Monomeric Flavonoids Research Articles

Diosmetin Promotes Early Embryonic Development in Pigs by Alleviating Oxidative Stress.

Diosmetin (DIOS), a natural flavonoid monomer derived from lemons and present in various plants such as spearmint and spider moss, exhibits antioxidant, anti-inflammatory, and antiaging properties. Nonetheless, its impact on early embryonic development in pigs remains unexplored. This study aimed to determine the influence of DIOS supplementation in an in vitro culture (IVC) medium on porcine embryo development and to elucidate the underlying mechanisms. Findings revealed that embryos cultured in IVC medium with 0.1 μM DIOS demonstrated an increased blastocyst formation rate, higher total cell number, reduced LC3B and CASPASE3 levels, elevated Nrf2 levels, decreased ROS, and enhanced GSH and mitochondrial membrane potential at the 4-cell embryonic stage. Additionally, the expression of proapoptotic genes (CAS3, CAS8, and BAX) and autophagy-related genes (BECLIN1, ATG5, LC3B, and P62) was downregulated, whereas the expression of embryonic development-related genes (CDK1 and CDK2), antioxidant-related genes (SOD1 and SOD2), and mitochondrial biogenesis-related genes (NRF2) was upregulated. These findings suggest that DIOS promotes early embryonic development in pigs by mitigating oxidative stress and enhancing mitochondrial function, thereby reducing autophagy and apoptosis levels.

Functional characterization of TrGSTF15, a glutathione S-transferase gene family member, on the transport and accumulation of anthocyanins and proanthocyanidins in Trifolium repens

Anthocyanins and proanthocyanidins (PAs) are important secondary metabolites in plants, high contents of which are an important goal for quality breeding of white clover (Trifolium repens). However, the involvement of glutathione S-transferase (GST) in the transport of anthocyanins and PAs remains unexplored in white clover. This study identified 153 different TrGSTs in white clover. At the transcriptional level, compared to other TrGSTFs, TrGSTF10 and TrGSTF15 are highly expressed in the ‘Purple’ white clover, and they may work with the anthocyanin biosynthesis structural genes CHS and CHI to contribute to pigment buildup in white clover. Subcellular localization confirmed that TrGSTF10 and TrGSTF15 are located in the cytoplasm. Additionally, molecular docking experiments showed that TrGSTF10 and TrGSTF15 have similar binding affinity with two flavonoid monomers. Overexpression of TrGSTF15 complemented the deficiency of anthocyanin coloring and PA accumulation in the Arabidopsis tt19 mutant. The initial findings of this research indicate that TrGSTF15 encodes an important transporter of anthocyanin and PA in white clover, thus providing a new perspective for the further exploration of related transport and regulatory mechanisms.

Evaluation of the stabilizing effect and ageing time indicator properties of poly(flavonoids) in a cyclic olefin copolymer

Few studies are concerned with the stabilization of polymers using natural polymeric polyphenols. There are no literature reports on the use of poly(flavonoids) produced by bio-chemical polymerization as stabilizers. The aim of the research was to analyse the stabilizing potential (anti-ageing UV) of poly(catechin) and poly(naringenin) in polymer compositions based on the thermoplastic elastomer of ethylene-norbornene copolymer (TOPAS Elastomer E-140). Poly(flavonoids) were obtained in a polymerization reaction with a cross-linking compound and then introduced into cyclic olefin copolymer TOPAS. For comparison, materials with monomeric catechin and naringenin were also prepared. The scope of research included the thermal analysis of the polymer compositions (Oxidation induction time OIT, Thermogravimetry TG), determination of carbonyl indices and ageing coefficients K (based on changes in mechanical properties) after UV ageing (400 h). In addition, the colour change after ageing of the samples was investigated. Samples containing polymeric forms of catechin and naringenin were more susceptible to degradation than samples with monomeric flavonoids. Inferior stabilizing properties of poly(flavonoids) were associated with steric hindrances and limited availability of hydroxyl groups to provide the antioxidant activity of the polymeric compounds. The work extends the literature data by providing an analysis of the stabilizing effect of synthetic poly(flavonoids) in polymer compositions.

