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1.
Int J Nanomedicine ; 19: 6519-6546, 2024.
Article de Anglais | MEDLINE | ID: mdl-38957181

RÉSUMÉ

Background: Salidroside (SAL) is the most effective component of Rhodiola rosea, a traditional Chinese medicine. Cryptotanshinone (CT) is the main fat-soluble extract of Salvia miltiorrhiza, exhibiting considerable potential for application in osteogenesis. Herein, a polycaprolactone/gelatin nanofiber membrane loaded with CT and SAL (PSGC membrane) was successfully fabricated via coaxial electrospinning and characterized. Methods and Results: This membrane capable of sustained and controlled drug release was employed in this study. Co-culturing the membrane with bone marrow mesenchymal stem cells and human umbilical vein endothelial cells revealed excellent biocompatibility and demonstrated osteogenic and angiogenic capabilities. Furthermore, drug release from the PSGC membrane activated the Wnt/ß-catenin signaling pathway and promoted osteogenic differentiation and vascularization. Evaluation of the membrane's vascularization and osteogenic capacities involved transplantation onto a rat's subcutaneous area and assessing rat cranium defects for bone regeneration, respectively. Microcomputed tomography, histological tests, immunohistochemistry, and immunofluorescence staining confirmed the membrane's outstanding angiogenic capacity two weeks post-operation, with a higher incidence of osteogenesis observed in rat cranial defects eight weeks post-surgery. Conclusion: Overall, the SAL- and CT-loaded coaxial electrospun nanofiber membrane synergistically enhances bone repair and regeneration.


Sujet(s)
Gélatine , Glucosides , Cellules endothéliales de la veine ombilicale humaine , Cellules souches mésenchymateuses , Nanofibres , Néovascularisation physiologique , Ostéogenèse , Phénanthrènes , Phénols , Polyesters , Rat Sprague-Dawley , Ostéogenèse/effets des médicaments et des substances chimiques , Animaux , Nanofibres/composition chimique , Gélatine/composition chimique , Polyesters/composition chimique , Glucosides/composition chimique , Glucosides/pharmacologie , Phénols/composition chimique , Phénols/pharmacologie , Phénanthrènes/composition chimique , Phénanthrènes/pharmacologie , Phénanthrènes/pharmacocinétique , Phénanthrènes/administration et posologie , Humains , Néovascularisation physiologique/effets des médicaments et des substances chimiques , Cellules endothéliales de la veine ombilicale humaine/effets des médicaments et des substances chimiques , Cellules souches mésenchymateuses/effets des médicaments et des substances chimiques , Cellules souches mésenchymateuses/cytologie , Rats , Mâle , Régénération osseuse/effets des médicaments et des substances chimiques , Membrane artificielle , Techniques de coculture , Libération de médicament , Différenciation cellulaire/effets des médicaments et des substances chimiques
2.
PLoS One ; 19(7): e0305343, 2024.
Article de Anglais | MEDLINE | ID: mdl-38968273

RÉSUMÉ

BACKGROUND: Salidroside (SAL), the main component of Rhodiola rosea extract, is a flavonoid with biological activities, such as antioxidative stress, anti-inflammatory, and hypolipidemic. In this study, the potential therapeutic targets and mechanisms of SAL against oxidative stress in retinal ganglion cells (RGCs) were investigated on the basis of in-vitro experiments, network pharmacology, and molecular docking techniques. METHODS: RGC oxidative stress models were constructed, and cell activity, reactive oxygen species (ROS), and apoptosis levels were examined for differences. The genes corresponding to rhodopsin, RGCs, and oxidative stress were screened from GeneCards, TCMSP database, and an analysis platform. The intersection of the three was taken, and a Venn diagram was drawn. Protein interactions, GO functional enrichment, and KEGG pathway enrichment data were analyzed by STRING database, Cytohubba plugin, and Metascape database. The key factors in the screening pathway were validated using qRT-PCR. Finally, molecular docking prediction was performed using MOE 2019 software, molecular dynamic simulations was performed using Gromacs 2018 software. RESULTS: In the RGC oxidative stress model in vitro, the cell activity was enhanced, ROS was reduced, and apoptosis was decreased after SAL treatment. A total of 16 potential targets of oxidative stress in SAL RGCs were obtained, and the top 10 core targets were screened by network topology analysis. GO analysis showed that SAL retinal oxidative stress treatment mainly involved cellular response to stress, transcriptional regulatory complexes, and DNA-binding transcription factor binding. KEGG analysis showed that most genes were mainly enriched in multiple cancer pathways and signaling pathways in diabetic complications, nonalcoholic fatty liver, and lipid and atherosclerosis. Validation by PCR, molecular docking and molecular dynamic simulations revealed that SAL may attenuate oxidative stress and reduce apoptosis in RGCs by regulating SIRT1, NRF2, and NOS3. CONCLUSION: This study initially revealed the antioxidant therapeutic effects and molecular mechanisms of SAL on RGCs, providing a theoretical basis for subsequent studies.


