The present study investigated the phenolic profiles and antioxidant properties of different fractions from
Royle fruits using molecular docking analysis to delineate their inhibition toward ...digestive enzymes. A total of 20 phenolics was identified and quantified. Rutin, quercetin-3-
-glucoside, and isorhamnetin-3-
-rutinoside were the major phenolic compounds in the total phenolic fraction and flavonoid-rich fraction. The anthocyanin-rich fraction mainly contained cyanidin-3-
-glucoside and cyanidin-3-
-rutinoside. All of the fractions exhibited strong radical scavenging activities and good inhibition on cellular reactive oxygen species (ROS) generation in H₂O₂-induced HepG2 cells, as evaluated by DPPH and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assays. Moreover, the powerful inhibitory effects of those fractions against pancreatic lipase and α-glucosidase were observed. The major phenolic compounds that were found in the three fractions also showed good digestive enzyme inhibitory activities in a dose-dependent manner. Molecular docking analysis revealed the underlying inhibition mechanisms of those phenolic standards against digestive enzymes, and the theoretical analysis data were consistent with the experimental results.
Background
Spinal cord injuries (SCIs) can cause a loss of neurons and associated sensory and motor functionality below the injured site. No approaches to treating SCIs in humans have been developed ...to date. Exosomes are extracellular vesicles that hold promise as a potential therapeutic modality when treating such injuries. The present study was thus designed to determine whether sonic hedgehog (Shh)-overexpressing bone mesenchymal stem cell (BMSC)-derived exosomes were protective in the context of SCIs.
Methods
Exosomes were extracted from control or Shh lentivirus-transduced BMSCs, yielding respective BMSC-Exo and BMSC-Shh-Exo preparations which were intravenously injected into SCI model rats. Shh expression in spinal cord tissues in these animals was then assessed via immunohistochemical staining, while Basso-Beattie-Bresnahan (BBB) scores were utilized to measure high limb motor function. Neuronal damage and regeneration within the spinal cord were additionally evaluated via terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), Nissl, hematoxylin and eosin, and immunofluorescent staining.
Results
Both BMSC-Exo and BMSC-Shh-Exo preparations significantly increased Shh expression in the spinal cord of SCI model rats and improved BBB scores in these treated animals, while also increasing the frequencies of Nissl- and NeuN-positive neurons are reducing the numbers of apoptotic and GFAP-positive neurons. While both treatments yielded some degree of benefit to treated animals relative to untreated controls, BMSC-Shh-Exos were more beneficial than were control BMSC-Exos.
Conclusions
Shh-overexpressing BMSC-derived exosomes represent an effective treatment that can facilitate SCI repair in rats.
The aim of this study was to compare the protective effects of three dietary flavonoids (apigenin-7-
-glucoside (A7G), isorhamnetin-3-
-rutinoside (I3R), and cyanidin-3-
-glucoside (C3G)) on advanced ...glycation end products (AGEs)-induced inflammation and vascular endothelial dysfunction. Furthermore, the potential mechanisms of varied effects of those three dietary flavonoids were analyzed by molecular docking analysis. Results showed that C3G (40 μM) achieved the best inhibition on inflammatory cytokines (TNF-α, IL-1β, and IL-6) in AGEs-induced RAW264.7 cells, followed by I3R, and A7G was the weakest. The molecular docking results also showed that C3G exhibited the closest binding with the receptor for AGE. However, I3R (40 μM) demonstrated the best effect in improving endothelial dysfunction in AGEs-induced EA.hy926 cells, followed by C3G, and A7G was the weakest, as evidenced by the molecular docking results of flavonoids with profilin-1. This work may provide knowledge and helpful suggestions regarding the benefits of dietary flavonoids in diabetic vascular complications.
The loss of neural ability leading to subsequent diminishing of motor function and the impairment below the location of the injury is a result of the SCI (Spinal Cord Injury). Among the many ...therapeutic agents for SCI, the exosomes considered as extracellular vesicles seem to be the most promising. Sonic Hedgehog (Shh) is an exosome-carrying protein. This Study's purpose was to identify whether Shh is required for exosomes from BMSCs (mesenchymal stem cells of the bone) and plays a protective effect on SCI.
Spinal cord injection with shRNA Shh-adeno associated virus (sh-Shh-AAV) were used to silence Shh. Exosomes were extracted from BMSCs. Rats that had suffered SCI were given intravenous injections of exosomes through the veins of the tail. Immunohistochemistry was used to identify the expression of Shh glycoprotein molecule as well as the expression of Gli-1 (glioma-associated oncogene homolog 1) in the rat spinal cord tissues. Western blot was performed to measure the levels of growth associated protein-43 (GAP-43). The BBB (Basso Beattie Bresnahan) score was used to assess the motor functions of the hind legs. In the same manner, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling or TUNEL and Nissl Staining was deployed to assess the level of regeneration of neurons and assess the level of histopathological damage in the tissues of the Spinal Cord.
