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The term "Long-COVID" (LC) is characterized by the aftereffects of COVID-19 infection. Various studies have suggested that Epstein-Barr virus (EBV) reactivation is among the significant reported causes of LC. However, there is a lack of in-depth research that could largely explore the pathogenic mechanism and pinpoint the key genes in the EBV and LC context. This study mainly aimed to predict the potential disease-associated common genes between EBV reactivation and LC condition using next-generation sequencing (NGS) data and reported naturally occurring biomolecules as inhibitors. We applied the bulk RNA-Seq from LC and EBV-infected peripheral blood mononuclear cells (PBMCs), identified the differentially expressed genes (DEGs) and the Protein-Protein interaction (PPI) network using the STRING database, identified hub genes using the cytoscape plugins CytoHubba and MCODE, and performed enrichment analysis using ClueGO. The interaction analysis of a hub gene was performed against naturally occurring bioflavonoid molecules using molecular docking and the molecular dynamics (MD) simulation method. Out of 357 common genes, 22 genes (CCL2, CCL20, CDCA2, CEP55, CHI3L1, CKAP2L, DEPDC1, DIAPH3, DLGAP5, E2F8, FGF1, NEK2, PBK, TOP2A, CCL3, CXCL8, DEPDC1, IL6, RETN, MMP2, LCN2, and OLR1) were classified as hub genes, and the remaining ones were classified as neighboring genes. Enrichment analysis showed the role of hub genes in various pathways such as immune-signaling pathways, including JAK-STAT signaling, interleukin signaling, protein kinase signaling, and toll-like receptor pathways associated with the symptoms reported in the LC condition. ZNF and MYBL TF-family were predicted as abundant TFs controlling hub genes' transcriptional machinery. Furthermore, OLR1 (PDB: 7XMP) showed stable interactions with the five shortlisted refined naturally occurring bioflavonoids, i.e., apigenin, amentoflavone, ilexgenin A, myricetin, and orientin compounds. The total binding energy pattern was observed, with amentoflavone being the top docked molecule (with a binding affinity of -8.3 kcal/mol) with the lowest total binding energy of -18.48 kcal/mol. In conclusion, our research has predicted the hub genes, their molecular pathways, and the potential inhibitors between EBV and LC potential pathogenic association. The in vivo or in vitro experimental methods could be utilized to functionally validate our findings, which would be helpful to cure LC or to prevent EBV reactivation. [ABSTRACT FROM AUTHOR]

In this study, the extraction, purification and metabolic enzyme inhibition potential of Selaginella doederleinii were investigated. In order to extract the total biflavonoids from S. doederleinii (SDTBs), the optimum extraction process was obtained by optimizing the ultrasonic extraction parameters using response-surface methodology. This resulted in a total biflavonoid content of 22.26 ± 0.35 mg/g. Purification of the S. doederleinii extract was carried out using octadecylsilane (ODS), and the transfer rate of the SDTBs was 82.12 ± 3.48% under the optimum purification conditions. We determined the effect of the SDTBs on α-glucosidase (AG), α-amylase and xanthine oxidase (XOD) and found that the SDTBs had an extremely potent inhibitory effect on AG, with an IC50 value of 57.46 μg/mL, which was much lower than that of the positive control. Meanwhile, they also showed significant inhibition of XOD and α-amylase, with IC50 values of 289.67 μg/mL and 50.85 μg/mL, respectively. In addition, molecular docking studies were carried out to understand the nature of the action of the biflavonoids on AG and XOD. The results showed that robustaflavone had the lowest binding energy to AG (−11.33 kcal/mol) and XOD (−10.21 kcal/mol), while, on the other hand, amentoflavone showed a good binding affinity to AG (−10.40 kcal/mol) and XOD (−9.962 kcal/mol). Moreover, molecular dynamics simulations verified the above results. [ABSTRACT FROM AUTHOR]

The difference on inhibitory effects of bioflavonoids inhibiting XOD activity assayed by varying test methods cause of us to be further in consideration. The reported test method creating a micro‐environment surrounding XOD in the absence of ⋅O2−, which is seemly different from the assay in vivo. So, the vitro test method for assaying XOD activity is necessary to be improved for selection of potential inhibitors in the presence of ⋅O2−. The inhibitory results demonstrated that bioflavonoids of MY, DMY, QUE and LUT are capable to be on effective IC50 values, but others are not. As well, their resulting inhibitions determined by the improved test method are much less than that reported in the literature, indicating that their chemical affinities with XOD become weaker. Moreover, DMY assayed on the inhibitions of XOD in the improved test method performs to be a better inhibitor, as compared to the assay of the reported test methods. Abasing on the transformation of DMY into MY in the presence of ⋅O2−, the good inhibition of DMY on XOD activity can be explained by the synergistic effect of MY. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effectiveness of hesperidin (HES) on testicular histopathological changes, biochemical changes, and semen characteristics in rats exposed to glyphosate (GLP). The control group was given a normal diet devoid of GLP and HES, the HES group was given 100 mg/kg/day HES with the normal diet, the GLP group was given GLP at the LD50/10 dose of normal feed, which was 787.85 mg/kg/day, and the GLP + HES group was given normal feed containing 787.85 mg/kg/day LD50/10 dose of GLP in addition to 100 mg/kg/day HES. GLP administration reduced sperm motility, sperm plasma membrane integrity, glutathione levels, and total antioxidant levels in the testicular tissues of rats. Moreover, it caused an increase in right testis and left epididymis weights, abnormal sperm counts, malondialdehyde levels, total oxidant status, and DNA damage. The HES treatment showed curative effects on these parameters. Furthermore, HES was effective in lessening the histopathological damage that was caused by GLP. The results showedthat HES protects spermatological parameters and DNA integrity, improves antioxidant defenses, and lowers the damage and lipid peroxidation caused by GLP in testicular tissue. [ABSTRACT FROM AUTHOR]

