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1.
Phytother Res ; 38(1): 384-399, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37992723

RESUMO

Acute myocardial infarction (MI) is one of the leading causes of mortality around the world. Prunella vulgaris (Xia-Ku-Cao in Chinese) is used in traditional Chinese medicine practice for the treatment of cardiovascular diseases. However, its active ingredients and mechanisms of action on cardiac remodeling following MI remain unknown. In this study, we investigated the cardioprotective effect of P. vulgaris on MI rat models. MI rats were treated with aqueous extract of P. vulgaris or phenolic acids from P. vulgaris, including caffeic acid, ursolic acid or rosmarinic acid, 1 day after surgery and continued for the following 28 days. Then the cardioprotective effect, such as cardiac function, inflammatory status, and fibrosis areas were evaluated. RNA-sequencing (RNA-seq) analysis, real-time polymerase chain reaction (PCR), western blotting, and ELISA were used to explore the underlying mechanism. In addition, ultra-high performance liquid chromatography/mass spectrometer analysis was used to identify the chemicals from P. vulgaris. THP-1NLRP3-GFP cells were used to confirm the inhibitory effect of P. vulgaris and phenolic acids on the expression and activity of NLRP3. We found that P. vulgaris significantly improved cardiac function and reduced infarct size. Meanwhile, P. vulgaris protected cardiomyocyte against apoptosis, evidenced by increasing the expression of anti-apoptosis protein Bcl-2 in the heart and decreasing lactate dehydrogenase (LDH) levels in serum. Results from RNA-seq revealed that the therapeutic effect of P. vulgaris might relate to NLRP3-mediated inflammatory response. Results from real-time PCR and western blotting confirmed that P. vulgaris suppressed NLRP3 expression in MI heart. We also found that P. vulgaris suppressed NLRP3 expression and the secretion of HMGB1, IL-1ß, and IL-18 in THP-1NLRP3-GFP cells. Further studies indicated that the active components of P. vulgaris were three phenolic acids, those were caffeic acid, ursolic acid, and rosmarinic acid. These phenolic acids inhibited LPS-induced NLRP3 expression and activity in THP-1 cells, and improved cardiac function, suppressed inflammatory aggregation and fibrosis in MI rat models. In conclusion, our study demonstrated that P. vulgaris and phenolic acids from P. vulgaris, including caffeic acid, ursolic acid, and rosmarinic acid, could improve cardiac function and protect cardiomyocytes from ischemia injury during MI. The mechanism was partially related to inhibiting NLRP3 activation.


Assuntos
Infarto do Miocárdio , Prunella , Ratos , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Prunella/metabolismo , Remodelação Ventricular , Infarto do Miocárdio/tratamento farmacológico , Miócitos Cardíacos , Fibrose , Ácidos Cafeicos/farmacologia
2.
J Am Chem Soc ; 145(2): 1247-1261, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36598864

RESUMO

Self-assembly of block copolymers (BCP) into uniform 3D structures in solution is an extremely rare phenomenon. Furthermore, the investigation of general prerequisites for fabricating a specific uniform 3D structure remains unknown and challenging. Here, through a simple one-pot direct self-assembly (heating and cooling) protocol, we show that uniform spherulite-like structures and their precursors can be prepared with various poly(ferrocenyldimethylsilane) (PFS) BCPs in a variety of polar and non-polar solvents. These structures all evolve from elongated lamellae into hedrites, sheaf-like micelles, and finally spherulites as the annealing temperature and supersaturation degree are increased. The key feature leading to this growth trajectory is the formation of secondary crystals by self-nucleation on the surface of early-elongated lamellae. We identified general prerequisites for fabricating PFS BCP spherulites in solution. These include corona/PFS core block ratios in the range of 1-5.5 that favor the formation of 2D structures as well as the development of secondary crystals on the basal faces of platelets at early stages of the self-assembly. The one-pot direct self-assembly provides a general protocol to form uniform spherulites and their precursors consisting of PFS BCPs that match these prerequisites. In addition, we show that manipulation of various steps in the direct self-assembly protocol can regulate the size and shape of the structures formed. These general concepts show promise for the fabrication and optimization of spherulites and their precursors from semicrystalline BCPs with interesting optical, electronic, or biomedical properties using the one-pot direct self-assembly protocol.

