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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]

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.

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]

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]

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.

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]

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]

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.

Moringa leaves contain a proper amount of antioxidants, amino acids, vitamins, hormones, macronutrients, and micronutrients. Therefore, it is applied as a natural, inexpensive, and simple-to-make biostimulant to boost nutritional value and growth parameters in a variety of plants. The main purpose of this study is to determine the optimal concentration of Moringa oleifera L. leaf extract (MLE) as an effective biostimulant to improve nutritional and physical quality in cabbage (Brassica oleracea var. capitata). To do this, three concentrations of MLE (6, 8, and 10%) were foliar sprayed to the plant leaves at a rate of 25 mL plant−1 for every two weeks from transplantation till harvest, while control plants (Ø) were sprayed with distilled water only. Our results show that MLE greatly increased cabbage growth, nutrient content, pigment content, and nutrient absorption, while a high concentration of 10% MLE could also significantly reduce nitrate content in cabbage leaves. In comparison to the control plants, sprays of 6%, 8%, and 10% MLE reduced nitrate content by 23%, 14%, and 12%, respectively. However, the lowest nitrate content was found for the plants sprayed with 6% MLE. Except for the dry matter, all the growth parameters, mineral content, and pigment content were significantly higher after spraying with 10% MLE, while better vitamin C and lower nitrate were found in the plants treated with 6% MLE. A Pearson correlation reveals that head weight has a positive correlation with head diameter, head height, chlorophyll a, and carotenoids at p levels of 0.01 and a positive correlation with chlorophyll b and vitamin C at p levels of 0.05. Vitamin C and dry matter, on the other hand, had a negative connection with nitrate content. [ABSTRACT FROM AUTHOR]

Background. Jostaberry is a berry crop which is rich in bioflavonoids and ascorbic acid; it has a pleasant aroma and taste, and can be a good raw material for the production of natural fruit and berry wines. Jostaberries have not been sufficiently studied in the scientific sphere as far as their processing into natural wines is concerned. The studies presented in this paper explore the quality, biological value, and aroma of jostaberries and some aspects of the technology used to process them. Material and methods. The materials were jostaberries grown in the conditions of the Central Forest Steppe zone of Ukraine, must in the process of fermentation, and wine from jostaberries with a volume fraction of ethyl alcohol not lower than 14%. Before fermentation, the must from jostaberries had a titrated acid content which was not higher than 8.3 g/dm³ and a sugar content (in terms of inverts) of 242 g/dm³. Results. The duration of must fermentation was set at 52 days. For the purpose of timely and objective control over the must fermentation process, an equation was developed which allowed the volume fraction of ethyl alcohol during the fermentation process to be calculated with an accuracy of 0.65% using the parabola equation, and the intensity of the accumulation of ethyl alcohol to be calculated according to its derivative. It had already been established that jostaberries were rich in bioflavonoids and vitamin C, and the suggested technology for processing them made it possible to preserve polyphenolic substances and vitamin C in the wine as much as possible. Pomegranate proved to be a dominant descriptor in the aroma of jostaberry wine. Conclusion. The presented studies show the prospects for processing jostaberries into natural wines, the latter being a high-quality and biologically valuable food product. [ABSTRACT FROM AUTHOR]

Background. The rapidly developing resistance of viruses to synthetic antiviral drugs indicates the need to use substances with multitarget action (to avoid polypharmacy and to improve the safety of treatment).Objective: systematic analysis of the scientific literature on the pharmacology of bioflavonoids with an emphasis on their antiviral action.Material and methods. More than 150,000 references of primary sources were found in the PubMed/MEDLINE database of biomedical publications, including 3282 references on the antiviral effects of bioflavonoids. A systematic computerized analysis of this array of publications was carried out in order to identify the main directions in the pharmacology of bioflavonoids with an emphasis on their antiviral, antibacterial and immunomodulatory effects. The literature analysis was carried out using modern methods of topological and metric analysis of big data.Results. The molecular mechanisms of action of baicalin, hesperidin, rutin, quercetin, leukodelphinidin bioflavonoids and epigallocatechin-3-gallate, curcumin polyphenols, their anti-inflammatory, antioxidant, antiviral, bactericidal, angioprotective, regenerative effects, and their prospects in therapy, prevention and rehabilitation of patients with COVID-19 and other respiratory viral infections were described in detail.Conclusion. Bioflavonoids and synergistic polyphenols exhibit not only multitarget antiviral effects by inhibiting the main protease, spike proteins, and other target proteins, but also pronounced anti-inflammatory, hepatoprotective, and immunomodulatory effects.