Sujet(s)
Apoptose , Glucosides , Simulation de docking moléculaire , Pharmacologie des réseaux , Stress oxydatif , Phénols , Espèces réactives de l'oxygène , Cellules ganglionnaires rétiniennes , Stress oxydatif/effets des médicaments et des substances chimiques , Phénols/pharmacologie , Phénols/composition chimique , Cellules ganglionnaires rétiniennes/effets des médicaments et des substances chimiques , Cellules ganglionnaires rétiniennes/métabolisme , Glucosides/pharmacologie , Glucosides/composition chimique , Apoptose/effets des médicaments et des substances chimiques , Espèces réactives de l'oxygène/métabolisme , Animaux , Rats , Simulation de dynamique moléculaire , Antioxydants/pharmacologie
3.
J Agric Food Chem ; 72(26): 15005-15012, 2024 Jul 03.
Article de Anglais | MEDLINE | ID: mdl-38888327

RÉSUMÉ

The chemical synthesis of anthocyanins, especially delphinidin-3-O-glucoside and petunidin-3-O-glucoside, is preferable due to the challenges associated with their extraction and purification. However, the reported methods for the synthesis are scarce and intricate. Our research focused on exploring a one-step ester-to-ketone process and optimizing the ring formation reaction, simplifying and improving the overall synthesis strategy. Through these attempts, we were able to achieve higher production yields of delphinidin-3-O-glucoside and petunidin-3-O-glucoside. According to the results of DPPH, ABTS, and FRAP, the antioxidant activity of anthocyanins was increased with the number of B ring hydroxyl substituent. Additionally, both delphinidin-3-O-glucoside and petunidin-3-O-glucoside exhibited no cytotoxicity effects, highlighting their potential for safe application in various fields.


Sujet(s)
Anthocyanes , Antioxydants , Glucosides , Anthocyanes/composition chimique , Anthocyanes/pharmacologie , Antioxydants/composition chimique , Antioxydants/pharmacologie , Antioxydants/synthèse chimique , Glucosides/composition chimique , Glucosides/pharmacologie , Glucosides/synthèse chimique , Humains
4.
Chem Biol Interact ; 398: 111110, 2024 Aug 01.
Article de Anglais | MEDLINE | ID: mdl-38876248

RÉSUMÉ

Non-alcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disorder that is linked to metabolic syndrome, mitochondrial dysfunction and impaired autophagy. Polydatin (PD), a natural polyphenol from Polygonum cuspidatum, exhibits various pharmacological effects and protects against NAFLD. The aim of this study was to reveal the molecular mechanisms and therapeutic potential of PD for NAFLD, with a focus on the role of mitochondrial autophagy mediated by sirtuin 3 (SIRT3), fork-head box O3 (FOXO3) and BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3), and by PTEN-induced putative kinase 1 (PINK1) and parkin (PRKN). We combined network pharmacology analysis, animal models and cell culture experiments to show that PD could regulate the mitochondrial autophagy pathway by modulating several key genes related to mitochondrial function, and ameliorate the liver function, histopathology and mitochondrial biogenesis of NAFLD mice and hepatocytes by activating the SIRT3-FOXO3-BNIP3 axis and the PINK1-PRKN-dependent mechanism of mitochondrial autophagy. We also identified the core targets of PD, including SIRT3, FOXO3A, CASP3, PARKIN, EGFR, STAT3, MMP9 and PINK, and confirmed that silencing SIRT3 could significantly attenuate the beneficial effect of PD. This study provided novel theoretical and experimental support for PD as a promising candidate for NAFLD treatment, and also suggested new avenues and methods for investigating the role of mitochondrial autophagy in the pathogenesis and intervention of NAFLD.


Sujet(s)
Protéine O3 à motif en tête de fourche , Glucosides , Souris de lignée C57BL , Mitochondries , Stéatose hépatique non alcoolique , Protein kinases , Sirtuine-3 , Stilbènes , Ubiquitin-protein ligases , Animaux , Protéine O3 à motif en tête de fourche/métabolisme , Sirtuine-3/métabolisme , Sirtuine-3/génétique , Glucosides/pharmacologie , Glucosides/usage thérapeutique , Glucosides/composition chimique , Stilbènes/pharmacologie , Stilbènes/usage thérapeutique , Souris , Stéatose hépatique non alcoolique/traitement médicamenteux , Stéatose hépatique non alcoolique/métabolisme , Stéatose hépatique non alcoolique/anatomopathologie , Ubiquitin-protein ligases/métabolisme , Ubiquitin-protein ligases/génétique , Protein kinases/métabolisme , Mâle , Mitochondries/effets des médicaments et des substances chimiques , Mitochondries/métabolisme , Humains , Protéines mitochondriales/métabolisme , Protéines mitochondriales/génétique , Autophagie/effets des médicaments et des substances chimiques , Foie/effets des médicaments et des substances chimiques , Foie/métabolisme , Foie/anatomopathologie , Hépatocytes/effets des médicaments et des substances chimiques , Hépatocytes/métabolisme , Protéines membranaires
5.
Int J Biol Macromol ; 273(Pt 2): 133205, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38885871

RÉSUMÉ

Although myricetin (3,3',4',5,5',7-hexahydroxyflavone, MYR) has a high antioxidant capacity and health functions, its use as a functional food material is limited owing to its low stability and water solubility. Amylosucrase (ASase) is capable of biosynthesizing flavonol α-glycoside using flavonols as acceptor molecules and sucrose as a donor molecule. Here, ASase from Deinococcus deserti (DdAS) efficiently biosynthesizes a novel MYR α-triglucoside (MYRαG3) using MYR as the acceptor molecule. Comparative homology analysis and computational simulation revealed that DdAS has a different active pocket for the transglycosylation reaction. DdAS produced MYRαG3 with a conversion efficiency of 67.4 % using 10 mM MYR and 50 mM sucrose as acceptor and donor molecules, respectively. The structure of MYRαG3 was identified as MYR 4'-O-4″,6″-tri-O-α-D-glucopyranoside using NMR and LC-MS. In silico analysis confirmed that DdAS has a distinct active pocket compared to other ASases. In addition, molecular docking simulations predicted the synthetic sequence of MYRαG3. Furthermore, MYRαG3 showed a similar DPPH radical scavenging activity of 49 %, comparable to MYR, but with significantly higher water solubility, which increased from 0.03 µg/mL to 511.5 mg/mL. In conclusion, this study demonstrated the efficient biosynthesis of a novel MYRαG3 using DdAS and highlighted the potential of MYRαG3 as a functional material.