In the case of the rats with SCI, the levels of display of Gli-1 and Shh showed dramatic improvement after the BMSCs exosome injections. In comparison to rats with SCI, the subjects of BMSCs exosomes group showed an improvement in their SCI, including a higher BBB score and Nissl body count, increasing GAP-43 expression, along with a much-decreased number of cells that suffered apoptosis. While the exosome effect on Spinal Cord Injury was completely ineffective in rats that had Shh silencing.
Exosomes secreted from BMSCs showed great effectiveness in the SCI healing with a vital involvement of Shh in this repair.
Acrylamide is a harmful substance that could be inhibited by natural products. Vine tea is an edible herb belonging to the Vitaceae family and has been approved by Chinese authorities as a new food ...ingredient in 2013. However, the effects of vine tea extract on acrylamide formation and bread quality are rarely investigated. In this study, the polyphenol composition of hot-water extract from vine tea was characterized by ultrahigh-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-ESI-HRMS/MS), and its effects on acrylamide formation, quality, and consumer acceptability of bread were investigated. Vine tea extract and its main polyphenol, dihydromyricetin, significantly inhibited the acrylamide formation in bread, especially the low dose of vine tea extract (1.25 g/kg), which decreased the acrylamide formation by 58.23%. The color and texture of bread were significantly affected by vine tea extract or dihydromyricetin, whereas the moisture content was not changed remarkably. Triangle and paired preference tests indicated that, although the aroma, appearance, and taste of the bread with vine tea extract significantly differ from those of the control bread, vine tea extract did not significantly affect the consumer acceptability. In conclusion, the addition of vine tea extract could be used to develop a new and healthy bread product with low acrylamide content.
Postprandial hyperglycemia can be reduced by inhibiting α-glucosidase activity. Common α-glucosidase inhibitors such as acarbose may have various side effects. Therefore, it is important to find ...natural products that are non-toxic and have high α-glucosidase-inhibitory activity. In the present study, a comprehensive computational analysis of 27 dietary flavonoid compounds with α-glucosidase-inhibitory activity was performed. These included flavonoids, flavanones, isoflavonoids, dihydrochalcone, flavan-3-ols, and anthocyanins. Firstly, molecular fingerprint similarity clustering analysis was performed on the target molecules. Secondly, multiple linear regression quantitative structure-activity relationship (MLR-QSAR) models of dietary flavonoids (2D descriptors and 3D descriptors optimized), with R
of 0.927 and 0.934, respectively, were constructed using genetic algorithms. Finally, the MolNatSim tool based on the COCONUT database was used to match the similarity of each flavonoid in this study, and to sequentially perform molecular enrichment, similarity screening, and QSAR prediction. After screening, five kinds of natural product molecule (2-(3,5-dihydroxyphenyl)-5,7-dihydroxy-4H-chromen-4-one, norartocarpetin, 2-(2,5-dihydroxyphenyl)-5,7-dihydroxy-4H-chromen-4-one, 2-(3,4-dihydroxyphenyl)-5-hydroxy-4H-chromen-4-one, and morelosin) were finally obtained. Their IC
values were 8.977, 31.949, 78.566, 87.87, and 94.136 µM, respectively. Pharmacokinetic predictions evaluated the properties of the new natural products, such as bioavailability and toxicity. Molecular docking analysis revealed the interaction of candidate novel natural flavonoid compounds with the amino acid residues of α-glucosidase. Molecular dynamics (MD) simulations and molecular mechanics/generalized Born surface area (MMGBSA) further validated the stability of these novel natural compounds bound to α-glucosidase. The present findings may provide new directions in the search for novel natural α-glucosidase inhibitors.
Cardiac dysfunction frequently emerges in the initial stages of cancer cachexia, posing a significant complication of the disease. Physical fitness is commonly recommended in these early stages of ...cancer cachexia due to its beneficial impacts on various aspects of the condition, including cardiac dysfunction. However, the direct functional impacts of exercise on the heart during cancer cachexia largely remain unexplored. In this study, we induced cancer cachexia in mice using a metastatic B16F10 melanoma model. Concurrently, these mice underwent a low-intensity exercise regimen to investigate its potential role in cardiac function during cachexia. Our findings indicate that exercise training can help prevent metastatic melanoma-induced muscle loss without significant alterations to body and fat weight. Moreover, exercise improved the melanoma-induced decline in left ventricular ejection fraction and fractional shortening, while also mitigating the increase in high-sensitive cardiac troponin T levels caused by metastatic melanoma in mice. Transcriptome analysis revealed that exercise significantly reversed the transcriptional alterations in the heart induced by melanoma, which were primarily enriched in pathways related to heart contraction. These results suggest that exercise can improve systolic heart function and directly influence the transcriptome of the heart during metastatic melanoma-induced cachexia.