Bioflavonoids are natural polyphenolic secondary metabolites that are medicinal. These compounds possess antitumor, cardioprotective, anti-inflammatory, antimicrobial, antiviral, and anti-psoriasis properties to mention a few. Plant species that contain bioflavonoids should be preserved as such. Also, the bioactivity of the bioflavonoids as neutraceutical compounds is compromised following extraction due to their sensitivity to environmental factors like light, pH, and temperature. In other words, the bioflavonoids’ shelf-life is affected. Scientists noticed that bioflavonoids have low solubility properties, poor absorption, and low bioavailability following consumption. Researchers came up with methods to encapsulate bioflavonoids in order to circumvent the challenges above and also to mask the unpleasant order these chemicals may have. Besides, scientists cryopreserve plant species that contain bioflavonoids. In this review, we discuss cryopreservation and bioflavonoid microencapsulation focusing mainly on vitrification, slow freezing, and freeze-drying microencapsulation techniques. In addition, we highlight bioflavonoid extraction techniques, medicinal properties, challenges, and future perspectives of cryopreservation and microencapsulation of bioflavonoids. Regardless of the uniqueness of cryopreservation and microencapsulation as methods to preserve bioflavonoid sources and bioflavonoids’ bioactivity, there are challenges reported. Freeze-drying technology is costly. Cryoprotectants damage the integrity of plant cells, to say the least. Researchers are working very hard to overcome these challenges. Encapsulating bioflavonoids via coaxial electrospray and then cryopreserving the micro/nanocapsules produced can be very interesting.

Grape seed proanthocyanidin (GSP) contains polyphenolic bioflavonoids ubiquitously found in the lignified portions of grape seeds from the winery and distillery industries, as an antioxidant. To explore its potential as a rumen modifier in methanogenesis inhibition, a 2 × 5 factorial experiment was conducted to determine the effect of GSP at 0, 15, 30, 60 and 120 mg/g of substrate on the rumen fermentation and methanogenesis of two representative total mixed rations (HY, a diet for high-yield (>2 kg/d) lactating cows, and LY, a diet for low-yield (<25 kg/d) lactating cows). By using the MIXED procedure, after a 48 h in vitro rumen incubation, increasing the GSP addition linearly decreased the in vitro dry matter digestion (IVDMD) and slowed down the rates of ration fermentation (RmaxS, g/h) and kinetic gas production (RmaxG, mL/h), with the decreases being more pronounced in the LY than HY group (p < 0.05). The GSP addition decreased hydrogen recovery (2Hrec) and altered the fermentation gas composition. The molar CH4 proportion was significantly reduced with both 60 and 120 mg GSP addition (p < 0.01). The total volatile fatty acid production was linearly decreased with the increasing GSP addition (p < 0.01). In addition, the GSP addition significantly decreased the ratio of methanogens to total bacteria (p < 0.05), and the reduction was notably greater in the HY than in the LY substrate (45.3% vs. 15.2% decrease), although the diversity of rumen methanogenic archaea was not affected in either the HY or the LY group. Bioinformatic analysis illustrated that the rumen archaeal community was predominated by a Methanobrevibacter genus (>72.5%), followed by Methanomassiliicoccus (>20.9%) and Methanosphaera (>1.0%). Methanobrevibacter could play an important role in methanogenesis in the presence of GSP, though it is usually considered to be the main hydrogenotrophic methanogen. In brief, the GSP addition presented high potential as a rumen modifier to mitigate methanogenesis by decreasing the ratio of methanogens to total bacteria. Methanobrevibacter could play an important role in methanogenesis in the presence of GSP. However, a relatively low administration level of GSP should be taken into consideration in order to obtain its inhibitory effect on CH4 emission, with a minimal negative effect on rumen digestion and fermentation. [ABSTRACT FROM AUTHOR]