Extraction of polyphenolic compounds from ginkgo leaves using deep eutectic solvents: A potential solution for the sustainable and environmentally friendly isolation of biflavonoids

Ginkgo (Ginkgo biloba L.) is one of the oldest trees on earth and its leaves are traditionally used as herbal medicine. The beneficial effects of ginkgo leaves are attributed to the presence of flavonoids and terpene trilactones. Monomeric flavonoids are frequently studied, but recently much attention has been paid to biflavonoids, dimeric flavonoids, due to their biological activity and potential pharmaceutical use. The development of a suitable and effective extraction protocol focusing on biflavonoids is increasingly in demand. Therefore, in this study, we developed an optimized extraction protocol using deep eutectic solvents (DESs) to extract flavonoids from ginkgo leaves, with special attention to biflavonoids. Initially, 250 DESs were screened using COSMOtherm software to identify those that could strongly solubilize biflavonoids and flavonoids, and the results obtained indicated 15 DESs. Among them, betaine: ethylene glycol (B:EG) 1:2 with 30 % H2O (w/w) showed higher extraction efficiency than the extraction performed with 80 % methanol. In a next step, the extraction with the selected DES was further optimized using a Box-Behnken experimental design. The results obtained showed that the optimum extraction conditions using the selected DES were as follows: Extraction time 45 minutes, the ratio of the initial mass of the shredded leaves to the volume of the DES 20:1 and the temperature 20 °C. Finally, the concentrations of the 5 most abundant biflavonoids in ginkgo leaves (amentoflavone, ginkgetin, isoginkgetin, bilobetin and sciadopitysin) in the extracts were determined using HPLC-DAD. The results showed that B:EG 1:2 with 20 % H2O (w/w) and 30 % H2O (w/w) were suitable for the extraction of all five biflavonoids.

Multiomics Analyses Reveal MsC3H29 Positively Regulates Flavonoid Biosynthesis to Improve Drought Resistance of Autotetraploid Cultivated Alfalfa (Medicago sativa L.).

Alfalfa (Medicago sativa subsp. sativa), the "queen of forage," is the most important perennial legume, with high productivity and an excellent nutritional profile. Medicago sativa subsp. falcata is a subspecies of the alfalfa complex and exhibits better drought tolerance. However, drought stress significantly hampers their development and yield. The molecular mechanisms underlying the aboveground and underground tissues of sativa and falcata responding to drought stress remain obscure. Here, we performed a comprehensive comparative analysis of the physiological and transcriptomic responses of sativa and falcata under drought stress. The results showed that photosynthesis was inhibited, and antioxidant enzymes were activated under drought stress. MsC3H29, a CCCH-type zinc finger protein, was identified as a hub gene through weighted gene coexpression network analysis (WGCNA) and was significantly induced by drought in underground tissue. The MsC3H29 protein was localized in the nucleus. Overexpression (OE) of MsC3H29 can increase the primary root length and fresh weight of transgenic alfalfa hairy roots, while RNA interference (RNAi) decreases them under drought stress. The 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA) staining revealed that MsC3H29 promoted drought tolerance of alfalfa hairy roots through decreasing ROS accumulation. The targeted metabolome analysis showed that the overexpression of MsC3H29 resulted in higher levels of accumulation for flavonoid monomers, including vicenin, daidzein, apigenin, isorhamnetin, quercetin, and tricin, in transgenic alfalfa hairy roots before and after drought stress, while RNAi led to a reduction. Our study provided a key candidate gene for molecular breeding to improve drought resistance in alfalfa.

The associations between dietary flavonoids intake and risk of depressive symptom in diabetic patients: Data from NHANES 2007–2008, 2009–2010, and 2017–2018

