sinks that prevent excessive sugar levels, sun blockers protecting the photosynthesis apparatus, antioxidants scavenging reactive oxygen species, providing camouflage, and attraction of pollinators and seed dispersers. Anthocyanins clearly fulfill different functions in different plant organs. It is currently believed that protective functions in leaves gave rise to the biosynthesis network and that flower and fruit coloration evolved later.

Fusarium wilt (FW) caused by Fusarium oxysporum f. sp. Cucumerinum (Foc) of cucumber is a destructive soil-borne disease in cucumber (Cucumis sativus.L). There is limited knowledge on molecular mechanisms to FW resistance-mediated defense responses in cucumber. In this study, metabolome and transcriptome profiling were carried out in two FW, resistant (NR) and susceptible (NS), near isogenic lines (NILs) before and after Foc inoculation. The NILs showed consistent and stable FW resistances in multiple greenhouse and laboratory screening tests. Widely targeted metabolomic analysis identified differentially accumulated metabolites (DMAs) with significantly more accumulation in NR in response to Foc infection including many phenolic acid and flavonoid compounds from the flavonoid biosynthesis pathway. Transcriptome analysis identified differentially expressed genes (DEGs) between the NILs upon Foc inoculation including genes for secondary metabolite biosynthesis in or transcription factor genes regulating the flavonoid biosynthesis pathway. Joint analysis of the metabolomic and transcriptomic data identified DAMs and DEGs closely associated with biosynthesis of phenolic acid and flavonoid DAMs. The association of these compounds with NR-conferred FW resistance was exemplified by in vivo assays in which two phenolic acid compounds, bis (2-ethylhexyl) phthalate and diisooctyl phthalate, and the flavonoid compound gallocatechin 3-O-gallate were shown to have significant inhibitory effect on Foc growth. The antifungal effect of three compounds seems to be a novel finding. We conclude that phenolic acids and flavonoids play an important role in NR mediated FW resistance in cucumber.

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

Cannabis, renowned for its historical medicinal use, harbours various bioactive compounds—cannabinoids, terpenes, and flavonoids. While major cannabinoids like THC and CBD have received extensive scrutiny for their pharmacological properties, emerging evidence underscores the collaborative interactions among these constituents, suggesting a collective therapeutic potential. This comprehensive review explores the intricate relationships and synergies between cannabinoids, terpenes, and flavonoids in cannabis. Cannabinoids, pivotal in cannabis's bioactivity, exhibit well-documented analgesic, anti-inflammatory, and neuroprotective effects. Terpenes, aromatic compounds imbuing distinct flavours, not only contribute to cannabis's sensory profile but also modulate cannabinoid effects through diverse molecular mechanisms. Flavonoids, another cannabis component, demonstrate anti-inflammatory, antioxidant, and neuroprotective properties, particularly relevant to neuroinflammation. The entourage hypothesis posits that combined cannabinoid, terpene, and flavonoid action yields synergistic or additive effects, surpassing individual compound efficacy. Recognizing the nuanced interactions is crucial for unravelling cannabis's complete therapeutic potential. Tailoring treatments based on the holistic composition of cannabis strains allows optimization of therapeutic outcomes while minimizing potential side effects. This review underscores the imperative to delve into the intricate roles of cannabinoids, terpenes, and flavonoids, offering promising prospects for innovative therapeutic interventions and advocating continued research to unlock cannabis's full therapeutic potential within the realm of natural plant-based medicine.

Scientific evidence increasingly supports the strong link between diet and health, acknowledging that a well-balanced diet plays a crucial role in preventing chronic diseases such as obesity, diabetes, cardiovascular issues, and certain types of cancer. This perspective opens the door to developing precision diets, particularly tailored for individuals at risk of developing cancer. It encompasses a vast research area and involves the study of an expanding array of compounds with multi-level "omics" compositions, including genomics, transcriptomics, proteomics, epigenomics, miRNomics, and metabolomics. We review here the components of the Southern European Atlantic Diet (SEAD) from both a chemical and pharmacological standpoint. The information sources consulted, complemented by crystallographic data from the Protein Data Bank, establish a direct link between SEAD and its anticancer properties. The data collected strongly suggest that SEAD offers an exceptionally healthy profile, particularly due to the presence of beneficial biomolecules in its foods. The inclusion of olive oil and paprika in this diet provides numerous health benefits, and science supports the anti-cancer properties of dietary supplements with biomolecules sourced from vegetables of the brassica genus. Nonetheless, further research is warranted in this field to gain deeper insights into the potential benefits of SEAD's bioactive compounds against cancer.

