类黄酮化合物在植物胁迫反应中作用的研究进展

植物胁迫发生时,一个明显的特征是在植物器官中积累红色与紫色类黄酮化合物。文章讨论了类黄酮化合物在植物胁迫保护中作用,如类黄酮化合物在抗植物UV—B辐射、抗病性以及铝毒害耐性等多方面的作用,也讨论了植物受胁迫时类黄酮积累的分子基础。     

Characterization of the induction and cellular role of the BaeSR two-component envelope stress response of Escherichia coli

The bacterial cell envelope is the interface between a bacterium and its environment and is constantly exposed to environmental changes. The BaeSR two-component system regulates one of six envelope stress responses in Escherichia coli and is induced by spheroplasting, overexpression of the pilin subunit PapG, and exposure to indole. The known BaeR regulon is small, consisting of eight genes, mdtABCD-baeSR, acrD, and spy, two of which encode the BaeSR two-component system itself. In this study, we investigated the molecular nature of the BaeS-inducing cue and the cellular role of the BaeSR envelope stress response. We demonstrated that at least two flavonoids and sodium tungstate are novel inducers of the BaeSR response. Interestingly, flavonoids and sodium tungstate led to much stronger induction of the BaeSR response in an mdtA efflux pump mutant, while indole did not. These findings are consistent with the hypothesis that flavonoids and sodium tungstate are natural substrates of the MdtABC efflux pump. Indole has recently been implicated in cell-cell signaling and biofilm repression through a putative interaction with the LuxR homologue SdiA. Using genetic analyses, we found that induction of the BaeSR response by indole occurs via a pathway separate from the SdiA biofilm pathway. Further, we demonstrated that the BaeSR response does not influence biofilm formation, nor is it involved in indole-mediated inhibition of biofilm formation. We hypothesize that the main function of the Bae response is to upregulate efflux pump expression in response to specific envelope-damaging agents.     

干旱胁迫对紫花苜蓿黄酮类化合物含量及其合成途径关键酶活性的影响

以3个紫花苜蓿(Medicago sativa)品种为试验材料,利用不同浓度(0、5%、10%、15％、20%、25%)的PEG 6000溶液模拟干旱胁迫,探究干旱胁迫对不同品种紫花苜蓿黄酮类化合物合成上游3个关键酶活性以及黄酮类化合物含量的影响。结果表明：(1)随着PEG 6000胁迫浓度的增加,3种紫花苜蓿叶片中PAL(苯丙氨酸解氨酶)、C4H(肉桂酸 4 羟基化酶)和4CL(4 香豆酸辅酶A连接酶)活性均呈先升高后降低的趋势,但不同酶类之间响应存在差异,即PAL活性在10% PEG 6000胁迫浓度下最高,C4H和4CL活性则在15% PEG 6000胁迫浓度下最高,且均显著高于相应对照。(2)3种紫花苜蓿植株地上部总黄酮含量和8种黄酮类化合物含量均随着PEG 6000胁迫浓度的增加呈先上升后下降的趋势,且均在10%~15% PEG 6000胁迫浓度时达到最高值,并显著高于相应对照。(3)各品种紫花苜蓿叶片黄酮类化合物含量与其关键酶活性呈不同程度的相关性,即紫花苜蓿黄酮类化合物合成途径上游3个关键酶活性与其地上部黄酮类化合物含量存在密切的关系。研究认为,不同程度的干旱胁迫可以通过促进黄酮类化合物合成途径上游关键酶活性的变化来调节紫花苜蓿植株中黄酮类化合物的合成,且适度干旱胁迫能显著促进相关酶活性增强和黄酮类化合物含量增加。     

Flavonoids of Inula britannica protect cultured cortical cells from necrotic cell death induced by glutamate