3.
J Transl Med ; 20(1): 352, 2022 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-35933342

RESUMO

PURPOSE: The purpose of this study was to observe the harm of circadian misalignment (CM), caused by an inverted photoperiod (IP), on the hearts of the adolescent Wistar rats, and to explore the mechanisms leading to harm. METHODS: An IP was used to create a CM model. A total of 174 Wistar rats were randomly divided into circadian alignment (CA) and CM groups (87 rats per group). The different activity rhythms of the two groups of rats were adjusted through different light/dark cycles for 90 days. We recorded the rhythmic activity trajectory and sleep time of the rats. After 90 days of modeling, we performed various analyses (i.e., blood pressure, weight, cardiac ultrasound tests, serological tests, cardiac tissue immunofluorescence, immunohistochemistry, transmission electron microscopy on myocardial mitochondria, western blotting, and quantitative polymerase chain reactions). RESULTS: (1) The IP protocol caused CM in rats. (2) CM rats showed significantly higher blood pressure during the day (resting phase). They also showed significantly higher serum levels of angiotensin II and epinephrine during the day compared to the CA rats. (3) CM caused up-regulation of gene expression of adrenergic receptors α1 (α1-AR) and ß1 (ß1-AR) and down-regulation of the glucocorticoid receptor (Gr) gene expression in rat hearts. It also caused downregulation of Bmal1 expression. In addition, the changes in Bmal1 and Per2 correlated with the changes in ß1-AR and α1-AR. (4) CM had adverse effects on multiple molecular proteins of the heart. (5) CM increased the collagen fibers in the rat heart and increased the destruction of mitochondria. (6) Eventually, CM caused a decrease in the pumping function of the heart and decreased the coronary blood flow rate. CONCLUSIONS: (1) CM significantly affected the cardiac structure and function in the adolescent rats through a variety of mechanisms. (2) CM can regulate the expression of myocardial clock genes, and it is likely to have an impact on the heart through this pathway.


Assuntos
Fatores de Transcrição ARNTL , Proteínas Circadianas Period , Fatores de Transcrição ARNTL/genética , Fatores de Transcrição ARNTL/metabolismo , Animais , Ritmo Circadiano , Regulação da Expressão Gênica , Coração/fisiologia , Proteínas Circadianas Period/genética , Proteínas Circadianas Period/metabolismo , Ratos , Ratos Wistar
4.
Rapid Commun Mass Spectrom ; 36(24): e9411, 2022 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-36195983

RESUMO

RATIONALE: Helwingia japonica (HJ), a traditional medicinal plant, is commonly used for the treatment of dysentery, blood in the stool, and scald burns. Three major HJ species, Helwingia japonica (Thunb.) Dietr. (QJY), Helwingia himalaica Hook. f. et Thoms. ex C. B. Clarke, and Helwingia chinensis Batal., share great similarities in both morphology and chemical constituents. The discrimination of medicinal plants directly affects their pharmacological and clinical effects. Here, we solved the taxonomy uncertainty of these three HJ species and explored the discrimination and study of other traditional medicines (TMs). METHODS: First, the anti-inflammatory effects of the three HJ species were compared using lipopolysaccharide (LPS)-induced inflammatory responses in mouse leukemia cells of monocyte macrophage (RAW) 264.7 cells. Then, plant metabolomics were performed in 48 batches of samples to discover chemical markers for discriminating different HJ species. Finally, network pharmacology was applied to explore the linkages among constituents, targets, and signaling pathways. RESULTS: In vitro experiments showed that the QJY exhibited the most potential anti-inflammatory activities. Meanwhile, 172 compounds were tentatively identified and eight metabolites with higher relative content in QJY were designated as chemical markers to distinguish QJY and the other two species. According to the property of absorbed in vivo, threonic acid, arginine, and tyrosine were selected to construct a component-target-pathway network. The network pharmacology analysis confirmed that the chemotaxonomy differentiation was consistent with the bioactive assessment. CONCLUSIONS: The present study demonstrates that bioactivity evaluation integrated with plant metabolomics and network pharmacology could be used as an effective approach to discriminate different TMs and discover the active compounds.