This research presents a comparative analysis of the yield and nutritional quality of lettuce (Lactuca sativa L.) cultivated in an aeroponic system with two distinct nutrient solutions: (i) commercial hydroponic fertilizers and (ii) aquaponic water without added fertilizers. Both systems were maintained under the same controlled conditions, enabling the comparison of growth parameters, leaf area, antioxidant activity, mineral content, and sensory characteristics of the lettuce. The hydroponic system demonstrated superior performance concerning the fresh weight of lettuce head and root, leaf count, and leaf area. In contrast, the aquaponic system produced a higher dry weight of lettuce heads and a more extensive root-to-shoot ratio. Concerning nutrient concentration, the hydroponic nutrient solution composition exhibited elevated levels of NO3–, P, NH4+, and K in contrast to the aquaponic nutrient solution, which had a more significant S, Cl–, Na, and Mg content. Regarding the nutritional value, lettuce from the hydroponic system exhibited significantly higher levels of K, S, P, Zn, Fe, Mn, and vitamin B2. In contrast, lettuce from the aquaponic system exceeded with higher content of Ca, Na, Mg, Al, B, and Si. Remarkably, the lettuce cultivated in the aquaponic system demonstrated significantly enhanced total flavonoid and phenol content, and antioxidant capacity compared to its hydroponically grown counterpart.

Zika virus (ZIKV) has been characterized as one of the potential pathogens and placed under future epidemic outbreaks by the WHO. However, lack of potential therapeutics can result in uncontrolled pandemic like other human pandemic viruses; therefore, prioritized effective therapeutics development has been recommended against ZIKV. In this context, the present study adopted the strategy to explore the lead compounds from Azadirachta indica against ZIKV via concurrent inhibition of the ZIKVpro and ZIKVRdRp proteins using molecular simulations. Initially, structure-based virtual screening of 44 bioflavonoids reported in Azadirachta indica against the crystal structures of targeted ZIKV proteins resulted in the identification of top four common bioflavonoids, viz. rutin, nicotiflorin, isoquercitrin, and hyperoside. These compounds showed substantial docking energy (-7.9 to -11.01 kcal/mol) and intermolecular interactions with essential residues of ZIKVpro (His51, Asp74, and Ser135) and ZIKVRdRp (Asp540, Ile799, and Asp665) by comparison to the reference compounds, O7N inhibitor (ZIKVpro) and Sofosbuvir inhibitor (ZIKVRdRp). Long interval molecular dynamics simulation (500 ns) on the selected docked poses reveals the stability of respective docked complexes contributed by intermolecular hydrogen bonds and hydrophobic interactions. The predicted complex stability was further supported by calculated end-point binding free energy using molecular mechanics generalized born surface area (MM/GBSA) method. Consequently, the identified common bioflavonoids are recommended as promising therapeutic inhibitors of ZIKVpro and ZIKVRdRp for further experimental assessment.

Extensive phytochemical and chromatographic analysis of different root fractions of Jatropha pelargoniifolia Courb. (Euphorbiaceae) resulted in the isolation and identification of 22 distinct secondary metabolite compounds. Two new compounds, 6-hydroxy-8-methoxycoumarin-7-O-β-D-glycopyranoside and (3-(2-(methylamino) ethyl)-1H-indol-2-yl) methanol, were isolated and identified for the first time from a natural source. In addition, other known compounds, such as hovetricoside C and N-methyltryptamine were isolated from Euphorbiaceae, and hordenine, N-methyltyramine, their salts, cynaroside and linarin were identified in Jatropha spp. for the first time. Some isolated metabolites, such as β-sitosterol, β-sitosterol glucoside, curcusons D and C, naringenin, apigenin, cleomiscosins B and A, spruceanol, propacin, jatrophadiketone, and uracil were previously identified in various Jatropha species. The structures of the isolated compounds were determined using different spectroscopic techniques. The anti-inflammatory, antinociceptive, antipyretic, and antioxidant activities were evaluated for some adequately available isolated compounds. Compounds showed significant antinociceptive activity compared with the standard analgesic drug indomethacin. The edema size was significantly reduced (p< 0.05–0.001) in the animals treated with low doses (5 and 10 mg/kg) of the isolated compounds compared with those treated with a high dose (100 mg/kg) of standard anti-inflammatory drug (phenylbutazone). Furthermore, all tested compounds showed a significant (p< 0.05–0.001) reduction in the rectal temperature of hyper-thermic mice.

Foods are mixed with saliva in the oral cavity and swallowed. During staying in the stomach, saliva is contentiously provided to mix with the ingested foods. Because a salivary component nitrite is protonated to produce active nitrous acid at acidic pH, the redox reactions of nitrous acid with phenolic compounds in foods become possible in the stomach. In the reactions, nitrous acid is reduced to nitric oxide (•NO), producing various products from phenolic compounds. In the products, stable hydroxybezoyl benzofuranone derivatives, which are produced from quercetin and its 7-O-glucoside, are included. Caffeic acid, chlorogenic acid, and rutin are oxidized to quinones and the quinones can react with thiocyanic acid derived from saliva producing stable oxathiolone derivatives. 6,8-Dinitrosocatechis are produced from catechins by the redox reaction, and the dinitrocatechins are oxidized further by nitrous acid producing the quinones, which can make charge transfer complexes with the dinitrosocatechin and can react with thiocyanic acid producing the stable thiocyanate conjugates. In this way, various products can be produced by the reactions of salivary nitrite with dietary phenolic compounds, and reactive and toxic quinones formed by the reactions are postulated to be removed in the stomach by thiocyanic acid derived from saliva.

