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Frontiers in Bioscience (Landmark... May 2024The present study aimed to investigate the anti-diabetic, anti-cholinesterase, and anti-inflammatory potential of extracts from different parts of , including leaves,...
BACKGROUND
The present study aimed to investigate the anti-diabetic, anti-cholinesterase, and anti-inflammatory potential of extracts from different parts of , including leaves, stem, and roots, as well as isolated column fractions (F-B-1 C, F-B-2 C, F-B-3 C, and F-B-4 C).
METHODS
The extracts and subsequent fractions were evaluated for their inhibitory activity against key enzymes involved in diabetes [α-glucosidase and α-amylase], neurodegenerative diseases [acetylcholinesterase and butyrylcholinesterase], and inflammation (cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX)).
RESULTS
The results showed that leaf extract exhibited the highest α-glucosidase inhibitory activity (73.84%) and α-amylase inhibitory activity (76.29%) at 1000 µg/mL. The stem extract (65.50%) and F-B-2 C fraction (69.67%) also demonstrated significant α-glucosidase inhibitory activity. In terms of anti-cholinesterase activity, the extracts of roots, leaves, and stem showed promising inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), with half maximal inhibitory concentration (IC50) values ranging from 50.50 to 474.83 µg/mL. The derived fractions (F-B-1 C, F-B-2 C, F-B-3 C, and F-B-4 C) also exhibited notable inhibition of AChE and BChE, with IC50 values from 91.85 to 337.94 µg/mL. Moreover, the F-B-3 C fraction demonstrated the highest COX-2 inhibitory potential (85.72%), followed by F-B-1 C (83.13%), the stem extract (80.85%), and the leaves extract (79.00%). The F-B-1 C fraction showed the highest 5-LOX inhibitory activity (87.63%), while the root extract exhibited the lowest inhibition (73.39%).
CONCLUSIONS
The results demonstrated promising bioactivity, suggesting the potential of as a source of natural compounds with therapeutic applications. Further studies are required to identify and isolate the active components responsible for these effects and to evaluate their efficacy and safety.
Topics: Ficus; Plant Extracts; Cholinesterase Inhibitors; Anti-Inflammatory Agents; Hypoglycemic Agents; Plant Leaves; Butyrylcholinesterase; Glycoside Hydrolase Inhibitors; alpha-Amylases; Lipoxygenase Inhibitors; Acetylcholinesterase; Arachidonate 5-Lipoxygenase; Plant Roots
PubMed: 38812295
DOI: 10.31083/j.fbl2905183 -
BMC Oral Health May 2024This longitudinal study assessed the association between salivary protein composition and the clinical onset/severity of oral mucositis (OM) in patients with head and...
INTRODUCTION
This longitudinal study assessed the association between salivary protein composition and the clinical onset/severity of oral mucositis (OM) in patients with head and neck tumours treated with intensity-modulated-radiotherapy (IMRT).
METHODS
Saliva samples/clinical data were obtained from 40 head and neck cancer patients treated at Guy's Hospital before -IMRT(T0) and after-IMRT (T1 = 6 m, T2 = 12 m) (ethics approval/consent). Salivary flow rate, total protein concentration, and secretion rate were determined from saliva samples and compared with pre-treatment values. OM was assessed, total/specific salivary proteins, including mucin 5B and 7, IgA, cystatin-S, albumin, and α-amylase, were quantified.
RESULTS
95% patients experienced OM during IMRT, with 33 subjects reaching grade 2&3. At T1, there was a significant reduction in salivary flow rate, total protein secretion rate, α-amylase and cystatin-S compared to baseline. Remarkably IMRT did not significantly alter mucin 5B and 7, or the IgA secretion rate at any time point. At T1, all the analyzed proteins were associated with the OM outcomes. In addition, there was a significant inverse correlation between IgA concentration at T0 and the severity of OM during IMRT.
CONCLUSION
This study revealed significant associations between several salivary proteins and OM in patients with head and neck cancer undergoing IMRT. Further longitudinal studies are needed to confirm these results.
CLINICAL SIGNIFICANCE
The study contributes to the understanding of certain salivary proteins association with OM. This could be the first step towards identifying potential salivary markers that could offer perspectives for personalized medicine approaches to improve their quality of life (QoL).