We previously reported 12 antioxidative flavonoids isolated from the n-BuOH extract of Inula britannica (Asteraceae). This prompted us to investigate further whether these flavonoids also showed antioxidative activity upon live cells grown in a culture system. Among the 12 flavonoids tested, only patuletin, nepetin, and axillarin protected primary cultures of rat cortical cells from oxidative stress induced by glutamate. These flavonoids exerted significant neuroprotective activity when they were administered either before or after the glutamate insult. Treatment with these flavonoids maintained the activities of such antioxidant enzymes as catalase, glutathione-peroxidase, and glutathione reductase, all of which play important roles in the antioxidative defense mechanism. Moreover, these three flavonoids also attenuated significant drops in glutathione induced by glutamate which is a routine concomitant of oxidative stress by inhibiting glutathione diminution. Accordingly, these flavonoids did not stimulate the synthesis of glutathione. With regard to structure-activity relationships, our results indicated that the 6-methoxyl group in the A ring and the 3', 4'-hydroxyl groups in the B ring are crucial for the protection against the oxidative stress; glycosylation greatly reduced their protective activities. Collectively, these results indicated that patuletin, nepetin, and axillarin strongly protect primary cultured neurons against glutamate-induced oxidative stress.     

Flavonoids, but not protein kinase C inhibitors, prevent stress protein synthesis during erythrophagocytosis.

Erythrophagocytosis induces in monocytes-macrophages the synthesis of stress proteins including the classical heat shock proteins (HSPs) and heme oxygenase (HO). To evaluate the role of oxygen radicals in this induction, we used the antioxidant flavonoids quercetin and kaempferol. These compounds inhibited HSP and HO synthesis, the latter being more sensitive. Quercetin and kaempferol also are inhibitors of protein kinase C (PKC). In order to determine whether inhibition of stress protein synthesis by flavonoids was mediated by their antioxidant properties or by PKC inhibition, we also tested more specific PKC antagonists, staurosporine and H-7. Staurosporine (SS) and H-7 decreased the synthesis of HSP70 and HSP83 but had no effect on HO. These data suggest that (1) erythrophagocytosis-related oxygen radicals are involved in the induction of the stress response in phagocytic cells, (2) the induction of HSPs and HO is differentially regulated, and (3) the effects of flavonoids on HO are linked to their scavenging activity rather than to PKC modulation.     

A chemical complementation approach reveals genes and interactions of flavonoids with other pathways

In addition to the classical functions of flavonoids in the response to biotic/abiotic stress conditions, these phenolic compounds have been implicated in the modulation of various developmental processes. These findings suggest that flavonoids are more integral components of the plant signaling machinery than traditionally recognized. To understand how flux through the flavonoid pathway affects plant cellular processes, we used wild‐type and chalcone isomerase mutant (transparent testa 5, tt5) seedlings grown under anthocyanin inductive conditions, in the presence or absence of the flavonoid intermediate naringenin, the product of the chalcone isomerase enzyme. Because flavonoid biosynthetic genes are expressed under anthocyanin inductive conditions regardless of whether anthocyanins are formed or not, this system provides an excellent opportunity to specifically investigate the molecular changes associated with increased flux through the flavonoid pathway. By assessing genome‐wide mRNA accumulation changes in naringenin‐treated and untreated tt5 and wild‐type seedlings, we identified a flavonoid‐responsive gene set associated with cellular trafficking, stress responses and cellular signaling. Jasmonate biosynthetic genes were highly represented among the signaling pathways induced by increased flux through the flavonoid pathway. In contrast to studies showing a role for flavonoids in the control of auxin transport, no effect on auxin‐responsive genes was observed. Taken together, our data suggest that Arabidopsis can sense flavonoids as a signal for multiple fundamental cellular processes.     

The biosynthesis of flavonoids is enhanced similarly by UV radiation and root zone salinity in L. vulgare leaves