BackgroundThe increasing incidence of depressive symptoms in diabetic patients contributes to the global burden of disease, but few epidemiological studies have evaluated the relationship between dietary flavonoids intake and depressive symptoms in diabetic patients in American adults. ObjectiveThis study intended to evaluate the associations of dietary flavonoids intake and depressive symptoms in diabetic patients in American adults. MethodsWe conducted a cross-sectional analysis of 1993 adults aged ≥20 years old who participated in the 2007–2008, 2009–2010, and 2017–2018 National Health and Nutrition Examination Surveys (NHANES). Chi-square test and independent-sample t-test were used to compare subjects' characteristics. Logistic regression model was further used to analyze the relationship between dietary flavonoid intake and depressive symptoms in diabetic patients. Restricted cubic spline (RCS) analysis was used to investigate the non-linear relationship between dietary flavonoid intake and the prevalence of depressive symptoms in diabetic patients. The weighted quartile sum (WQS) regression was used to analyze the effect of 29 flavonoids monomers. ResultsThe results showed that the total flavonoid intake in the third quartile (OR, 0.635; 95 % CI,0.419–0.962; P, 0.032) was significantly associated with a reduced risk of depressive symptoms in diabetic patients compared with the lowest quartile. And there was a U-shaped association between dietary flavonoid intake and risk of depressive symptoms in diabetic patients. Top contributors of flavonoid monomers were eriodictyol, naringenin, and theaflavin-3′-gallate, accounting for a percentage of 30.83 %, 22.17 %, and 6.92 %, respectively. ConclusionModerate (56.07–207.12 mg/day) dietary flavonoid intake was associated with a reduced risk of depressive symptoms in diabetic patients. The important flavonoid monomers were eriodictyol, naringenin, and theaflavin-3′-gallate.

Enantioselective Synthesis of Flavonoids and Their Diverse Applications in Nutrition, Health, and Medicine: A Mini Review

AbstractEnantioselective synthesis, which yields one enantiomer in higher concentration or purity than the other, has transformed the production of flavonoids. Flavonoids, which are found in large quantities in nature and are known to exhibit a diverse array of physiological activities, are an ideal choice for enantioselective synthesis due to the significance of chirality in their therapeutic effects. Enantioselective synthesis is used in the medicinal, nutraceutical, and agrochemical sectors to produce flavonoids, which are useful in the development of novel therapeutics with improved effectiveness and fewer adverse reactions. The ability to obtain specific enantiomers of flavonoids facilitates the elucidation of biochemical strategies and the relationship between structure and activity, thereby providing avenues for tailored drug design and optimization. This review highlights the critical role that enantioselective synthesis plays in achieving the full potential of flavonoids for a variety of therapeutic and non‐therapeutic applications. It also discusses the challenges and prospects of enantioselective syntheses to create relevant classes of flavonoid monomers, emphasizing their applications in the field. The review focused on the synthetic methods for fabricating native flavonoids and their analogs, highlighting the critical role that enantioselective synthesis of flavonoids plays in maximizing their therapeutic potential for enhancing human health and wellbeing.

Isoliquiritigenin reduces experimental autoimmune prostatitis by facilitating Nrf2 activation and suppressing the NLRP3 inflammasome pathway

BackgroundChronic prostatitis and chronic pelvic pain syndrome (CP/CPPS) lead to severe irritation and impaired sperm quality in males. However, current therapeutic options often fail to achieve satisfactory effects. Consequently, the investigation of novel treatment strategies or remedies holds substantial clinical importance. As a flavonoid monomer, isoliquiritigenin (ISL) has been shown to possess anti-inflammatory activity, especially in several chronic nonspecific-inflammatory conditions. Thus, an exploration of the possible anti-inflammatory effects of ISL on CP/CPPS, a chronic aseptic inflammation of the prostate, has significant potential. MethodsAn experimental autoimmune prostatitis (EAP) model was used for the evaluation of the anti-inflammatory effects of ISL. It was found that ISL treatment could reduce the secretion and invasion of pro-inflammatory cytokines in prostate tissue. In EAP mice, ISL treatment also reduced oxidative stress (OS) and activation of the NLRP3 inflammasome. In vitro, ISL upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and inhibited NLRP3 inflammasome activation in RAW264.7 macrophages exposed to lipopolysaccharide (LPS). ResultsTreatment with ISL treatment relieved prostate inflammation and pelvic pain in EAP mice. Both in vivo and in vitro, ISL treatment activated Nrf2/HO-1 signaling, which in turn inhibited oxidative stress and activation of the NLRP3 inflammasome. Blockade of Nrf2/HO-1 signaling abolished the inhibitory effects of ISL on oxidative stress and NLRP3 inflammasome activation. ConclusionsIsoliquiritigenin reduced experimental autoimmune prostatitis by facilitating Nrf2 activation and suppressing the NLRP3 inflammasome pathway.