Ulcerative colitis is a gastrointestinal problem with increasing prevalence. In this study, the effect of hesperidin (commonly found in citrus white peel) on colitis was investigated. For this purpose, 28 Wistar albino female rats, 3-- 4 months old and weighing between 250--350 g, were used in the study. Rats were randomly divided into four groups: control (n=7), colitis (n=7), protective effect (n=7), and treatment (n=7) groups. Colitis was induced in rats with acetic acid (except control), and hesperidin was then administered at 150 mg/kg for 1 week before and after colitis. At the end of the study, IFN-γ and IL-6 values in blood, TAS, TOS, and OSI in tissue were evaluated. Intestinal tissues were assessed visually by haematoxylin and eosin staining. Our results showed that the levels of IFN-γ and IL-6 were highest in the colitis group and lowest in the treatment group, with statistical significance. The most histopathological damage was seen in the colitis group, while less prevalent in the treatment and control groups. The results of the study show that hesperidin had limited protective and therapeutic effects on experimental colitis mouse models. [ABSTRACT FROM AUTHOR]

The oil palm tree (Elaeis guineensis) is potentially being exploited in the pharmaceutical and nutraceutical industries due to the significant bioactive potential of its leaf bioflavonoids. However, these phytocompounds are prone to degradation when exposed to excessive heat, light, and oxygen, making it essential to implement a protective mechanism for their stabilization. This research aimed to optimize the conditions for microencapsulation of oil palm leaf extract (OPLE) using spray drying technology. A single-factor experimental design was used to examine important parameters such as extract-to-wall material ratio, pH value, inlet air temperature and feed flow rate. Natural polymers such as gum Arabic (GA), maltodextrin (MD), modified starch (MS), β-cyclodextrin (BCD), and their combinations were used as encapsulating agents. The novelty of the study lies in the successful optimization of spray drying conditions that yielded high retention of bioactive compounds. Specifically, OPLE microcapsules prepared with maltodextrin at a feed flow rate of 30%, an inlet air temperature of 180 °C, an extract-to-wall material ratio of 30:70, and a pH of 7 retained 77.18% of total flavonoid content, 81.52% of total phenolic content, and demonstrated 82.22% DPPH radical inhibition. These optimized microcapsules exhibited desirable properties, including satisfactory bulk density, low moisture content, high solubility, and low hygroscopicity. Furthermore, the microcapsules demonstrated no cytotoxicity on Hs27 human skin fibroblast cell lines at a concentration of 10 mg/mL and revealed promising anti-inflammatory activity, surpassing the efficacy of a commercially available drug. These findings provide a novel foundation for the development of high-value active ingredients for nutraceuticals, with significant potential for industrial applications. Highlights: Spray drying microencapsulation preserves bioflavonoids from oil palm leaves. Optimized OPLE microcapsules used maltodextrin at 180 °C, 30% flow, 30:70 ratio, pH 7. OPLE microcapsules retained 81.52% phenolics, 77.18% flavonoids, and 82.22% DPPH inhibition. [ABSTRACT FROM AUTHOR]

Hesperidin is a citrus bioflavonoid and has numerous pharmacological actions. Hesperidin’s effect on testicular dysfunction has not been well researched. Hence, the present study is aims to investigate the effect of hesperidin on aluminium chloride (AlCl3)-induced testicular dysfunction in rats. Both vitamin C (200 mg/kg) and hesperidin (50, 100, and 200 mg/kg) were administered orally for 21 days. At the end of the study, the blood samples were obtained from all animals for investigation of biochemical and hematological parameters. Then, bilateral orchiectomy was carried out to remove testicles from the animals, and sperm was collected and examined under a microscope. Finally, organs such as the liver, kidney, and testicles were also collected and utilized for histopathological analysis. Part of the liver sample was used for determination of antioxidant enzymes such as reduced glutathione (GSH) and catalase (CAT) levels. The rats administered with AlCl3 showed elevated levels of biochemical and hematological parameters and a reduction in levels of sperm count, sperm motility, and oxidative stress parameters, whereas the rats administered with vitamin C/hesperidin (200 and 400 mg/kg) were able to ameliorate AlCl3-induced testicular dysfunction by attenuating AlCl3-induced changes in biochemical and hematological parameters, sperm motility, sperm count, and oxidative stress. Both vitamin C and hesperidin had significant ameliorative effects against AlCl3-induced testicular dysfunction.

