A 1:1 flavone cocrystal with cyclic trimeric perfluoro-o-phenyl-enemercury.

The title compound, systematic name tris-(µ2-perfluoro-o-phenyl-ene)(µ2-3-phenyl-4H-chromen-4-one)-triangulo-trimercury, [Hg3(C6F4)3(C15H10O2)], crystallizes in the monoclinic P21/n space group with one flavone (FLA) and one cyclic trimeric perfluoro-o-phenyl-enemercury (TPPM) mol-ecule per asymmetric unit. The FLA mol-ecule is located on one face of the TPPM acceptor and is linked in an asymmetric coordination of its carbonyl oxygen atom with two Hg centers of the TPPM macrocycle. The angular-shaped complexes pack in zigzag chains where they stack via two alternating TPPM-TPPM and FLA-FLA stacking patterns. The distance between the mean planes of the neighboring TPPM macrocycles in the stack is 3.445 (2) Å, and that between the benzo-γ-pyrone moieties of FLA is 3.328 (2) Å. The neighboring stacks are inter-digitated through the shortened F⋯F, CH⋯F and CH⋯π contacts, forming a dense crystal structure.

Neuroprotective roles of flavonoid "hispidulin" in the central nervous system: A review.

Interest in naturally occurring phytochemicals has been on the increase, they are believed to reduce the risk of brain disorders. Hispidulin (HN) is a phenolic flavonoid compound with various pharmacological and biological effects on the central nervous system. It belongs to the flavone class of flavonoids. It can be found in different plant materials, especially fruits and vegetables. The literature used in this review was collected from credible scientific databases including ScienceDirect, Scopus, PubMed, Google Scholar, and Hindawi without time restriction, using relevant keywords, such as HN, brain, central nervous system, flavonoids, and flavones. HN was discovered to possess pro-apoptotic properties, act as an antioxidant, inhibit cytokine production and toll-like receptor 4 expression, as well as impede nuclear factor kappa beta and mitogen-activated protein kinase B. HN was also found to inhibit lipid peroxidation in vitro and reduce brain edema in mice. These pharmacological potentials suggest that HN is a promising candidate for neuroprotection in CNS disorders like depression and epilepsy. This review provides an update on the scientific literature concerning how these activities could help provide various forms of neuroprotection in the CNS. Additional experimental data on the effects of HN in models of neurological disorders and neuroprotection should be explored further. Based on the current study, HN is a promising candidate for neuroprotection of the CNS.

Computational Investigation about the Effects of Solvent Polarity and Chalcogen Element Electronegativity on ESIPT Behaviors for the Et2N-Substituted Flavonoid.

Inspired by the outstanding nature of flavonoid derivatives in the fields of chemistry and medicine, in this work we mainly focus on exploring the photo-induced properties of the novel Et2N-substituted flavonoid (ENF) fluorophore theoretically. Considering the potential photo-induced properties in different solvents and the chalcogen atomic electronegativity-associated photoexcitation, by time-dependent density functional theory (TDDFT) methods we primarily explore the intramolecular hydrogen bonding interactions and photo-induced charge redistribution behaviors. Via comparing geometrical data and the infrared (IR) spectral shifts-associated hydroxy moiety of ENF, we confirm that the intramolecular hydrogen bond O-H···O should be enhanced with facilitating an excited-state intramolecular proton-transfer (ESIPT) reaction. Particularly, the charge reorganization around hydrogen bonding moieties further reveals the tendency of ESIPT behavior. Combined with the construction of the potential energy surface and the search for reaction transition states, we finally confirmed the solvent-polarity-regulated behaviors as well as the chalcogen elements' electronegativity-dependent ESIPT mechanisms for the ENF fluorophore. We sincerely wish our work could accelerate the further development and applications of flavonoid derivatives.

Effects of Sea-Buckthorn Flavonoids on Growth Performance, Serum Inflammation, Intestinal Barrier and Microbiota in LPS-Challenged Broilers.

