Polymethoxylated flavone variations and in vitro biological activities of locally cultivated Citrus varieties in China.

Citrus peels are rich in polymethoxylated flavones (PMFs), which have beneficial health and pharmacological properties. In this study, the profiles, variations, and biological activities of PMFs in the peel extracts of 27 Citrus varieties (eight species) native to China were investigated. UPLC-QTOF-MS/MS analysis revealed that mandarin accumulated more diversity and higher detectable PMF contents. Wangcangzhoupigan (ZPG) possessed the highest antioxidant capacity. Gailiangcheng (GLC) and Bingtangcheng (BTC), sweet oranges showed excellent inhibitory effects against pancreatic lipase and α-glucosidase, respectively. Most citrus extracts effectively inhibited the production of ROS and pro-inflammatory cytokines, while increasing the accumulation of anti-inflammatory cytokines. In addition, Limeng (LM), Cupig-oushigan (GSG), and Yanxiwanlu (YXWL) showed anti-proliferative effects against DU145 and PC3 cancer cells. This study provides a comprehensive PMF profile and biological activities of various citrus species and will benefit future functional citrus breeding practices aimed at designing plants rich in total or specific PMFs for health benefits.

Synergistic effect of phenylpropanoids and flavonoids with antibiotics against Gram-positive and Gram-negative bacterial strains.

CONTEXT: The increase in bacterial resistance to currently available medications, which increases mortality rates, treatment costs is a global problem, and highlights the need for novel classes of antibacterial agents or new molecules that interact synergistically with antimicrobials. OBJECTIVE: The current work explores the potential synergistic effects of certain natural phenylpropanoids and flavonoids on ciprofloxacin (CIP), ampicillin (AMP), gentamicin (GEN), and tetracycline (TET). MATERIALS AND METHODS: The adjuvant role of cinnamic acid, p-coumaric acid, caffeic acid, ferulic acid, ferulic acid methyl ester, sinapic acid, apigenin, and luteolin was evaluated by determining the MIC (minimal inhibitory concentration) values of antibiotics in the presence of subinhibitory concentrations (200, 100, and/or 50 µM) of the compounds in Gram-positive and Gram-negative bacterial strains using a 2-fold broth microdilution method. The 96-well plates were incubated at 37 °C for 18 h, and dimethyl sulfoxide was used as a solvent control. RESULTS: The combination of luteolin with CIP, reduced the MIC values of the antibiotic from 0.625 to 0.3125 µM and to 0.078 µM in 100 and 200 µM concentration, respectively, in sensitive Staphylococcus aureus. Sinapic acid decreased the MIC value of CIP from 0.625 to 0.3125 µM in S. aureus, from 1.56 to 0.78 µM in Klebsiella pneumoniae, and the MIC of GEN from 0.39 to 0.095 µM in Pseudomonas aeruginosa strains. DISCUSSION AND CONCLUSIONS: These findings are useful in delaying the development of resistance, as the required antibacterial effect can be achieved with the use of lower concentrations of antibiotics.

A smartphone-based electrochemical sensing platform for the portable and simultaneous determination of flavonoids in Citri Reticulatae Pericarpium.

BACKGROUND: The efficient and timely determination of polymethoxylated flavones (PMFs, primarily nobiletin and tangeretin) and flavanone glycosides (primarily hesperidin) in Citri Reticulatae Pericarpium (CRP) is of paramount importance for the production of CRP and the evaluation of its efficacy. Conventional analytical methods including chromatography-based approaches commonly provide high sensitivity and selectivity, but require bulky equipment and complicated procedures performed by professional technicians and are thus inconvenient in practical applications. Therefore, there is a clear need for portable and miniaturized sensing platforms that can rapidly and simultaneously detect PMFs and hesperidin in CRP product. RESULTS: A state-of-the-art three-dimensional porous graphene electrode was first fabricated by direct laser scribing of a poly(ether-ether-ketone) (PEEK) film for electrocatalysis of nobiletin, tangeretin and hesperidin. Kinetic analysis was conducted to investigate the reaction mechanisms of these three flavonoids at such prepared PEEK-laser induced graphene (PEEK-LIG) electrodes. Since the as-prepared PEEK-LIG electrodes exhibited high electrocatalytic efficiency towards these three flavonoids, a portable electrochemical sensing platform assembled with a smartphone, a miniatured electrochemical workstation, and an integrated PEEK-LIG microchip was developed. Consequently, the developed portable electrochemical sensing platforms exhibited great sensitivity and low detection limits for both PMFs and hesperidin. More importantly, tests conducted on real CRP extract samples demonstrated that the developed portable electrochemical sensing platform exhibited high validity, high reliability, as well as excellent reproducibility. SIGNIFICANCE: This is the inaugural report on the portable and simultaneous determination of PMFs and hesperidin in the pericarp of Citrus Reticulata, which may be utilized for differentiating CRP products. Furthermore, the portable and powerful electrochemical sensing platforms developed could also potentially be applied for a wide range of analytes, thanks to their simple and rapid fabrication and determination processes.