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the post-transcriptional level. The mechanism of miRNA action includes degradation of mRNA or suppression of its translation. MicroRNA-155 is one of the most studied miRNAs. Its expression increases on the background of tumor and inflammatory processes or infectious diseases, which is accompanied by increased production of proinflammatory cytokines. miRNA-155 often plays a negative role in the above conditions. Presumably, suppression or activation of mi-RNA-155 expression can lead to a change in the disease course by changing cellular metabolism. Therefore, a search for modulators of its expression is a relevant goal. Possible targets of miRNA-155 and its effects incurred in various cells and tissues and the possibility of pharmacological regulation of miRNA-155 are reviewed herein. Antisense oligonucleotides (anti-miRNAs, for example, an oligonucleotide called Cobomarsen) can act as direct inhibitors of miRNA-155. Moreover, compounds that suppress its expression (steroid hormones, bioflavonoids, and some others) are also being studied. [ABSTRACT FROM AUTHOR]

For the first time, to optimize the creation of new neuroprotective agents based on bioflavonoids, we applied information technologies; these include docking analysis to calculate the binding of candidate molecules to the pharmacological target protein transthyretin as well as a program of virtual screening of NO scavengers. As a result of this approach, the substance catechin was isolated from candidate molecules—quercetin, catechin, Epicatechin gallate, Epicatechin, Procyanidin B1, Procyanidin B2, Procyanidin B3, and Catechin-3-gallate—according to docking analysis. As a result of virtual screening, catechin was identified as a potential NO scavenger (55.15% prediction). The results of the prediction were confirmed by in vitro experiments. Course administration of catechin to animals with experimental multiple sclerosis (MS) against the background of methylprednisolone administration completely eliminated lethal cases, reduced the number of diseased animals by 20% as well as prevented the development of severe neurological symptoms by 20% (compared to the methylprednisolone group) and by 60% compared to the control group. Course administration of catechin with methylprednisolone leads to a decrease in the neurodegradation markers in the cytosol of rats, with EAE: NSE by 37% and S-100 by 54.8%. The combined administration of methylprednisolone significantly exceeds the combination of methylprednisolone with the reference drug mexidol by the degree of NSE reduction. The obtained results indicate a significant neuroprotective effect of ocular combinations of methylprednisolone and catechin. The above-mentioned confirms the correctness of the bioflavonoid selection with the help of a virtual screening program. [ABSTRACT FROM AUTHOR]

Herbal standardization is a crucial aspect in the field of herbal medicine and nutraceutical products. It refers to the process of developing and implementing standards to ensure the consistency, quality, and efficacy of herbal products. One important class of bioactive compounds that is widely distributed in plants is bioflavonoids, natural polyphenolic compounds. The significant pharmacological properties of bioflavonoids include antioxidant, anti-inflammatory, anti-diabetic, anti-aging and antimicrobial properties are promising therapeutic nutraceutical agents in the management of several acute and chronic diseases. However, the exploitation of these bioflavonoids demands systematic standardization approaches covering from extraction to enrichment of high-quality standardized multicomponent botanical extract in order to meet the desired efficacy. Hence, this review describes on the plant innovative processing technologies comprising of drying, solvent, extraction technique and adsorbent technologies accompanied with the established quality control methods using high end analytical instrument and omics technology. The importance of bioactive compound standardization and global demand of flavonoid in various applications are also highlighted. [ABSTRACT FROM AUTHOR]

Functional foods enriched with plant polyphenol anthocyanins attract particular attention due to their health-promoting properties, including antitumor activity. We evaluated the effects of a grain diet rich in anthocyanins in a mouse model of Lewis lung carcinoma. Mice of the C57BL/6 strain were fed with wheat of near-isogenic lines differing in the anthocyanin content for four months prior to tumor transplantation. Although a significant decrease in the size of the tumor and the number of metastases in the lungs was revealed in the groups with both types of grain diet, the highest percentage of animals without metastases and with attenuated cell proliferation in the primary tumor were observed in the mice with the anthocyanin-rich diet. Both grain diets reduced the body weight gain and spleen weight index. The antitumor effects of the grain diets were associated with the activation of different mechanisms: immune response of the allergic type with augmented interleukin(IL)-9 and eotaxin serum levels in mice fed with control grain vs. inhibition of the IL-6/LIF system accompanied by a decrease in the tumor-associated M2 macrophage marker arginase 1 gene mRNA levels and enhanced autophagy in the tumor evaluated by the mRNA levels of Beclin 1 gene. Thus, anthocyanin-rich wheat is suggested as a promising source of functional nutrition with confirmed in vivo antitumor activity. [ABSTRACT FROM AUTHOR]