Sujet(s)
Deinococcus , Flavonoïdes , Glucosides , Glucosyltransferases , Solubilité , Deinococcus/enzymologie , Glucosyltransferases/composition chimique , Glucosyltransferases/métabolisme , Flavonoïdes/composition chimique , Flavonoïdes/métabolisme , Flavonoïdes/biosynthèse , Glucosides/composition chimique , Glucosides/biosynthèse , Glucosides/métabolisme , Antioxydants/composition chimique , Antioxydants/métabolisme , Simulation de docking moléculaire
6.
Food Res Int ; 188: 114510, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38823887

RÉSUMÉ

The aim of this study was to explore the copigmentation effect of gallic acid on red wine color and to dissect its mechanism at the molecular level. Three-dimensional studies, e.g., in model wine, in real wine and in silico, and multiple indicators, e.g., color, spectrum, thermodynamics and phenolic dynamics, were employed. The results showed that gallic acid significantly enhanced the color quality and stability of red wine. Physico-chemical interactions and chemical transformations should be the most likely mechanism, and physico-chemical interactions are also a prerequisite for chemical transformations. QM calculations of the physico-chemical interactions proved that the binding between gallic acid and malvidin-3-O-glucoside is a spontaneous exothermic reaction driven by hydrogen bonding and dispersion forces. The sugar moiety of malvidin-3-O-glucoside and the phenolic hydroxyl groups of gallic acid affect the formation of hydrogen bonds, while the dispersion interaction was related to the stacking of the molecular skeleton.


Sujet(s)
Anthocyanes , Couleur , Acide gallique , Glucosides , Liaison hydrogène , Thermodynamique , Vin , Acide gallique/composition chimique , Vin/analyse , Glucosides/composition chimique , Anthocyanes/composition chimique , Théorie quantique , Phénols/composition chimique
7.
Chem Biol Interact ; 397: 111087, 2024 Jul 01.
Article de Anglais | MEDLINE | ID: mdl-38823536

RÉSUMÉ

Xanthine oxidase (XO) plays a critical role in purine catabolism, catalyzing the conversion of hypoxanthine to xanthine and xanthine to uric acid, contributing to superoxide anion production. This process is implicated in various human diseases, particularly gout. Traditional XO inhibitors, such as allopurinol and febuxostat, while effective, may present side effects. Our study focuses on Asphodelus microcarpus, a plant renowned for traditional anti-inflammatory uses. Recent investigations into its phenolic-rich flowers, notably abundant in luteolin derivatives, reveal its potential as a natural source of XO inhibitors. In the present research, XO inhibition by an ethanolic flowers extract from A. microcarpus is reported. In silico docking studies have highlighted luteolin derivatives as potential XO inhibitors, and molecular dynamics support that luteolin 7-O-glucoside has the highest binding stability compared to other compounds and controls. In vitro studies confirm that luteolin 7-O-glucoside inhibits XO more effectively than the standard inhibitor allopurinol, with an IC50 value of 4.8 µg/mL compared to 11.5 µg/mL, respectively. These findings underscore the potential therapeutic significance of A. microcarpus in managing conditions related to XO activity. The research contributes valuable insights into the health-promoting properties of A. microcarpus and its potential application in natural medicine, presenting a promising avenue for further exploration in disease management.


Sujet(s)
Antienzymes , Lutéoline , Simulation de docking moléculaire , Xanthine oxidase , Xanthine oxidase/antagonistes et inhibiteurs , Xanthine oxidase/métabolisme , Antienzymes/composition chimique , Antienzymes/pharmacologie , Lutéoline/composition chimique , Lutéoline/pharmacologie , Extraits de plantes/composition chimique , Extraits de plantes/pharmacologie , Glucosides/composition chimique , Glucosides/pharmacologie , Simulation de dynamique moléculaire , Fleurs/composition chimique , Allopurinol/pharmacologie , Allopurinol/composition chimique , Humains , Sites de fixation
8.
Chem Res Toxicol ; 37(6): 1053-1061, 2024 Jun 17.
Article de Anglais | MEDLINE | ID: mdl-38847154

RÉSUMÉ

Poisoning caused by the mushroom Amanita phalloides, due to the toxin α-amanitin, accounts for approximately 90% of food poisoning deaths in China with no specific antidotes. To investigate the role of salidroside (Sal) in α-amanitin (α-AMA)-induced mitophagy, mouse liver cells AML-12 were exposed to α-AMA in the presence of Sal or not. Intracellular reactive oxygen species (ROS) levels were measured using a ROS detection kit, mitochondrial activity was evaluated using a mitochondrial red fluorescent probe kit or JC-1 dye, and protein expression levels of PINK1, Parkin, LC3 II, P62, Bax, Bcl-2, Caspase 3, Cleaved-Caspase 3, PARP I, and Cleaved-PARP I were detected through Western blot. Results demonstrated that α-AMA led to increased intracellular ROS levels, cell apoptosis, and decreased mitochondrial membrane potential. Notably, expression levels of mitophagy-related proteins PINK1, Parkin, and LC3 increased significantly while the P62 protein expression decreased remarkably. Furthermore, Sal reversed the α-AMA-induced decrease in cell viability and mitochondrial membrane potential and increase in intracellular ROS level. In addition, Sal promoted expression levels of PINK1, Parkin, and LC3 II while suppressing the Bax/Bcl-2 ratio, Cleaved-Caspase 3, and Cleaved-PARP I as well as P62. The results above proved that salidroside alleviates α-AMA-induced mouse liver cells damage via promoting PINK1/Parkin-mediated mitophagy and reducing cell apoptosis.