RESEARCH QUESTION
What is the association between salivary proteins and the occurrence and severity of OM in head and neck cancer patients?
AIM
To assess the association between salivary protein composition with the clinical onset/severity of oral mucositis (OM) in head and neck cancer patients treated with intensity modulated radiotherapy.
NULL HYPOTHESIS
There is no association between salivary proteins and onset/severity of OM in HNC patients.
Topics: Humans; Longitudinal Studies; Head and Neck Neoplasms; Stomatitis; Male; Salivary Proteins and Peptides; Female; Middle Aged; Radiotherapy, Intensity-Modulated; Aged; Saliva; Adult; alpha-Amylases
PubMed: 38811865
DOI: 10.1186/s12903-024-04400-9 -
Nutrients May 2024Metabolic syndrome is a global health problem. The use of functional foods as dietary components has been increasing. One food of interest is forest onion extract (FOE)....
Novel Functional Food Properties of Forest Onion ( Merr.) Phytochemicals for Treating Metabolic Syndrome: New Insights from a Combined Computational and In Vitro Approach.
Metabolic syndrome is a global health problem. The use of functional foods as dietary components has been increasing. One food of interest is forest onion extract (FOE). This study aimed to investigate the effect of FOE on lipid and glucose metabolism in silico and in vitro using the 3T3-L1 mouse cell line. This was a comprehensive study that used a multi-modal computational network pharmacology analysis and molecular docking in silico and 3T3-L1 mouse cells in vitro. The phytochemical components of FOE were analyzed using untargeted ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS). Next, an in silico analysis was performed to determine FOE's bioactive compounds, and a toxicity analysis, protein target identification, network pharmacology, and molecular docking were carried out. FOE's effect on pancreatic lipase, α-glucosidase, and α-amylase inhibition was determined. Finally, we determined its effect on lipid accumulation and MAPK8, PPARG, HMGCR, CPT-1, and GLP1 expression in the preadipocyte 3T3-L1 mouse cell line. We showed that the potential metabolites targeted glucose and lipid metabolism in silico and that FOE inhibited pancreatic lipase levels, α-glucosidase, and α-amylase in vitro. Furthermore, FOE significantly ( < 0.05) inhibits targeted protein expressions of MAPK8, PPARG, HMGCR, CPT-1, and GLP-1 in vitro in 3T3-L1 mouse cells in a dose-dependent manner. FOE contains several metabolites that reduce pancreatic lipase levels, α-glucosidase, α-amylase, and targeted proteins associated with lipid and glucose metabolism in vitro.
Topics: Animals; Mice; Metabolic Syndrome; Onions; 3T3-L1 Cells; Phytochemicals; Plant Extracts; Molecular Docking Simulation; Lipid Metabolism; Functional Food; Lipase; alpha-Amylases; Glucose; Network Pharmacology; PPAR gamma; Tandem Mass Spectrometry; alpha-Glucosidases; Computer Simulation
PubMed: 38794679
DOI: 10.3390/nu16101441 -
Pharmacology Research & Perspectives Jun 2024This study aimed to examine the effect of acute exogenous melatonin administration on salivary cortisol and alpha-amylase (sCort and sAA) as representatives of the HPA... (Randomized Controlled Trial)
Randomized Controlled Trial
This study aimed to examine the effect of acute exogenous melatonin administration on salivary cortisol and alpha-amylase (sCort and sAA) as representatives of the HPA axis and the sympathetic nervous system, respectively. A single-dose prolonged-release melatonin (2 mg) or a placebo tablet was given to healthy volunteers (n = 64) at 20:00 h in a crossover design. The saliva was collected at six time points (20:00, 21:00, awakening, 30 min after awakening, 10:00, and 12:00 h) and was measured for sCort, sAA, and salivary melatonin (sMT) levels. Pulse rates and sleep parameters were also collected. Melatonin was effective in improving sleep onset latency by 7:04 min (p = .037) and increasing total sleep time by 24 min (p = .006). Participants with poor baseline sleep quality responded more strongly to melatonin than participants with normal baseline sleep quality as they reported more satisfaction in having adequate sleep (p = .017). Melatonin administration resulted in higher sCort levels at awakening time point (p = .023) and a tendency of lower sAA levels but these were not significant. Melatonin ingestion at 20:00 h resulted in a marked increase in sMT levels at 21:00 h and remained higher than baseline up to at least 10:00 h (p < .001). Melatonin increases sCort levels at certain time point with a tendency to lower sAA levels. These opposing effects of melatonin suggested a complex interplay between melatonin and these biomarkers. Also, the results confirmed the positive acute effect of a single-dose melatonin on sleep quality.