This work was designed to comparatively investigate 27 dietary flavonoids that act as α-glucosidase inhibitors and insulin sensitizers. On the basis of the results of an in vitro experiment of ...α-glucosidase inhibition, myricetin (IC50 = 11.63 ± 0.36 μM) possessed the strongest inhibitory effect, followed by apigenin-7-O-glucoside (IC50 = 22.80 ± 0.24 μM) and fisetin (IC50 = 46.39 ± 0.34 μM). A three-dimensional quantitative structure–activity relationship model of α-glucosidase inhibitors with good predictive capability comparative molecular field analysis, q 2 = 0.529, optimum number of components (ONC) = 10, R 2 = 0.996, F = 250.843, standard error of estimation (SEE) = 0.064, and two descriptors; comparative similarity index analysis, q 2 = 0.515, ONC = 10, R 2 = 0.997, F = 348.301, SEE = 0.054, and four descriptors was established and indicated that meta positions of ring B favored bulky and minor, electron-withdrawing, and hydrogen bond donor groups. The presence of electron-donating and hydrogen bond acceptor groups at position 4′ of ring B could improve α-glucosidase activity. Position 3 of ring C favored minor, electron-donating, and hydrogen bond donor groups, whereas position 7 of ring A favored bulky and hydrogen bond acceptor groups. Molecular docking screened five flavonoids (baicalein, isorhamnetin-3-O-rutinoside, apigenin-7-O-glucoside, kaempferol-7-O-β-glucoside, and cyanidin-3-O-glucoside) that can act as insulin sensitizers and form strong combinations with four key protein targets involved in the insulin signaling pathway. Apigenin-7-O-glucoside (60 μM) can effectively improve insulin resistance, and glucose uptake increased by approximately 73.06% relative to the model group of insulin-resistant HepG2 cells. Therefore, apigenin-7-O-glucoside might serve as the most effective α-glucosidase inhibitor and insulin sensitizer. This work may guide diabetes patients to improve their condition through dietary therapy.
•Quercetin/rutin quenched 7S/11S statically and 11S showed higher affinity.•Rutin showed higher binding affinity to 7S/11S via hydrophobic interactions.•Quercetin bonded to 7S/11S via van der Waals ...and hydrogen bonding interactions.•Quercetin/rutin altered secondary structures and surface hydrophobicity of 7S/11S.•The flavonoids affected the thermal stability and antioxidant capacity of 7S/11S.
The purpose of this research was to comparatively investigate the interactions between bioactive flavonoids (quercetin and rutin) and two predominant soy proteins (β-conglycinin and glycinin), and the structural and functional properties of their complexes. The binding affinities of quercetin/rutin toward 7S/11S were structure-dependent, in that rutin had a higher binding affinity than that of quercetin, and 11S exhibited higher affinity toward quercetin/rutin than that of 7S. The interactions in the 7S/11S–quercetin complexes were driven by van der Waals forces and hydrogen-bonding interactions, whereas the 7S/11S–rutin complexes exhibited hydrophobic interactions. Binding to quercetin or rutin altered the secondary structures (decrease in the α-helix and random coil contents and increase in the β-sheet content), decreased the surface hydrophobicity and thermal stability, and enhanced the antioxidant capacity of 7S and 11S. These findings provide valuable information that can facilitate the design of custom-tailored protein–flavonoid macromolecules.
•Ultra-high pressure (UHP) affected phenolics and bioactivities of oil palm fruits.•UHP remarkably increased bioaccessibility of different phenolic fractions (DPFs).•UHP significantly enhanced ...antioxidant and cytoprotective activities of DPFs.•UHP dramatically upgraded the inhibitory effects of DPFs on intracellular ROS.
The present work investigated the phenolic profiles, antioxidant activities, and cytoprotective effects of the free, esterified, and insoluble-bound phenolic fractions from oil palm fruits treated under ultra-high pressure (UHP). Results showed that UHP treatment significantly increased the total phenolic and flavonoid contents of all three phenolic fractions (p < 0.05). A total of 11 and 12 phenolic compounds were detected and quantified in non-treated and UHP-treated fruits, with caffeic acid having the highest concentration in insoluble-bound phenolic fractions with 8.68 and 11.27 mg/g of dry extract, respectively. The antioxidant activities, intracellular reactive oxygen species inhibition, and cytoprotective effects of all three phenolic fractions were dramatically enhanced after UHP pretreatment (p < 0.05). Therefore, UHP-treated oil palm fruits with increased bioactivities could be used in functional food or the nutraceutical industry to enhance their applications and economic value.
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