Herein, we applied DNA Barcoding for the genetic characterization of Sideritis syriaca subsp. syriaca (Lamiaceae; threatened local Cretan endemic plant), using seven molecular markers of cpDNA. Five fertilization schemes were evaluated comparatively in a pilot cultivation in Crete. Chemical fertilizers (ChF), integrated nutrient management fertilizers (INM) and two biostimulants were utilized (foliar and soil application). Plant growth, leaf chlorophyll fluorescence and colour were assessed, and leaf content of chlorophyll, key antioxidants (carotenoids, flavonoids, phenols), and minerals were evaluat-ed. Fertilization regime did not affect leaf colour but induced distinct differences in leaf shape altering quality characteristics. INM-foliar and ChF-soil application promoted yield, without affecting tissue water content or biomass partitioning to inflorescences. ChF-foliar application was the most stimulato-ry treatment for enhanced antioxidant compound content, while INM-biostimulant was the least effec-tive one. In conclusion, adverse fertilization options appear as optimal when considering yield or anti-oxidant compound content. New DNA sequence datasets for the plastid regions of petB/petD, rpoC1, psbK-psbI and atpF/atpH have been deposited in the GenBank for S. syriaca subsp. syriaca while the mo-lecular markers rbcL, trnL/trnF, psbA/trnH were compared to those of another 15 Sideritis species re-trieved from the GenBank, constructing a phylogenetic tree to show their genetic relatedness.

Is it possible that the addition of wild-growing flowers with anti-inflammatory applications can improve the antioxidant properties of rapeseed and multifloral honey? The study objective was a comparative analysis of two honey varieties enriched by flowers of six plant species, based on the content of the antioxidant capacity as well as total flavonoids and phenolic content. Experiments demonstrated that at each level of enrichment there was an improvement in antioxidant properties compared to honey of both varieties without additives, especially in the case of dried flowers. Primula veris L. and Pulmonaria officinalis L. improved the antioxidant properties and phenolic content most effectively in honey at all levels of enrichment. Rapeseed-type honey produces a better matrix for the incorporation of natural plant metabolites into honey. The content of biologically active substances in honey enriched with flowers gives hope for new applications of health-promoting substances contained in wild plants.

The present study was to investigate effects of total flavonoids from Taraxacum mongolicum Hand.-Mazz. (FT) on fermentation quality, antioxidant status and microbial community of Caragana korshinskii Kom. (CK) silage. CK was ensiled with no additive (CON), 1% FT and 2% FT on a fresh weight (FW) basis for 60 days. The results showed that 1% FT and 2% FT groups displayed higher DM content than CON group, and 2% FT group had the best effect on nutrient preservation. Compared with CON and 1% FT groups, 2% FT group exhibited the best silage fermentation quality and the highest antioxidant activity, including increased lactic acid, acetic acid concentrations and the activities of antioxidant enzymes, as well as decreased pH and the ammonia nitrogen (NH₃-N) concentration. Moreover, 2% FT addition significantly affected the microbial community, such as increased abundance of Lactobacillus and decreased abundances of Pseudomonas and unidentified Cyanobacteria. The abundances of Lactobacillus parafarraginis and Lactobacillus brevis were negatively correlated to pH, while they were positively correlated with T-AOC, GSH-Px and CAT activities. In conclusion, 2% FT may be used as additives to inhibit the growth of undesirable microorganisms and promote fermentation quality and antioxidant activity of CK silage.

Based on recent computational and experimental studies, hesperidin, a bioactive flavonoid abundant in citrus peel, stands out for its high binding affinity to the main cellular receptors of SARS-CoV-2, outperforming drugs already recommended for clinical trials. Thus, it is very promising for prophylaxis and treatment of COVID-19, along with other coexistent flavonoids such as naringin, which could help restraining the pro-inflammatory overreaction of the immune system. Controlled hydrodynamic cavitation processes showed the highest speed, effectiveness and efficiency in the integral and green aqueous extraction of flavonoids, essential oils and pectin from citrus peel waste. After freeze-drying, the extracted pectin showed high quality and excellent antioxidant and antibacterial activities, attributed to flavonoids and essential oils adsorbed and concentrated on its surface. This study reviews the recent evidence about hesperidin as a promising molecule, and proposes a feasible and affordable process based on hydrodynamic cavitation for the integral aqueous extraction of citrus peel waste resulting in hesperidin-rich products, either aqueous extracts or pectin tablets. The uptake of this process on a relevant scale is urged, in order to achieve large-scale production and distribution of hesperidin-rich products. Meanwhile, experimental and clinical studies could determine the effective doses either for therapeutic and preventive purposes.