Topics: Humans; Melatonin; Saliva; Hydrocortisone; Male; Cross-Over Studies; Adult; Female; Young Adult; alpha-Amylases; Sleep; Sleep Quality; Double-Blind Method; Healthy Volunteers; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Delayed-Action Preparations
PubMed: 38764237
DOI: 10.1002/prp2.1205 -
Scientific Reports May 2024Horse welfare is the product of multiple factors, including behavioral and physiological adjustments to cope with stressful situation regarding environment and housing...
Horse welfare is the product of multiple factors, including behavioral and physiological adjustments to cope with stressful situation regarding environment and housing condition. Collectively, it is supposed that a horse kept in the wild has a lower level of stress than other housing system, and the aim of the present study was to investigate the level of stress in domestic horses reared in the wild and then moved to human controlled housing, through saliva analysis. Twelve clinically healthy Catria (Italian local breed) mares, usually reared in the wild, were moved into collective paddocks for a folkloric event. Saliva samples were obtained before and after the change of housing condition to evaluate stress biomarkers including salivary cortisol, salivary alpha-amylase, and butyrylcholinesterase (BChol). The mares were also scored using the Welfare Aggregation and Guidance (WAG) Tool to highlight the presence of abnormal behaviors. Despite the absence of differences in behavioral scores between wild and paddocks, salivary cortisol and BChol were found to be higher in the wild and lower when mares were moved to paddocks. The highest concentrations in stress biomarkers like salivary cortisol and BChol in the wild was unexpected, but the need for managing hierarchical relationships, and the exposure to feral animals, predators, and weather changes, might explain these findings. The overall results of the present study may provide further knowledge toward stress response in domesticated horses living in the wild moved to human controlled housing system.
Topics: Animals; Horses; Saliva; Hydrocortisone; Female; Animals, Wild; Biomarkers; Butyrylcholinesterase; Stress, Psychological; Stress, Physiological; Animal Welfare; Housing, Animal; Behavior, Animal; alpha-Amylases; Animals, Domestic
PubMed: 38760454
DOI: 10.1038/s41598-024-62172-2 -
Open Biology May 2024Most successes in computational protein engineering to date have focused on enhancing one biophysical trait, while multi-trait optimization remains a challenge....
Most successes in computational protein engineering to date have focused on enhancing one biophysical trait, while multi-trait optimization remains a challenge. Different biophysical properties are often conflicting, as mutations that improve one tend to worsen the others. In this study, we explored the potential of an automated computational design strategy, called CamSol Combination, to optimize solubility and stability of enzymes without affecting their activity. Specifically, we focus on α-amylase (BLA), a hyper-stable enzyme that finds diverse application in industry and biotechnology. We validate the computational predictions by producing 10 BLA variants, including the wild-type (WT) and three designed models harbouring between 6 and 8 mutations each. Our results show that all three models have substantially improved relative solubility over the WT, unaffected catalytic rate and retained hyper-stability, supporting the algorithm's capacity to optimize enzymes. High stability and solubility embody enzymes with superior resilience to chemical and physical stresses, enhance manufacturability and allow for high-concentration formulations characterized by extended shelf lives. This ability to readily optimize solubility and stability of enzymes will enable the rapid and reliable generation of highly robust and versatile reagents, poised to contribute to advancements in diverse scientific and industrial domains.
Topics: alpha-Amylases; Solubility; Enzyme Stability; Protein Engineering; Bacterial Proteins; Mutation; Bacillus licheniformis; Algorithms; Models, Molecular
PubMed: 38745462
DOI: 10.1098/rsob.240014 -
Molecules (Basel, Switzerland) Apr 2024This study synthesized a novel oat -glucan (OBG)-Cr(III) complex (OBG-Cr(III)) and explored its structure, inhibitory effects on α-amylase and α-glucosidase, and...