Sujet(s)
Apoptose , Glucosides , Mitochondries , Mitophagie , Phénols , Protein kinases , Espèces réactives de l'oxygène , Ubiquitin-protein ligases , Animaux , Apoptose/effets des médicaments et des substances chimiques , Ubiquitin-protein ligases/métabolisme , Phénols/pharmacologie , Phénols/composition chimique , Glucosides/pharmacologie , Glucosides/composition chimique , Souris , Protein kinases/métabolisme , Mitophagie/effets des médicaments et des substances chimiques , Mitochondries/effets des médicaments et des substances chimiques , Mitochondries/métabolisme , Espèces réactives de l'oxygène/métabolisme , Potentiel de membrane mitochondriale/effets des médicaments et des substances chimiques , Lignée cellulaire , Survie cellulaire/effets des médicaments et des substances chimiques
9.
Food Chem ; 453: 139622, 2024 Sep 30.
Article de Anglais | MEDLINE | ID: mdl-38761729

RÉSUMÉ

For health and safety reasons, the search for green, healthy, and low-calorie sweeteners with good taste has become the demand of many consumers. Furthermore, the need for sugar substitutes of natural origin has increased dramatically. In this review, we briefly discussed the safety and health benefits of stevia sweeteners and enumerated some examples of physiological functions of steviol glycosides (SGs), such as anti-inflammatory, anti-obesity, antihypertensive, anti-diabetes, and anticaries, citing various evidence related to their application in the food industry. The latest advances in emerging technologies for extracting and purifying SGs and the process variables and operational strategies were discussed. The impact of the extraction methods and their comparison against the conventional techniques have also been demonstrated. These technologies use minimal energy solvents and simplify subsequent purification stages, making viable alternatives suitable for a possible industrial application. Furthermore, we also elucidated the potential for advancing and applying the natural sweeteners SGs.


Sujet(s)
Diterpènes de type kaurane , Extraits de plantes , Stevia , Édulcorants , Stevia/composition chimique , Diterpènes de type kaurane/isolement et purification , Diterpènes de type kaurane/composition chimique , Édulcorants/isolement et purification , Édulcorants/composition chimique , Extraits de plantes/composition chimique , Extraits de plantes/isolement et purification , Humains , Glucosides/isolement et purification , Glucosides/composition chimique , Animaux , Hétérosides/isolement et purification , Hétérosides/composition chimique
10.
Molecules ; 29(10)2024 May 10.
Article de Anglais | MEDLINE | ID: mdl-38792098

RÉSUMÉ

The olive oil industry recently introduced a novel multi-phase decanter with the "Leopard DMF" series, which gives a by-product called pâté, made up of pulp and olive wastewater with a high content of phenolic substances and without pits. This study aims to create a new culture medium, the Olive Juice Broth (OJB), from DMF pâté, and apply it to select bacteria strains able to survive and degrade the bitter substances normally present in the olive fruit. Thirty-five different bacterial strains of Lactiplantibacillus plantarum from the CREA-IT.PE Collection of Microorganisms were tested. Seven strains characterized by ≥50% growth in OJB (B31, B137, B28, B39, B124, B130, and B51) showed a degradation of the total phenolic content of OJB ≥ 30%. From this set, L. plantarum B51 strain was selected as a starter for table olive production vs. spontaneous fermentation. The selected inoculant effectively reduced the debittering time compared to spontaneous fermentation. Hydroxytyrosol, derived from oleuropein and verbascoside degradation, and tyrosol, derived from ligstroside degradation, were produced faster than during spontaneous fermentation. The OJB medium is confirmed to be useful in selecting bacterial strains resistant to the complex phenolic environment of the olive fruit.


Sujet(s)
Milieux de culture , Fermentation , Olea , Phénols , Olea/microbiologie , Olea/métabolisme , Olea/composition chimique , Phénols/métabolisme , Phénols/composition chimique , Milieux de culture/composition chimique , Lactobacillales/métabolisme , Huile d'olive/composition chimique , Huile d'olive/métabolisme , Alcool phénéthylique/métabolisme , Alcool phénéthylique/composition chimique , Alcool phénéthylique/analogues et dérivés , Glucosides d'iridoïdes/métabolisme , Glucosides/métabolisme , Glucosides/composition chimique , Lactobacillus plantarum/métabolisme , Polyphénols
11.
J Pharm Biomed Anal ; 246: 116222, 2024 Aug 15.
Article de Anglais | MEDLINE | ID: mdl-38763106

RÉSUMÉ

Zhenwu Decoction (ZWD), a classic formula from Zhang Zhongjing's "Treatise on Typhoid Fever" in the Han Dynasty, consists of five traditional Chinese medicines: Aconiti Lateralis Radix Praeparata (ALRP), Paeoniae Radix Alba, Poria Cocos, Ginger, and Rhizoma Atractylodis Macrocephalae. To evaluate the chemical constituent consistency of ZWD before and after compatibility, an ultra-performance liquid chromatography-electrospray ionization-quadrupole time-of-flight mass spectrometry was established to comprehensively study the constituents of ZWD. By normalizing the peak area, the pairwise compatibility of ALRP and the other four medicinal herbs, as well as the compatibility of the entire formula were studied, respectively. Multivariate statistical analysis was used to identify the differences. The processed data were analyzed by principal component analysis and supervised orthogonal partial least squared discriminant analysis, and an S-plot was generated to compare the differences in the chemical composition of the two types of decoction samples. The results showed that during the decoction process of ZWD, a total of seven components were recognized as differential compounds before and after compatibility of ZWD, namely 6-gingerol, zingerone, benzoylhypaconine, hypaconitine, benzoylaconine, paeoniflorin and fuziline. The results of this study provide basic data reference for understanding the law of ZWD compatibility and are valuable for the compatibility study of other herbal medicines.