Agathisflavone is a natural biflavone with restricted occurrence in plants. This biflavone presents several biological activities and can be important to developing new drugs. Obtaining such a molecule on a large scale for in vivo tests is a challenge. To date, there are no reports regarding its synthesis; thus, it is important to improve and develop methods for the purification of this bioactive compound from natural sources. Previous studies indicated that the leaves of Poincianella pyramidalis (Leguminosae) had agathisflavone predominantly. However, obtaining this compound requires some steps of chromatographic procedures and extraction with organic solvents. This paper compares four procedures for the purification of agathisflavone from its leaves, two by traditional chromatographic techniques and by complexation with inorganic bases. The purification in the automatic flash chromatography in two steps provides a high-yield extraction; the two procedures using alkaline extraction and the traditional method reduced to three steps provided the compound with similar yields. The biflavone was identified by TLC, and HPLC analysis showed that it was isolated with > 99% of purity. Thus, the applied methodologies provided the purification of this compound employing less volume of solvents, the number of chromatographic column procedures, and time-consuming, with increased yields.

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.

One of the adverse outcomes of acute inflammatory response is progressing to the chronic stage or transforming into an aggressive process, which can develop rapidly and result in the multiple organ dysfunction syndrome. The leading role in this process is played by the Systemic Inflammatory Response that is accompanied by the production of pro- and anti-inflammatory cytokines, acute phase proteins, and reactive oxygen and nitrogen species.The purpose of this review that highlights both the recent reports and the results of the authors' own research is to encourage scientists to develop new approaches to the differentiated therapy of various SIR manifestations (low- and high-grade systemic inflammatory response phenotypes) by modulating redox-sensitive transcription factors with polyphenols and to evaluate the saturation of the pharmaceutical market with appropriate dosage forms tailored for targeted delivery of these compounds.Redox-sensitive transcription factors such as NFκB, STAT3, AP1 and Nrf2 have a leading role in mechanisms of the formation of low- and high-grade systemic inflammatory phenotypes as variants of SIR. These phenotypic variants underlie the pathogenesis of the most dangerous diseases of internal organs, endocrine and nervous systems, surgical pathologies, and post-traumatic disorders.The use of individual chemical compounds of the class of polyphenols, or their combinations can be an effective technology in the therapy of SIR. Administering natural polyphenols in oral dosage forms is very beneficial in the therapy and management of the number of diseases accompanied with low-grade systemic inflammatory phenotype. The therapy of diseases associated with high-grade systemic inflammatory phenotype requires medicinal phenol preparations manufactured for parenteral administration.

Objective: The aim of this study is to investigate the effect of topical 5% hesperidin application on healing. Materials and Methods: After 48 rats were randomized and divided into 7 groups, on the first day, an epithelial defect was created in the center of the cornea with the help of microkeratome under intraperitoneal ketamine + xylazine and topical 5% proparacaine anesthesia for the groups to be infected with keratitis according to the groups mentioned below. An amount of 0.05 mL of the solution containing 108 colony-forming units/ mL Pseudomonas aeruginosa (PA-ATC27853) will be taken and inoculated per rat. At the end of the 3 days incubation period, rats with keratitis will be added to the groups, and active substances and antibiotics will be given topically together with other groups for 10 days. At the end of the study, the ocular tissues of the rats will be removed and examined histopathologically. Results: A clinically significant reduction in inflammation was detected in the groups using hesperidin. No transforming growth factor-β1 staining was detected in the group in which keratitis + hesperidin was treated topically. In the group in which hesperidin toxicity was examined, mild inflammation and thickening of the corneal stroma layer were observed, and it was evaluated as a negative transforming growth factor-β1 expression in the lacrimal gland tissue. Corneal epithelial damage was minimal in the keratitis group, and the toxicity group was treated with only hesperidin when compared to the other groups. Conclusion: Topical hesperidin drops may be an important therapeutic factor in tissue healing and in the fight against inflammation in the treatment of keratitis. [ABSTRACT FROM AUTHOR]

The purpose of the investigation was to evaluate the effect of the selected bioflavonoids curcumin, resveratrol and baicalin on the wound healing process in an in vitro model. In the study, Balb3t3 and L929 cell lines were used. The first step was the evaluation of the cytotoxicity of the substances tested (MTT assay). Then, using the scratch test (ST), the influence of bioflavonoids on the healing process was evaluated in an in vitro model. The second stage of the work was a mathematical analysis of the results obtained. On the basis of experimental data, the parameters of the Brian and Cousens model were determined in order to determine the maximum value of the cellular and metabolic response that occurs for the examined range of concentrations of selected bioflavonoids. In the MTT assays, no cytotoxic effect of curcumin, resveratrol and baicalin was observed in selected concentrations, while in the ST tests for selected substances, a stimulatory effect was observed on the cell division rate regardless of the cell lines tested. The results obtained encourage further research on the use of substances of natural origin to support the wound healing process. [ABSTRACT FROM AUTHOR]

