Protective effect of total flavonoid C-glycosides from Abrus mollis extract on lipopolysaccharide-induced lipotoxicity in mice

Abrus mollis is a widely used traditional Chinese medicine for treating acute and chronic hepatitis, steatosis, and fibrosis. It was found that the total flavonoid C-glycosides from Abrus mollis extract(AME) showed potent antioxidant, anti-inflammatory, and hepatoprotective activities. To further investigate the hepatoprotective effect of AME and its possible mechanisms, lipopolysaccharide(LPS)-induced liver injury models were applied in the current study. The results indicated that AME significantly attenuated LPS-induced lipid accumulation in mouse primary hepatocytes as measured by triglyceride(TG) and total cholesterol(TC) assays and Oil Red O staining. Meanwhile, AME exerted a protective effect on LPS-induced liver injury as shown by decreased liver index, serum aminotransferase levels, and hepatic lipid accumulation. Real-time PCR and immunoblot data suggested that AME reversed the LPS-mediated lipid metabolism gene expression, such as sterol regulatory element-binding protein-1(SREBP-1), fatty acid synthase(FAS), and acetyl-CoA carboxylase 1(ACC1). In addition, LPS-induced overexpression of activating transcription factor 4(ATF4), X-box-binding protein-1(XBP-1), and C/EBP homologous protein(CHOP) were dramatically reversed by AME. Furthermore, AME also decreased the expression of LPS-enhanced interleukin-6(IL-6) and cyclooxygenase-2(COX-2). Here, it is demonstrated for the first time that AME ameliorated LPS-induced hepatic lipid accumulation and that this effect of AME can be attributed to its modulation of hepatic de novo fatty acid synthesis. This study also suggested that the hepatoprotective effect of AME may be related to its down-regulation of unfolded protein response(UPR) activation.

Anti-inflammatory and hepatoprotective effects of total flavonoid C-glycosides from Abrus mollis extracts

The aim of this study was to evaluate the anti-inflammatory and hepatoprotective effects of the total flavonoid C-glycosides isolated from Abrus mollis extracts(AME). In the anti-inflammatory tests, xylene-induced ear edema model in mice and carrageenan-induced paw edema model in rats were applied. The hepatoprotective effects of AME were evaluated with various in vivo models of acute and chronic liver injury, including carbon tetrachloride(CCl4)-induced hepatitis in mice, D-galactosamine(D-GalN)-induced hepatitis in rats, as well as CCl4-induced hepatic fibrosis in rats. In the acute inflammation experiment, AME significantly suppressed xylene-induced ear edema and carrageenan-induced paw edema, respectively. In the acute hepatitis tests, AME significantly attenuated the excessive release of ALT and AST induced by CCl4 and D-GalN. In CCl4-induced hepatic fibrosis model, AME alleviated liver injury induced by CCl4 shown by histopathological sections of livers and improved liver function as indicated by decreased liver index, serum ALT, AST, TBIL, and ALP levels and hydroxyproline contents in liver tissues, and increased serum ALB and GLU levels. These results indicated that AME possesses potent anti-inflammatory activity in acute inflammation models and hepatoprotective activity in both acute and chronic liver injury models. In conclusion, AME is a potential anti-inflammatory and hepatoprotective agent and a viable candidate for treating inflammation, hepatitis, and hepatic fibrosis.

Flavonoid C-glycosides from the seeds of Hovenia dulcis Thunb.

Ten known flavonoid C-glycosides identified as 2′′-O-β-D-glucopyranosyl isovitexin(1),spinosin(2),6′′′-acetyl spinosin(3),6′′′-p-hydroxycinnamoyl-2′′O-β-D-glucopyranosyl isovitexin(4),6′′′-p-hydroxy-cinnamoyl spinosin(5),6′′′-(E)-feruloyl O-β-Dglucopyranosyl isovitexin(6),isospinosin(7),isovitexin(8),swertisin(9),swertiajaponin(10)were purified from the seeds of Hovenia dulcis Thunb.Their structures were confirmed by spectroscopic data analysis and comparison with previous literature.All compounds were obtained from H.dulcis for the first time.