This study explored the correlation between concentrations of phenolic compounds (phenols, tannins, and flavonoids) and the versatility of woody medicinal plants in the Caatinga, a seasonally dry forest region in Brazil. We examined whether these compounds influence the versatility of plants used by populations, given their known therapeutic properties. Plants were categorized as high or low versatility based on their relative importance (RI) values ​​at the regional level. Samples collected in Catimbau National Park, Pernambuco, were analyzed using colorimetric methods: Folin-Ciocalteu reagent for total phenols, casein precipitation for tannins, and aluminum chloride complexation for flavonoids. Contrary to expectations, no significant differences in phenolic compound concentrations were found between the high and low versatility groups. Higher levels of total phenols and tannins were observed in Myracrodruon urundeuva and Anadenanthera colubrina, both highly versatile species. However, less versatile species, such as Mimosa tenuiflora and Schinopsis brasiliensis, also showed high levels. Flavonoid content, notably lower than phenols and tannins, did not show significant variation between groups. Although phenolic compounds contribute to the therapeutic properties of medicinal plants, their concentration alone does not determine the versatility of plants in the Caatinga. Versatility is more likely influenced by ecological conditions, cultural practices, and species availability. This study highlights the need to integrate multiple perspectives in ethnopharmacological research.

Dark pigmentation can be observed in various parts of the plant, ranging from foliage to petals to berries. The molecular basis of black pigmentation appears to vary among species, with anthocyanins playing a significant role, although specific anthocyanin types and their mechanisms differ. These findings suggest that the development of phenotypes is species-specific or varies between larger taxonomic groups; this is further supported by the polyphyletic nature of dark pigmentation. Additionally, several different regulatory mechanisms have been described for the occurrence of dark pigmentation. Firstly, the repression or knockout of the competing flavone biosynthesis has been shown to lead to darker pigmentation while another mechanism is based on the activation and upregulation of the anthocyanin biosynthesis genes in the presence of MYB transcription factors. Potential ecological functions of dark pigmentation were identified as the protection of the photosynthesis apparatus, camouflage against herbivores, and the attraction of pollinators. Promising industrial applications include microbial factories for the production of natural food colourants, induction of novel phenotypes for the ornamental plant industry and lastly the increase of anthocyanins within agriculturally relevant crops.

Since the 1970s, the usefulness of nailfold capillaroscopy (NFC) in the diagnosis of rheumatological disorders such as systemic sclerosis has been well known, and further studies also showed that NFC can detect non-rheumatic diseases such as diabetes, glaucoma, dermatitis, Alzheimer disease, and so on. In the past decade, the morphological changes in the nailfold capillary have been also reported in the unhealthy lifestyle habits such as smoking, inappropriate diets, sleep shortage, and even psychological stress which presents slow blood flow. Therefore, study in the relationships between the morphology of nailfold capillaries and lifestyle habits has high potential to understand the unhealthy state, or even predict the pre-disease condition. So, simple, inexpensive, and non-invasive methods such as NFC are constantly needed for routine health checkups. Thus, we undertook a systematic search in PubMed database, and summarized the studies reporting the assessment of morphological NFC in order to undertake a comprehensive review on the usefulness of NFC not only in clinical diagnosis, but also in unhealthy dietary lifestyle improvements. Here in this review paper, we finally summarized the dietary and lifestyle health promotion strategy judging from NFC- and the other relating-measurement from the viewpoint of healthy microvascular blood flow and endothelial function.

Due to combined climate and biodiversity crisis, the sustainable utilization of phytogenetic resources stands as one-way alternative while nutrient management strategies gain an increasing role in agriculture. Building on previous studies regarding the Endangered local endemic of Crete (Greece) Carlina diae (Asteraceae) with medicinal and ornamental value, this investigation focused on its pilot cultivation and fertilization (foliar or root application). Foliar application included chemical fertilizer (conventional) or integrated nutrient management (INM). Root application consisted of chemical fertilizer, biostimulant, or INM with biostimulant. Above-ground biomass content of nutrients, together with leaf chlorophyll fluorescence and colour parameters (SPAD meter, DA meter, Chroma Meter) were determined. The leaf content of chlorophyll, three key antioxidant compounds and minerals’ titers were also assessed. The fertilization scheme did not influence plant growth and visually perceived quality (leaf color and shape). Notably, foliar INM fertilization increased biomass partitioning to inflorescences (harvestable organ for either medicinal or ornamental purposes), and decreased tissue water content (facilitating processing). Considering all three antioxidants together, INM with biostimulant appeared the optimum scheme, being associated with the highest (carotenoids, phenolics) or the second highest (flavonoid) content. In C. diae, therefore, INM fertilization was optimal for upgrading yield (foliar) and herbal quality in terms of antioxidant profile (INM with biostimulant), which might be embraced as an eco-friendly approach for high quality yields.