The experiment investigated the effects of sea-buckthorn flavonoids (SF) on lipopolysaccharide (LPS)-challenged broilers. A total of 288 one-day-old male broilers were randomly assigned to 4 groups, with 6 replicates of 12 broilers each. The experiment lasted for 20 days. The diet included two levels of SF (0 or 1000 mg/kg) and broilers intraperitoneally injected with 500 µg/kg LPS on 16, 18, and 20 days, or an equal amount of saline. LPS challenge decreased final body weight, average daily gain, and average daily feed intake, increased feed-to-gain ratio, and elevated serum IL-1ß, IL-2, TNF-α, D-LA, and endotoxin levels. Moreover, it resulted in a reduction in the IL-10 level. LPS impaired the intestinal morphology of the duodenum, jejunum, and ileum, down-regulated the mRNA relative expression of Occludin, ZO-1, and MUC-2 in the jejunum mucosa, up-regulated the mRNA relative expression of TLR4, MyD88, NF-κB, and IL-1ß, and increased the relative abundance of Erysipelatoclostridium in broilers (p < 0.05). However, SF supplementation mitigated the decrease in growth performance, reduced serum IL-1ß, IL-2, and D-LA levels, increased IL-10 levels, alleviated intestinal morphological damage, up-regulated mRNA expression of Occludin and ZO-1, down-regulated the mRNA expression of TLR4, NF-κB, and IL-lß in jejunum mucosal (p < 0.05), and SF supplementation presented a tendency to decrease the relative abundance of proteobacteria (0.05 < p < 0.1). Collectively, incorporating SF can enhance the growth performance, alleviate serum inflammation, and improve the intestinal health of broilers, effectively mitigating the damage triggered by LPS-challenges.

Anti-tumor effect of dandelion flavone on multiple myeloma cells and its mechanism.

BACKGROUND: Multiple myeloma (MM) is a prevalent hematologic malignancy characterized by the uncontrolled proliferation of monoclonal plasma cells in the bone marrow and excessive monoclonal immunoglobulin production, leading to organ damage. Despite therapeutic advancements, recurrence and drug resistance remain significant challenges. OBJECTIVE: This study investigates the effects of dandelion flavone (DF) on MM cell proliferation, migration, and invasion, aiming to elucidate the mechanisms involved in MM metastasis and to explore the potential of traditional Chinese medicine in MM therapy. METHODS: DF's impact on myeloma cell viability was evaluated using the CCK-8 and colony formation assays. Cell mobility and invasiveness were assessed through wound healing and transwell assays, respectively. RT-PCR was employed to quantify mRNA levels of MMP-2, MMP-9, TIMP-1, and TIMP-2. Apoptotic rates and molecular markers were analyzed via flow cytometry and RT-PCR. The PI3K/AKT signaling pathway was studied using Western blot and ELISA, with IGF-1 and the PI3K inhibitor LY294002 used to validate the findings. RESULTS: DF demonstrated dose-dependent inhibitory effects on MM cell proliferation, migration, and invasion. It reduced mRNA levels of MMP-2 and MMP-9 while increasing those of TIMP-1 and TIMP-2. Furthermore, DF enhanced the expression of pro-apoptotic proteins and inhibited M2 macrophage polarization by targeting key molecules and enzymes. The anti-myeloma activity of DF was mediated through the inhibition of the PI3K/AKT pathway, as evidenced by diminished phosphorylation and differential effects in the presence of IGF-1 and LY294002. CONCLUSION: By modulating the PI3K/AKT pathway, DF effectively inhibits MM cell proliferation, migration, and invasion, and induces apoptosis, establishing a novel therapeutic strategy for MM based on traditional Chinese medicine.

Facile Synthesis and Applications of Flavonoid-Heterocyclic Derivatives.

Flavonoids belong to the polyphenol group that naturally exists in fruits, vegetables, tea, and grains. Flavonoids, as secondary metabolites, show indispensable contributions to biolog-ical processes and the responses of plants to numerous environmental factors. The bioactivity of flavonoids depends on C6-C3-C6 ring substitution patterns that exhibit bioactive antioxidant, an-timicrobial, antifungal, antitumor, and anti-inflammatory properties. The synthesis of flavonoids has been reported by various methodologies. Therefore, the present review systematically sum-marizes the synthesis of recent heterocyclic flavonoid derivatives via facile synthetic approaches since the research in flavonoids is useful for therapeutic and biotechnology fields.