Sujet(s)
Médicaments issus de plantes chinoises , Métabolomique , Spectrométrie de masse ESI , Spectrométrie de masse en tandem , Médicaments issus de plantes chinoises/composition chimique , Médicaments issus de plantes chinoises/analyse , Spectrométrie de masse ESI/méthodes , Chromatographie en phase liquide à haute performance/méthodes , Spectrométrie de masse en tandem/méthodes , Métabolomique/méthodes , Alcools gras/analyse , Alcools gras/composition chimique , Analyse en composantes principales , Catéchols/analyse , Catéchols/composition chimique , Zingiber officinale/composition chimique , Glucosides/analyse , Glucosides/composition chimique , Monoterpènes/analyse , Monoterpènes/composition chimique , Benzoates/analyse , Benzoates/composition chimique , Composés pontés/analyse , Composés pontés/composition chimique , Analyse multifactorielle , Paeonia/composition chimique , Aconitum/composition chimique , Aconitine/analogues et dérivés
12.
Zhongguo Zhong Yao Za Zhi ; 49(10): 2754-2765, 2024 May.
Article de Chinois | MEDLINE | ID: mdl-38812176

RÉSUMÉ

This study deciphered the ameliorating effect and molecular mechanism of the total glucosides of White Paeony Capsules(TGP) in the treatment of mice model with acute lung injury(ALI) via NOD-like receptor thermal protein domain associated protein 3(NLRP3) signaling pathway of the inflammasome. The study established an inflammasome activation model of primed bone marrow-derived macrophages(BMDMs), and its molecular mechanism was investigated by Western blot(WB), immunofluorescence staining, enzyme-linked immunosorbent assay(ELISA), and flow cytometry. C57BL/6J mice were randomly divided into a blank control group, a TGP group, a model group(LPS group), LPS+low-and high-dose TGP groups, LPS+MCC950 group, and LPS+MCC950+TGP group, with eight mice per group. The ALI model was induced in mice. Finally, bronchoalveolar lavage fluid(BALF) and lung tissue were collected. Lung index and lung weight wet-to-dry ratio were determined for each group of mice. The pathological changes in lung tissue were observed through hematoxylin-eosin(HE) staining. The number of neutrophils in the BALF of each group was detected using flow cytometry. The levels of interleukin(IL)-1ß, IL-6, and tumor necrosis factor(TNF)-α in the BALF were determined by ELISA. The expressions of IL-1ß, IL-18, IL-6, and TNF-α in the lung tissue were determined by real-time quantitative PCR(RT-qPCR). This study demonstrated that TGP dramatically blocked the activation of the NLRP3 inflammasome by inhibiting the production of upstream mitochondrial reactive oxygen species(mtROS) and the subsequent oligomerization of apoptosis-associated specks(ASC). Additionally, in the ALI mice model, compared with the blank control group, the model group showed alveolar structure rupture, thic-kening of alveolar septa, and dramatically increased lung index, lung weight wet-to-dry ratio in lung tissue, neutrophil count, and inflammatory factor levels. Compared with the model group, the pathological morphology of lung tissue was significantly ameliorated in the TGP and MCC950 groups, and the lung index and lung weight wet-to-dry ratio were significantly reduced. Neutrophil counts were reduced, and levels of inflammatory factors were significantly downregulated. Notably, compared with the MCC950 group, there was no significant difference in effect in the MCC950+TGP group. Collectively, the study reveals that TGP may ameliorate ALI in mice by inhibiting the activation of NLRP3 inflammasome, providing a safe and effective drug candidate for the prevention or treatment of ALI/ARDS.


Sujet(s)
Lésion pulmonaire aigüe , Médicaments issus de plantes chinoises , Glucosides , Inflammasomes , Souris de lignée C57BL , Protéine-3 de la famille des NLR contenant un domaine pyrine , Paeonia , Animaux , Lésion pulmonaire aigüe/traitement médicamenteux , Lésion pulmonaire aigüe/métabolisme , Lésion pulmonaire aigüe/immunologie , Protéine-3 de la famille des NLR contenant un domaine pyrine/métabolisme , Protéine-3 de la famille des NLR contenant un domaine pyrine/génétique , Glucosides/pharmacologie , Glucosides/composition chimique , Souris , Inflammasomes/métabolisme , Inflammasomes/effets des médicaments et des substances chimiques , Mâle , Paeonia/composition chimique , Médicaments issus de plantes chinoises/administration et posologie , Médicaments issus de plantes chinoises/pharmacologie , Médicaments issus de plantes chinoises/composition chimique , Capsules , Poumon/effets des médicaments et des substances chimiques , Poumon/immunologie , Poumon/métabolisme , Humains , Interleukine-1 bêta/génétique , Interleukine-1 bêta/immunologie , Interleukine-1 bêta/métabolisme
13.
Spectrochim Acta A Mol Biomol Spectrosc ; 318: 124460, 2024 Oct 05.
Article de Anglais | MEDLINE | ID: mdl-38761477