Disrupted biological function, manifesting through the hallmarks of aging, poses as one of the largest threats to healthspan and risk of disease development, such as metabolic disorders, cardiovascular ailments, and neurodegeneration. In recent years, numerous geroprotectors, senolytics, and other nutraceuticals have emerged as potential disruptors of aging and may be viable interventions in the immediate state of human longevity science. In this review, we focus on the decrease of nicotinamide adenine dinucleotide (NAD+) with age and the supplementation of NAD+ precursors, such as nicotinamide mononucleotide (NMN) or nicotinamide riboside (NR), in combination with other geroprotective compounds to restore youthful NAD+ levels. Furthermore, these geroprotectors may enhance the efficacy of NMN supplementation while concurrently providing their own numerous health benefits. By analyzing the prevention of NAD+ degradation through inhibition of CD38 or supporting protective downstream agents of SIRT1, we provide a potential framework of the CD38/NAD+/SIRT1 axis through which geroprotectors may enhance the efficacy of NMN supplementation and reduce the risk of age-related diseases, thereby potentiating healthspan in humans.

Flavonoids comprise a large group of structurally diverse polyphenolic compounds of plant origin and are abundantly found in human diet such as fruits, vegetables, grains, tea, dairy products, red wine and so on. Major classes of flavonoids include flavonols, flavones, flavanones, flavanols, anthocyanidins, isoflavones, and chalcones. Owing to their potential health benefits and medicinal significance, flavonoids are now considered as an indispensable component in a variety of medicinal, pharmaceutical, nutraceutical, and cosmetic preparations. However, flavonoids play a significant role in preventing cardiovascular diseases (CVDs), which could be mainly due to their antioxidant, antiatherogenic, and antithrombotic effects. Epidemiological and in vitro/in vivo evidences of antioxidant effects support the cardioprotective function of dietary flavonoids. Further, the inhibition of LDL oxidation and platelet aggregation following regular consumption of food containing flavonoids and moderate consumption of red wine might protect against atherosclerosis and thrombosis. A study suggests that daily intake of 100 mg of flavonoids through diet may reduce the risk of developing morbidity and mortality due to coronary heart disease (CHD) by approximately 10%. This review summarizes dietary flavonoids with their sources and potential health implications in CVDs including various redox-active cardioprotective (molecular) mechanisms with antioxidant effects. Pharmacokinetic (oral bioavailability, drug metabolism), toxicological and therapeutic aspects of dietary flavonoids are also addressed herein with future directions for the discovery and development of useful drug candidates/ therapeutic molecules.

Grapefruit and lemon pectin obtained from the respective waste citrus peels via hydrodynamic cavitation in water only are powerful, broad-scope antimicrobial alternatives to antibiotics against Gram-negative and -positive pathogens. Dubbed IntegroPectin, these pectic polymers functionalized with citrus flavonoids and terpenes show superior antimicrobial activity when compared to commercial citrus pectin. Similarly to commercial pectin, lemon IntegroPectin determined ca. 3 log reduction of Staphylococcus aureus cells, while an enhanced activity of commercial citrus pectin was detected in the case of Pseudomonas aeruginosa cells with a minimal bactericidal concentration (MBC) of 15 mg mL-1. Although grapefruit and lemon IntegroPectin share equal MBC in the case of P. aeruginosa cells, grapefruit IntegroPectin shows boosted activity upon exposure of S. aureus cells with a 40 mg mL-1 biopolymer concentration being sufficient to achieve complete killing of the bacterial cells. Insight on the mechanism of action of these biocompatible antimicrobials and their effect on bacterial cells, at the morphological level, were obtained indirectly through Fourier Transform Infrared spectroscopy and directly through scanning electron microscopy. In the era of antimicrobial resistance, these results are of great societal and sanitary relevance as they open new avenues to develop innovative antimicrobials for the treatment of polymicrobial infections unlikely to develop drug resistance.

Flavonoids, polyphenols with anti-oxidative activity have high potential as novel therapeutics for neurodegenerative disease, but their applicability is rendered by their poor water solubility and chemical instability under physiological conditions. In this study, this is overcome by delivering flavonoids to model cell membranes (unsaturated DOPC) using prepared and characterized biodegradable mesoporous silica nanoparticles, MSNs. Quercetin, myricetin and myricitrin have been investigated in order to determine the relationship between flavonoid structure and protective activity towards oxidative stress i.e. lipid peroxidation induced by addition of hydrogen peroxide and/or Cu²⁺ ions. Among investigated flavonoids, quercetin showed the most enhanced and prolonged protective anti-oxidative activity. The nanomechanical (Young modulus) measurement of the MSNs treated DOPC membranes during lipid peroxidation confirmed attenuated membrane damage. By applying combination of experimental techniques (AFM, force spectroscopy, ELS, DLS), this work generated detailed knowledge about the effects of flavonoid loaded MSNs on the elasticity of model membranes, especially under oxidative stress conditions. Results from this study will pave the way towards the development of innovative and improved markers for oxidative stress-associated neurological disorders. In addition, the obtained could be extended to designing effective delivery systems of other high potential bioactive molecules with an aim to improve human health in general.