Metabolomic and transcriptomic analysis of flavonoids biosynthesis mechanisms in mulberry fruit (Hongguo 2) under exogenous hormone treatments.

The mulberry fruit is prized for its superior nutrition value and abundant color due to its high flavone content. To enhance comprehension of flavone biogenesis induced by external hormones, we sprayed exogenous ethylene (ETH), indoleacetic acid (IAA) and spermine (SPM) on mulberry fruit (Hongguo 2) during its color-changed period. The levels of anthocyanin, titratable acid, soluble sugar and endogenous hormones were determined after hormone treatment, integrated transcriptome and metabolome analysis were performed for mechanism exploration. Our results indicated that exogenous ETH, SPM, and IAA play important roles in mulberry ripening, including acid reduction, sugar increase and flavonoid synthesis.

Prophylactic effects of apigenin against hyperglycemia-associated amnesia via activation of the Nrf2/ARE pathway in zebrafish.

The escalating focus on ageing-associated disease has generated substantial interest in the phenomenon of cognitive impairment linked to diabetes. Hyperglycemia exacerbates oxidative stress, contributes to ß-amyloid accumulation, disrupts mitochondrial function, and impairs cognitive function. Existing therapies have certain limitations, and apigenin (AG), a natural plant flavonoid, has piqued interest due to its antioxidant, anti-inflammatory, and anti-hyperglycemic properties. So, we anticipate that AG might be a preventive medicine for hyperglycemia-associated amnesia. To test our hypothesis, naïve zebrafish were trained to acquire memory and pretreated with AG. Streptozotocin (STZ) was administered to mimic hyperglycemia-induced memory dysfunction. Spatial memory was assessed by T-maze and object recognition through visual stimuli. Acetylcholinesterase (AChE) activity, antioxidant enzyme status, and neuroinflammatory genes were measured, and histopathology was performed in the brain to elucidate the neuroprotective mechanism. AG exhibits a prophylactic effect and improves spatial learning and discriminative memory of STZ-induced amnesia in zebrafish under hyperglycemic conditions. AG also reduces blood glucose levels, brain oxidative stress, and AChE activity, enhancing cholinergic neurotransmission. AG prevented neuronal damage by regulating brain antioxidant response elements (ARE), collectively contributing to neuroprotective properties. AG demonstrates a promising effect in alleviating memory dysfunction and mitigating pathological changes via activation of the Nrf2/ARE mechanism. These findings underscore the therapeutic potential of AG in addressing memory dysfunction and neurodegenerative changes associated with hyperglycemia.

[Effects of epimedium total flavone capsules on post-stroke cognitive impairment in rats].

To investigate the effect of epimedium total flavone capsules on post-stroke cognitive impairment(PSCI) in rats. The transient middle cerebral artery occlusion(tMCAO) model was constructed on selected rats, and rats with impaired neurological function were randomly divided into the model group, low, middle, and high dose groups of epimedium total flavone capsules, and nimodipine tablet group. The cognitive function of rats was measured after administration. Pathological changes in brain tissue were observed after hematoxylin-eosin staining(HE). Neuronal nuclei(NeuN) and glial fibrillary acidic protein(GFAP) distribution in brain tissue were tested by immunofluorescent staining. The level of amyloid beta 1-42(Aß_(1-42)), neuron specific enolase(NSE), acetylcholine(ACH), dopamine(DA), 5-hydroxytryptamine(5-HT), norepinephrine(NE), interleukin-1ß(IL-1ß), tumor necrosis factor-α(TNF-α), and hypersensitive C-reactive protein(hs-CRP) in rat serum was tested. Moreover, Western blot was utilized to test the expression of nuclear factor-kappaB(NF-κB), p-NF-κB, alpha inhibitor of NF-κB(IκBα) protein, and p-IκBα protein in the hippocampus. The experimental results showed that epimedium total flavone capsules can improve the cognitive function of model rats, and the mechanism may be related to the regulation of the expression of p-IκBα and p-NF-κB proteins, so as to inhibit inflammatory response induced by ischemia-reperfusion.