Duplicated chalcone synthase(CHS)genes modulate flavonoid production in tea plants in response to light stress

In tea plants,the abundant flavonoid compounds are responsible for the health benefits for the human body and define the astringent flavor profile.While the downstream mechanisms of flavonoid biosynthesis have been extensively studied,the role of chalcone synthase(CHS)in this secondary metabolic process in tea plants remains less clear.In this study,we compared the evolutionary profile of the flavonoid metabolism pathway and discovered that gene duplication of CHS occurred in tea plants.We identified three CsCHS genes,along with a CsCHS-like gene,as potential candidates for further functional investigation.Unlike the CsCHS-like gene,the CsCHS genes effectively restored flavonoid production in Arabidopsis chs-mutants.Additionally,CsCHS transgenic tobacco plants exhibited higher flavonoid compound accumulation compared to their wild-type counterparts.Most notably,our examination of promoter and gene expression levels for the selected CHS genes revealed distinct responses to UV-B stress in tea plants.Our findings suggest that environmental factors such as UV-B exposure could have been the key drivers behind the gene duplication events in CHS.

Quantification of Total Phenols, Total Flavonoids, Total Anthocyanins and Evaluation of Antioxidant and Antiradical Activities of Detarium Senegalense Extracts from Chad

The aim of the present work is to assess the value of Detarium Senegalense by determining the content of total phenols, total flavonoids and total anthocyanins, and by evaluating the free radical scavenging activity of Detarium Senegalense extracts. For this purpose, sequential extraction using solvents of increasing polarity was essential. The various extracts obtained underwent phytochemical and biochemical analyses. Phytochemical screening revealed the presence of flavonoids, alkaloids, tannins, polyphenols, anthocyanins and steroids/terpenes. Quantitative analysis of total polyphenols, total flavonoids and total anthocyanins yielded the following results: total flavonoids (0.803 ± 0029 mg EQ/100g P for acetone extract of roots and 0.871 ± 0.401 mg EQ/100g P for methanol extract of leaves);total polyphenols (23.298 ± 12.68 mg EAG/100g P for acetone extract of roots and 24.69 ± 0.49 401 mg EAG/100g P for methanol extract of leaves);total monomeric anthocyanins (44.697 ± 0.939 mg EC3G/100g P and 16.699 ± 0.193 mg EC3G/100g P respectively for acetone and methanol extracts of stem bark). DPPH free radical scavenging activity was 1.674 ± 0.023 mg/mL for the acetone extract and 0.934 ± 0.24 mg/mL for the methanol extract of roots. .

Antiglycating effects of citrus flavonoids and associated mechanisms

Glycation of proteins and DNA forms advanced glycation end products(AGEs)causing cell and tissue dysfunction and subsequent various chronic diseases,in particular,metabolic and age-related diseases.Targeted AGE inhibition includes scavengers of reactive carbonyl species(RCS)such as methylglyoxal(MG),glyoxalase-1 enhancers,Nrf2/ARE pathway activators,AGE/RAGE formation inhibitors and other antiglycatng agents.Citrus flavonoids have demonstrated antioxidant and anti-inflammatory effects and are also found to be effective antiglycating agents.Herein,we reviewed the up to date progress of the antiglycation effects of citrus flavonoids and associated mechanisms.Major citrus flavonoids,hesperedin and its aglycone,hesperetin,inhibited glycation by scavenging MG forming mono-or di-flavonoid adducts with MG,enhanced the activity of glyoxase-1,activated Akt/Nrf2 signal pathway while inhibiting AGE/RAGE/NF-κB pathway,reduced the formation of Nε-(carboxylmethyl)lysine(CML)and pentosidine,inhibited aldol reductase activity and decreased the levels of fructosamine.The antiglycating activity and mechanisms of other flavonoids was also summarized in this review.In conclusion,citrus flavonoids possess effective antiglycating activity via different mechanisms,yet there are many challenging questions remaining to be studied in the near future such as in vivo testing and human study of citrus flavonoids for efficacy,effectiveness and adverse effects of citrus flavonoids as a functional food in managing high levels of AGEs and controlling AGE-induced chronic diseases,diabetic complications in particular.