A Compressive Review on Source, Toxicity and Biological Activity of Flavonoid.

Flavonoids are biologically active chemicals in various fruits, plants, vegetables, and leaves, which have promising uses in medicinal science. The health properties of these natural chemicals are widely accepted, and efforts are underway to extract the specific components referred to as flavonoids. Flavonoids demonstrate a diverse range of bio-activities, anticancer, antioxidant activity, anti-cholinesterase activity, antiinflammatory activity, antimalarial activity, antidiabetic activity, neurodegenerative disease, cardiovascular effect, hepatoprotective effects, and antiviral and antimicrobial activity. This study aims to examine the prevailing trends in flavonoid investigation studies, elucidate the activity of flavonoids, examine their various func-tions and uses, assess the potential of flavonoids as preventive medications for chronic diseases, and outline future research opportunities in this field. This review explores the diverse functions of flavonoids in preventing and managing various diseases.

Functional, Chemical, and Phytotoxic Characteristics of Cestrum parqui L'Herit: An Overview.

Cestrum parqui L'Herit. (Solanaceae family) is a species of forest shrub, self-incompatible and specialized in pollination, widespread in the subtropical area of the planet, and now widely distributed also in the Mediterranean area. The constituents of its leaves have antimicrobial, anticancer, insecticidal, antifeedant, molluscicidal, and herbicidal properties. The spread of this species represents a valuable source of compounds with high biological value. Various research groups are engaged in defining the chemical composition of the different parts of the plant and in defining its properties in view of important and promising commercial applications. To date, there are only a few incomplete reports on the potential applications of C. parqui extracts as selective natural pesticides and on their potential phytotoxic role. Scientific knowledge and the use of extraction techniques for these components are essential for commercial applications. This article summarizes the research and recent studies available on the botany, phytochemistry, functional properties, and commercial applications of C. parqui.

Association of dietary flavonoid intake with the prevalence and all-cause mortality of depressive symptoms: Findings from analysis of NHANES.

BACKGROUND: This study aimed to explore the relationship between flavonoids intake and the prevalence and all-cause mortality of depressive symptoms in American adults. METHODS: Analyzing 2007-2008, 2009-2010, and 2017-2018 NHANES data, we examined the association between dietary flavonoid and depressive symptoms, including specific subclasses assessment and mortality outcomes tracking until December 31, 2019. Our methodology included weighted multivariate logistic regression, weighted cox proportional hazards regression and restricted cubic spline (RCS) models, supported by stratified and sensitivity analyses. RESULTS: Among the 12,340 participants in total, 1129 exhibited depressive symptoms. The multiple logistic regression analysis showed a significant reduction in total flavonoid and subclass intake in individuals with current depressive symptoms. Adjusted odds ratios (ORs) for the highest quartiles were 0.69 for anthocyanidins and 0.63 for flavones. Interaction effects emerged in non-hypertensive, higher-income, and normal-weight groups for flavones intake. The RCS model indicated an L-shaped association between depressive symptoms and total flavonoid intake, with inflection points at 346 mg/day. During a median follow-up of 119 months, 148 deaths occurred among patients with depressive symptoms. Hazard ratios (HRs) for all-cause mortality showed a significant positive correlation between total flavonoid intake and survival in model 1 (HR = 0.56), with an optimal intake range of 45.2-948.3 mg/day according to the RCS model. LIMITATIONS: The study relied on U.S. population survey data, potentially limiting generalizability. Unmeasured confounding factors may exist, and genetic factors were not considered. CONCLUSIONS: Adequate intake of flavonoids, especially anthocyanidins and flavones, is associated with reduced odds of depressive symptoms. Additionally, optimal intake ranges of flavonoid intake for mental health benefits were observed for all-cause mortality in population with depressive symptoms.