Solubilization mechanism of α-glycosylated naringin based on self-assembled nanostructures and its application to skin formulation.

We previously reported that α-glycosylated naringin (naringin-G), synthesized by enzyme-catalyzed transglycosylation, can enhance the solubility of poorly water-soluble compounds without surface-active property. However, the solubilization mechanism has not been fully elucidated. In this study, the solubilization mechanism of naringin-G was investigated using nuclear magnetic resonance (NMR) spectroscopy, and its application in skin formulations was further investigated. 1H NMR and dynamic light scattering measurements at various concentrations confirmed the self-assembled nanostructures of naringin-G above a critical aggregation concentration of approximately 2.2 mg/mL. Two-dimensional 1H-1H nuclear Overhauser effect spectroscopy and solubility tests revealed that flavone with poor water solubility, could be solubilized in its self-assembled structure with a stoichiometric relationship with naringin-G. When naringin-G was included in the skin formulation, the permeated amount and permeability coefficient (Papp) of flavones improved up to four times with increasing amounts of naringin-G. However, flavone solubilization by adding an excessive amount of naringin-G resulted in a decreased permeated amount and Papp of flavones, indicating the interplay between the apparent solubility and skin permeability of flavones. Naringin-G, which forms a nanoaggregate structure without exhibiting surface-active properties, has the potential to enhance the solubility and skin permeation of poorly water-soluble compounds.

5,7-dihydroxy-3',4',5'-trimethoxyflavone mitigates lead induced neurotoxicity in rats via its chelating, antioxidant, anti-inflammatory and monoaminergic properties.

Chronic exposure to lead (Pb) induces neurodegenerative changes in animals and humans. Drugs with strong antioxidant properties are effective against Pb-mediated neurotoxicity. In a prior study, we identified 5,7-dihydroxy-3',4',5'-trimethoxyflavone (TMF) from Ocimum basilicum L. leaves as a potent antioxidant and neuroprotective compound. This research explores TMF's neuroprotective effects against Pb-induced brain toxicity in rats to establish it as a therapeutic agent. Rats received lead acetate (100 mg/kg, orally, once daily) for 30 days to induce brain injury, followed by TMF treatment (5 and 10 mg/kg, oral, once daily) 30 min later. Cognitive and motor functions were assessed using Morris Water Maze and horizontal bar tests. Lead, monoamine oxidase (MAO) A and B enzymes, reduced glutathione (GSH), thiobarbituric acid reactive species (TBARS), Tumor necrosis factor-alpha (TNF-α), and IL-6 levels were measured in the hippocampus and cerebellum. Pb exposure impaired cognitive and motor functions, increased Pb, TBARS, TNF-α, and IL-6 levels, and compromised MAO A & B and GSH levels. TMF reversed Pb-induced memory and motor deficits and normalized biochemical anomalies. TMF's neuroprotective effects against lead involve chelating, antioxidant, anti-inflammatory, and monoaminergic properties, suggesting its potential as a treatment for metal-induced brain injury.

Polyphenols of the Inuleae-Inulinae and Their Biological Activities: A Review.

Polyphenols are ubiquitous plant metabolites that demonstrate biological activities essential to plant-environment interactions. They are of interest to plant food consumers, as well as to the food, pharmaceutical and cosmetic industry. The class of the plant metabolites comprises both widespread (chlorogenic acids, luteolin, quercetin) and unique compounds of diverse chemical structures but of the common biosynthetic origin. Polyphenols next to sesquiterpenoids are regarded as the major class of the Inuleae-Inulinae metabolites responsible for the pharmacological activity of medicinal plants from the subtribe (Blumea spp., Dittrichia spp., Inula spp., Pulicaria spp. and others). Recent decades have brought a rapid development of molecular and analytical techniques which resulted in better understanding of the taxonomic relationships within the Inuleae tribe and in a plethora of data concerning the chemical constituents of the Inuleae-Inulinae. The current taxonomical classification has introduced changes in the well-established botanical names and rearranged the genera based on molecular plant genetic studies. The newly created chemical data together with the earlier phytochemical studies may provide some complementary information on biochemical relationships within the subtribe. Moreover, they may at least partly explain pharmacological activities of the plant preparations traditionally used in therapy. The current review aimed to systematize the knowledge on the polyphenols of the Inulae-Inulinae.