Transcriptome Sequencing for Sugar and Flavonoid Metabolism in Prunus persica‘Jinxiangyu’

In this study,high performance liquid chromatography(HPLC)and RNA-seq transcriptome sequencing were used to study the changes in soluble sugar components and flavonoids in Prunus persica‘Jinxiangyu’at different developmental stages(20–90 d after flowering)and screen the key genes regulating the formation of soluble sugar and flavonoids in the fruits.The results showed that 60–85 d after flowering was the key stage of quality formation of Prunus persica‘Jinxiangyu’,and the content of soluble sugar,soluble solid,fructose,and sucrose in the fruit increased significantly during this period.The sugar content of ripe fruits was mainly fructose and sucrose.The content of kaempferol glycoside was low in the fruit.Quercetin glycoside content was higher in the young fruit stage and decreased with fruit maturity.There were no anthocyanin compounds in the fruit.The expression levels of genes involved in flavonoid metabolism(ANS,DFR,F3H,FLS,4CL1,etc.)were low in the fruit.A total of 181 differentially expressed genes were identified during fruit development to participate in five sugar metabolism pathways,among which the SDH gene had a higher expression level,which continuously rised in the later stage of fruit development.It mainly promoted the accumulation of fructose content in the later stage of fruit development.The expression levels of SPS1,SS,and SS1 genes were continuously up-regulated,which played a key role in sucrose regulation.The higher expression levels of SUS3 and INVA genes in the early stage of fruit development promoted the degradation of sucrose.

Analysis of Lavandulyl Flavonoids from Sophora flavescens with Antiinflammatory Activity Based on Molecular Network Technology

[Objectives]This study was conducted to screen lavandulyl flavonoids with anti-inflammatory activity from Sophora flavescens.[Methods]35 compounds were screened from traditional Chinese medicine S.flavescens using the nitric oxide(NO)anti-inflammatory activity model.[Results]Five components,8(xanthohumol),13(kurarinol),27(4-methoxysalicylic acid),28(b-resorcic acid)and 30(b-resorcic acid),exhibited significant anti-inflammatory activity,with IC 50 values of 5.99,4.76,6.96,3.41 and 5.22μM,respectively.Especially,8(xanthohumol)and 13(kurarinol)were typical lavandulyl flavonoids in S.flavescens,which were worth further exploration.Furthermore,UPLC-Q-Exactive and GNPS molecular networking technique were used for rapid analysis of lavandulyl flavonoids from S.flavescens.A total of 15 components were identified.[Conclusions]This work lays a theoretical foundation for further separation and analysis of lavandulyl flavonoids with anti-inflammatory activity from S.flavescens.

Research Progress of Deep Eutectic Solvents in Extraction of Plant Flavonoids

As a new type of green solvents,deep eutectic solvents(DESs)have the advantages of strong extraction ability,designability,simple preparation,low price,recoverability and biodegradation,and show great application potential in the field of plant flavonoid extraction.In this paper,the definition,classification and preparation methods of DESs were introduced.The effects of DES composition,molar ratio of DES components,water content of DES systems,liquid-material ratio,extraction temperature,extraction time and extraction auxiliary techniques on the extraction yield of plant flavonoids were expounded.The recycling methods of DESs were summarized.Existing problems of DESs in the field of plant flavonoids extraction were pointed out,and further research direction and trend were analyzed and prospected.