Assuntos
Medicamentos de Ervas Chinesas , Plantas Medicinais , Camundongos , Animais , Farmacologia em Rede , Metabolômica , Anti-Inflamatórios/farmacologia , Células RAW 264.7 , Medicamentos de Ervas Chinesas/metabolismo
5.
J Am Chem Soc ; 143(16): 6266-6280, 2021 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-33856800

RESUMO

Fiber-like (1D) core-crystalline micelles of uniform length can be obtained in protocols involving multiple steps from block copolymers (BCPs) in which crystallization of the core-forming polymer drives the self-assembly. Here we report a systematic study that shows that adding small amounts (<5 w/w%) of a homopolymer corresponding to the core-forming block of the BCP enables uniform 1D micelles (mean lengths Ln = 0.6 to 9.7 µm) to be obtained in a single step, simply by heating the mixture in a selective solvent followed by slow cooling. A series of poly(ferrocenyldimethylsilane) (PFS) BCPs with different corona-forming blocks and different compositions as well as PFS homopolymers of different lengths were examined. Dye labeling and confocal fluorescence microscopy showed that the homopolymer ends up in the center of the micelle, signaling that it served as the initial seed for epitaxial micelle growth. The rate of unimer addition was strongly enhanced by the length of the PFS block, and this enabled more complex structures to be formed in one-pot self-assembly experiments from mixtures of two or three BCPs with different PFS block lengths. Furthermore, BCP mixtures that included PFS-b-PI (PI = polyisoprene) and PFS-b-PDMS with similar PFS block lengths resulted in simultaneous addition to growing micelles, resulting in a patchy block that could be visualized by staining the vinyl groups of the PI with Pt nanoparticles. This approach also enabled scale up, so that uniform 1D micelles of controlled architecture can be obtained at concentrations of 10 w/w % solids or more.

6.
Angew Chem Int Ed Engl ; 60(19): 10950-10956, 2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-33626229

RESUMO

One-dimensional (1D) and 2D structures by crystallization-driven self-assembly of block copolymers (BCPs) can form fascinating hierarchical structures through secondary self-assembly. But examples of 3D structures formed via hierarchical self-assembly are rare. Here we report seeded growth experiments in decane of a poly(ferrocenyldimethylsilane) BCP with an amphiphilic corona forming block in which lenticular platelets grow into classic spherulite-like uniform colloidally stable structures. These 3D objects are spherically symmetric on the exterior, but asymmetric near the core, where there is a more open structure consisting of sheaf-like leaves. The most remarkable aspect of these experiments is that growth stops at different stages of growth process, depending upon how much unimer is added in the seeded growth step. The system provides a model for studying spherulitic growth where real-time observations on their growth at different stages remains challenging.

8.
Int J Mol Sci ; 21(3)2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-32013250

RESUMO

Lung squamous cell carcinoma (LUSC) has a poor prognosis, in part due to poor therapeutic response and limited therapeutic alternatives. Lichens are symbiotic organisms, producing a variety of substances with multiple biological activities. (+)-Usnic acid, an important biologically active metabolite of lichens, has been shown to have high anti-cancer activity at low doses. However, there have been no reports regarding the effect of (+)-usnic acid on LUSC cells. This study found that (+)-usnic acid reduced viability and induced apoptosis in LUSC cells by reactive oxygen species (ROS) accumulation. (+)-Usnic acid induced mitochondria-derived ROS production via inhibition of complex I and complex III of the mitochondrial respiratory chain (MRC). Interestingly, the elimination of mitochondrial ROS by Mito-TEMPOL only partially reversed the effect of (+)-usnic acid on cellular ROS production. Further study showed that (+)-usnic acid also induced ROS production via reducing Nrf2 stability through disruption of the PI3K/Akt pathway. The in vitro and in vivo xenograft studies showed that combined treatment of (+)-usnic acid and paclitaxel synergistically suppressed LUSC cells. In conclusion, this study indicates that (+)-usnic acid induces apoptosis of LUSC cells through ROS accumulation, probably via disrupting the mitochondrial respiratory chain (MRC) and the PI3K/Akt/Nrf2 pathway. Therefore, although clinical use of (+)-usnic acid will be limited due to toxicity issues, derivatives thereof may turn out as promising anticancer candidates for adjuvant treatment of LUSC.