Abstract A natural product is a compound or substance originating from a living organism and found in nature. Daidzein belongs to the class of bioflavonoids, which are plant‐derived compounds with various biological activities. Predominantly exists in soybeans and several legumes in either glycoside or aglycone forms. Its primary chemical constituents include metabolites like equol and trihydroxy isoflavone, generated through the influence of intestinal bacteria. Daidzein has exhibited pharmacological impacts on different ailments, including cardiovascular disease, cancer, diabetes, skin disorders, osteoporosis, and neurodegenerative disorders. Daidzein's mechanisms of action involve interactions with estrogen receptors, as well as its antioxidant and anti‐inflammatory properties, along with its ability to regulate apoptosis and the cell cycle. In efforts to enhance its solubility, stability, bioavailability, and targeting, daidzein has been innovatively formulated into novel dosage forms, including nanoparticles, liposomes, microemulsions, and nanosuspensions. As a promising nutraceutical, daidzein presents multiple health benefits and holds potential for various clinical applications. Additional investigation is required to comprehend the molecular mechanisms of this phenomenon and assess its safety. The purpose of this review is to provide a short description of the therapeutic properties, chemical composition, traditional use, toxicology profile, new insights on the dosage form, and future prospects of daidzein.

The term "Long-COVID" (LC) is characterized by the aftereffects of COVID-19 infection. Various studies have suggested that Epstein–Barr virus (EBV) reactivation is among the significant reported causes of LC. However, there is a lack of in-depth research that could largely explore the pathogenic mechanism and pinpoint the key genes in the EBV and LC context. This study mainly aimed to predict the potential disease-associated common genes between EBV reactivation and LC condition using next-generation sequencing (NGS) data and reported naturally occurring biomolecules as inhibitors. We applied the bulk RNA-Seq from LC and EBV-infected peripheral blood mononuclear cells (PBMCs), identified the differentially expressed genes (DEGs) and the Protein–Protein interaction (PPI) network using the STRING database, identified hub genes using the cytoscape plugins CytoHubba and MCODE, and performed enrichment analysis using ClueGO. The interaction analysis of a hub gene was performed against naturally occurring bioflavonoid molecules using molecular docking and the molecular dynamics (MD) simulation method. Out of 357 common genes, 22 genes (CCL2, CCL20, CDCA2, CEP55, CHI3L1, CKAP2L, DEPDC1, DIAPH3, DLGAP5, E2F8, FGF1, NEK2, PBK, TOP2A, CCL3, CXCL8, DEPDC1, IL6, RETN, MMP2, LCN2, and OLR1) were classified as hub genes, and the remaining ones were classified as neighboring genes. Enrichment analysis showed the role of hub genes in various pathways such as immune-signaling pathways, including JAK-STAT signaling, interleukin signaling, protein kinase signaling, and toll-like receptor pathways associated with the symptoms reported in the LC condition. ZNF and MYBL TF-family were predicted as abundant TFs controlling hub genes' transcriptional machinery. Furthermore, OLR1 (PDB: 7XMP) showed stable interactions with the five shortlisted refined naturally occurring bioflavonoids, i.e., apigenin, amentoflavone, ilexgenin A, myricetin, and orientin compounds. The total binding energy pattern was observed, with amentoflavone being the top docked molecule (with a binding affinity of –8.3 kcal/mol) with the lowest total binding energy of −18.48 kcal/mol. In conclusion, our research has predicted the hub genes, their molecular pathways, and the potential inhibitors between EBV and LC potential pathogenic association. The in vivo or in vitro experimental methods could be utilized to functionally validate our findings, which would be helpful to cure LC or to prevent EBV reactivation.

Abnormal nucleotide insertions of C9orf72, which forms a complex with Smith–Magenis syndrome chromosomal region candidate gene 8 (SMCR8) protein and WD repeat-containing protein 41 (WDR41) protein, are associated with an autosomal-dominant neurodegenerative frontotemporal dementia and/or amyotrophic lateral sclerosis type 1 (FTDALS1). The differentially expressed in normal and neoplastic cells (DENN) domain-containing C9orf72 and its complex with SMCR8 and WDR41 function as a guanine-nucleotide exchange factor for Rab GTP/GDP-binding proteins (Rab GEF, also called Rab activator). Among Rab proteins serving as major effectors, there exists Rab11a. However, it remains to be established which Rab protein is related to promoting or sustaining neuronal morphogenesis or homeostasis. In this study, we describe that the knockdown of Rab11a decreases the expression levels of neuronal differentiation marker proteins, as well as the elongation of neurite-like processes, using N1E-115 cells, a well-utilized neuronal differentiation model. Similar results were obtained in primary cortical neurons. In contrast, the knockdown of Rab11b, a Rab11a homolog, did not significantly affect their cell morphological changes. It is of note that treatment with hesperetin, a citrus flavonoid (also known as Vitamin P), recovered the neuronal morphological phenotypes induced by Rab11a knockdown. Also, the knockdown of Rab11a or Rab11b led to a decrease in glial marker expression levels and in morphological changes in FBD-102b cells, which serve as the oligodendroglial differentiation model. Rab11a is specifically involved in the regulation of neuronal morphological differentiation. The knockdown effect mimicking the loss of function of C9orf72 is reversed by treatment with hesperetin. These findings may reveal a clue for identifying one of the potential molecular and cellular phenotypes underlying FTDALS1. [ABSTRACT FROM AUTHOR]