Optimization of Extraction Process for Total Flavonoids from Penthorum chinense Pursh and Comparison of Their Contents from Different Parts

[Objectives]This study was conducted to optimize the extraction process of total flavonoids from Penthorum chinense Pursh and compare their contents from different parts.[Methods]Single factor and orthogonal experiments were designed to optimize the extraction process of total flavonoids from P.chinense Pursh with the volume fraction of ethanol,the ratio of material to liquid,heating reflux extraction time and extraction times as factors,and the content of total flavonoids as the index.A verification test was carried out.The optimized extraction process was adopted to compare the contents of total flavonoids from different parts of P.chinense Pursh.[Results]The best extraction process was extracting the powder of P.chinense Pursh for 2.0 h with 20 times of 55%ethanol by reflux twice.Under this condition,the contents of total flavonoids were 3.63%,8.90%,11.28%,and 4.36%from stems,leaves,flowers and whole grass of P.chinense Pursh,respectively.[Conclusions]The process is reasonable,feasible and stable,and can effectively extract total flavonoids from P.chinense Pursh.The contents of total flavonoids from different parts of P.chinense Pursh were quite different,and the value was higher in the leaves and flowers,so the proportions of leaves and flowers should be paid attention to in the industrial processing of P.chinense Pursh.

The Protective Effects of Flavonoids from Scutellaria Baicalensis Georgi Stems and Leaves on Oligodendrocyte Damage Induced by Aβ1-42

Aim: This study aimed to investigate the protective effects of flavonoids from the stem and leaves of Scutellaria baicalensis Georgi (SSFs) against Aβ1-42-induced oligodendrocytes (OL) damage. Methods: Immunofluorescence was used for the detection of myelin-associated glycoprotein (MAG), a characteristic protein of rat oligodendrocytes (OLN-93 cells). To evaluate the potential protective effects of SSFs on OLN-93 cells injured by Aβ1-42, an injury model was established by subjecting OLN-93 cells to Aβ1-42 exposed. Cell morphology was examined using an inverted microscope, while cell viability was assessed using the colorimetric method of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Additionally, lactate dehydrogenase (LDH) was measured using the pyruvic acid reduction assay. The Ginkgo biloba leaf extract (GBE) injection was used as a positive control. Results: A total of >95% of the MAG immunofluorescence-positive cells were identified as oligodendrocytes. Gradually increasing concentrations of SSFs impaired the cells, and the maximum nondetrimental dose for OLN-93 cells was 75 mg/L. This study assessed the effects of SSFs on OLN-93 cells damaged by Aβ1-42. The results indicated that SSFs significantly improved OLN-93 cell morphological abnormal changes, increased the OLN-93 cell survival rate, and reduced LDH release. Conclusion: SSFs can alleviate Aβ1-42-induced damage of OL.

Determination of Total Flavonoids in Acanthopanax senticosus(Rupr. et Maxim.) Harms by Enzymolysis and Its Technological Optimization

In order to optimize the ultrasonic extraction technique for the total flavonoid of leaf yellows plus, the contents of 21 leaf yellows plus total flavonoid from four regions in Heilongjiang Province were comparatively analyzed. The ultrasonic extraction technology was optimized by Box-Behnken response surface method, and the total flavonoid content of 21 kinds of Acanthopanax senticosus(Rupr. et Maxim.) Harms from different producing areas were analyzed by cluster analysis. The optimal process conditions were determined as ultrasonic time 30 min, solid-liquid ratio 1 : 12 and ultrasonic power 250 W, and the average yield of the total flavonoid was 1.453 mg·g^ (-1). By optimizing the ultrasonic-assisted extraction method, the total flavonoid content from different producing areas was compared in the experiment, which provided certain data support for the optimization of the extraction process in the future and laid a certain theoretical foundation for the quality analysis of Chinese medicinal materials.

