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• Background New roles for flavonoids, as developmental regulators and/or signalling molecules, have recently been proposed in eukaryotic cells exposed to a wide range of environmental stimuli. In plants, these functions are actually restricted to flavonols, the ancient and widespread class of flavonoids. In mosses and liverworts, the whole set of genes for flavonol biosynthesis - CHS, CHI, F3H, FLS and F3'H - has been detected. The flavonol branch pathway has remained intact for millions of years, and is almost exclusively involved in the responses of plants to a wide array of stressful agents, despite the fact that evolution of flavonoid metabolism has produced > 10 000 structures. • Scope Here the emerging functional roles of flavonoids in the responses of present-day plants to different stresses are discussed based on early, authoritative views of their primary functions during the colonization of land by plants. Flavonols are not as efficient as other secondary metabolites in absorbing wavelengths in the 290-320 nm spectral region, but display the greatest potential to keep stress-induced changes in cellular reactive oxygen species homeostasis under control, and to regulate the development of individual organs and the whole plant. Very low flavonol concentrations, as probably occurred in early terrestrial plants, may fully accomplish these regulatory functions. • Conclusions During the last two decades the routine use of genomic, chromatography/mass spectrometry and fluorescence microimaging techniques has provided new insights into the regulation of flavonol metabolism as well as on the inter- and intracellular distribution of stress-responsive flavonols. These findings offer new evidence on how flavonols may have performed a wide array of functional roles during the colonization of land by plants. In our opinion this ancient flavonoid class is still playing the same old and robust roles in presentday plants.

Metal-based nanoparticles have gained tremendous popularity because of their interesting physical, biological, optical, and magnetic properties. These nanoparticles can be synthesized using a variety of different physical, chemical, and biological techniques. The biological means are largely preferred as it provides an environmentally benign, green, and cost-effective route for the biosynthesis of nanoparticles. These bioresources can act as a scaffold, thereby playing the role of reducing as well as capping agents in the biosynthesis of nanoparticles. Medicinal plants tend to have a complex phytochemical constituent such as alcohols, phenols, terpenes, alkaloids, saponins, and proteins, while microbes have key enzymes which can act as reducing as well as stabilizing agent for NP synthesis. However, the mechanism of biosynthesis is still highly debatable. Herein, the present review is directed to give an updated comprehensive overview towards the mechanistic aspects in the biosynthesis of nanoparticles via plants and microbes. Various biosynthetic pathways of secondary metabolites in plants and key enzyme production in microbes have been discussed in detail, along with the underlying mechanisms for biogenic NP synthesis.

Drought stress triggers a series of physiological and biochemical changes in tea plants. It is well known that flavonoids, lignin and long-chain fatty acids play important roles in drought resistance. However, changes in proteins related to these three metabolic pathways in tea plants under drought stress have not been reported. We analysed the proteomic profiles of tea plants by tandem mass tag and liquid chromatography-tandem mass spectrometry. A total of 4789 proteins were identified, of which 11 and 100 showed up- and downregulation, respectively. The proteins related to the biosynthesis of lignin, flavonoids and long-chain fatty acids, including phenylalanine ammonia lyase, cinnamoyl-CoA reductase, peroxidase, chalcone synthase, flavanone 3-hydroxylase, flavonol synthase, acetyl-CoA carboxylase 1,3-ketoacyl-CoA synthase 6 and 3-ketoacyl-CoA reductase 1, were downregulated. However, the contents of soluble proteins, malondialdehyde, total phenols, lignin and flavonoids in the tea plants increased. These results showed that tea plants might improve drought resistance by inhibiting the accumulation of synthases related to lignin, flavonoids and long-chain fatty acids. The proteomic spectrum of tea plants provides a scientific basis for studying the pathways related to lignin, flavonoid and long-chain fatty acid metabolism in response to drought stress.

Blue light extensively regulates multiple physiological processes and secondary metabolism of plants. Although blue light quantity (fluence rate) is important for plant life, few studies have focused on the effects of different blue light intensity on plant secondary metabolism regulation, including tea plants. Here, we performed transcriptomic and metabolomic analyses of young tea shoots (one bud and two leaves) under three levels of supplemental blue light, including low-intensity blue light (LBL, 50 μmol m–2 s–1), medium-intensity blue light (MBL, 100 μmol m–2 s–1), and high-intensity blue light (HBL, 200 μmol m–2 s–1). The total number of differentially expressed genes (DEGs) in LBL, MBL and HBL was 1, 7 and 1097, respectively, indicating that high-intensity blue light comprehensively affects the transcription of tea plants. These DEGs were primarily annotated to the pathways of photosynthesis, lipid metabolism and flavonoid synthesis. In addition, the most abundant transcription factor (TF) families in DEGs were bHLH and MYB, which have been shown to be widely involved in the regulation of plant flavonoids. The significantly changed metabolites that we detected contained 15 lipids and 6 flavonoid components. Further weighted gene co-expression network analysis (WGCNA) indicated that CsMYB (TEA001045) may be a hub gene for the regulation of lipid and flavonoid metabolism by blue light. Our results may help to establish a foundation for future research investigating the regulation of woody plants by blue light.