Assuntos
Apoptose/efeitos dos fármacos , Benzofuranos/farmacologia , Complexo de Proteínas da Cadeia de Transporte de Elétrons/metabolismo , Mitocôndrias/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Animais , Antineoplásicos Fitogênicos/farmacologia , Benzofuranos/química , Benzofuranos/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Complexo de Proteínas da Cadeia de Transporte de Elétrons/antagonistas & inibidores , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos , Mitocôndrias/metabolismo , Fator 2 Relacionado a NF-E2/antagonistas & inibidores , Paclitaxel/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transplante Heterólogo
9.
Chem Biol Interact ; 393: 110970, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38513930

RESUMO

Liver regeneration after liver tumor resection or liver transplantation is crucial, the remaining liver frequently fails to regenerate in some patients. Oleanolic acid (OA), a pentacyclic triterpenoid compound which has been shown to protect against various liver diseases. However, the effect of OA on liver regeneration after partial hepatectomy (PHx) is still unclear. In this study, the results showed that OA (50 mg/kg, twice daily) treatment induced liver mass restoration and increased the liver-to-body weight ratio of mice following PHx. Meanwhile, OA promoted hepatocyte proliferation and increased the number of BrdU-, Ki67-and PCNA-positive cells. Furthermore, OA increased the nuclear accumulation of PXR and induced the expression of PXR downstream proteins such as CYP3A11, UGT1A1 and GSTM2 in mice, as well as in AML12 and HepRG cells. Luciferase reporter assay and nuclear localization of PXR further demonstrated the effect of OA on PXR activation in vitro. Molecular docking simulation showed that OA could interact with the PXR active sites. Moreover, OA inhibited the expression of FOXO1, RBL2 and CDKN1B, and increased the expression of PCNA, CCND1 and CCNE1 in vivo and in vitro. Silencing of Pxr further confirmed that OA-mediated upregulation of proliferation-related proteins depended on PXR. The current study illustrated that OA exhibited a significant promoting effect on liver regeneration following PHx, potentially through regulation of the PXR signaling pathway to accelerate liver recovery.


Assuntos
Hepatectomia , Ácido Oleanólico , Humanos , Camundongos , Animais , Regeneração Hepática , Receptor de Pregnano X/metabolismo , Ácido Oleanólico/farmacologia , Hepatócitos , Antígeno Nuclear de Célula em Proliferação/metabolismo , Simulação de Acoplamento Molecular , Fígado , Transdução de Sinais , Camundongos Endogâmicos C57BL
10.
Adv Sci (Weinh) ; 11(19): e2308771, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38477509

RESUMO

Endotoxemia-related acute liver injury has a poor prognosis and high mortality, and macrophage polarization plays a central role in the pathological process. Pregnane X receptor (PXR) serves as a nuclear receptor and xenosensor, safeguarding the liver from toxic stimuli. However, the effect and underlying mechanism of PXR activation on endotoxemic liver injury remain largely unknown. Here, the expression of PXR is reported in human and murine macrophages, and PXR activation modified immunotypes of macrophages. Moreover, PXR activation significantly attenuated endotoxemic liver injury and promoted macrophage M2 polarization. Macrophage depletion by GdCl3 confirmed the essential of macrophages in the beneficial effects observed with PXR activation. The role of PXR in macrophages is further validated using AAV8-F4/80-Pxr shRNA-treated mice; the PXR-mediated hepatoprotection is impaired, and M2 polarization enhancement is blunted. Additionally, treatment with PXR agonists inhibited lipopolysaccharide (LPS)-induced M1 polarization and favored M2 polarization in BMDM, Raw264.7, and THP-1 cells. Further analyses revealed an interaction between PXR and p-STAT6 in vivo and in vitro. Moreover, blocking Pxr or Stat6 abolished the PXR-induced polarization shift. Collectively, macrophage PXR activation attenuated endotoxin-induced liver injury and regulated macrophage polarization through the STAT6 signaling pathway, which provided a potential therapeutic target for managing endotoxemic liver injury.