Inhibitory Effect of Flavonoid Glycosides from Chlorophytum comosum on Nasopharyngeal Carcinoma 5-8F Cells and Its Mechanism

[Objectives]To study the inhibitory activity of two flavonoid glycosides isolated from Chlorophytum comosum Laxum R.Br on human nasopharyngeal carcinoma(NPC)cell line 5-8F in vitro and its mechanism.[Methods]The flavonoid glycosides were isolated and purified from the ethanol alcoholic extract of the roots of Liliaceae plant Chlorophytum comosum by silica gel column chromatography,macroporous resin column chromatography,Sephadex LH-20,and reverse column chromatography(ODS).The inhibitory activity of flavonoid glycosides on human nasopharyngeal carcinoma cells was analyzed by CCK-8 method,and the potential mechanism was preliminarily analyzed by molecular docking.[Results]Two flavonoid glycosides were identified as isovitexin 2″-0-rhamnoside and 7-2″-di-O-β-glucopyranosylisovitexin.Two flavonoid glycosides showed promising inhibitory effect on human nasopharyngeal carcinoma cell line 5-8F,with IC_(50) values of 24.8 and 27.5μmol/L,respectively.Molecular docking results showed that the potential targets of two flavonoid glycosides include CyclinD1,Bcl-2β-Catenin,ILK,TGF-β,in addition,two glycosides showed higher predicted binding affinity towards CyclinD1,which verifies the cytotoxicity of the two compounds on human nasopharyngeal carcinoma cell line 5-8F in vitro.[Conclusions]Two flavonoid glycosides are the active molecules in Chlorophytum comosum that can inhibit the proliferation of human nasopharyngeal carcinoma cells,and have the potential to be used in the research and development of anti nasopharyngeal carcinoma drugs.

Pilot study on the effect of flavonoids on arterial stiffness and oxidative stress in chronic kidney disease

BACKGROUND Flavonoids,the main class of polyphenols,exhibit antioxidant and antihypertensive properties.AIM To prospectively investigate the impact of flavonoids on arterial stiffness in patients with chronic kidney disease(CKD)stagesⅠ-Ⅳ.METHODS In this prospective,single-arm study,CKD patients with arterial hypertension and diabetes mellitus were enrolled.Baseline demographic,clinical,and laboratory variables were recorded.Patients received daily treatment with a phenol-rich dietary supplement for 3 months.Blood pressure,arterial stiffness(carotidfemoral pulse wave velocity,central pulse pressure),and oxidative stress markers(protein carbonyls,total phenolic compound,total antioxidant capacity)were measured at baseline and at study end.RESULTS Sixteen patients(mean age:62.5 years,87.5%male)completed the study.Following intervention,peripheral systolic blood pressure decreased significantly by 14 mmHg(P<0.001).Carotid-femoral pulse wave velocity decreased from 8.9 m/s(baseline)to 8.2 m/s(study end)(P<0.001),and central pulse pressure improved from 59 mmHg to 48 mmHg(P=0.003).Flavonoids also reduced oxidative stress markers including protein carbonyls(P<0.001),total phenolic compound(P=0.001),and total antioxidant capacity(P=0.013).CONCLUSION Flavonoid supplementation in CKD patients shows promise in improving blood pressure,arterial stiffness,and oxidative stress markers.

Determination of total flavonoids content in buckwheat and inhibition of α-amylase activity

Diabetes is one of the most difficult chronic diseases to cure in the world,which seriously affects people’s health and quality of life.Flavonoids in buckwheat can regulate blood glucose levels by inhibitingα-amylase activity.Therefore,sweet buckwheat produced in Inner Mongolia was used as the research object,and buckwheat fl avonoids were extracted by ultrasonic-assisted extraction method.Total fl avonoids content was determined by ultraviolet-visible spectrophotometry.With acarbose as the positive control,the inhibition test ofα-amylase was carried out by DNS colorimetry to study the inhibition behavior of fl avonoids onα-amylase activity.The results showed that the extraction process of flavonoids was stable and reliable,and the established method for the determination of flavonoids was simple,accurate and reproducible.The total flavonoids content of buckwheat samples was 2.706 mg/g,buckwheat total fl avonoids extraction solution had an inhibitory eff ect onα-amylase,and its median inhibition concentration(IC_(50))was 38.53 mg/mL.The results of this experiment provide a technical reference for the development and utilization of fl avonoids in Inner Mongolia sweet buckwheat,and provide a theoretical reference for the development and application of flavonoid-rich hypoglycemic food.