Flavonoids have recently been suggested to have the potential to serve as antioxidants other than effective UV attenuators in photoprotection. Here, we tested the hypothesis that flavonoids accumulate in response to “excess light” in the presence or in the absence of UV radiation. In a UV exclusion experiment, we grew Ligustrum vulgare plants outdoors under 30% or 100% sunlight irradiance, by cutting-off the whole UV waveband. These plants were also exposed to UV irradiance or supplied with 125 mM NaCl at the root zone. Leaves of plants under 100% sunlight irradiance suffered from excess light, which was exacerbated greatly by root zone salinity stress. Salinity stress repressed the activities of antioxidant enzymes, particularly in full sunlight, and led to severe leaf oxidative damage. Dihydroxy B-ring-substituted flavonoids, namely quercetin 3-O- and luteolin 7-O-glycosides, accumulated steeply in response to sunlight irradiance in the absence of UV radiation. UV radiation and root zone NaCl increased, to a similar degree, the concentration of these flavonoids, which have a great potential to scavenge various forms of reactive oxygen. Treatment-induced changes in leaf phenylpropanoid concentration affected antioxidant activities to a greater extent than the UV-screening capacities of leaf extracts. Early responses to an abrupt increase in sunlight irradiance included a steep increase in the concentrations of quercetin derivatives and cyanidin 3-O-glucoside, with the latter negligibly absorbing in the UV-spectral region. In contrast, effective UV attenuators, such as hydroxycinnamates and monohydroxy B-ring flavonoids, were unresponsive to the light treatments. Overall, these findings lead to the hypothesis that flavonoids may have an important antioxidant function in photoprotection. This hypothesis is further corroborated by the large distribution of quercetin and luteolin derivatives in the vacuoles of mesophyll, not only in the corresponding compartments of epidermal cells, but also in full sunlight-treated leaves in the absence of UV radiation. Future experiments aimed at evaluating the relative contribution of flavonoids within the complex antioxidant defense systems operating in the leaf are needed to help conclusively address the relevance of their antioxidant functions in photoprotection.     

Arabidopsis Flavonoid Mutants Are Hypersensitive to UV-B Irradiation

Increases in the terrestrial levels of ultraviolet-B (UV-B) radiation (280 to 320 nm) due to diminished stratospheric ozone have prompted an investigation of the protective mechanisms that contribute to UV-B tolerance in plants. In response to UV-B stress, flowering plants produce a variety of UV-absorptive secondary products derived from phenylalanine. Arabidopsis mutants with defects in the synthesis of these compounds were tested for UV-B sensitivity. The transparent testa-4 (tt4) mutant, which has reduced flavonoids and normal levels of sinapate esters, is more sensitive to UV-B than the wild type when grown under high UV-B irradiance. The tt5 and tt6 mutants, which have reduced levels of UV-absorptive leaf flavonoids and the monocyclic sinapic acid ester phenolic compounds, are highly sensitive to the damaging effects of UV-B radiation. These results demonstrate that both flavonoids and other phenolic compounds play important roles in vivo in plant UV-B protection.     

Flavonoid Dihydroquercetin, unlike Quercetin, Fails to Inhibit Expression of Heat Shock Proteins under Conditions of Cellular Stress

Modification by natural flavonoids quercetin and dihydroquercetin of the in vitro cell response to hyperthermal and chemical stress was studied. Quercetin completely inhibited the synthesis and intracellular accumulation of 70-kD heat shock protein (HSP70) in response to hyperthermia or to treatment with sodium arsenite, whereas dihydroquercetin in the same or higher doses had no such effect. Stress exposures under conditions of the quercetin-inhibited HSP70 expression significantly increased the percentage of dead and damaged cells compared to the same exposures in the absence of quercetin. On the contrary, dihydroquercetin virtually failed to increase the damage and death of the stress-exposed cells which displayed typical induction of HSP70. The findings suggest a new strategy for pharmacological use of these flavonoids with similar structure.     

Clone-specific responses in leaf phenolics of willows exposed to enhanced UVB radiation and drought stress