RÉSUMÉ

As one innate immune pattern recognition receptor, Toll-like receptor 4 (TLR4) recently has been considered as a critical player in glucolipid metabolism. Blueberries contain high level of anthocyanins, especially malvidin-3-glucoside (Mv-3-glc), which contribute the anti-inflammatory, hypoglycemic, and hypolipidemic effects. It is speculated that Mv-3-glc is able to possess these functions by binding to TLR4. Here, the noncovalent interactions of Mv-3-glc and TLR4 was explored through multi-techniques including fluorescence and ultraviolet-visible (UV-Vis) absorption spectroscopy, as well as molecular docking. The results demonstrated that Mv-3-glc was able to quench TLR4 intrinsic fluorescence effectively. A stable complex was formed spontaneously and the reaction was exothermic. The degree of binding of Mv-3-glc to TLR4 showed a strong dependence on the chemical concentration, temperature, and pH values. The negative signs for enthalpy (ΔH = -69.1 ± 10.8 kJ/mol) and entropy (ΔS = -105.0 ± 12.3 J/mol/K) from the interaction of the Mv-3-glc and TLR4 shows that the major driving forces are the hydrogen bonding and van der Waals' force, which is consistent with the molecular docking results. In addition, molecular docking predicted that the active center with specific amino acid residues, Phe126, Ser127, Leu54, Ile153, and Tyr131 was responsible for the site of Mv-3-glc binding to TLR4/myeloid differentiation protein-2 (MD-2). These findings confirmed that Mv-3-glc could bind to TLR4, which would be beneficial to understand the target therapeutic effects of blueberry anthocyanins on TLR4 in regulating glucolipid metabolism.


Sujet(s)
Anthocyanes , Glucosides , Simulation de docking moléculaire , Spectrométrie de fluorescence , Récepteur de type Toll-4 , Récepteur de type Toll-4/métabolisme , Récepteur de type Toll-4/composition chimique , Glucosides/composition chimique , Glucosides/métabolisme , Anthocyanes/composition chimique , Anthocyanes/métabolisme , Anthocyanes/pharmacologie , Humains , Liaison aux protéines , Spectrophotométrie UV , Thermodynamique , Liaison hydrogène , Sites de fixation
14.
Drug Des Devel Ther ; 18: 1439-1457, 2024.
Article de Anglais | MEDLINE | ID: mdl-38707616

RÉSUMÉ

Background: Acteoside, an active ingredient found in various medicinal herbs, is effective in the treatment of diabetic kidney disease (DKD); however, the intrinsic pharmacological mechanism of action of acteoside in the treatment of DKD remains unclear. This study utilizes a combined approach of network pharmacology and experimental validation to investigate the potential molecular mechanism systematically. Methods: First, acteoside potential targets and DKD-associated targets were aggregated from public databases. Subsequently, utilizing protein-protein interaction (PPI) networks, alongside GO and KEGG pathway enrichment analyses, we established target-pathway networks to identify core potential therapeutic targets and pathways. Further, molecular docking facilitated the confirmation of interactions between acteoside and central targets. Finally, the conjectured molecular mechanisms of acteoside against DKD were verified through experimentation on unilateral nephrectomy combined with streptozotocin (STZ) rat model. The underlying downstream mechanisms were further investigated. Results: Network pharmacology identified 129 potential intersected targets of acteoside for DKD treatment, including targets such as AKT1, TNF, Casp3, MMP9, SRC, IGF1, EGFR, HRAS, CASP8, and MAPK8. Enrichment analyses indicated the PI3K-Akt, MAPK, Metabolic, and Relaxin signaling pathways could be involved in this therapeutic context. Molecular docking revealed high-affinity binding of acteoside to PIK3R1, AKT1, and NF-κB1. In vivo studies validated the therapeutic efficacy of acteoside, demonstrating reduced blood glucose levels, improved serum Scr and BUN levels, decreased 24-hour urinary total protein (P<0.05), alongside mitigated podocyte injury (P<0.05) and ameliorated renal pathological lesions. Furthermore, this finding indicates that acteoside inhibits the expression of pyroptosis markers NLRP3, Caspase-1, IL-1ß, and IL-18 through the modulation of the PI3K/AKT/NF-κB pathway. Conclusion: Acteoside demonstrates renoprotective effects in DKD by regulating the PI3K/AKT/NF-κB signaling pathway and alleviating pyroptosis. This study explores the pharmacological mechanism underlying acteoside's efficacy in DKD treatment, providing a foundation for further basic and clinical research.


Sujet(s)
Diabète expérimental , Néphropathies diabétiques , Glucosides , Simulation de docking moléculaire , Pharmacologie des réseaux , Phénols , Polyphénols , Streptozocine , Néphropathies diabétiques/traitement médicamenteux , Néphropathies diabétiques/métabolisme , Animaux , Rats , Glucosides/pharmacologie , Glucosides/composition chimique , Diabète expérimental/traitement médicamenteux , Diabète expérimental/métabolisme , Mâle , Phénols/pharmacologie , Phénols/composition chimique , Rat Sprague-Dawley
15.
Braz J Biol ; 84: e278323, 2024.
Article de Anglais | MEDLINE | ID: mdl-38747858