Dairy producers are continuously searching for environmentally friendly and economically sustainable alternatives to increase pasture herbage yield and reduce reliance on chemical fertilisers. A possible means to reduce fertiliser reliance is the use of biostimulants. Biostimulants such as fulvic acid and bioflavonoids help to increase N uptake efficiency, thereby increasing herbage quantity and quality. The aim of this study was to determine the effects of a soil application of a carbohydrate-derived fulvic acid and bioflavonoid biostimulant on herbage yield and nutritive composition of a mixed perennial ryegrass–clover pasture. Biostimulant treatment resulted in a lower ryegrass component of the mixed sward, in both winter and summer grazing cycles. However, the nutritive composition and total herbage yield of the pasture were not significantly affected by biostimulant treatment. The treatment did show a tendency to affect total herbage yield within a season. This suggests that total herbage yield could be increased if additional N fertiliser is applied together with a biostimulant soil treatment, although further investigation is needed to confirm this postulation. Biostimulant treatments have the potential to lead to reduced fertiliser inputs on perennial ryegrass–clover pastures as they may increase nutrient uptake efficiency. [ABSTRACT FROM AUTHOR]

Abstract Background Plaque-induced gingivitis is a chronic inflammatory condition characterized by complete reversibility of tissue damage once the periodontal biofilm has been disorganised. The aim of this study was to evaluate the efficacy of two commercially available mouthwashes (MWs) versus a chlorhexidine (CHX) 0.12% MW in reducing gingival bleeding (GB) in adults with plaque-induced gingivitis. Methods The present study was a double-blind, parallel, randomized controlled trial involving 6492 gingival sites (i.e. 39 subjects × 28 teeth × 6 sites/tooth) aged 18–75 years. During a 2-week period, subjects were randomized to receive MWs: a control CHX 0.12% MW (group C, 1818 sites); a MW test containing CHX 0.09% + Citrox®/P complex (group CX, 2628 sites); a MW test based on natural compounds (group P, 2016 sites). GB was assessed at the inclusion visit (T0) and after 2 weeks of MW use (T1). Analyses of GB were compared between groups and then restricted to subjects with bleeding sites between 10 and 30% (moderate gingivitis) or ≥ 30% (severe gingivitis) at T0. Pairwise comparisons were made between groups and logistic regression was used to identify correlates of GB (T1). Results For total bleeding site analysis, GB reduction between T0 and T1 ranged from 23% (C), 26% (CX) and 36% (P), respectively (all p

In this study, the extraction, purification and metabolic enzyme inhibition potential of Selaginella doederleinii were investigated. In order to extract the total biflavonoids from S. doederleinii (SDTBs), the optimum extraction process was obtained by optimizing the ultrasonic extraction parameters using response-surface methodology. This resulted in a total biflavonoid content of 22.26 ± 0.35 mg/g. Purification of the S. doederleinii extract was carried out using octadecylsilane (ODS), and the transfer rate of the SDTBs was 82.12 ± 3.48% under the optimum purification conditions. We determined the effect of the SDTBs on α-glucosidase (AG), α-amylase and xanthine oxidase (XOD) and found that the SDTBs had an extremely potent inhibitory effect on AG, with an IC50 value of 57.46 μg/mL, which was much lower than that of the positive control. Meanwhile, they also showed significant inhibition of XOD and α-amylase, with IC50 values of 289.67 μg/mL and 50.85 μg/mL, respectively. In addition, molecular docking studies were carried out to understand the nature of the action of the biflavonoids on AG and XOD. The results showed that robustaflavone had the lowest binding energy to AG (−11.33 kcal/mol) and XOD (−10.21 kcal/mol), while, on the other hand, amentoflavone showed a good binding affinity to AG (−10.40 kcal/mol) and XOD (−9.962 kcal/mol). Moreover, molecular dynamics simulations verified the above results.