Quercetin-loaded mesoporous nano-delivery system remodels osteoimmune microenvironment to regenerate alveolar bone in periodontitis via the miR-21a-5p/PDCD4/NF-κB pathway

BackgroundImpaired osteo-/angiogenesis, excessive inflammation, and imbalance of the osteoimmune homeostasis are involved in the pathogenesis of the alveolar bone defect caused by periodontitis. Unfortunately, there is still a lack of ideal therapeutic strategies for periodontitis that can regenerate the alveolar bone while remodeling the osteoimmune microenvironment. Quercetin, as a monomeric flavonoid, has multiple pharmacological activities, such as pro-regenerative, anti-inflammatory, and immunomodulatory effects. Despite its vast spectrum of pharmacological activities, quercetin’s clinical application is limited due to its poor water solubility and low bioavailability.ResultsIn this study, we fabricated a quercetin-loaded mesoporous bioactive glass (Quercetin/MBG) nano-delivery system with the function of continuously releasing quercetin, which could better promote the bone regeneration and regulate the immune microenvironment in the alveolar bone defect with periodontitis compared to pure MBG treatment. In particular, this nano-delivery system effectively decreased injection frequency of quercetin while yielding favorable therapeutic results. In view of the above excellent therapeutic effects achieved by the sustained release of quercetin, we further investigated its therapeutic mechanisms. Our findings indicated that under the periodontitis microenvironment, the intervention of quercetin could restore the osteo-/angiogenic capacity of periodontal ligament stem cells (PDLSCs), induce immune regulation of macrophages and exert an osteoimmunomodulatory effect. Furthermore, we also found that the above osteoimmunomodulatory effects of quercetin via macrophages could be partially blocked by the overexpression of a key microRNA——miR-21a-5p, which worked through inhibiting the expression of PDCD4 and activating the NF-κB signaling pathway.ConclusionIn summary, our study shows that quercetin-loaded mesoporous nano-delivery system has the potential to be a therapeutic approach for reconstructing alveolar bone defects in periodontitis. Furthermore, it also offers a new perspective for treating alveolar bone defects in periodontitis by inhibiting the expression of miR-21a-5p in macrophages and thereby creating a favorable osteoimmune microenvironment.Graphical

The inhibition of β-catenin activity by luteolin isolated from Paulownia flowers leads to growth arrest and apoptosis in cholangiocarcinoma

To develop an inhibitor targeting the Wnt/β-catenin signaling pathway, flavonoid monomer that can interact with β-catenin was isolated from Paulownia flowers. Luteolin may form stable hydrogen bonds with β-catenin by molecular docking. Fluorescence quenching analysis determined the physical interaction between luteolin and β-catenin. The binding of luteolin to β-catenin caused a loss of α-helical structure and induced a conformational change through circular dichroism spectroscopy. Luteolin inhibits the activity of the Wnt signaling, causing cholangiocarcinoma (CCA) cell cycle arrest in the G2/M phase, leading to cell apoptosis and inhibition of cell migration. In addition, transcriptome and proteomics analysis showed that the differentially expressed proteins were significantly enriched in the Wnt/β-catenin pathway. β-catenin protein in the nucleus was significantly decreased, while C-Myc and cyclin D1 in the CCA cells were significantly decreased after luteolin treatment. Additionally, activation of the Wnt/β-catenin signaling reversed the inhibitory effect of luteolin on the migration of CCA cells. Therefore, luteolin can directly interact with β-catenin and act as an inhibitor of β-catenin, inhibiting proliferation and reducing the migration ability of CCA cells by inhibiting the Wnt/β-catenin pathway. This study provides a scientific basis for the development of Wnt/β-catenin pathway inhibitors and the prevention and treatment of CCA.

A Comparative Analysis of Radical Scavenging, Antifungal and Enzyme Inhibition Activity of 3'-8″-Biflavones and Their Monomeric Subunits.