Emerging evidence suggests that dietary-derived flavonoids have the potential to improve human memory and neuro-cognitive performance via their ability to protect vulnerable neurons, enhance existing neuronal function and stimulate neuronal regeneration. Long-term potentiation (LTP) is widely considered to be one of the major mechanisms underlying memory acquisition, consolidation and storage in the brain and is known to be controlled at the molecular level by the activation of a number of neuronal signalling pathways. These pathways include the phosphatidylinositol-3 kinase/protein kinase B/Akt (Akt), protein kinase C, protein kinase A, Ca–calmodulin kinase and mitogen-activated protein kinase pathways. Growing evidence suggests that flavonoids exert effects on LTP, and consequently memory and cognitive performance, through their interactions with these signalling pathways. Of particular interest is the ability of flavonoids to activate the extracellular signal-regulated kinase and the Akt signalling pathways leading to the activation of the cAMP-response element-binding protein, a transcription factor responsible for increasing the expression of a number of neurotrophins important in LTP and long-term memory. One such neurotrophin is brain-derived neurotrophic factor, which is known to be crucial in controlling synapse growth, in promoting an increase in dendritic spine density and in enhancing synaptic receptor density. The present review explores the potential of flavonoids and their metabolite forms to promote memory and learning through their interactions with neuronal signalling pathways pivotal in controlling LTP and memory in human subjects.

Polar transport of the plant hormone auxin controls many aspects of plant growth and development. A number of synthetic compounds have been shown to block the process of auxin transport by inhibition of the auxin efflux carrier complex. These synthetic auxin transport inhibitors may act by mimicking endogenous molecules. Flavonoids, a class of secondary plant metabolic compounds, have been suggested to be auxin transport inhibitors based on their in vitro activity. The hypothesis that flavonoids regulate auxin transport in vivo was tested in Arabidopsis by comparing wild-type (WT) and transparent testa (tt4) plants with a mutation in the gene encoding the first enzyme in flavonoid biosynthesis, chalcone synthase. In a comparison between tt4 and WT plants, phenotypic differences were observed, including three times as many secondary inflorescence stems, reduced plant height, decreased stem diameter, and increased secondary root development. Growth of WT Arabidopsis plants on naringenin, a biosynthetic precursor to those flavonoids with auxin transport inhibitor activity in vitro, leads to a reduction in root growth and gravitropism, similar to the effects of synthetic auxin transport inhibitors. Analyses of auxin transport in the inflorescence and hypocotyl of independent tt4 alleles indicate that auxin transport is elevated in plants with a tt4 mutation. In hypocotyls of tt4, this elevated transport is reversed when flavonoids are synthesized by growth of plants on the flavonoid precursor, naringenin. These results are consistent with a role for flavonoids as endogenous regulators of auxin transport.

Dietary Reference Intake (DRI) values exist for vitamins and minerals, and provide a guideline on the optimal dose range to avoid deficiency and prevent toxicity. Polyphenols are widely distributed in plant foods, and have been linked to improved human health through reduced risk of chronic diseases, especially cardiovascular. Although they do not cause classical deficiencies, recently they have been discussed as ‘lifespan essentials because they are needed to achieve a full lifespan by reducing the risk of a range of chronic diseases. A recent meta analysis shows promising actions of polyphenols from cocoa, soya and tea on flow mediated dilation, blood pressure and LDL cholesterol. Many epidemiological studies support the action of polyphenols or polyphenol-rich foods on health, but there are still many gaps in our knowledge. More adequately powered, randomised, placebo controlled human studies are needed on polyphenols. There is a large number of structurally different polyphenols which are relevant for health, and obtaining enough information to set a DRI for each of these will not be feasible in the foreseeable future. A new approach is needed, and a new way of thinking, which would apply not only to polyphenols but also to other phytochemicals. Today, a target intake value of polyphenols as ‘lifespan essentials’ needs to be based on the amount of polyphenols in ‘5-a-day’. We are heading in the right direction towards a DRI, but bioavailability and dose-effects, including toxic levels, need to be established before DRIs can be considered.

Flavonoids are natural polyphenolic compounds present in a wide spectrum of plants that have a beneficial effect on human health. In the context of cardiovascular diseases related to plaque and thrombus formation, flavonoids exhibit an anti-aggregatory effect. Previously, it has been reported that all tested flavonoids exhibit an antiaggregatory effect on platelet aggregation when measured by impedance aggregometry on whole blood, in the test of aggregation induced by adenosine diphosphate (ADP). As not all flavonoids have the same targets within signaling pathways, an assumption of a common non-specific mechanism related to lipophilicity is to be considered. To test this hypothesis, reverse-phase thin layer chromatography was used to assess the lipophilicity of flavonoids; impedance aggregometry was used for testing of platelet aggregation and flow cytometry to monitor the influence of flavonoids on platelet activation. Lipophilicity analysis showed a highly negative correlation of log and for groups of flavones and flavanones. As determined by flow cytometry, the exposition of receptors necessary for the promotion of platelet activation and primary clot formation was diminished, ., lowered expression of the activated form of integrin αIIbβ3 was observed in the presence of flavanone. Platelet membrane stabilization by flavonoids as a mechanism of antiaggregatory effect has been supported by impedance aggregometry experiments when specific inhibitors of platelet aggregation signaling pathways (U73122, indomethacin, verapamil) were used in the presence of a weak (ADP) and a strong (TRAP-6) agonist of aggregation. While individual flavonoids can have specific targets within aggregation signaling pathways, all flavonoids share a common non-specific mechanism of platelet aggregation inhibition related to their lipophilicity and membrane stabilization that, to some extent, contributes to their antiaggregatory effect.

A quantitative structure – antioxidant activity relationship (QSAR) study of 36 flavonoids was performed using the partial least squares projection of latent structures (PLS) method. The chemical structures of the flavonoids have been characterized by constitutional descriptors, two-dimensional topological and connectivity indices. Our PLS model gave a proper description and a suitable prediction of the antioxidant activities of a diverse set of flavonoids having clustering tendency.