The mechanism of Callistephus chinensis flavonoid compounds in the treatment of diabetes using network pharmacology and molecular docking

The purpose of this project is used for exploring the mechanism of Callistephus chinensis in the treatment of diabetes by network pharmacology and molecular docking methods.The target of Callistephus chinensis was obtained from SwissTargetPrediction database,while the target related to diabetes was obtained from GeneCards and OMIM databases.The target was added in String database to build the protein interaction network.GO biological process enrichment analysis and KEGG pathway enrichment analysis were carried out by Metascape software,then the target-pathway network was constructed.Molecular docking was carried out in Discovery Studio 2016 Client software to verify the binding force of Callistephus chinensis flavonoid compounds with key targets.In this study,10 potential active components were selected from the flavonoid monomer compounds of Callistephus chinensis.1847 biological processes(BP),126 cell compositions(CC)and 256 molecular functions(MF)were obtained by GO enrichment analysis;a total of 194 pathways were involved in KEGG enrichment analysis of 192 cross targets.Network analysis showed that quercetin was the main active component of flavonoids in the treatment of diabetes,AKT1,TNF,VEGFA,EGFR,SRC and other related signals were in relation to the treatment of diabetes.This study showed that Callistephus chinensis flavonoid compounds play a role in the treatment of diabetes by regulating multi-target and multi-pathway.

Mechanism of Rosae Rugosae Flos flavonoids in the treatment of hyperlipidemia and optimization of extraction process based on network pharmacology

This study aims to identify a natural plant chemical with hypolipidemic effects that can be used to treat high cholesterol without adverse reactions.Through network pharmacology screening,it was found that Rosae Rugosae Flos(RF)flavonoids had potential therapeutic effects on hyperlipidemia and its mechanism of action was discussed.TCMSP and GeneCards databases were used to obtain active ingredients and disease targets.Venn diagrams were drawn to illustrate the findings.The interaction network diagram was created using Cytoscape 3.8.0 software.The PPI protein network was constructed using String.GO and KEGG enrichment analysis was performed using Metascape.The results revealed 2 active flavonoid ingredients and 60 potential targets in RF.The key targets,including CCL2,PPARG,and PPARA,were found to play a role in multiple pathways such as the AGE-RAGE signaling pathway,lipid and atherosclerosis,and cancer pathway in diabetic complications.The solvent extraction method was optimized for efficient flavonoid extraction based on network pharmacology prediction results.This was achieved through a single factor and orthogonal test,resulting in an optimum process with a reflux time of 1.5 h,a solid-liquid ratio of 1:13 g/mL,and an ethanol concentration of 50%.

Optimization of extraction process for total flavonoids of Sophorae Flos for the treatment of hyperlipidemia based on network pharmacology and molecular docking

This study aimed to investigate the mechanism of action of Sophora Flos(SF)in the treatment of hyperlipidemia(HLP)using network pharmacology and molecular docking methods,and to optimize the extraction process of the predicted active components.The STRING database was used for protein interaction analysis and PPI network construction via Cytoscape 3.9.1.Pymol was employed for docking and visualization.An extensive review of SF identifi ed 6 active ingredients,297 related objectives,84 disease objectives,and 57 total objectives.After protein interaction and topology analysis,18 core targets were identified.These included 146 gene function entries(P<0.05).Active compounds,mainly flavonoids,can modulate the expression of various proteins such as TNF,IL-6,IL-1β,PPARG,and TGFB1 to achieve therapeutic effects on HLP.The network pharmacology and molecular docking results suggested that the active fl avonoids component in SF may be related to the treatment of hyperlipidemia.Therefore,the orthogonal experiment method was used to optimize the extraction process of total fl avonoid from SF using ethanol refl ux extraction,based on a single factor experiment.The effects of refl ux time,solid-liquid ratio,ethanol concentration,and other factors on the extraction of total fl avonoid from SF were investigated.The optimum process conditions were refl ux time of 1.25 h,solid-liquid ratio of 1:15 g/mL and ethanol concentration of 60%.Using these conditions,the purity of total fl avonoid extracted from SF was 70.33±0.22%.