Biflavonoids are dimeric forms of flavonoids that have recently gained importance as an effective new scaffold for drug discovery. In particular, 3'-8″-biflavones exhibit antiviral and antimicrobial activity and are promising molecules for the treatment of neurodegenerative and metabolic diseases as well as cancer therapies. In the present study, we directly compared 3'-8″-biflavones (amentoflavone, bilobetin, ginkgetin, isoginkgetin, and sciadopitysin) and their monomeric subunits (apigenin, genkwanin, and acacetin) and evaluated their radical scavenging activity (with DPPH), antifungal activity against mycotoxigenic fungi (Alternaria alternata, Aspergillus flavus, Aspergillus ochraceus, Fusarium graminearum, and Fusarium verticillioides), and inhibitory activity on enzymes (acetylcholinesterase, tyrosinase, α-amylase, and α-glucosidase). All the tested compounds showed weak radical scavenging activity, while antifungal activity strongly depended on the tested concentration and fungal species. Biflavonoids, especially ginkgetin and isoginkgetin, proved to be potent acetylcholinesterase inhibitors, whereas monomeric flavonoids showed higher tyrosinase inhibitory activity than the tested 3'-8″-biflavones. Amentoflavone proved to be a potent α-amylase and α-glucosidase inhibitor, and in general, 3'-8″-biflavones showed a stronger inhibitory potential on these enzymes than their monomeric subunits. Thus, we can conclude that 3'-8″-dimerization enhanced acetylcholinesterase, α-amylase, and α-glucosidase activities, but the activity also depends on the number of hydroxyl and methoxy groups in the structure of the compound.

Vitexin ameliorated diabetic nephropathy via suppressing GPX4-mediated ferroptosis

Diabetic nephropathy (DN) is common complication of diabetes. Ferroptosis is an atypical form of iron-dependent modulated necrosis and have been proven to contribute to the progress of diabetic nephropathy. Vitexin, a flavonoid monomer derived from medicinal plants that has various biological activities including anti-inflammatory and anticancer effects, has not been investigated in diabetic nephropathy studies. However, whether vitexin has a protective effect on diabetic nephropathy remains unclear. In this study, the roles and mechanism of vitexin on alleviating DN were explored in vivo and in vitro. The protective effect of vitexin in diabetic nephropathy were evaluated by in vitro and in vivo experiment. In this research, we validated that vitexin protect HK-2 against HG-induced damage. Besides, vitexin pretreatment also reduced fibrosis (Collagen type I Col I, TGF-β1). Furthermore, vitexin inhibited ferroptosis induced by HG, accompanied by changes of morphological, decrease of ROS, Fe2+ and MDA, and increased GSH levels. Meanwhile, vitexin up-regulated the protein expression of GPX4 and SLC7A11 in HG-induced HK-2 cells. Moreover, knockdown of GPX4 by shRNA migrated the protective effect of vitexin on HG-challenged HK-2 and reversed the ferroptosis induced by vitexin. Consistent with in vitro, vitexin alleviated renal fibrosis, damage and ferroptosis in DN rat. In conclusion, our findings revealed that vitexin could alleviate diabetic nephropathy by attenuated ferroptosis via activating GPX4.

Identification of Binding Sites in the Nucleotide-Binding Domain of P-Glycoprotein for a Potent and Nontoxic Modulator, the Amine-Containing Monomeric Flavonoid FM04.

We have previously discovered an amine-containing flavonoid monomer FM04 as a potent P-glycoprotein (P-gp) inhibitor (EC50 = 83 nM). Here, a series of photoactive FM04 analogues were synthesized and used together with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify the FM04-binding sites on P-gp. Point mutations around the photo-crosslinked sites were made for verification. Together with the results from mutational studies, molecular docking, and molecular dynamics simulations, it was found that FM04 can interact with Q1193 and I1115 in the nucleotide-binding domain 2 (NBD2) of human P-gp. It was proposed that FM04 can inhibit P-gp in 2 novel mechanisms. FM04 can either bind to (1) Q1193, followed by interacting with the functionally critical residues H1195 and T1226 or (2) I1115 (a functionally critical residue itself), disrupting the R262-Q1081-Q1118 interaction pocket and uncoupling ICL2-NBD2 interaction and thereby inhibiting P-gp. Q1118 would subsequently be pushed to the ATP-binding site and stimulate ATPase.

Amentoflavone inhibits hepatitis B virus infection via the suppression of preS1 binding to host cells.