This study synthesized a novel oat -glucan (OBG)-Cr(III) complex (OBG-Cr(III)) and explored its structure, inhibitory effects on α-amylase and α-glucosidase, and hypoglycemic activities and mechanism in vitro using an insulin-resistant HepG2 (IR-HepG2) cell model. The Cr(III) content in the complex was found to be 10.87%. The molecular weight of OBG-Cr(III) was determined to be 7.736 × 10 Da with chromium ions binding to the hydroxyl groups of OBG. This binding resulted in the increased asymmetry and altered spatial conformation of the complex along with significant changes in morphology and crystallinity. Our findings demonstrated that OBG-Cr(III) exhibited inhibitory effects on α-amylase and α-glucosidase. Furthermore, OBG-Cr(III) enhanced the insulin sensitivity of IR-HepG2 cells, promoting glucose uptake and metabolism more efficiently than OBG alone. The underlying mechanism of its hypoglycemic effect involved the modulation of the c-Cbl/PI3K/AKT/GLUT4 signaling pathway, as revealed by Western blot analysis. This research not only broadened the applications of OBG but also positioned OBG-Cr(III) as a promising Cr(III) supplement with enhanced hypoglycemic benefits.
Topics: Humans; Chromium; Hypoglycemic Agents; beta-Glucans; Hep G2 Cells; alpha-Glucosidases; alpha-Amylases; Insulin Resistance; Glucose; Signal Transduction; Glucose Transporter Type 4; Avena; Glycoside Hydrolase Inhibitors; Coordination Complexes
PubMed: 38731488
DOI: 10.3390/molecules29091998 -
Bioorganic Chemistry Jun 2024Diabetes mellitus is a metabolic disease characterized by hyperglycemia, which can be counteracted by the inhibition of α-glucosidase (α-Glu) and α-amylase (α-Amy),...
Diabetes mellitus is a metabolic disease characterized by hyperglycemia, which can be counteracted by the inhibition of α-glucosidase (α-Glu) and α-amylase (α-Amy), enzymes responsible for the hydrolysis of carbohydrates. In recent decades, many natural compounds and their bioinspired analogues have been studied as α-Glu and α-Amy inhibitors. However, no studies have been devoted to the evaluation of α-Glu and α-Amy inhibition by the neolignan obovatol (1). In this work, we report the synthesis of 1 and a library of new analogues. The synthesis of these compounds was achieved by implementing methodologies based on: phenol allylation, Claisen/Cope rearrangements, methylation, Ullmann coupling, demethylation, phenol oxidation and Michael-type addition. Obovatol (1) and ten analogues were evaluated for their in vitro inhibitory activity towards α-Glu and α-Amy. Our investigation highlighted that the naturally occurring 1 and four neolignan analogues (11, 22, 26 and 27) were more effective inhibitors than the hypoglycemic drug acarbose (α-Amy: 34.6 µM; α-Glu: 248.3 µM) with IC value of 6.2-23.6 µM toward α-Amy and 39.8-124.6 µM toward α-Glu. Docking investigations validated the inhibition outcomes, highlighting optimal compatibility between synthesized neolignans and both the enzymes. Concurrently circular dichroism spectroscopy detected the conformational changes in α-Glu induced by its interaction with the studied neolignans. Detailed studies through fluorescence measurements and kinetics of α-Glu and α-Amy inhibition also indicated that 1, 11, 22, 26 and 27 have the greatest affinity for α-Glu and 1, 11 and 27 for α-Amy. Surface plasmon resonance imaging (SPRI) measurements confirmed that among the compounds studied, the neolignan 27 has the greater affinity for both enzymes, thus corroborating the results obtained by kinetics and fluorescence quenching. Finally, in vitro cytotoxicity of the investigated compounds was tested on human colon cancer cell line (HCT-116). All these results demonstrate that these obovatol-based neolignan analogues constitute promising candidates in the pursuit of developing novel hypoglycemic drugs.