Toxoplasmosis and cancer are life-threatening diseases with worldwide distribution. However, currently used chemosynthetic treatments are not devoid of their own intrinsic problems. Natural metabolites are gaining attention due to their lower side effects. In this study, we investigated for the first time Zamia floridana leaves extract and its different fractions for their toxoplasmocidal activity, using Virulent RH Toxoplasma gondii, and cytotoxic activity against MCF-7 and HCT-116 cancer cell lines using MTT assay. The n-butanol fraction was the most potent fraction against T. gondii with an EC50 of 7.16 ± 0.4 µg/mL compared to cotrimoxazole (4.18 ± 0.3 µg/mL). In addition, the n-BuOH fraction showed a significant cytotoxicity against MCF-7 and HCT-116 with IC50 of 12.33 ± 1.1 and 17.88 ± 1.4 µg/mL, respectively, compared to doxorubicin (4.17 ± 0.2 and 5.23 ± 0.3 µg/mL, respectively), with higher safety index against normal cell line (WISH). Therefore, the n-BuOH fraction was investigated for its phytochemicals using extensive chromatographic techniques, which led to the isolation of six compounds that were fully characterized using different spectroscopic techniques. Three biflavonoids (1, 2 and 4) in addition to two phenolic acid derivatives (3 and 5) and a flavonoid glycoside (6) were isolated. Compounds (1, 3, 5 and 6) were reported for the first time from Z. floridana. In silico docking studies for toxoplasmocidal and cytotoxic effects of these compounds revealed that compounds (1, 2, 4 and 6) have promising inhibition potential of either thymidylate synthase-dihydrofolate reductase (TS-DHFR) or cyclin dependent kinase 2 (CDK2) target proteins. This study is considered the first report of chemical and biological investigation of Z. floridana leaves. [ABSTRACT FROM AUTHOR]

Biflavonoids, particularly 3′-8′′-biflavones, have emerged as promising candidates for drug discovery due to their diverse biological activities. In this study, we investigated the comparative effects of 3′-8′′- biflavones (amentoflavone, bilobetin, ginkgetin, isoginkgetin, and sciadopitysin) and their monomeric subunits (apigenin, genkwanin, acacetin) on various parameters. We assessed their radical scavenging activity, antifungal potential against mycotoxigenic fungi, and inhibitory effects on key enzymes. While all compounds exhibited weak radical scavenging activity, their antifungal efficacy varied depending on concentration and fungal species. Notably, ginkgetin and isoginkgetin demonstrated potent acetylcholinesterase inhibition, whereas monomeric flavonoids displayed stronger tyrosinase inhibition. Amentoflavone exhibited notable inhibitory effects on α-amylase and α-glucosidase, with 3′-8′′- biflavones generally showing enhanced enzyme inhibitory activity compared to monomeric subunits. Overall, our findings suggest that 3′-8′′-dimerization enhances certain enzyme activities, albeit influenced by the compound's structural features such as the presence of hydroxyl and methoxy groups. [ABSTRACT FROM AUTHOR]

Most medicines are coming with toxic and detrimental side effects. In addition, microbials are resisting the medicine. Therefore, alternative drugs with low toxic and side effects and low microbial resistance are needed. Plants offer good potential candidates due to a broad range of chemicals they contain. These chemicals have been studied, and research is still going on to probe chemical properties of plant chemicals. In China, traditional Chinese medicine is practised, whereby plant extracts are obtained, and then sold in packages for reasons like memory enhancement, cancer treatment, boosting immune system, and so on. Among the herbs cultivated in China is Polygonati rhizoma (PGR). This plant contains various bioflavonoids such as diosgenin, kaempferol, catechin, daidzein, and 3 ′ -methoxydaidzein. In this review, we discussed the pharmacological effects of these chemicals, including luteolin antimicrobial activity in a manner that it circumvents antibiotic resistance; rutin antivenom property; kaempferol as an agent that mitigates neuropathic pain; genistein anticancer property; isorhamnetin's ability to alleviate chronic obstructive pulmonary diseases (COPD); proanthocyanidins' ability to deal with diabetic neuropathy and analgesic property of catechin. [ABSTRACT FROM AUTHOR]