RÉSUMÉ

This study aims to evaluate the anti-cancer-related inflammation activity of Cyperus rotundus bioactive compounds. The component of C. rotundus was analyzed using LC-HRMS. The drug-likeness of all compounds were analyzed using swissADME webserver. In addition, the analysis of inhibition potential of compounds against NF-κB and iNOS were carried out using molecular docking in PyRx software. This study found 1-Nitro-2-phenoxybenzene, ethyl 4-(acetylamino)-3-phenyl-2-thioxo-2,3-dihydro-1,3-thiazole-5-carboxylate, and nootkatone passed all the parameters of drug-likeness including Lipinski, ghose, veber, egan, and muege. Based on molecular docking, verbascoside A and n-Pentyl isopentyl phthalate has the lowest binding affinity against iNOS (-10 and -8.9 kcal/mol, respectively). In addition, verbascoside A and maltopentaose have binding affinity of -7.6 and -6.6 kcal/mol, respectively, for NF-κB. The anti-cancer activity of verbascoside A, maltopentaose, and n-Pentyl isopentyl phthalate, according to PASS analysis were anti-inflammatory, antineoplastic, chemopreventive, and chemoprotectant. The cytotoxic effect prediction showed that these compounds were relatively selective to kill tumor cell but not non-tumor cell. Rat toxicity analysis showed maltopentaose was non-toxic, where n-Pentyl isopentyl phthalate was only toxic (class IV) for intravenous administration. perMM analysis showed verbascoside A and n-Pentyl isopentyl phthalate can translocate and across the cell membrane.


Sujet(s)
Cyperus , Simulation de docking moléculaire , Facteur de transcription NF-kappa B , Nitric oxide synthase type II , Transduction du signal , Cyperus/composition chimique , Facteur de transcription NF-kappa B/métabolisme , Nitric oxide synthase type II/métabolisme , Nitric oxide synthase type II/antagonistes et inhibiteurs , Transduction du signal/effets des médicaments et des substances chimiques , Animaux , Rats , Simulation numérique , Extraits de plantes/pharmacologie , Extraits de plantes/composition chimique , Glucosides/pharmacologie , Glucosides/composition chimique , Humains
16.
J Pharm Biomed Anal ; 245: 116184, 2024 Aug 01.
Article de Anglais | MEDLINE | ID: mdl-38692214

RÉSUMÉ

The plant of Paeonia lactiflora Pall. belongs to Ranunculaceae, and its root can be divided into two categories according to different processing methods, which included that one was directly dried without peeling the root of the P. lactiflora (PR), and the other was peeled the root of the P. lactiflora (PPR) after boiled and dried. To evaluate the difference of chemical components, UPLC-ESI-Q-Exactive Focus-MS/MS and UPLC-QQQ-MS were applied. The distribution of chemical components in different tissues was located by laser microdissection (LMD), especially the different ingredients. A total of 86 compounds were identified from PR and PPR. Four kind of tissues were isolated from the fresh root of the P. lactiflora (FPR), and 54 compounds were identified. Especially the content of gallic acid, albiflorin, and paeoniflorin with high biological activities were the highest in the cork, but they were lower in PR than that in PPR, which probably related to the process. To illustrate the difference in pharmacological effects of PR and PPR, the tonifying blood and analgesic effects on mice were investigated, and it was found that the tonifying blood and analgesic effects of PPR was superior to that of PR, even though PR had more constituents. The material basis for tonifying blood and analgesic effect of the root of P. lactiflora is likely to be associated with an increase in constituents such as paeoniflorin and paeoniflorin lactone after boiled and peeled. The study was likely to provide some theoretical support for the standard and clinical application.


Sujet(s)
Glucosides , Monoterpènes , Paeonia , Racines de plante , Spectrométrie de masse en tandem , Paeonia/composition chimique , Racines de plante/composition chimique , Animaux , Souris , Spectrométrie de masse en tandem/méthodes , Chromatographie en phase liquide à haute performance/méthodes , Glucosides/analyse , Glucosides/composition chimique , Mâle , Monoterpènes/pharmacologie , Monoterpènes/analyse , Monoterpènes/composition chimique , Microdissection/méthodes , Acide gallique/analyse , Acide gallique/composition chimique , Extraits de plantes/composition chimique , Extraits de plantes/pharmacologie , Lasers , Analgésiques/pharmacologie , Analgésiques/composition chimique , Analgésiques/analyse , Médicaments issus de plantes chinoises/composition chimique , Médicaments issus de plantes chinoises/pharmacologie , Spectrométrie de masse ESI/méthodes , , Composés pontés
17.
J Biochem Mol Toxicol ; 38(6): e23735, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38773908

RÉSUMÉ

Cancer is one of the major causes of death worldwide, with more than 10 million deaths annually. Despite tremendous advances in the health sciences, cancer continues to be a substantial global contributor to mortality. The current treatment methods demand a paradigm shift that not only improves therapeutic efficacy but also minimizes the side effects of conventional medications. Recently, an increased interest in the potential of natural bioactive compounds in the treatment of several types of cancer has been observed. Ononin, also referred to as formononetin-7-O-ß-d-glucoside, is a natural isoflavone glycoside, derived from the roots, stems, and rhizomes of various plants. It exhibits a variety of pharmacological effects, including Antiangiogenic, anti-inflammatory, antiproliferative, proapoptotic, and antimetastatic activities. The current review presents a thorough overview of sources, chemistry, pharmacokinetics, and the role of ononin in affecting various mechanisms involved in cancer. The review also discusses potential synergistic interactions with other compounds and therapies. The combined synergistic effect of ononin with other compounds increased the efficacy of treatment methods. Finally, the safety studies, comprising both in vitro and in vivo assessments of ononin's anticancer activities, are described.