Molecular insights into flavone-mediated quorum sensing interference: A novel strategy against Serratiamarcescens biofilm-induced antibiotic resistance".

Antibiotic resistance poses a significant challenge in modern medicine, urging the exploration of innovative approaches to combat bacterial infections. Biofilms, complex bacterial communities encased in a protective matrix, contribute to resistance by impeding antibiotic efficacy and promoting genetic exchange. Understanding biofilm dynamics is crucial for developing effective antimicrobial therapies against antibiotic resistance. This study explores the potential of flavone to combat biofilm-induced antibiotic resistance by employing in-vitro biochemical, cell biology, and Insilico (MD simulation), approaches. Flavone exhibited potent antibacterial effects with a low minimum inhibitory concentration by inducing intracellular reactive oxygen species. Flavones further inhibited the formation of biofilms by 50-60 % and disrupted the pre-formed biofilms by reducing the extracellular polysaccharide substance protective layer formed on the biofilm by 80 %. Quorum sensing (QS) plays a crucial role in bacterial pathogenicity and flavone significantly attenuated the production of QS-induced virulence factors like urease, protease, lipase, hemolysin and prodigiosin pigment in a dose-dependent manner. Further Insilico molecular docking studies along with molecular dynamic simulations run for 100 ns proved the stable binding affinity of flavone with QS-specific proteins which are crucial for biofilm formation. This study demonstrates the therapeutic potential of flavone to target QS-signaling pathway to combat S.marcescens biofilms.

Transcriptomic and targeted metabolomic analyses provide insights into the flavonoids biosynthesis in the flowers of Lonicera macranthoides.

BACKGROUND: Flavonoids are one of the bioactive ingredients of Lonicera macranthoides (L. macranthoides), however, their biosynthesis in the flower is still unclear. In this study, combined transcriptomic and targeted metabolomic analyses were performed to clarify the flavonoids biosynthesis during flowering of L. macranthoides. RESULTS: In the three sample groups, GB_vs_WB, GB_vs_WF and GB_vs_GF, there were 25, 22 and 18 differentially expressed genes (DEGs) in flavonoids biosynthetic pathway respectively. A total of 339 flavonoids were detected and quantified at four developmental stages of flower in L. macranthoides. In the three sample groups, 113, 155 and 163 differentially accumulated flavonoids (DAFs) were detected respectively. Among the DAFs, most apigenin derivatives in flavones and most kaempferol derivatives in flavonols were up-regulated. Correlation analysis between DEGs and DAFs showed that the down-regulated expressions of the CHS, DFR, C4H, F3'H, CCoAOMT_32 and the up-regulated expressions of the two HCTs resulted in down-regulated levels of dihydroquercetin, epigallocatechin and up-regulated level of kaempferol-3-O-(6''-O-acetyl)-glucoside, cosmosiin and apigenin-4'-O-glucoside. The down-regulated expressions of F3H and FLS decreased the contents of 7 metabolites, including naringenin chalcone, proanthocyanidin B2, B3, B4, C1, limocitrin-3,7-di-O-glucoside and limocitrin-3-O-sophoroside. CONCLUSION: The findings are helpful for genetic improvement of varieties in L.macranthoides.

Mechanisms of flavonoid inhibition of Maillard reaction product formation in relation to whole grains processing.