The role of natural flavonoids on neuroinflammation as a therapeutic target for Alzheimer's disease:a narrative review

Alzheimer's disease is a neurodegenerative disease that affects a large proportion of older adult people and is characterized by memory loss,progressive cognitive impairment,and various behavioral disturbances.Although the pathological mechanisms underlying Alzheimer's disease are complex and remain unclear,previous research has identified two widely accepted pathological characteristics:extracellular neuritic plaques containing amyloid beta peptide,and intracellular neurofibrillary tangles containing tau.Furthermore,research has revealed the significant role played by neuroinflammation over recent years.The inflammatory microenvironment mainly consists of microglia,astrocytes,the complement system,chemokines,cytokines,and reactive oxygen intermediates;collectively,these factors can promote the pathological process and aggravate the severity of Alzheimer's disease.Therefore,the development of new drugs that can target neuroinflammation will be a significant step forward for the treatment of Alzheimer's disease.Flavonoids are plant-derived secondary metabolites that possess various bioactivities.Previous research found that multiple natural flavonoids could exert satisfactory treatment effects on the neuroinflammation associated with Alzheimer's disease.In this review,we describe the pathogenesis and neuroinflammatory processes of Alzheimer's disease,and summarize the effects and mechanisms of 13 natural flavonoids(apigenin,luteolin,naringenin,quercetin,morin,kaempferol,fisetin,isoquercitrin,astragalin,rutin,icariin,mangiferin,and anthocyanin)derived from plants or medicinal herbs on neuroinflammation in Alzheimer's disease.As an important resource for the development of novel compounds for the treatment of critical diseases,it is essential that we focus on the exploitation of natural products.In particular,it is vital that we investigate the effects of flavonoids on the neuroinflammation associated with Alzheimer's disease in greater detail.

GOLDEN 2-LIKE transcription factors regulate chlorophyll biosynthesis and flavonoid accumulation in response to UV-B in tea plants

Flavonoids are critical secondary metabolites that determine the health benefits and flavor of tea,while chlorophylls are important contributors to the appearance of tea.However,transcription factors(TFs)that can integrate both chlorophyll biosynthesis and flavonoid accumulation in response to specific light signals are rarely identified.In this study,we report that the GOLDEN 2-LIKE TF pair,CsGLK1 and CsGLK2,orchestrate UV-B-induced responses in the chlorophyll biosynthesis and flavonoid accumulation of tea leaves.The absence of solar UV-B reduced the transcriptional expression of CsGLKs in the tea leaves and was highly correlated with a decrease in flavonoid levels(especially flavonol glycosides)and the expression of genes and TFs involved in chlorophyll biosynthesis and flavonoid accumulation.In vivo and in vitro molecular analyses showed that CsGLKs could be regulated by the UV-B signal mediator CsHY5,and could directly bind to the promoters of gene and TF involved in light-harvesting(CsLhcb),chlorophyll biosynthesis(CsCHLH,CsHEMA1,and CsPORA),and flavonoid accumulation(CsMYB12,CsFLSa,CsDFRa,and CsLARa),eventually leading to UV-B-induced responses in the chlorophylls and flavonoids of tea leaves.Furthermore,UV-B exposure increased the levels of total flavonoids,CsGLK1 protein,and expression of CsGLKs and target genes in the tea leaves.These results indicate that CsGLKs may modulate tea leaf characteristics by regulating chlorophyll biosynthesis and flavonoid accumulation in response to solar UV-B.As the first report on UV-B-induced changes in flavonoid and chlorophyll regulation mediated by CsGLKs,this study improves our understanding of the environmental regulations regarding tea quality and sheds new light on UV-B-induced flavonoid responses in higher plants.