Hepatitis B virus (HBV) is a leading cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Current therapeutic drugs for chronic HBV infection use IFN and nucleos(t)ide analogs; however, their efficacy is limited. Thus, there is an urgent need to develop new antivirals for HBV therapy. In this study, we identified a plant-derived polyphenolic bioflavonoid, amentoflavone, as a new anti-HBV compound. Amentoflavone treatment dose-dependently inhibited HBV infection in HBV-susceptible cells with HepG2-hNTCP-C4 and primary human hepatocyte PXB-cells. A mode-of-action study showed that amentoflavone inhibits the viral entry step, but not the viral internalization and early replication processes. Attachment of HBV particles as well as HBV preS1 peptide to HepG2-hNTCP-C4 cells was inhibited by amentoflavone. The transporter assay revealed that amentoflavone partly inhibits uptake of sodium taurocholate cotransporting polypeptide (NTCP)-mediated bile acid. Furthermore, effect of various amentoflavone analogs on HBs and HBe production from HBV-infected HepG2-hNTCP-C4 cells was examined. Robustaflavone exhibited comparable anti-HBV activity to that of amentoflavone and an amentoflavone-7,4', 4‴-trimethyl ether derivative (sciadopitysin) with moderate anti-HBV activity. Cupressuflavone or the monomeric flavonoid apigenin did not exhibit the antiviral activity. Amentoflavone and its structurally related biflavonoids may provide a potential drug scaffold in the design of a new anti-HBV drug inhibitor targeting NTCP.

Anti-Helicobacter pylori activity of Fagopyrum Tataricum (L.) Gaertn. Bran flavonoids extract and its effect on Helicobacter pylori-induced inflammatory response.

Tartary buckwheat flavonoids have a variety of effects on anti-inflammatory, anti-oxidation, as well as anti-tumor and are valuable for academic research and industrial application. Helicobacter pylori (H.pylori) infection is associated with various gastrointestinal diseases in humans, and an increase in its resistance has led to the failure of many drugs. In this study, we quantified the main monomers of tartary buckwheat (Fagopyrum Tataricum (L.) Gaertn.) bran flavonoids extract through HPLC analysis. Then, we investigated the anti-H.pylori activity and the effect on cell inflammation of tartary buckwheat flavonoids extract and its four main flavonoid monomers (rutin, quercetin, kaempferol, and nicotiflorin). The results showed that tartary buckwheat flavonoids extract and its four flavonoid monomers could inhibit the growth of H.pylori and down-regulate the expression of proinflammatory factors IL-6, IL-8, and CXCL-1 in H.pylori-induced GES-1 cells. Moreover, we also confirmed that tartary buckwheat flavonoids extract could reduce the expression of virulence factor gene of H.pylori. In summary, tartary buckwheat can alleviate the cell inflammation induced by H.pylori, which provides a theoretical basis for the development of tartary buckwheat healthcare products.

The research progress on the anxiolytic effect of plant-derived flavonoids by regulating neurotransmitters.

Phytopharmaceuticals have attracted a lot of attention due to their multicomponent and multiple targets. The natural phenolic chemicals known as flavonoids are found in a wide variety of plants, fruits, vegetables, and herbs. Recently, they have been found to have modulatory effects on anxiety disorders, with current research focusing on the modulation of neurotransmitters. There has not yet been a review of the various natural flavonoid monomer compounds and total plant flavonoids that have been found to have anxiolytic effects. The study on the anti-anxiety effects of plant-derived flavonoids on neurotransmitters was reviewed in this paper. We, therefore, anticipate that further study on the conformational interaction underlying flavonoids' anti-anxiety effects will offer a theoretical framework for the creation of pertinent treatments.

Effects of flavonoids on membrane adaptation of food-associated bacteria

The effects of naringenin and the biflavonoids amentoflavone and tetrahydroamentoflavone on select bacterial lipids (carotenoids, fatty acids, and menaquinones) and membrane fluidity based on Laurdan generalized polarization were investigated. For this purpose, the pigment-forming food-associated microorganisms Staphylococcus xylosus (DSM 20266T and J70), Staphylococcus carnosus DSM 20501T, and Micrococcus luteus (ATCC 9341 and J3) were studied.The results suggest an envelope stress response by microorganisms due to flavonoids and an employment of adaptive mechanisms using carotenoids, fatty acids, and menaquinones. The flavonoid monomer naringenin impacted carotenoids, fatty acids, menaquinones, and membrane fluidity. Naringenin significantly influenced the carotenoid profile, particularly by an increase in the relative proportion of 4,4′-diaponeurosporenoic acid in Staphylococcus xylosus. Amentoflavone caused changes mainly in the membrane of Micrococcus luteus and decreased the menaquinone content. Tetrahydroamentoflavone mainly affected the carotenoids in the investigated strains.The noticeably different CCS value of tetrahydroamentoflavone compared to naringenin and amentoflavone revealed further insights into the structure-dependent effects of flavonoids.This study provides valuable insights into the response of pigment-forming food-associated microorganisms to naringenin, amentoflavone, and tetrahydroamentoflavone, which is important for the targeted and safe application of the latter as natural preservatives and useful for further research on the mechanisms of action.