Assuntos
Endotoxinas , Macrófagos , Receptor de Pregnano X , Animais , Humanos , Masculino , Camundongos , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/genética , Modelos Animais de Doenças , Endotoxemia/metabolismo , Endotoxemia/genética , Lipopolissacarídeos , Fígado/metabolismo , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Receptor de Pregnano X/metabolismo , Receptor de Pregnano X/genética , Transdução de Sinais , Feminino
11.
Fitoterapia ; 174: 105841, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38296170

RESUMO

Prunella vulgaris (PV) is a medicine and food homologous plant, but its quality evaluation seldom relies on the polysaccharides (PVPs). In this work, we established the multi-level fingerprinting and in vitro anti-inflammatory evaluation approaches to characterize and compare the polysaccharides of P. vulgaris collected from the major production regions in China. PVPs prepared from 22 batches of samples gave the content variation of 5.76-24.524 mg/g, but displayed high similarity in the molecular weight distribution. Hydrolyzed oligosaccharides with degrees of polymerization 2-14 were characterized with different numbers of pentose and hexose by HILIC-MS. The tested 22 batches of oligosaccharides exhibited visible differences in peak abundance, which failed to corelate to their production regions. All the PVPs contained Gal, Xyl, and Ara, as the main monosaccharides. Eleven batches among the tested PVPs showed the significant inhibitory effects on NO production on LPS-induced RAW264.7 cells at 10 µg/mL, but the exerted efficacy did not exhibit correlation with the production regions. Conclusively, we, for the first time, investigated the chemical features of PVPs at three levels, and assessed the chemical and anti-inflammatory variations among the different regions of P. vulgaris samples.


Assuntos
Prunella , Prunella/química , Estrutura Molecular , Polissacarídeos/farmacologia , Polissacarídeos/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Oligossacarídeos
12.
Heliyon ; 9(6): e16117, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37274662

RESUMO

Lasianthus, belonging to Rubiaceae, has been verified to improve clinical syndrome in immune diseases (e.g., hepatitis, nephritis, and rheumatoid arthritis). Both the anti-inflammatory function and chemical composition of Lasianthus vary considerably between different species but few studies focus. So essential it is to explore lasianthus and further search for anti-inflammatory substances. The target of this artical is to analyze the anti-inflammatory activity and chemical composition of lasianthus of different species. And the subsequent active compounds were explored. Primary, the anti-inflammatory activity among seven species of lasianthus (e.g., L. fordii., L. wallichii., L. hookeri C., L. verticillatus., L. sikkimensis., L. appressihirtus., and L. hookeri var) were evaluated by vitro experiments (RAW 264.7 cells). Next, UHPLC/Q-Orbitrap-MS-based metabolomics and the mass defect filter (MDF) algorithm were performed to explore metabolites. In addition, principal component analysis (PCA) was to screen out differential compounds in seven species. Finally, the correlation analysis between activities and composition to rapidly discover the active compounds (compounds were verified pharmacologically). Among the 7 species of lasianthus, the L. fordii. and L. hookeri C indicated the best anti-inflammatory activity. Untargeted metabolomics and MDF show 112 compounds, classified into six dominant types (e.g., flavonoids, phenolic acids, alkaloids, iridoids, coumarins, and anthraquinones). Furthermore, 33 differential metabolites were confirmed by PCA. Then according to correlation analysis and pharmacological validation, 7 compounds IC50<100 (e.g., scopoletin, asperulosidic acid, chlorogenic acid, ferulic acid, betaine, syringic acid, and emodin) were verified as anti-inflammatory compounds and conduct quantitative analysis. Metabolomics integrated with activities evaluation might be a rapid and effective strategy to explore the active compounds from natural products.

13.
Chem Sci ; 13(2): 396-409, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-35126972

RESUMO

Self-assembly of crystalline-coil block copolymers (BCPs) in selective solvents is often carried out by heating the mixture until the sample appears to dissolve and then allowing the solution to cool back to room temperature. In self-seeding experiments, some crystallites persist during sample annealing and nucleate the growth of core-crystalline micelles upon cooling. There is evidence in the literature that the nature of the self-assembled structures formed is independent of the annealing time at a particular temperature. There are, however, no systematic studies of how the rate of cooling affects self-assembly. We examine three systems based upon poly(ferrocenyldimethylsilane) BCPs that generated uniform micelles under typical conditions where cooling took pace on the 1-2 h time scale. For example, several of the systems generated elongated 1D micelles of uniform length under these slow cooling conditions. When subjected to rapid cooling (on the time scale of a few minutes or faster), branched structures were obtained. Variation of the cooling rate led to a variation in the size and degree of branching of some of the structures examined. These changes can be explained in terms of the high degree of supersaturation that occurs when unimer solutions at high temperature are suddenly cooled. Enhanced nucleation, seed aggregation, and selective growth of the species of lowest solubility contribute to branching. Cooling rate becomes another tool for manipulating crystallization-driven self-assembly and controlling micelle morphologies.