Ten compounds, including three new bioflavonoids (1–3) and seven known compounds (4–10), were identified in the ethyl acetate fraction of the 85 % ethanol extract of Selaginella delicatula. The structures of the new compounds were determined through spectroscopic data analysis, and their absolute configurations were established using circular dichroism (CD). All the isolated compounds were tested for their antiproliferative effects on MCF‐7, HepG2, and HEK 293T cells. Compounds 1 and 5 exhibited significant cytotoxicity against MCF‐7 cells, effectively inhibiting their proliferation. Meanwhile, compounds 1, 2, 5, and 7 respectively exhibited strong inhibitory effects on HepG2 cells. Furthermore, when we combined the IC50 values of compounds 3, 5, and 7 on HEK 293T cells, we discovered that they selectively inhibited cell growth. [ABSTRACT FROM AUTHOR]

Objective: Rutin, also called vitamin P, is a flavonoids from plants. Previous studies have indicated that rutin can alleviate the injury of tissues and cells by inhibiting oxidative stress and ameliorating inflammation. There is no report on the protective effects of rutin on goat rumen epithelial cells (GRECs) at present. Hence, we investigated whether rutin can alleviate lipopolysaccharide (LPS)-induced damage in GRECs. Methods: GRECs were cultured in basal medium or basal medium containing 1 µg/mL LPS, or 1 µg/mL LPS and 20 µg/mL rutin. Six replicates were performed for each group. After 3-h culture, the GRECs were harvested to detect the relevant parameters. Results: Rutin significantly enhanced the cell activity (p<0.05) and transepithelial electrical resistance (TEER) (p<0.01) and significantly reduced the apoptosis rate (p<0.05) of LPSinduced GRECs. Rutin significantly increased superoxide dismutase, glutathione peroxidase, and catalase activity (p<0.01) and significantly decreased lactate dehydrogenase activity and reactive oxygen species and malondialdehyde (MDA) levels in LPS-induced GRECs (p<0.01). The mRNA and protein levels of interleukin 6 (IL-6), IL-1β, and C-X-C motif chemokine ligand 8 (CXCL8) and the mRNA level of tumor necrosis factor-α (TNF-α) and chemokine C-C motif ligand 5 (CCL5) were significantly increased in LPS-induced GRECs (p<0.05 or p<0.01), while rutin supplementation significantly decreased the mRNA and protein levels of IL-6, TNF-α, and CXCL8 in LPS-induced GRECs (p<0.05 or p<0.01). The mRNA level of toll-like receptor 2 (TLR2), and the mRNA and protein levels of TLR4 and nuclear factor κB (NF-κB) was significantly improved in LPS-induced GRECs (p<0.05 or p<0.01), whereas rutin supplementation could significantly reduce the mRNA and protein levels of TLR4 (p<0.05 or p<0.01). In addition, rutin had a tendency of decreasing the protein levels of CXCL6, NF-κB, and inhibitor of nuclear factor kappa-B alpha (0.05< p<0.10). Rutin could significantly decreased interferon regulatory factor 3 mRNA expression in LPS-induced GRECs (p<0.05), whereas interferon induced protein with tetratricopeptide repeats 3 (IFIT3) and toll-interacting protein (TOLLIP) mRNA expression was not significantly different between the groups. LPS reduced the tight junction protein zonula occludin 1 (ZO-1) level in GRECs whereas rutin enhanced it. Rutin significantly improved tight junction protein Claudin-1 mRNA expression in LPS-induced GRECs (p<0.01), but could not affect tight junction protein Occludin mRNA expression. Conclusion: Rutin alleviated LPS-induced barrier damage in GRECs by improving oxidation resistance and anti-inflammatory activity, which may be related to TLR/NF-κB signaling pathway inhibition. [ABSTRACT FROM AUTHOR]

This article reviews the source and properties of rutin (vitamin P), its general physiological and medicinal effects and their mechanisms, but the main subject of it is the currently available knowledge concerning the character and mechanisms of action of rutin on female reproductive processes. The available data demonstrate the stimulatory action of rutin on female reproductive processes: it can promote ovarian follicles development and ovulation, ovarian cyclicity, and viability of ovarian cells. On the other hand, it can suppress ovarian cancer cell and tumour development by inhibition of cell proliferation and growth and activation of their apoptosis and death. Furthermore, it could be able to prevent other reproductive disorders (ischaemia, polycystic ovarian syndrome, toxic effects of chemotherapy, nanoparticles and toluene). Rutin could exert its effects via changes in the release and reception of gonadotropin, ovarian steroid hormones, prostaglandins, cytokines, VEGF, as well as in intracellular regulators and markers of oxidative and inflammatory processes, proliferation, apoptosis and angiogenesis. [ABSTRACT FROM AUTHOR]