Sujet(s)
Isoflavones , Tumeurs , Isoflavones/pharmacologie , Isoflavones/composition chimique , Isoflavones/usage thérapeutique , Humains , Animaux , Tumeurs/traitement médicamenteux , Tumeurs/métabolisme , Tumeurs/anatomopathologie , Glucosides/pharmacologie , Glucosides/usage thérapeutique , Glucosides/composition chimique , Antinéoplasiques d'origine végétale/pharmacologie , Antinéoplasiques d'origine végétale/composition chimique , Antinéoplasiques d'origine végétale/usage thérapeutique , Hétérosides/pharmacologie , Hétérosides/usage thérapeutique , Hétérosides/composition chimique , Antinéoplasiques/pharmacologie , Antinéoplasiques/usage thérapeutique , Antinéoplasiques/composition chimique
18.
J Sep Sci ; 47(11): e2300924, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38819784

RÉSUMÉ

Mas-related G protein-coupled receptor X2 (MrgprX2) is acknowledged as a mast cell-specific receptor, playing a crucial role in orchestrating anaphylactoid responses through mast cell degranulation. It holds promise as a target for regulating allergic and inflammatory diseases mediated by mast cells. Polygonum cuspidatum (PC) has shown notable anti-anaphylactoid effects, while its pharmacologically active components remain unclear. In this study, we successfully utilized MrgprX2 high-expressing cell membrane chromatography (CMC), in conjunction with liquid chromatography-mass spectrometry (LC-MS), to identify active anti-anaphylactoid components in PC. Our study pinpointed polydatin, resveratrol, and emodin-8-O-ß-d-glucoside as potential anti-anaphylactoid compounds in PC. Their anti-anaphylactoid activities were evaluated through ß-aminohexosidase and histamine release assays, demonstrating a concentration-dependent inhibition for both ß-aminohexosidase and histamine release. This approach, integrating MrgprX2 high-expression CMC with LC-MS, proves effective in screening potential anti-anaphylactoid ingredients in natural herbal medicines. The findings from this study illuminated the anti-anaphylactoid properties of specific components in PC and provided an efficient method for the drug development of natural products.


Sujet(s)
Polygonum cuspidatum , Récepteurs couplés aux protéines G , Récepteur aux neuropeptides , Récepteurs couplés aux protéines G/métabolisme , Polygonum cuspidatum/composition chimique , Récepteur aux neuropeptides/métabolisme , Récepteur aux neuropeptides/antagonistes et inhibiteurs , Humains , Spectrométrie de masse , Membrane cellulaire/effets des médicaments et des substances chimiques , Membrane cellulaire/métabolisme , Membrane cellulaire/composition chimique , Chromatographie en phase liquide , Protéines de tissu nerveux/métabolisme , Protéines de tissu nerveux/antagonistes et inhibiteurs , Mastocytes/effets des médicaments et des substances chimiques , Mastocytes/métabolisme , Extraits de plantes/pharmacologie , Extraits de plantes/composition chimique , Glucosides/pharmacologie , Glucosides/composition chimique , Glucosides/analyse , Structure moléculaire ,
19.
Food Chem ; 453: 139617, 2024 Sep 30.
Article de Anglais | MEDLINE | ID: mdl-38788642

RÉSUMÉ

The copigmentation effect between malvidin-3-O-glucoside and caffeic acid was comprehensive inquiry on the model wine solution, theoretical simulation and real wine. Thermodynamic parameters were determined by UV/Visible spectroscopy and Isothermal titration calorimetry (ITC). Theoretical data were obtained employing a dispersion-corrected density functional approach. The effects in real wines were investigated by adding the caffeic acid during different fermentation periods. Results shown that the copigmentation reaction between caffeic acid and malvidin-3-O-glucoside is a spontaneous exothermic reaction driven by hydrogen bonding and dispersions forces. Computations show that the polyhydroxyl sugar moiety and phenolic hydroxyl groups are the key active sites. The addition of caffeic acid in post-alcohol fermentation samples evidences an improving color characteristics in the wine.


Sujet(s)
Anthocyanes , Acides caféiques , Couleur , Glucosides , Thermodynamique , Vin , Acides caféiques/composition chimique , Vin/analyse , Glucosides/composition chimique , Anthocyanes/composition chimique , Liaison hydrogène , Structure moléculaire , Fermentation
20.
Zhongguo Zhong Yao Za Zhi ; 49(5): 1255-1259, 2024 Mar.
Article de Chinois | MEDLINE | ID: mdl-38621972

RÉSUMÉ

The components with hypoglycemic activity in Plumeria rubra were isolated and purified by various column chromatography techniques and activity tracing methods. The physical and chemical properties of all the purified monomer compounds were characterized and analyzed, and a total of six compounds were isolated and identified, including 6″-acetyl-6-hydroxy-benzyl-benzoate-2-O-ß-D-glucoside(1), 6-acetyl-6-hydroxy-benzyl-benzoate-2-O-ß-D-glucoside-(1→6″)-ß-D-glucoside(2), 2-hydroxy-6-methoxy-benzyl-benzoate-2-O-ß-D-glucoside(3), 6-hydroxy-benzyl-benzoate-2-O-ß-D-glucoside(4), 6-hydroxy-benzyl-benzoate-2-O-ß-D-glucoside-(1→6″)-ß-D-glucoside(5), and 6-hydroxy-benzyl-benzoate-2-O-ß-D-glucoside-(1→6″)-ß-D-xyloside(6). Compounds 1 and 2 were new compounds, and compounds 3-6 were isolated from Plumeria for the first time. The α-glucosidase inhibitory activity of six identified compounds was tested. The results show that compounds 1-6 show certain inhibitory activity with an IC_(50) value ranging from 8.2 to 33.5 µmol·L~(-1).


Sujet(s)
Apocynaceae , Glucosides , Glucosides/composition chimique , Benzoates
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