14.
Exp Neurol ; 347: 113908, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34710402

RESUMO

Long-term shift work can cause circadian misalignment, which has been linked to anxiety and depression. However, the associated pathophysiologic changes have not been described in detail, and the mechanism underlying this association is not fully understood. To address these points, we used a rat model of CM induced by long-term variable photoperiod exposure [L-VP] (ie, for 90 days). We compared the numbers of neurons, astrocytes, and dendritic spines; dendrite morphology; long-term potentiation (LTP), long-term depression (LTD) and paired-pulse ratio (PPR); expression of glutamate receptor [N-methyl-d-aspartate receptor (NMDAR) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)] subunits and brain-derived neurotrophic factor (BDNF) in the medial prefrontal cortex (mPFC); and the anxiety and depression behaviors between rats in the circadian misalignment (CM) and circadian alignment (CA, with normal circadian rhythm) groups. The results showed that L-VP reduced the number of neurons and astrocytes in the mPFC and decreased the number of dendritic spines, dendrite complexity, LTP, LTD, PPR, and expression of glutamate receptors (GluR1, GluR2, GluR3, NMDAR2A, and NMDAR2B) and BDNF in the mPFC. L-VP also induced anxiety and depression-like behaviors, as measured by the open field test, elevated plus-maze, sucrose preference test, and forced swim test. These results suggest that CM induces a loss of neurons and astrocytes and synaptic damage in surviving pyramidal cells in the mPFC might be involved in the pathophysiology of anxiety and depression.


Assuntos
Ansiedade/patologia , Depressão/patologia , Fotoperíodo , Córtex Pré-Frontal/patologia , Animais , Ansiedade/etiologia , Ansiedade/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Depressão/etiologia , Depressão/metabolismo , Masculino , Técnicas de Cultura de Órgãos , Córtex Pré-Frontal/metabolismo , Ratos , Ratos Wistar , Receptores de N-Metil-D-Aspartato/metabolismo , Fatores de Tempo
15.
Toxicol Sci ; 190(1): 54-63, 2022 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-36073954

RESUMO

St. John's wort (SJW) is a medicinal herb remedy for mild depression. However, long-term use of SJW has raised safety concerns in clinical practice because of drug-drug interactions. Excessive use of acetaminophen (APAP) causes severe hepatotoxicity, but whether SJW modulates APAP-induced liver injury remains unclear. In this study, the effect of long-term SJW administration on APAP-induced acute hepatotoxicity and the involved mechanisms were investigated. Morphological and biochemical assessments clearly demonstrated that SJW exacerbates APAP-induced toxicity. Moreover, SJW markedly promoted glutathione depletion and increased the levels of the APAP-cysteine and APAP-N-acetylcysteinyl adducts in mice, which enhanced APAP metabolic activation and aggravated APAP-induced liver injury. To further elucidate APAP metabolic activation in liver injury induced by SJW, the activities and expression levels of CYP2E1 and CYP3A were measured. The results showed that the activities and expression levels of CYP2E1 and CYP3A were increased after SJW treatment. Furthermore, the PXR-CYP signaling pathway was activated by SJW, and its downstream target genes were upregulated. Collectively, this study demonstrated that the long-term administration of SJW extract led to the metabolic activation of APAP and significantly exacerbated APAP-induced liver injury, which may suggest caution for the clinical use of SJW and APAP.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Hypericum , Camundongos , Animais , Acetaminofen/toxicidade , Acetaminofen/metabolismo , Hypericum/metabolismo , Citocromo P-450 CYP2E1 , Citocromo P-450 CYP3A/metabolismo
16.
Chem Sci ; 11(18): 4631-4643, 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-34122918