New combined Inverse-QSAR and molecular docking method for scaffold-based drug discovery.

Computer-aided drug discovery plays a vital role in developing novel medications for various diseases. The COVID-19 pandemic has heightened the need for innovative approaches to design lead compounds with the potential to become effective drugs. Specifically, designing promising inhibitors of the SARS-CoV-2 main protease (Mpro) is crucial, as it plays a key role in viral replication. Phytochemicals, primarily flavonoids and flavonols from medicinal plants, were screened. Fifty small molecules were selected for molecular docking analysis against SARS-CoV-2 Mpro (PDB ID: 6LU7). Binding energies and interactions were analyzed and compared to those of the anti-SARS-CoV-2 inhibitor Nirmatrelvir. Using these 50 structures as a training set, a QSAR model was built employing simple, reversible topological descriptors. An inverse-QSAR analysis was then performed on 29 = 512 hydroxyl combinations at nine possible positions on the flavone and flavonol scaffold. The model predicted three novel, promising compounds exhibiting the most favorable binding energies (-8.5 kcal/mol) among the 512 possible hydroxyl combinations: 3,6,7,2',4'-pentahydroxyflavone (PF9), 6,7,2',4'-tetrahydroxyflavone (PF11), and 3,6,7,4'-tetrahydroxyflavone (PF15). Molecular dynamics (MD) simulations demonstrated the stability of the PF9/Mpro complex over 300 ns of simulation. These predicted structures, reported here for the first time, warrant synthesis and further evaluation of their biological activity through in vitro and in vivo studies.

Validating the nutraceutical and neuroprotective pharmacodynamics of flavones.

Neurodegenerative disorders are generally characterized by progressive neuronal loss and cognitive decline, with underlying mechanisms involving oxidative stress, protein aggregation, neuroinflammation, and synaptic dysfunction. Currently, the available treatment options only improve the symptoms of the disease but do not stop disease progression; neurodegeneration. This underscores the urgent need for novel therapeutic strategies targeting multiple neurodegenerative pathways alongside the conventional therapeutic strategies available. Emerging evidence demonstrates that flavones a subgroup of flavonoids found abundantly in various dietary sources, have surfaced as promising candidates for neuroprotection due to their multifaceted pharmacological properties. Flavones possess the potency to modulate these pathophysiological processes through their antioxidant, anti-inflammatory, and neurotrophic activities. Additionally, flavones have been shown to interact with various cellular targets, including receptors and enzymes, to confer neuroprotection. Though there are ample evidence available, the nutraceutical and neuroprotective pharmacodynamics of flavones have not been very well established. Hence, the current review aims to explores the therapeutic potential of flavones as nutraceuticals with neuroprotective effects, focusing on their ability to modulate key pathways implicated in neurodegenerative diseases. The current article also aims to actuate supplementary research into flavones as potential agents for alleviating neurodegeneration and improving patient outcomes in neurodegenerative disorders globally.

Flavonoids-Enriched Vegetal Extract Prevents the Activation of NFκB Downstream Mechanisms in a Bowel Disease In Vitro Model.

Inflammatory bowel disease (IBD) incidence has increased in the last decades due to changes in dietary habits. IBDs are characterized by intestinal epithelial barrier disruption, increased inflammatory mediator production and excessive tissue injury. Since the current treatments are not sufficient to achieve and maintain remission, complementary and alternative medicine (CAM) becomes a primary practice as a co-adjuvant for the therapy. Thus, the intake of functional food enriched in vegetal extracts represents a promising nutritional strategy. This study evaluates the anti-inflammatory effects of artichoke, caihua and fenugreek vegetal extract original blend (ACFB) in an in vitro model of gut barrier mimicking the early acute phases of the disease. Caco2 cells cultured on transwell supports were treated with digested ACFB before exposure to pro-inflammatory cytokines. The pre-treatment counteracts the increase in barrier permeability induced by the inflammatory stimulus, as demonstrated by the evaluation of TEER and CLDN-2 parameters. In parallel, ACFB reduces p65NF-κB pro-inflammatory pathway activation that results in the decrement of COX-2 expression as PGE2 and IL-8 secretion. ACFB properties might be due to the synergistic effects of different flavonoids, indicating it as a valid candidate for new formulation in the prevention/mitigation of non-communicable diseases.