Topics: alpha-Amylases; alpha-Glucosidases; Glycoside Hydrolase Inhibitors; Lignans; Structure-Activity Relationship; Humans; Molecular Structure; Dose-Response Relationship, Drug; Molecular Docking Simulation; Hypoglycemic Agents; Enzyme Inhibitors
PubMed: 38723423
DOI: 10.1016/j.bioorg.2024.107392 -
Molecules (Basel, Switzerland) Apr 2024We prepared network polysaccharide nanoscopic hydrogels by crosslinking water-soluble chitosan (WSCS) with a carboxylate-terminated maltooligosaccharide crosslinker via...
We prepared network polysaccharide nanoscopic hydrogels by crosslinking water-soluble chitosan (WSCS) with a carboxylate-terminated maltooligosaccharide crosslinker via condensation. In this study, the enzymatic elongation of amylose chains on chitosan-based network polysaccharides by glucan phosphorylase (GP) catalysis was performed to obtain assembly materials. Maltoheptaose (Glc) primers for GP-catalyzed enzymatic polymerization were first introduced into WSCS by reductive amination. Crosslinking of the product with the above-mentioned crosslinker by condensation was then performed to produce Glc-modified network polysaccharides. The GP-catalyzed enzymatic polymerization of the α-d-glucose 1-phosphate monomer from the Glc primers on the network polysaccharides was conducted, where the elongated amylose chains formed double helices. Enzymatic disintegration of the resulting network polysaccharide assembly successfully occurred by α-amylase-catalyzed hydrolysis of the double helical amyloses. The encapsulation and release of a fluorescent dye, Rhodamine B, using the CS-based network polysaccharides were also achieved by means of the above two enzymatic approaches.
Topics: Chitosan; Fluorescent Dyes; Polysaccharides; Rhodamines; Hydrogels; alpha-Amylases; Hydrolysis; Amylose; Polymerization; Oligosaccharides; Glucosephosphates; Glucans
PubMed: 38675624
DOI: 10.3390/molecules29081804 -
Scientific Reports Apr 2024Copper-doped ZnO nanoparticles with the formula ZnO, where x = 0.0, 0.03, 0.05, and 0.07 were produced using the co-precipitation process. Physical, chemical, and...
Copper-doped ZnO nanoparticles with the formula ZnO, where x = 0.0, 0.03, 0.05, and 0.07 were produced using the co-precipitation process. Physical, chemical, and structural properties were properly examined. Powdered X-ray diffraction (P-XRD) patterns revealed the formation of hexagonal wurtzite crystal structure in all samples, through atomic substitutional incorporation in the Cu-doped ZnO lattice. The presence of Cu ions and their dissolution in the host ZnO crystal structure was supported by FT-IR spectra. HR-TEM images were used to assess the average size, morphology, and shape regularity of the synthesized samples. The form and homogeneity of the ZnO changed when Cu ions were substituted, as evidenced by FE-SEM/EDX analysis. The presence of copper signals in the Cu-doped samples indicates that the doping was successful. The decrease in zeta potential with an increased copper doping percentage designates that the nanoparticles (NPs) are more stable, which could be attributed to an increase in the ionic strength of the aqueous solution. The synthesized NPs were evaluated for their substantial in vitro antioxidant properties. In addition, the antimicrobial efficacy of the materials was tested against pathogenic microorganisms. Regarding the anti-diabetic activity, the 7Cu ZnO sample showed the highest inhibitory effect on the α-amylase enzyme. No variations were observed in the activities of the acetylcholinesterase enzyme (AChE) and proteinase enzymes with ZnO and samples doped with different concentrations of Cu. Therefore, further studies are recommended to reveal the in-vitro anti-diabetic activity of the studied doped samples. Finally, molecular docking provided valuable insights into the potential binding interactions of Cu-doped ZnO with α-amylase, FabH of E. coli, and Penicillin-binding proteins of S. aureus. These outcomes suggest that the prepared materials may have an inhibitory effect on enzymes and hold promise in the battle against microbial infections and diabetes.
Topics: Zinc Oxide; Molecular Docking Simulation; Spectroscopy, Fourier Transform Infrared; Copper; Escherichia coli; Staphylococcus aureus; Acetylcholinesterase; Ions; alpha-Amylases
PubMed: 38641640
DOI: 10.1038/s41598-024-59088-2