Whole grains (WG) are beneficial to health but have reduced sensory quality, partly attributable to inhibition of Maillard reaction products (MRP) by WG phenolics. The study investigated how major flavonoid classes in cereals affect Maillard reaction pathways. Flavonoids were reacted with xylose-lysine aqueous system at 160 °C/12 min. Additionally, breads were made with catechin, and wheat and sorghum bran fortification. Low Mw MRP were profiled using UPLC-MS/MS, while melanoidins were characterized using fluorescence spectroscopy and HPSEC-MALS. The flavonoids significantly (p < 0.05) reduced both melanoidin content (by 33-86%) and Mw (3.5-15 kDa vs 20 kDa control), leading to lighter bread crust. Flavonoids inhibited MRP via direct condensation with early-stage amines and carbonyls into stable adducts, and reduction of late-stage polymerization reactions, increasing accumulation of cyclic N-containing intermediates. Inhibitory trend was flavones>flavanones>flavanols. C-Ring π-bond dramatically enhance flavonoid MRP inhibition; thus flavone-rich cereal grains are likely to strongly impact MRP-dependent sensory attributes of WG products.

[Study on chemical components of Hypericum himalaicum and mechanism of anti-inflammatory based on network pharmacology and molecular docking technology].

The chemical constituents of ethyl acetate from Hypericum himalaicum were isolated by silica gel column chromatography, gel column chromatography, and high-performance liquid chromatography. The structure of the isolated compounds was identified by modern spectral techniques(NMR, MS, IR, and UV), and the potential anti-inflammatory targets and action pathways were analyzed and predicted by network pharmacology and molecular docking methods.Ten compounds were isolated from H. himalaicum and identified as 5,9,11-trihydroxy-3,3-dimethyl-3H,8H-benzo[6,7][1,4]dioxepino[2,3-f]chromen-8-one(1), betulinic acid(2), demethyltorosaflavone C(3), kaempferol(4), quercetin(5), hyperwightin B(6), toxyloxanthone B(7), 1,7-dihydroxy-xanthone(8), emodin(9), and 1,7-dihydroxy-4-methoxy-xanthone(10). Among them, compound 1 was a new compound, and compounds 2-10 were isolated from H. himalaicum for the first time. Network pharmacology screened 60 key anti-inflammatory targets. By acting on TNF, AKT1, CASP3, and other key targets, involving PI3K-AKT signaling pathway, IL-17 signaling pathway, VEGF signaling pathway, MAPK signaling pathway, and other signaling pathways, and phosphorylation, cell migration and movement, protein tyrosine kinase, and other biological processes were regulated to achieve anti-inflammatory effects. The results of molecular docking show that the above components have good binding properties with the core targets.

Characterization of Neuropeptides from Spodoptera litura and Functional Analysis of NPF in Diet Intake.

Neuropeptides are involved in many biological processes in insects. However, it is unclear what role neuropeptides play in Spodoptera litura adaptation to phytochemical flavone. In this study, 63 neuropeptide precursors from 48 gene families were identified in S. litura, including two neuropeptide F genes (NPFs). NPFs played a positive role in feeding regulation in S. litura because knockdown of NPFs decreased larval diet intake. S. litura larvae reduced flavone intake by downregulating NPFs. Conversely, the flavone intake was increased if the larvae were treated with NPF mature peptides. The NPF receptor (NPFR) was susceptible to the fluctuation of NPFs. NPFR mediated NPF signaling by interacting with NPFs to regulate the larval diet intake. In conclusion, this study suggested that NPF signaling regulated diet intake to promote S. litura adaptation to flavone, which contributed to understanding insect adaptation mechanisms to host plants and provide more potential pesticidal targets for pest control.

Simultaneous quantitation of 15 bioactive components in Yupingfeng granules by LC-MS/MS.