A P1-like MYB transcription factor boosts biosynthesis and transport of C-glycosylated flavones in duckweed.

C-glycosylated flavones (CGFs) are the main flavonoids in duckweed (Lemna turionifera), known for their diverse pharmacological activities and nutritional values. However, the molecular mechanisms underlying flavonoid metabolism in duckweed remain poorly understood. This study identified a P1-Like R2R3-MYB transcription factor, LtP1L, as a crucial regulator of CGF biosynthesis and transport in L. turionifera. Over-expression of LtP1L led to a six-fold increase in CGF levels, whereas the CRISPR-mediated knockdown of LtP1L caused a drastic 74.3 % decrease in CGF contents compared with the wild type. LtP1L specifically activated the expression of genes encoding key enzymes involved in the biosynthesis of CGFs, including flavanone 3'-hydroxylases (F3'H), flavanone 2-hydroxylases (F2H), and C-glycosyltransferase (CGT). Meanwhile, LtP1L activated genes associated with phenylalanine and phenylpropanoid biosynthesis pathways, such as 3-deoxy-7-phosphoheptulonate synthase (DHS), phenylalanine ammonia-lyase (PAL), cinnamate 4-hydroxylase (C4H), and 4-coumarate: CoA ligase (4CL), redirecting carbon metabolic flux towards flavonoid pathway at the early stages of phenylalanine synthesis. In addition, LtP1L directly bound to a novel AC-like cis-element in the promoter of a tonoplast-localized ATP-binding cassette (ABC) transporter LtABCC4 and activated its expression. Furthermore, the preference of LtABCC4 for isoorientin over orientin during vacuolar transport was evidenced by the significant reduction of isoorientin compared to orientin in the Ltabcc4crispr lines. Altogether, LtP1L acts as a crucial transcriptional orchestrator in coordinating the biosynthesis and intracellular transport of CGFs in duckweed.

CD44/PD-L1-mediated networks in drug resistance and immune evasion of breast cancer stem cells: Promising targets of natural compounds.

Cancer stem cells (CSCs) significantly interfere with immunotherapy, leading to challenges such as low response rates and acquired resistance. PD-L1 expression is associated with the CSC population's overexpression of CD44. Mounting evidence suggests that the breast cancer stem cell (BCSC) marker CD44 and the immune checkpoint PD-L1 contribute to treatment failure through their networks. Natural compounds can overcome therapy resistance in breast cancer by targeting mechanisms underlying resistance in BCSCs. This review provides an updated insight into the CD44 and PD-L1 networks of BCSCs in mediating metastasis and immune evasion. The review critically examines existing literature, providing a comprehensive understanding of the topic and emphasizing the impact of natural flavones on the signaling pathways of BCSCs. Additionally, the review discusses the potential of natural compounds in targeting CD44 and PD-L1 in breast cancer (BC). Natural compounds consistently show potential in targeting regulatory mechanisms of BCSCs, inducing loss of stemness, and promoting differentiation. They offer a promising approach for developing alternative therapeutic strategies to manage breast cancer.

Efficient synthesis and evaluation of therapeutic potential of fluorine containing 2-arylchromen-4-ones.

A large series of 2-arylchromen-4-ones containing from 1 to 3 fluorine atoms or a trifluoromethyl group in the structure was synthesized by condensation of fluorinated 2-hydroxyacetophenones with benzaldehydes in an alkaline medium and subsequent oxidative cyclization of the resulting 2'-hydroxychalcones by action of I2 in DMSO. The cytotoxicity of the obtained compounds was studied in glioblastoma cell line, SNB19, and in a monkey-derived normal kidney epithelium cell line, Vero. In addition, antiglycation activity of the obtained compounds was evaluated. The inhibitory activity of some fluorinated 2-arylchromen-4-ones against acetylcholinesterase, butyrylcholinesterase and carboxylesterase as well their primary antioxidant activity in ABTS and FRAP tests were investigated. Screening of the synthesized compounds for their inhibitory activity against influenza A virus A/Puerto Rico/8/34 (H1N1) in the MDCK cell culture revealed that fluorinated compounds 32, 31 and 39 showed manifest antiviral effects (with IS = 57, 38 and 25 correspondingly) that makes this series of new biologically attractive fluorinated heterocycles promising for further development and in-depth study.

Secondary Metabolites and Antioxidant Activity against Moko Disease as a Defense Mechanism of Musa spp. from the Ecuadorian Coast Area.