The effects of enhanced UVB radiation and drought stress on willow secondary phenolics were studied using the leaves of 8‐week‐old micropropagated plantlets from interspecific hybrids (Salix myrsinites L. ×S. myrsinifolia Salisb.) and pure species (S. myrsinifolia). The plantlets were subjected for 4 weeks to two levels of UVB radiation (ambient, enhanced) and two levels of watering (well‐watered, drought‐stressed) according to a 2 × 2 factorial design. Enhanced UVB radiation increased the total concentration of flavonoids and phenolic acids in all plantlets, while the total concentration of salicylates remained unaffected. Drought stress reduced the total concentration of salicylates and phenolic acids in S. myrsinifolia plantlets, while in hybrids only phenolic acids were affected. The response of phenolic acids to enhanced UVB in drought‐stressed plantlets was different from that in well‐watered ones, indicating that drought stress limited the accumulation of phenolic acids under enhanced UVB radiation. Flavonoids increased in response to enhanced UVB radiation in drought‐stressed plantlets, although drought caused serious physiological stress on growth. There were significant differences between hybrid and S. myrsinifolia plantlets with respect to the composition of phenolics and between families and clones with respect to their concentration. In addition, the response of salicylates, flavonoids and phenolic acids to enhanced UVB and drought stress was clone‐specific, which may indicate that climatic changes will alter the genetic composition of northern forests.     

Callus and cell suspension culture of <Emphasis Type="Italic">Viola odorata</Emphasis> as in vitro production platforms of known and novel cyclotides

Callus from Opuntia streptacantha (cv. Tuna loca), Opuntia megacantha (cv. Rubí reina), and Opuntia ficus-indica (cv. Rojo vigor) were exposed to jasmonic acid (JA) and abiotic stress (drought and UV light) to improve the metabolite production. The callus growth curves, phenolic acids and flavonoids content, antioxidant activity and phenylalanine ammonia lyase (PAL) activity were analyzed under normal and stress conditions. In O. streptacantha callus, the phenolics concentration increased 1.6 to 3 times times in presence of 5% PEG or after irradiation with UV light for 240 min, respectively, while flavonoids triplicate with UV light. A significant increase in antioxidant activity was observed in calli from the three Opuntia species in media with 50 µM JA. The relationships between metabolites/PAL activity, and metabolites/antioxidant activity were analyzed using a surface response methodology. Results showed that PAL activity, induced with PEG and UV, correlated with flavonoids content in O. megacantha and O. ficus-indica calli; PAL activity was related to both flavonoids and phenolics compounds in O. ficus-indica and O. megacantha calli exposed to JA, but only to flavonoids in O. streptacantha callus. In general, the JA stimulated simultaneously the metabolic pathways for phenolics and flavonoids synthesis, while abiotic stress induced mainly flavonoids route. As the stressed Opuntia calli exhibited as high antioxidant activity as cladodes, they are a promising system for research on antioxidant biosynthesis and/or to identify new compounds with antioxidant properties.     

A comprehensive systematic review of the therapeutic effects and mechanisms of action of quercetin in sepsis

BackgroundSepsis is a life-threatening condition caused by a dysregulated host response to infection. Several studies have indicated that flavonoids exhibit a wide variety of biological actions including free radical scavenging and antioxidant activities. Quercetin, one of the most extensively distributed flavonoids in the vegetables and fruits, presents various biological activities including modulation of oxidative stress, anti-infectious, anti-inflammatory, and neuroprotective activities.MethodsThe present systematic review was conducted according to the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statements. We searched Web of Sciences, Google Scholar, PubMed, Scopus, and Embase databases up to February 2021 by using the relevant keywords.ResultsOut of 672 records screened, 35 articles met the study criteria. The evidence reviewed here indicates that quercetin supplementation may exert beneficial effects on sepsis by attenuating inflammation and oxidative stress, downregulating the mRNA expression of toll-like receptors (TLRs), modulating the immune response, and alleviating sepsis-related organ dysfunctions.ConclusionDue to the promising therapeutic effects of quercetin on sepsis complications and the lack of clinical trials in this regard, future human randomized clinical trials are warranted.     