Flavonoids are secondary plant metabolites involved in biological activity that are present in plentiful proportions in many plant origin foods and beverages. Owing to their chemical difference and qualities that make them beneficial for human health, they have received a lot of focus in research. This review therefore presents an account on the chemical structure of flavonoids, food sources and their metabolism with emphasis on bioavailability. And they also examine their antioxidant, anti-inflammatory, anticancer, cardiovascular protective, neuroprotective, and antimicrobial properties and reveal related molecular processes. In addition, it overviews the clinical data concerning their possible use in the prevention and treatment of chronic diseases. Some of the problems that attend current flavonoid research are also dealt with; such issues as variation in the bioactivity of flavonoids and scarcity of clinical studies. This review is designed to present current state of knowledge and to provoke further research concerning the further potential of flavonoids in enhancing human health.

Abiotic stress is responsible for significant reduction in crop plant productivity worldwide. Ultraviolet (UV) radiation is a natural component of sunlight and a permanent environmental stimulus. This study investigated the distinct responses of young wheat and einkorn plants to excessive UV-B radiation (180 min at λmax 312 nm) following foliar pretreatment with 1 µM synthetic cytokinin 4PU-30. Results demonstrated that UV radiation significantly amplified hydrogen peroxide levels in both wheat and einkorn, with einkorn exhibiting more pronounced increase compared to wheat. This elevation indicated the induction of oxidative stress by UV radiation in the two genotypes. Intensified antioxidant enzyme activities and increased accumulation of typical stress markers and non-enzyme protectants were evidenced. Transcriptional activity of genes encoding key antioxidant enzymes was also investigated aiming to elucidate the genetic regulation of the antioxidant systems in both wheat and einkorn seedlings. Our results suggested a role for POX1 and POX7 genes in the UV-B tolerance of the two wheat species as well as a cytokinin stimulated UV-B stress response in einkorn mediated through upregulation of the tau subfamily gene GSTU6. Based on these findings it could be concluded that 4PU-30 had the potential of alleviating oxidative stress by attenuating the symptoms of superfluous UV-B illumination in the two examined plant species.

The extraction of grape processing waste (wine pomace) via microwave-hydrodiffusion and gravity (MHG) from three different cultivars grown in Sicily (Syrah, Perricone and Nero d’Avola) rapidly affords aqueous extracts highly concentrated in valued biophenols including flavonoids, anthocyanins and phenolic acids. The method does not employ organic solvent, acid or base and does not require grinding or freeze drying of the wine pomace nor separation of the grape skins from seeds and stem. All the extracts have a pronounced stability as shown by their red-violet color fully retained after storage for more than a year (15 months) in freezer under air. Concentrations of phenolics up to 2000 ppm were detected in the aged extracts of Sicily’s local cultivar Perricone, which also has the highest content of flavonoids. These findings provide a simple and economically viable extraction route to biophenol-rich red extracts that can be used as food colorants as well as to formulate nutraceutical, cosmetic and personal care products starting from an agricultural by-product available in >10 million tonne yearly amount.

Several strategies promote phyllosphere colonization by soil-born Trichoderma plant-beneficial strains. One of these is foliar spraying with suspensions containing large amounts of chlamydospores – spores with a thick cell wall structure that makes them highly resistant to harsh environmental conditions. Trichoderma biomass was produced by cultivation on cornmeal medium and compared by microscopic and thermogravimetric analysis with the biomass produced in potato dextrose broth. Both analyses revealed higher chlamydospores content and thicker mycelium in the fungal biomass produced on cornmeal medium. The Trichoderma suspension rich in chlamydospores was sprayed on bitter gourd (Momordica charantia) leaves at two concentration levels, 106 and 108 ufc/ml. The effect of these treatments on plant physiological parameters, leaf photosynthetic pigments, polyphenol and flavonoid contents, antioxidant activity of leaves and fruits and yield was compared to the control (plants sprayed with water) and to the experimental treatment sprayed with 108 ufc propagules produced in potato dextrose broth. The effect of chlamydospore-rich suspensions on plant physiological parameters was more pronounced and long-lasting compared with the other treatments. The treatment with chlamydospore-rich suspension enhanced the accumulation of polyphenols and flavonoids in the leaves and fruits and increased the antioxidant activity. The application of the foliar treatment with Trichoderma suspensions did not modify the cytocompatibility of the extracts from fruits determined on L929 cells.