The Musa spp. represents the most commonly produced, transitioned, and consumed fruit around the globe, with several important applications in the biotechnology, pharmaceutical, and food industries. Moko disease is produced by Ralstonia solanacearum-a factor with a high impact on all crops in Ecuador, representing one of the biggest phytosanitary problems. Four of the most common varieties of Musa spp. were tested to identify the metabolic reaction of plants facing Moko disease. The phenolic and flavonoid content has been evaluated as a defense system, and the α-diphenyl-α-picrylhydrazyl free-radical-scavenging method (DPPH), free-radical-scavenging activity (ABTS), ferric-reducing antioxidant power (FRAP) assays, and liquid chromatography and mass spectrometry (LC-MS) have been adapted to analyze the active compounds with the antioxidant capacity necessary to counteract the pathogenic attack. Our results indicate that all the studied varieties of Musa spp. react in the same way, such that the diseased samples showed a higher accumulation of secondary metabolites with antioxidant capacity compared with the healthy ones, with high active compound synthesis identified during the appearance of Moko disease symptoms. More than 40 compounds and their derivatives (from kaempferol and quercetin glycosides) with protective roles demonstrate the implication of the Musa spp. defense system against R. solanacearum infection.

Structural and Interactional Analysis of the Flavonoid Pathway Proteins: Chalcone Synthase, Chalcone Isomerase and Chalcone Isomerase-like Protein.

Chalcone synthase (CHS) and chalcone isomerase (CHI) catalyze the first two committed steps of the flavonoid pathway that plays a pivotal role in the growth and reproduction of land plants, including UV protection, pigmentation, symbiotic nitrogen fixation, and pathogen resistance. Based on the obtained X-ray crystal structures of CHS, CHI, and chalcone isomerase-like protein (CHIL) from the same monocotyledon, Panicum virgatum, along with the results of the steady-state kinetics, spectroscopic/thermodynamic analyses, intermolecular interactions, and their effect on each catalytic step are proposed. In addition, PvCHI's unique activity for both naringenin chalcone and isoliquiritigenin was analyzed, and the observed hierarchical activity for those type-I and -II substrates was explained with the intrinsic characteristics of the enzyme and two substrates. The structure of PvCHS complexed with naringenin supports uncompetitive inhibition. PvCHS displays intrinsic catalytic promiscuity, evident from the formation of p-coumaroyltriacetic acid lactone (CTAL) in addition to naringenin chalcone. In the presence of PvCHIL, conversion of p-coumaroyl-CoA to naringenin through PvCHS and PvCHI displayed ~400-fold increased Vmax with reduced formation of CTAL by 70%. Supporting this model, molecular docking, ITC (Isothermal Titration Calorimetry), and FRET (Fluorescence Resonance Energy Transfer) indicated that both PvCHI and PvCHIL interact with PvCHS in a non-competitive manner, indicating the plausible allosteric effect of naringenin on CHS. Significantly, the presence of naringenin increased the affinity between PvCHS and PvCHIL, whereas naringenin chalcone decreased the affinity, indicating a plausible feedback mechanism to minimize spontaneous incorrect stereoisomers. These are the first findings from a three-body system from the same species, indicating the importance of the macromolecular assembly of CHS-CHI-CHIL in determining the amount and type of flavonoids produced in plant cells.

Antibacterial and Antioxidant Activity of Synthetic Polyoxygenated Flavonoids.

Flavonoids are an abundant class of naturally occurring compounds with broad biological activities, but their limited abundance in nature restricts their use in medicines and food additives. Here we present the synthesis and determination of the antibacterial and antioxidant activities of twenty-two structurally related flavonoids (five of which are new) by scientifically validated methods. Flavanones (FV1-FV11) had low inhibitory activity against the bacterial growth of MRSA 97-7. However, FV2 (C5,7,3',4' = OH) and FV6 (C5,7 = OH; C4' = SCH3) had excellent bacterial growth inhibitory activity against Gram-negative E. coli (MIC = 25 µg/mL for both), while Chloramphenicol (MIC = 25 µg/mL) and FV1 (C5,7,3' = OCH3; 4' = OH) showed inhibitory activity against Gram-positive L. monocytogenes (MIC = 25 µg/mL). From the flavone series (FO1-FO11), FO2 (C5,7,3',4' = OH), FO3 (C5,7,4' = OH; 3' = OCH3), and FO5 (C5,7,4' = OH) showed good inhibitory activity against Gram-positive MRSA 97-7 (MIC = 50, 12, and 50 µg/mL, respectively), with FO3 being more active than the positive control Vancomycin (MIC = 25 µg/mL). FO10 (C5,7= OH; 4' = OCH3) showed high inhibitory activity against E. coli and L. monocytogenes (MIC = 25 and 15 µg/mL, respectively). These data add significantly to our knowledge of the structural requirements to combat these human pathogens. The positions and number of hydroxyl groups were key to the antibacterial and antioxidant activities.