Background: Plaque-induced gingivitis is a chronic inflammatory condition characterized by complete reversibility of tissue damage once the periodontal biofilm has been disorganised. The aim of this study was to evaluate the efficacy of two commercially available mouthwashes (MWs) versus a chlorhexidine (CHX) 0.12% MW in reducing gingival bleeding (GB) in adults with plaque-induced gingivitis. Methods: The present study was a double-blind, parallel, randomized controlled trial involving 6492 gingival sites (i.e. 39 subjects × 28 teeth × 6 sites/tooth) aged 18–75 years. During a 2-week period, subjects were randomized to receive MWs: a control CHX 0.12% MW (group C, 1818 sites); a MW test containing CHX 0.09% + Citrox®/P complex (group CX, 2628 sites); a MW test based on natural compounds (group P, 2016 sites). GB was assessed at the inclusion visit (T0) and after 2 weeks of MW use (T1). Analyses of GB were compared between groups and then restricted to subjects with bleeding sites between 10 and 30% (moderate gingivitis) or ≥ 30% (severe gingivitis) at T0. Pairwise comparisons were made between groups and logistic regression was used to identify correlates of GB (T1). Results: For total bleeding site analysis, GB reduction between T0 and T1 ranged from 23% (C), 26% (CX) and 36% (P), respectively (all p < 0.05). Multiple comparison between groups showed that group C was significantly less effective (p < 0.05) than groups CX and P. Splitting the analysis, in patients with severe gingivitis (≥ 30% bleeding sites at T0), all MWs had a positive effect on GB with a reduction at T1 of 36% (C), 33% (CX) and 42% (P), respectively. While GB reduction between T0 and T1, was significant for all groups, the comparison among groups showed no significant difference between group C and CX, whereas the improvement was significant for group P. On the other hand, in adults with moderate gingivitis (< 30% bleeding sites at T0), only CX and P had a positive effect on GB reduction at T1(9% in CX and 2% in P, respectively), although the differences between the three groups were not significant. Conclusion: The daily use of MWs with natural components (groups P and CX) for 2 weeks should be considered positively as an adjunct to individual oral prophylaxis to reduce GB compared to the control MW containing CHX 0.12% (group C) in healthy adults with plaque-induced gingivitis. For subjects with severe gingivitis, it is advisable to first use natural MW (P) and then MW based on CHX 0.09% with natural components (CX), compared to MW with CHX 0.12% (C). For adults with moderate gingivitis, P and CX can be advisable, even if no definitive recommendations can be drawn. Trial Registration: ACTRN12622000215729, 07/02/2022. [ABSTRACT FROM AUTHOR]

There are approximately 24 million cases of Alzheimer's disease (AD) worldwide, and the number of cases is expected to increase four-fold by 2050. AD is a neurodegenerative disease that leads to severe dementia in most patients. There are several neuropathological signs of AD, such as deposition of amyloid beta (Aβ) plaques, formation of neurofibrillary tangles (NFTs), neuronal loss, activation of inflammasomes, and declining autophagy. Several of these hallmarks are linked to the gut microbiome. The gastrointestinal (GI) tract contains microbial diversity, which is important in regulating several functions in the brain via the gut-brain axis (GBA). The disruption of the balance in the gut microbiota is known as gut dysbiosis. Recent studies strongly support that targeting gut dysbiosis with selective bioflavonoids is a highly plausible solution to attenuate activation of inflammasomes (contributing to neuroinflammation) and resume autophagy (a cellular mechanism for lysosomal degradation of the damaged components and recycling of building blocks) to stop AD pathogenesis. This review is focused on two bioflavonoids, specifically epigallocatechin-3-gallate (EGCG) and genistein (GS), as a possible new paradigm of treatment for maintaining healthy gut microbiota in AD due to their implications in modulating crucial AD signaling pathways. The combination of EGCG and GS has a higher potential than either agent alone to attenuate the signaling pathways implicated in AD pathogenesis. The effects of EGCG and GS on altering gut microbiota and GBA were also explored, along with conclusions from various delivery methods to increase the bioavailability of these bioflavonoids in the body. [ABSTRACT FROM AUTHOR]

Pigmented purpuric dermatosis (PPD) comprises a group of skin conditions characterized by flat, nonpalpable petechiae and purpura as a result of capillaritis. Although the precise cause of PPD is as yet unknown, increased vascular permeability and capillary fragility are key factors in its pathophysiology. PPD has diverse clinical presentations, but the histopathology of all these variants essentially remains the same. The initial purpuric lesions develop a golden-brown hue owing to hemosiderin absorption and eventually progress to chronic pigmentary changes. These lesions, which often affect the lower limbs, are either asymptomatic or accompanied by moderate pruritus, and can be difficult to diagnose and treat. There are several subtypes of clinical presentations that have been documented over the years. In order to accurately diagnose PPD, a thorough clinical evaluation and, occasionally, a biopsy may be required. It is essential to identify the condition and reassure patients of its benign nature. Treatment is usually necessary due to the chronic nature of the condition, its consequences on physical and mental well-being, and the presence of significant lesions or itching. In this review, we outline the various prevalent PPDs and discuss their etiopathogenesis, clinical features, and diagnostic and treatment modalities. [ABSTRACT FROM AUTHOR]