Abstract: Rhizobia are soil proteobacteria able to engage in a nitrogen-fixing symbiotic interaction with legumes which involves root rhizobial infection and bacterial invasion of new organs formed by the plant in response to the presence of appropriate bacterial partners. This interaction relies on a complex molecular dialogue between both symbionts. Bacterial N-acetyl-glucosamine oligomers called Nod factors are indispensable in most cases for early steps of the symbiotic interaction. In addition, different rhizobial surface polysaccharides, such as exopolysaccharides (EPS), may also be symbiotically relevant. EPS are acidic polysaccharides located out of the cell with little or no cell association that carry out important roles both in free-life and in symbiosis. EPS production is very complexly modulated and, frequently, co-regulated with that of Nod factors, but the type of co-regulation varies depending on the rhizobial strain. Many studies point out a signalling role of EPS-derived oligosaccharides in root infection and nodule invasion but, in certain symbiotic couples, EPS can be dispensable for a successful interaction. In summary, the complex regulation of the production of rhizobial EPS varies in different rhizobia and the relevance of this polysaccharide in symbiosis with legumes depends on the specific interacting couple.

Nymphaea lotus L. is the medicinal plant that has long been used as food, cosmetic and traditional medicines in Africa and Asia since the ancient time. Its flavonoids and other interesting phytochemical compounds from rhizome, leaf, and the whole flowers have been reported in the previous published researches. However, stamens, which are essential for reproductive functions, may also represent new alternative sources of potential antioxidant flavonoids as investigated in this study. The innovative green chemistry method i.e. ultrasound-assisted extraction (USAE) as well as macroporous resin (MPR) purification procedure were employed in this current research. The optimal ultrasound-assisted extraction condition is 90 % (v/v) aqEtOH with 34.65 khz ultrasonic frequency and 46 minutes of extraction time. Comparing with heat reflux extraction (HRE) conventional method, the significant gain of 1.35 total flavonoids content was obtained using optimized USAE conditions, jumping to 2.80 when this USAE associated with MPR purification. Not only in vitro cell free antioxidant activity of N. lotus stamen extracts, but also in cellulo antioxidant investigation using yeast model showed the same trend to indicate that the best antioxidant flavonoid can be found in USAE coupled with MPR purification. Moreover, the key antioxidant genes expression in yeast model such as SIR2 and SOD2 were also expressed at the highest level in yeast cell treated with the extract from USAE together with MPR purification. Consequently, it can be seen that the USAE combined with MPR purification can help to enhance the flavonoids antioxidant potential of the stamens extract from this medicinal species.

Plants are exposed to a variety of abiotic and biotic stresses leading to increased formation of reactive oxygen species (ROS) in plant cells. ROS are capable of oxidizing proteins, pigments, lipids, nucleic acids, and other cell molecules, disrupting their functional activity. During the process of evolution, numerous antioxidant systems were formed in plants, including antioxidant enzymes and low-molecular-weight non-enzymatic antioxidants. Antioxidant systems perform neutralization of ROS and therefore prevent oxidative damage of cell components. In the present review, we focus on the biosynthesis of non-enzymatic antioxidants in higher plant cells such as ascorbic acid (vitamin C), glutathione, flavonoids, isoprenoids, including carotenoids, tocopherol (vitamin E), ubiquinone and plastoquinone. Their functioning and their reactivity with respect to individual ROS are described. The review is also devoted to the modern genetic engineering methods, which are widely used to change the quantitative and qualitative content of the non-enzymatic antioxidants in cultivated plants. These methods allow to obtain various plant lines with given properties in a rather short time. The most successful approaches for plant transgenesis and plant genome editing for the enhancement of the biosynthesis and the content of these antioxidants are discussed.

Pomegranate (Punica granatum L.) is well known for its high content in bioactives including polyphenols, flavonoids and tannins, which have been shown to exhibit a wide range of biological activity such as antioxidant, antimicrobial and anticancer effects. It is worth noting that the majority of these molecules are found in the peels (PP), which are usually disposed of after processing, causing a significant amount of waste, amounting to more than 3.6 million t/y. This work investigates MW-assisted extraction (MAE) in water for the recovery of antioxidants from PP, including the optimization of temperature and extraction times. The total phenolics, anthocyanin, flavonoid and tannin contents of the recovered extracts have been determined, as have their antioxidant activities, which were found to be 356.35 mgGAE/gextr., 303.97 µgCy3G/gextr., 37.28 mgQE/gextr., 56.48 mgGAE/gextr. and 1.43 µmolTE/gextr., respectively (according to the adopted reference). All results have been compared with those obtained using a conventional protocol. In addition, the potential for water recycling by means of nanofiltration downstream in optimized MAE has been investigated, leading to overall water reuse of approx. 75%. Energy consumption (20.92W/mgGAE) and the common green metrics, RME, E-Factor and PMI (PME), have been considered in evaluating the proposed PP valorization strategy. Finally, the biological activity of the main products has been assessed. The antimicrobial properties of the PP extracts against three Gram-positive and three Gram-negative bacteria, and their antiproliferative activity towards human cancer cells have been tested. The S. aureus bacteria was the most susceptible to the PP extracts. All tested products displayed antiproliferative activity in HeLa cells when higher concentrations were tested, with D-PP/NF being the most effective. This result was also confirmed in a clonogenic analysis, which generally indicated the possible anti-cancer activity of pomegranate peel extracts obtained using this green approach.