Objective: Medicinal plants having antioxidant potential possess numerous constituents which are responsible for different beneficial effects and are used as an alternative resource of medicine to lessen diseases linked with oxidative stress. Flavonoids are identified in the plants since ages and display wide spectrum of biological actions that might be able to stimulate the steps which are disturbed in different diseases. Flavonoids are significant natural compounds with various biologic properties, among which the most common is the anti-oxidant potential. Citrus flavonoids establish an important stream of flavonoids. Naringin, very common flavonoids present in the diet, belongs to the family of flavanone. It is the principal constituent of citrus family that contains flavonoids for example tomatoes, grapefruits and oranges. Materials and Methods: In this article, we reviewed naringin with respect to sources, chemical property, pharmacokinetics, pharmacological activity, and novel formulations. The literature survey has been done by searching different databases such as Psyc INFO, Science Direct, PubMed, EMBASE, Google, Google Scholar, Medline. Results: Naringin is known to behave as an antioxidant and possess anti-inflammatory, anti-apoptotic, anti-atherosclerotic, neuroprotective, anti-psychotic, anti-asthmatic, anti-diabetic, hepatoprotective, anti-tussive, cardioprotective, and anti-obesity activity. Further clinical studies using large sample sizes remain essential to obtain the appropriate dose and form of naringin for averting diseases. Furthermore, the therapeutic approach of these bioflavonoids is significantly inappropriate due to the lack of clinical evidence. Different plants must be explored further to find these bioflavonoids in them. Conclusion: The results of this exploration provides biological actions of bioflavonoid (naringin), predominantly on pharmacological and novel dosage forms of naringin. [ABSTRACT FROM AUTHOR]

Abstract The achachairu (Garcinia humilis (Vahl) C.D. Adams) is a Bolivian fruit species that adapts well to tropical and sub-tropical climates and may feasibly be disseminated in other parts of the world. Data from the literature has revealed that both the plant and the fruit exhibited promising compounds for both nutritional and pharmacological purposes. This work aimed to review available publications involving the achachairu (G. humilis) through a bibliometric analysis using data from the Web of Science© (WOS) database. For greater precision and completeness in the research, the filters used included both the scientific nomenclature, and the popular name of the fruit, G. humilis and achachairu, respectively. The data-gathering stage yielded only 29 works containing the terms used in the search. Comprising 25 publications, Brazil was the country having the most records in the database, possibly because its climate is favorable for achachairu cultivation. Among the main research focus areas were attributes related to its chemical structure and pharmacological properties, particularly Guttiferone A, the compound responsible for the gastroprotective, antinociceptive and antiproliferative properties of its fruit, which occurs primarily in its seed. The peel also exhibited a bioactive and antioxidant composition. Thus, these two parts of the fruit, which are considered underutilized, due to the exclusive consumption of the fruit pulp, may have the potential for other purposes. Finally, considering the scarce scientific data regarding this matrix, which has a diversity of positive characteristics for the pharmacological and food industries, this bibliometric analysis revealed an opportunity for further research.

Citrus bioflavonoids are polyphenolic plant-derived pigments found in high levels in oranges, lemons, grapefruits and other citrus fruits. The three most abundant types of citrus bioflavonoids are hesperidin, naringenin and eriocitrin. Citrus bioflavonoids have long been known to possess powerful free radical-scavenging properties and cardioprotective effects. The study involved the analysis of 10 commercially available citrus bioflavonoid supplements from three different countries: Australia, the United States and Canada. The supplements were tested for their citrus bioflavonoid content which varied from 0.8 to 33.3% w/w. The daily bioflavonoid dose varied from 19 mg to 560 mg. Hesperidin was the major citrus bioflavonoid in nine out of ten supplements. One supplement was found to contain less than 10% of the quantity of rutin claimed to have been added. The DPP-4 inhibitory potential, compared through an estimation of rutin equivalence, ranged from 1.9 mg to 400 mg per day. This data highlights the variability between the supplements in their potential to inhibit DPP-4 for subsequent health benefits. [ABSTRACT FROM AUTHOR]