Yupingfeng granules (YPFG) is commonly used in the treatment of immunological diseases, inflammations, and pulmonary diseases. Several studies have found that chromones, flavones, and saponins were the major bioactive compounds of YPFG. However, few studies have reported accurate quantification methods of these compounds. This study aimed to establish a simple and rapid method by using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to determine 15 bioactive compounds in YPFG. The experimental parameters including extraction methods, extraction solvents, extraction time, solid-liquid ratio, and LC-MS/MS condition were optimized. The linearity, precision, repeatability, stability, and recovery of the established method were evaluated. The contents of 15 bioactive compounds in seven batches of YPFG samples were analyzed by the established method and the results were compared with the values determined by HPLC. The optimal extraction condition was to extract 0.1 g of YPFG by ultrasound with 50 mL 50% ethanol for 30 min. A Waters ACQUITY UPLCBEH C18 column using the 0.1% formic acid water solution and acetonitrile as mobile phase with a gradient elution was applied to the chromatographic separation. The linearity, precision, repeatability, stability, and recovery of the method were within acceptable ranges. Compared with HPLC analysis methods in Chinese Pharmacopoeia and literature, the established method was faster, simpler, more accurate, and more reliable. The method of simultaneous determination of 15 components in YPFG by LC-MS might provide a basis for the study of the bioactive compounds and the improvement of the quality standard of YPFG.

Flavonoids: A treasure house of prospective pharmacological potentials.

Flavonoids are organic compounds characterized by a range of phenolic structures, which are abundantly present in various natural sources such as fruits, vegetables, cereals, bark, roots, stems, flowers, tea, and wine. The health advantages of these natural substances are renowned, and initiatives are being taken to extract the flavonoids. Apigenin, galangin, hesperetin, kaempferol, myricetin, naringenin, and quercetin are the seven most common compounds belonging to this class. A thorough analysis of bibliographic records from reliable sources including Google Scholar, Web of Science, PubMed, ScienceDirect, MEDLINE, and others was done to learn more about the biological activities of these flavonoids. These flavonoids appear to have promising anti-diabetic, anti-inflammatory, antibacterial, antioxidant, antiviral, cytotoxic, and lipid-lowering activities, according to evidence from in vitro, in vivo, and clinical research. The review contains recent trends, therapeutical interventions, and futuristic aspects of flavonoids to treat several diseases like diabetes, inflammation, bacterial and viral infections, cancers, and cardiovascular diseases. However, this manuscript should be handy in future drug discovery. Despite these encouraging findings, a notable gap exists in clinical research, hindering a comprehensive understanding of the effects of flavonoids at both high and low concentrations on human health. Future investigations should prioritize exploring bioavailability, given the potential for high inter-individual variation. As a starting point for further study on these flavonoids, this review paper may promote identifying and creating innovative therapeutic uses.

Gh4CL20/20A involved in flavonoid biosynthesis is essential for male fertility in cotton (Gossypium hirsutum L.).

Flavonoids have been shown to play an essential role in plant growth and fertility. 4-Coumarate CoA ligase (4CL) is one of the indispensable enzymes involved in the biosynthesis of flavonoids. However, the role of 4CL and flavonoids in impact on cotton fertility is still unknown. In this study, on the basis of identification of an additional Gh4CL gene, Gh4CL20A, by using an updated G. hirsutum genome, we found that Gh4CL20A and its homologous Gh4CL20 were preferentially expressed in petals and stamens. The petals of the loss-of-function Gh4CL20/Gh4CL20A mutant generated by CRISPR/Cas9 gene editing remained white until wilting. Notably, the mutant showed indehiscent anthers, reduced number of pollen grains and pollen viability, leading to male sterility. Histological analysis revealed that abnormal degradation of anther tapetum at the tetrad stage and abnormal pollen grain development at the mature stage caused male sterility of the gene editing mutant. Analysis of the anther transcriptome identified a total of 10574 and 11962 genes up- and down-regulated in the mutant, respectively, compared to the wild-type. GO, KEGG, and WGCNA analyses linked the abnormality of the mutant anthers to the defective flavonoid biosynthetic pathway, leading to decreased activity of 4CL and chalcone isomerase (CHI) and reduced accumulation of flavonoids in the mutant. These results imply a role of Gh4CL20/Gh4CL20A in assuring proper development of cotton anthers by regulating flavonoid metabolism. This study elucidates a molecular mechanism underlying cotton anther development and provides candidate genes for creating cotton male sterile germplasm that has the potential to be used in production of hybrid seeds.