Purpose: Fabrication of edible hydrogels envisaged as functional foods is the key objective of this work. A value addition in terms of utilization of a bioresource, 'kinnow' mandarin peels, by using its bioflavonoids (as polymethoxyflavone nanoparticles) impregnated into the hydrogels is aimed as a significant contribution in product development. Doing so would pave the way for further work on the study of release characteristics from the suitable matrix. The background of this work lies in the pre-systemic metabolism of flavonoids in the gastrointestinal tract. Finding a suitable matrix as a carrier of flavonoids to prevent this premature metabolism, thereby leading to a gastro-resistant edible hydrogel is the significance of this work. Methods: In present work, mono-hydrogels were prepared using casein by enzyme assisted gelation; and hybrid hydrogels were prepared from casein and alginate by electrostatically driven complexation method. Further, the fabricated hydrogels were tested for their rheological as well as mechanical properties. Also, the capacity of hydrogels to uphold the flavonoid poly-lactic-co-glycolic acid (PLGA) nanoparticles was investigated in terms of porosity measurements and morphological studies. Results: Gel behavior studies revealed shear thinning nature of hydrogels and a high resistance to deformation when subjected to a force. The hybrid hydrogels were found to have two key features, low porosity and appearance of hard lamellar structure, which ensured holding of flavonoid PLGA nanoparticles, as visualized by Cryo Scanning Electron Microscopy (Cryo-SEM) and Confocal Laser Scanning Microscope (CLSM). Conclusion: This work exemplifies biomass to biovalue conversion, thereby suggesting sustainable utilization of a bioresource. The double layered carrier system entrapping bioflavonoids is a step towards developing functional foods, as it forms a basis for understanding of the carrier systems vis-à-vis the intended application. [ABSTRACT FROM AUTHOR]

A natural polyphenolic substance generated from plant metabolites is called a bioflavonoid. By using a conductometric technique, various interactions between the polar, hydrophilic, and hydrophobic components of quercetin (QUE)/7-hydroxy flavone (7-HF), and nicotinamide (NAM) in a hydro-ethanolic medium were examined. Quercetin (3,3',4',5,7-pentahydroxyflavone) and 7-hydroxyflavone (7-hydroxy-2-phenylchromen-4-one) belongs to the class of bioflavonoids. In this present work, the interactions of these two bioflavonoids with nicotinamide (NAM), a hydrogen bond donor (HBD) have been studied by analyzing different parameters derived from experimental electrical conductivity data. The solutions of QUE/7-HF- NAM were prepared using mixed solvents of ethanol (30 and 40 wt %) in 0.5 and 1.0 of NAM. Using the specific conductance (K) values the limiting molar conductance was evaluated at different temperatures (T = 293.15–313.15 K with 5 K interval). The thermodynamic parameters (change in enthalpy entropy , free energy , and activation energy associated with their interaction has also been determined. Each of these parameters were interpreted in the light of the existing molecular interactions between QUE/7‑HF–NAM in water-ethanol mixed solvents. [ABSTRACT FROM AUTHOR]

For the first time, to optimize the creation of new neuroprotective agents based on bioflavonoids, we applied information technologies; these include docking analysis to calculate the binding of candidate molecules to the pharmacological target protein transthyretin as well as a program of virtual screening of NO scavengers. As a result of this approach, the substance catechin was isolated from candidate molecules—quercetin, catechin, Epicatechin gallate, Epicatechin, Procyanidin B1, Procyanidin B2, Procyanidin B3, and Catechin-3-gallate—according to docking analysis. As a result of virtual screening, catechin was identified as a potential NO scavenger (55.15% prediction). The results of the prediction were confirmed by in vitro experiments. Course administration of catechin to animals with experimental multiple sclerosis (MS) against the background of methylprednisolone administration completely eliminated lethal cases, reduced the number of diseased animals by 20% as well as prevented the development of severe neurological symptoms by 20% (compared to the methylprednisolone group) and by 60% compared to the control group. Course administration of catechin with methylprednisolone leads to a decrease in the neurodegradation markers in the cytosol of rats, with EAE: NSE by 37% and S-100 by 54.8%. The combined administration of methylprednisolone significantly exceeds the combination of methylprednisolone with the reference drug mexidol by the degree of NSE reduction. The obtained results indicate a significant neuroprotective effect of ocular combinations of methylprednisolone and catechin. The above-mentioned confirms the correctness of the bioflavonoid selection with the help of a virtual screening program.

Interest in organic polyphenol compounds increases if these natural compounds are coordinated with transition metal ions. In this study, four metal complexes were synthesized with flavonoid extracts, and reliable techniques were used for characterization. These complexes showcase unique coloring, low pH, and conductivity levels, with X-ray diffraction revealing varying crystallinity among flavonoid extracts and certain complexes. Fourier transform infrared spectrophotometer exhibits a specific stretching vibration (442–486 cm−1 ν M−O), indicating flavonoid metal complex formation formation. UV–visible spectrum of flavonoid extracts displays absorption bands at 280 and 340 nm, shifting upon metal ion binding to unveil new absorption bands for each complex, producing three peaks between 260–660 nm. The 1HNMR results showed that the proton signals in all complexes shifted to a high field relative to their ligand, possibly due to increased coupling caused by the coordination effect and thus increased planarity of the flavonoid molecules. These organic metal complexes display heightened antioxidant, antimicrobial, and anticancer properties compared to extracts, with enhanced cytotoxicity against THP-1 and Calu-3 cell lines, notably Cu(II) displaying superior cytotoxic effects with IC50 values of 18 and 56 μg/mL for THP-1 and Calu-3 cells respectively.