Coumarins and flavones from Ficus erecta and their anti-inflammatory activity.

ETHNOPHARMACOLOGICAL RELEVANCE: Ficus erecta, a traditional Chinese She Ethnomedicine, has been historically utilized to treat various inflammatory conditions such as arthritis, nephritis, and osteoporosis. However, the underlying mechanisms accounting for its anti-inflammatory activity, as well as its active components, largely remain elusive. AIM OF THE STUDY: The purpose of this research was to investigate the chemical constituents of F. erecta that contribute to its anti-inflammatory effects. MATERIALS AND METHODS: Coumarins and flavones were obtained from the 95% EtOH extract of F. erecta using virous column chromatography and reversed-phase semipreparative HPLC. The structures of the new compounds were elucidated by extensive analysis of spectroscopic methods, including HRESIMS, 1D and 2D NMR spectra, and CD experiments. Cultured macrophage RAW264.7 cells were utilized for the anti-inflammatory experiments. MTT cell viability assay, Griess reagent method, ELISA, and Western blot experiments were employed to evaluate the anti-inflammatory activity and investigate the related mechanism. RESULTS: Four new (1-4) and eleven previously identified (5-16) coumarins, together with one new (17) and six known flavones (18-23) were isolated from the whole plant of F. erecta. Compounds 7 and 17 significantly reduced nitric oxide (NO) and prostaglandin E2 (PGE2) production without cytotoxic effects. Furthermore, compounds 7 and 17 reduced the production of proinflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 in a concentration-dependent manner. Western blot analysis indicated that compounds 7 and 17 suppressed the expression of iNOS, COX-2, and p-IκBα in LPS-stimulated RAW264.7 macrophage cells. CONCLUSION: The current phytochemical investigations revealed that coumarins and flavones represent the primary chemical constituents of F. erecta. Compounds 7 and 17 exhibit potent anti-inflammatory properties, linked with the inhibition of NF-κB activation by preventing the degradation of IκBα phosphorylation. These compounds may serve as promising candidates for treating or preventing certain inflammatory diseases.

Efficacy of substances containing 3 types of active ingredients-saponins, flavones, and alkaloids in regulation of cytokines in autoimmune diseases a systematic review and Meta-analysis based on animal studies.

OBJECTIVE: To investigate the efficacy of substances containing 3 types of active ingredients-saponins, flavones, and alkaloids on experimental animals with autoimmune diseases (AIDs). METHODS: The protocol for this systematic review and Meta-analysis was prospectively registered with PROSPERO (CRD42023395741). Searches were conducted in the China National Knowledge Infrastructure, Wanfang, Chinese Science and Technology Journals, China Biomedical, PubMed, Cochrane Library, and Embase databases to screen for animal studies investigating the therapeutic effects of saponins, flavones, or alkaloids on autoimmune diseases; consequently, corresponding data extraction tables were prepared. Systematic Review Centre for Laboratory Animal Experimentation was used to assess the risk of methodological bias in the included literature. RevMan 5.4 was used for the Meta-analysis on the 8 serum cytokines. RESULTS: A total of 31 studies were included, all of which were randomized controlled studies. Meta-analysis indicated that substances rich in saponins, flavones, and alkaloids reduced serum levels of interleukin (IL)-1ß [standardized mean difference (SMD) = -1.94, 95% confidence interval (CI) (-2.99, -0.90), P = 0.0003], IL-6 [SMD = -1.65, 95% CI (-2.33, -0.97,) P < 0.000 01], IL-17 [SMD = -2.41, 95% CI (-3.61, -1.20), P < 0.0001], tumor necrosis factor (TNF)-α [SMD = -1.84, 95% CI (-2.61, -1.06), P < 0.0001], and interferon (IFN)-γ [SMD = -1.54, 95% CI (-2.43, -0.65), P = 0.0007], but increased serum levels of IL-4 [SMD = 1.30, 95% CI (0.15, 2.44), P = 0.03) and IL-10 [SMD = 2.05, 95% CI (1.39, 2.70), P < 0.000 01) in animal models. However, no significant regulatory effect of these three active components was observed on serum levels of IL-2 [SMD = -0.63, 95% CI (-1.82, 0.57), P = 0.30]. CONCLUTIONS: Substances containing saponins, flavones, and alkaloids regulated the changes of immune-related cytokines, it may be a novel dietary substance to relieve and control autoimmune diseases in the future.