Effects of uptake of flavonoids on oxidative stress induced by hydrogen peroxide in human intestinal Caco-2 cells

The relation between the uptake of flavonoids and the response of human colon adenocarcinoma Caco-2 cells exposed to oxidative stress induced by hydrogen peroxide (H(2)O(2)) was examined. Flavonoid aglycones were incorporated into Caco-2 cells in a concentration- and time-dependent manner, but neither glycosides nor unstable myricetin were incorporated into the cells. The incorporated flavonoids reduced the reactive oxygen species (ROS) induced by H(2)O(2) in the cells in proportion to the amount incorporated and the radical scavenging activity of flavonoids. But, flavonoids with high radical scavenging activity also generated H(2)O(2). The activity decreasing intracellular ROS was inversely related to the H(2)O(2) scavenging activity of flavonoids. Therefore, the decrease in the amount of intracellular ROS induced by H(2)O(2) was not directly due to the scavenging of H(2)O(2), but rather to the scavenging of ROS generated from H(2)O(2). These results suggest that strong antioxidative flavonoids have both a cytoprotective effect owing to the scavenging of ROS and cytotoxic effect caused by the generation of H(2)O(2).     

Significance of flavonoids in plant resistance and enhancement of their biosynthesis

The roles of flavonoids in plant defence against pathogens, herbivores, and environmental stress are reviewed and their significant contribution to plant resistance is discussed. The induction of flavonoids is of particular interest for gathering evidence of their roles. Tools are mentioned which may enhance flavonoid biosynthesis and accumulation. These include metabolic engineering and UV light. The induction of defence-related flavonoids is modified by other determining factors and competition between growth and secondary metabolism may exist. In an evolutionary context, stress-related oxidative pressure may have been a major trigger for the distribution and abundance of flavonoids. UV protection is one of their most significant, or even the most significant, functional role for flavonoids. The multi-functionality of these compounds, however, often complicates the interpretation of experimental results but, overall, it supports the importance of flavonoids.     

Regulation, evolution, and functionality of flavonoids in cereal crops

Flavonoids are plant secondary metabolites that contribute to the adaptation of plants to environmental stresses, including resistance to abiotic and biotic stress. Flavonoids are also beneficial for human health and depress the progression of some chronic diseases. The biosynthesis of flavonoids, which belong to a large family of phenolic compounds, is a complex metabolic process with many pathways that produce different metabolites, controlled by key enzymes. There is limited knowledge about the composition, biosynthesis and regulation of flavonoids in cereals. Improved understanding of the accumulation of flavonoids in cereal grains would help to improve human nutrition through these staple foods. The biosynthesis of flavonoids, scope for altering the flavonoid composition in cereal crops and benefits for human nutrition are reviewed here.     

Influence of metal ions on flavonoid protection against asbestos-induced cell injury

Influence of metal ions (Fe2+, Fe3+, Cu2+, Zn2+) on the protective effect of rutin, dihydroquercetin, and green tea epicatechins against in vitro asbestos-induced cell injury was studied. Metals have been found to increase the capacity of rutin and dihydroquercetin to protect peritoneal macrophages against chrysotile asbestos-induced injury. The data presented here show that this effect is due to the formation of flavonoid metal complexes, which turned out to be more effective radical scavengers than uncomplexed flavonoids. At the same time epicatechins and their metal complexes have similar antiradical properties and protective capacities against the asbestos induced injury of macrophages. Metal complexes of all flavonoids were found to be considerably more potent than parent flavonoids in protecting red blood cells against asbestos-induced injury. It was also found that the metal complexes of all flavonoids were absorbed by chrysotile asbestos fibers considerably better than uncomplexed compounds and probably for this reason flavonoid metal complexes have better protective properties against asbestos induced hemolysis. Thus, the results of the present study show that flavonoid metal complexes may be effective therapy for the inflammatory response associated with the inhalation of asbestos fiber. The advantage of their application could be the strong increase in ROS scavenging by flavonoids and finally a better cell protection under the conditions of cellular oxidative stress.     

Common regulatory themes in meristem development and whole-plant homeostasis

The maintenance of meristems throughout plant ontogeny allows the development of a diversity of structural forms from the same genetic base. Examination of the common and contrasting features of these meristems leads to the outline of common regulatory themes in meristem development. In particular, by including comparisons with embryogenesis research, we see that hormones and factors that are generally attributed roles in stress response, such as redox potential, carotenoids, flavonoids, brassinosteroids, jasmonic acid and ethylene, are emerging as major candidates for long-distance or short-distance signalling molecules in meristem development. In each case, hormone response appears to be influenced greatly by the developmental window or transition stage at which the meristem resides.