Extracts from parts of coniferous trees have received increased interest due to their valuable bioactive compounds and properties, useful for plenty of experimental and consolidated applications, in fields comprising nutraceutics, cosmetics, pharmacology, food preservation, and stimulation of plant growth. However, the variability of the bioactive properties, the complexity of the extraction methods, and the use of potentially harmful synthetic chemicals, still represent an obstacle to the spreading of such valuable natural compounds. Hydrodynamic cavitation is emerging as a promising innovative technique for the extraction of precious food components and by-products from waste raw material of the agro-food production chain, which can improve processing efficiency, reduce resource consumption, and produce healthy, high-quality products. In this study, a process based on controlled hydrodynamic cavitation was applied for the first time to the production of aqueous solutions of silver fir (Abies Alba Mill.) needles with enhanced antioxidant activity. The observed levels of the in vitro antioxidant activity, comparable or higher than those found for reference substances, pure extracts, and other water extracts and beverages, highlight the very good potential of the HC process for the creation of solvent-free, aqueous solutions endowed with bioactive compounds extracted from silver fir needles.

Abstract This study focuses on the toxicity assessment of various flavonoids, with particular emphasis on Hesperidin. Among the investigated compounds, Hesperidin exhibits notable potential and low toxicity in both short and long-term evaluations. The toxicity parameters for Hesperidin include a low Max. Tolerated Dose (Human) (0.525 log mg/kg/day), indicative of its minimal potential harm to humans. Additionally, its Oral Rat Acute Toxicity (LD50) (2.506 mol/kg) suggests a relatively low acute toxicity level. The Oral Rat Chronic Toxicity (LOAEL) (3.167 log mg/kg_bw/day) signifies a higher dose threshold for observing adverse effects over the long term. Furthermore, Hesperidin demonstrates low Minnow Toxicity (7.131 log mM), suggesting minimal impact on aquatic organisms. Overall, this comprehensive assessment positions Hesperidin as a promising flavonoid with favorable properties and minimal toxicity.

The aggregate aftermath of persistent inflammation in patients with inflammatory bowel disease (IBD) places them at increased risk for the advancement to colitis-associated colorectal cancer (CACRC). CACRC is preceded by IBD, the highly heterogenous, pharmacologically incurable, pertinacious, reverting/worsening, and immune-mediated inflammatory pathologies of the colon and rectum. The molecular and immunological basis of CACRC is highly correlated with the length/duration and stringency/severity of colon inflammation predisposed by the exogenous/free hemoglobin alpha chain (HbαC) the byproduct of infiltrating immune cells, extravasated erythrocytes, and macrophage erythrophagocytosis. The exogenous free HbαC prompts oxygen-free radical-arbitrated DNA damage (DNAD) through increased cellular reactive oxygen species (ROS) exacerbated by decreased tissue antioxidant defenses. Mitigation of Fenton reaction via pharmaceutical therapy would attenuate the ROS, promote apoptosis, DNAD repair, and subsequent prevent the incidence of CACRC. Three pharmaceutical options that attenuate hemoglobin toxicity include haptoglobin, deferoxamine, and flavonoids (vitamins C/E). Haptoglobin’s clearance rare from plasma is inversely correlated with its size; the smaller the size, the faster the clearance. Thus, the administration of Hp1-1 may prove to be beneficial. Furthermore, deferoxamine’s hydrophilic structure limits its ability to cross cell membranes. Thus, it may be beneficial if administered intracellularly to avoid the higher plasma concentrations and longer incubation periods associated with extracellular administration. Finally, the effectiveness of flavonoids and natural herb antioxidants is associated with high reactivity of hydroxyl substituents. Multiple analyses are currently underway to assess the clinical context of CACRC and outline the molecular basis of HbαC-induced ROS pathogenesis by exposing colonocytes and/or colonoids to HbαC. These cells are then treated with haptoglobin, deferoxamine (DFO), and flavonoids in order to separate free HbαC and measure their impact on hydroxyl radical formation therapies. The molecular pathogenesis of sporadic colorectal cancer (SCRC) i.e., “inflammation-dysplasia-carcinoma” progression sequence is well described, but the immunopathogenesis of CACRC herein reviewed is broadly still in prodromal stage/phase to be validated and understood. Therefore this timely review outlines the molecular and immunological basis of disease pathogenesis and the pharmaceutical intervention as a protective measure for CACRC.