Regulation of myocardial ischemia reperfusion injury signal pathway by flavonoid monomer

Acute myocardial infarction seriously endangers the health of people due to its high morbidity and high mortality. Reperfusion strategy is the preferred treatment strategy for acute myocardial infarction. However, reperfusion may lead to additional heart damage, namely myocardial ischemia reperfusion injury(MIRI). Therefore, how to reduce myocardial ischemia reperfusion injury has become one of the urgent problems to be solved in cardiovascular disease. Traditional Chinese medicine(TCM) has the multi-component, multi-channel, and multi-target advantages in the treatment of MIRI, which offers new ideas in this aspect. TCM containing flavonoids has a variety of biological activities and plays a significant role in the treatment of MIRI, which has great research and development application value. TCM containing flavonoids can regulate multiple signaling pathways of MIRI, such as phosphatidylinositol 3 kinase/kinase B(PI3K/Akt) signaling pathway, Janus kinase/signal transducer and activator of transcriptions(JAK/STAT) signaling pathway, adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK) signaling pathway, mitogen-activated protein kinase(MAPK) signaling pathway, nuclear factor-erythroid 2-related factor 2/antioxidant response element(Nrf2/ARE) signaling pathway, nuclear factor kappa-B(NF-κB) signaling pathway, silent information regulator 1(Sirt1) signaling pathway, and Notch signaling pathway. It reduces MIRI by inhibiting calcium overload, improving energy metabolism, regulating autophagy, and inhibiting ferroptosis and apoptosis. Therefore, a review has been made based on the regulation of relative signaling pathways against MIRI by TCM containing flavonoids, thus providing theoretical support and potential therapeutic strategies for TCM to alleviate MIRI.

Wogonoside improves high-fat diet-induced hyperlipidemia and aortic injury in ApoE -/- mice by upregulating SIRT1 expression

This study aimed to evaluate the effect of Wogonoside (Wog), a flavonoid monomer, on hyperlipidemia and explore its possible mechanisms. APOE -/- mice were used to establish the animal model of hyperlipidemia by feeding the high-fat diet (HFD). The serum level of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), and inflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA), oil red O staining, and real-time PCR assay. The oxidative stress was measured by ELISA assay. Immunoblot assay and ELISA assay were used to detect the mechanism of Wogonoside on hyperlipidemia. We found that Wogonoside ameliorated lipid metabolism disorders in ApoE -/- mice induced by HFD (P<0.01). Wogonoside also ameliorated HFD-induced inflammation in ApoE -/- mice (P<0.01). Wogonoside ameliorated oxidative stress in HFD-induced ApoE -/- mice (P<0.01). Further study showed that Wogonoside improved HFD-induced hyperlipidemia and inflammation by upregulating SIRT1 expression (P<0.01). These results suggested that Wogonoside has the potential to be used as a promising approach for the intervention of hyperlipidemia.

Tissue-Specific Profiling of Biflavonoids in Ginkgo (Ginkgo biloba L.).

Biflavonoids are flavonoid dimers that are much less studied than monomeric flavonoids. Their precise distribution among plants and their role in plants is still unknown. Here, we have developed a HPLC-DAD method that allows us to separate and simultaneously determine the five major biflavonoids (amentoflavone, bilobetin, ginkgetin, isoginkgetin, and sciadopitysin) in ginkgo (Ginkgo biloba L.). We performed tissue-specific profiling of biflavonoids in ten different plant parts: tree bark, twigs bark, twigs without bark, buds, leaf petioles, leaf blades, seed stalks, sarcotesta, nutshells, and kernels. We did not detect biflavonoids in plant parts not in direct contact with the environment (twigs without bark, nutshells, and kernels). We found the highest total biflavonoids content in leaves, where sciadopitysin was predominant. In contrast, in the bark, amentoflavone was the predominant biflavonoid, suggesting that more methylated biflavonoids accumulate in leaves and seeds. This is probably related to their biological function, which remains to be determined.