Polymethoxylated flavones from the leaves of Vitex negundo have fungal-promoting and antibacterial activities during the production of broad bean koji.

Broad bean paste is a popular condiment in Asian countries. Leaves of Vitex negundo Linn. were used extensively in China during the koji-making of broad bean paste. Spreading V. negundo leaves on raw broad beans during fermentation was able to facilitate the rapid growth of fungi to form mature koji. We isolated two strains of fungi from mature koji, and four strains of bacteria from the rotten broad beans resulting from a failed attempt. According to microbial activity assays, two polymethoxylated flavones, 5-hydroxy-3,6,7,8,3',4'-hexamethoxy flavone (HJ-1) and 5,4'-dihydroxy-3,6,7,8,3'-pentamethoxy flavone (HJ-2) were isolated from V. negundo leaves, and the fungal growth promotion and inhibition of bacterial growth of these two compounds were found to improve the production of broad bean koji. This study reveals the compounds present in V. negundo leaves with bioactivity against important microbes in koji manufacture, and provides a theoretical basis for the application of V. negundo in broad bean paste production.

Antigout effects and mechanisms of total flavonoids from prunus tomentosa.

BACKGROUND: In recent years, hyperuricemia and acute gouty arthritis have become increasingly common, posing a serious threat to public health. Current treatments primarily involve Western medicines with associated toxic side effects. OBJECTIVE: This study aims to investigate the therapeutic effects of total flavones from Prunus tomentosa (PTTF) on a rat model of gout and explore the mechanism of PTTF's anti-gout action through the TLR4/NF-κB signaling pathway. METHODS: We measured serum uric acid (UA), creatinine (Cr), blood urea nitrogen (BUN), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), and interleukin-6 (IL-6) levels using an enzyme-linked immunosorbent assay (ELISA). Histopathological changes were observed using HE staining, and the expression levels of relevant proteins were detected through Western blotting. RESULTS: After PTTF treatment, all indicators improved significantly. PTTF reduced blood levels of UA, Cr, BUN, IL-1ß, IL-6, and TNF-α, and decreased ankle swelling. CONCLUSIONS: PTTF may have a therapeutic effect on animal models of hyperuricemia and acute gouty arthritis by reducing serum UA levels, improving ankle swelling, and inhibiting inflammation. The primary mechanism involves the regulation of the TLR4/NF-κB signaling pathway to alleviate inflammation. Further research is needed to explore deeper mechanisms.

The interaction of plant flavones with amphotericin B: Consequences for its pore-forming ability.

The growth of antibiotic resistance to antifungal drugs contributes to the search for new ways to enhance their effectiveness and reduce toxicity. The undeniable advantage of polyene macrolide antibiotic amphotericin B (AmB) which ensures low pathogen resistance is its mechanism of action related to the formation of transmembrane pores in target lipid membranes. Here, we investigated the effects of plant flavones, chrysin, wogonin, baicalein, apigenin, scutellarein, luteolin, morin and fisetin on the pore-forming activity of AmB in the sterol-enriched membranes by electrophysiological assays. Сhrysin, wogonin, baicalein, apigenin, scutellarein, and luteolin were shown to decrease the AmB pore-forming activity in the bilayers composed of palmitoyloleylphosphocholine independently of their sterol composition. Morin and fisetin led to the increase and decrease in the AmB pore-forming activity in the ergosterol- and cholesterol-containing bilayers respectively. Differential scanning microcalorimetry of the gel-to-liquid crystalline phase transition of membrane forming lipids, molecular dynamics simulations, and absorbance spectroscopy revealed the possibility of direct interactions between AmB and some flavones in the water and/or in the lipid bilayer. The influence of these interactions on the antibiotic partitioning between aqueous solution and membrane and/or its transition between different states in the bilayer was discussed.