RESUMO

We describe a polyferrocenyldimethylsilane (PFS) block copolymer (BCP), PFS27-b-P(TDMA65-ran-OEGMA69) (the subscripts refer to the mean degrees of polymerization), in which the corona-forming block is a random brush copolymer of hydrophobic tetradecyl methacrylate (TDMA) and hydrophilic oligo(ethylene glycol) methyl ether methacrylate (OEGMA). Thus, the corona is amphiphilic. This BCP generates a remarkable series of different structures when subjected to crystallization-driven self-assembly (CDSA) in solvents of different polarity. Long ribbon-like micelles formed in isopropanol, and their lengths could be controlled using both self-seeding and seeded growth protocols. In hexanol, the BCP formed more complex structures. These objects consisted of oval platelets connected to long fiber-like micelles that were uniform in width but polydisperse in length. In octane, relatively uniform rectangular platelets formed. Finally, a distinct morphology formed in a mixture of octane/hexanol, namely uniform oval structures, whose height corresponded to the fully extended PFS block. Both long and short axes of these ovals increased with the initial annealing temperature and with the BCP concentration. The self-seeding protocol also afforded uniform two-dimensional structures. Seeded growth experiments, in which a solution of the BCP in THF was added to a colloidal solution of the oval micelles led to a linear increase in area while maintaining the aspect ratio of the ovals. These experiments demonstrate the powerful effect of the amphiphilic corona chains on the CDSA of a core crystalline BCP in solvents of different hydrophilicity.

17.
Chem Commun (Camb) ; 56(33): 4595-4598, 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32211641

RESUMO

This work presents a simple approach to access uniform fiber-like micelles by single-step crystalization-driven co-self-assembly of a polyferrocenyldimethylsilane (PFS) block copolymer with a trace of a PFS homopolymer. The length of micelles in the µm range could be controlled by changing the amount of homopolymer in the mixture.

18.
ACS Appl Mater Interfaces ; 7(45): 25039-44, 2015 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-26197062

RESUMO

We report a new and simple approach to prepare a class of silica-reinforced liposomes with hybrid core-shell nanostructures. The amphiphilic natural structure of lipids was exploited to sequester hydrophobic molecules, namely precursor TEOS and pyrene, in the hydrophobic midplane of liposomal bilayer assemblies in the aqueous phase. Subsequent interfacial hydrolysis of TEOS at the bilayer/water interface and ensuing condensation within the hydrophobic interstices of the lipid bilayer drives silica formation in situ, producing a novel class of silica-lipid hybrid liposils. Structural characterization by scanning- and transmission electron microscopy confirm that the liposils so generated preserve closed topologies and size-monodipersity of the parent lecithin liposomes, and DSC-TGA and XRD measurements provide evidence for the silica coating. Monitoring fluorescence measurements using embedded pyrene yield detailed information on microenvironment changes, which occur during sol-gel process and shed light on the structural evolution during silica formation. We envisage that liposils formed by this simple, new approach, exploiting the hydrophobic core of the lipid bilayer to spatially localize silica-forming precursors enables preparation of stable liposils exhibiting capacity for cargo encapsulation, bicompatibility, and fluorescence monitoring, more generally opening a window for construction of stable, functional hybrid materials.


Assuntos
Bicamadas Lipídicas/química , Transição de Fase , Dióxido de Silício/química , Animais , Varredura Diferencial de Calorimetria , Galinhas , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Silanos/química , Espectrometria de Fluorescência , Termogravimetria , Difração de Raios X
19.
Nanoscale Res Lett ; 9(1): 2498, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26089005

RESUMO

Pt-loaded multi-walled carbon nanotubes (Pt/MCNTs) and magnetically responsive Pt-Fe3O4/MCNT catalysts were prepared by a stepwise loading of preformed Pt and Fe3O4 nanoparticles onto multi-walled carbon nanotubes (MCNTs). The structure, composition, and magnetism of the catalysts were characterized by X-ray diffraction (XRD), TEM, H2-O2 titration, inductively coupling plasma-atomic emission spectroscopy (ICP-AES), and superconducting quantum interference device (SQUID) techniques. Ascribed to the well-controlled particle size in the preformed Pt colloids, Pt particles in the consequent Pt/MCNT and Pt-Fe3O4/MCNT catalysts are of high uniformity and dispersion. The prepared Pt catalysts show an excellent catalytic performance in the liquid phase hydrogenation of 3-methylcrotonaldehyde, one of typical α,ß-unsaturated aldehydes. A very high selectivity to 3-methylcrotonalcohol of 98% at a conversion of about 80% was available on the magnetic Pt-Fe3O4/MCNT catalyst. The magnetic catalyst, with good superparamagnetism, can be easily recovered from the liquid phase system under the external magnetic field. Moreover, both the Pt/MCNT and magnetic Pt-Fe3O4/MCNT catalysts show a good recyclability, confirmed by five cycles of reusage.

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