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1.
Food Res Int ; 188: 114508, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38823847

RESUMO

Procyanidins, which are oligomerized flavan-3-ols with a polyphenolic structure, are bioactive substances that exhibit various biological effects. However, the relationship between the degree of polymerization (DP) of procyanidins and their bioactivities remains largely unknown. In this study, the preventive effects of procyanidins with different DP (EC, PB2 and PC1) on glucose improvement and liver lipid deposition were investigated using a high-fat diet/streptozotocin-induced diabetes mouse model. The results demonstrated that all the procyanidins with different DP effectively reduced fasting blood glucose and glucose/insulin tolerance, decreased the lipid profile (total cholesterol, triglyceride, and low-density lipoprotein cholesterol content) in serum and liver tissue as well as the liver oil red staining, indicating the improvement of glucose metabolism, insulin sensitivity and hepatic lipid deposition in diabetic mice. Furthermore, the procyanidins down-regulated expression of glucose regulated 78-kDa protein (GRP78) and C/EBP homologous protein (CHOP), indicating a regulation role of endoplasmic reticulum (ER) stress. The inhibition of ER stress by tauroursodeoxycholic acid (TUDCA) treatment abolished the effects of procyanidins with different DP in PA-induced HepG2 cells, confirming that procyanidins alleviate liver hyperlipidemia through the modulation of ER stress. Molecular docking results showed that EC and PB2 could better bind GRP78 and CHOP. Collectively, our study reveals that the structure of procyanidins, particularly DP, is not directly correlated with the improvement of blood glucose and lipid deposition, while highlighting the important role of ER stress in the bioactivities of procyanidins.


Assuntos
Glicemia , Diabetes Mellitus Experimental , Dieta Hiperlipídica , Chaperona BiP do Retículo Endoplasmático , Metabolismo dos Lipídeos , Fígado , Proantocianidinas , Animais , Proantocianidinas/farmacologia , Dieta Hiperlipídica/efeitos adversos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Masculino , Metabolismo dos Lipídeos/efeitos dos fármacos , Camundongos , Glicemia/metabolismo , Glicemia/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Células Hep G2 , Humanos , Polimerização , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Simulação de Acoplamento Molecular , Biflavonoides/farmacologia , Camundongos Endogâmicos C57BL , Estreptozocina , Resistência à Insulina , Catequina/farmacologia
2.
PeerJ ; 12: e17488, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38827303

RESUMO

Epigallocatechin gallate (EGCG), an active constituent of tea, is recognized for its anticancer and anti-inflammatory properties. However, the specific mechanism by which EGCG protects osteoblasts from cadmium-induced damage remains incompletely understood. Here, the action of EGCG was investigated by exposing MC3T3-E1 osteoblasts to EGCG and CdCl2 and examining their growth, apoptosis, and differentiation. It was found that EGCG promoted the viability of cadmium-exposed MC3T3-E1 cells, mitigated apoptosis, and promoted both maturation and mineralization. Additionally, CdCl2 has been reported to inhibit both the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) and nuclear factor erythroid 2-related factor 2/heme oxygenase-1(Nrf2/HO-1) signaling pathways. EGCG treatment attenuated cadmium-induced apoptosis in osteoblasts and restored their function by upregulating both signaling pathways. The findings provide compelling evidence for EGCG's role in attenuating cadmium-induced osteoblast apoptosis and dysfunction through activating the PI3K/AKT/mTOR and Nrf2/HO-1 pathways. This suggests the potential of using EGCG for treating cadmium-induced osteoblast dysfunction.


Assuntos
Apoptose , Catequina , Heme Oxigenase-1 , Fator 2 Relacionado a NF-E2 , Osteoblastos , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Serina-Treonina Quinases TOR , Catequina/análogos & derivados , Catequina/farmacologia , Apoptose/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Animais , Camundongos , Serina-Treonina Quinases TOR/metabolismo , Transdução de Sinais/efeitos dos fármacos , Heme Oxigenase-1/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Cádmio/toxicidade , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Proteínas de Membrana
3.
Appl Microbiol Biotechnol ; 108(1): 322, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38713216

RESUMO

Schisandra henryi is an endemic species of medicinal potential known from traditional Chinese medicine. As part of this study, a complex biotechnological and phytochemical assessment was conducted on S. henryi with a focus on phenolic compounds and antioxidant profiling. The following in vitro cultures were tested: microshoot agar and callus, microshoot agitated, and suspension, along with the microshoot culture in PlantForm bioreactors. Qualitative profiling was performed by ultra-high-performance liquid chromatography with a photodiode array detector coupled with ion-trap mass spectrophotometry with electrospray ionization and then quantitative analysis by high-performance liquid chromatography with a diode array detector using standards. In the extracts, mainly the compounds from procyanidins were identified as well as phenolic acids (neochlorogenic acid, caffeic acid, protocatechuic acid) and catechin. The highest content of phenolic compounds was found for in vitro agar microshoot culture (max. total content 229.87 mg/100 g DW) and agitated culture (max. total content 22.82 mg/100 g DW). The max. TPC measured using the Folin-Ciocalteu assay was equal to 1240.51 mg GAE/100 g DW (agar microshoot culture). The extracts were evaluated for their antioxidant potential by the DPPH, FRAP, and chelate iron ion assays. The highest potential was indicated for agar microshoot culture (90% of inhibition and 59.31 nM/L TEAC, respectively). The research conducted on the polyphenol profiling and antioxidant potential of S. henryi in vitro culture extracts indicates the high therapeutic potential of this species. KEY POINTS: • Different types of S. henryi in vitro cultures were compared for the first time. • The S. henryi in vitro culture strong antioxidant potential was determined for the first time. • The polyphenol profiling of different types of S. henryi in vitro cultures was shown.


Assuntos
Antioxidantes , Biflavonoides , Fenóis , Extratos Vegetais , Schisandra , Antioxidantes/farmacologia , Antioxidantes/química , Fenóis/análise , Fenóis/química , Cromatografia Líquida de Alta Pressão , Schisandra/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Proantocianidinas/química , Proantocianidinas/farmacologia , Proantocianidinas/análise , Hidroxibenzoatos/análise , Hidroxibenzoatos/química , Catequina/química , Catequina/análise , Catequina/metabolismo , Catequina/farmacologia , Reatores Biológicos
4.
J Oleo Sci ; 73(5): 709-716, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38692893

RESUMO

Epigallocatechin-3-gallate (EGCG), a polyphenol derived from Green Tea, is one of the sources of natural bioactive compounds which are currently being developed as medicinal ingredients. Besides other biological activities, this natural compound exhibits anti-cariogenic effects. However, EGCG has low physical-chemical stability and poor bioavailability. Thus, the purpose of this study was to develop and characterize lipid-chitosan hybrid nanoparticle with EGCG and to evaluate its in vitro activity against cariogenic planktonic microorganisms. Lipid-chitosan hybrid nanoparticle (LCHNP-EGCG) were prepared by emulsion and sonication method in one step and characterized according to diameter, polydispersity index (PdI), zeta potential (ZP), encapsulation efficiency (EE), mucoadhesion capacity and morphology. Strains of Streptococcus mutans, Streptococcus sobrinus and Lactobacillus casei were treated with LCHNP- EGCG, and minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were evaluated. LCHNP-EGCG exhibited a size of 217.3 ± 5.1 nm with a low polydispersity index (0.17) and positive zeta potential indicating the presence of chitosan on the lipid nanoparticle surface (+33.7 mV). The LCHNP-EGCG showed a spherical morphology, high stability and a mucoadhesive property due to the presence of chitosan coating. In addition, the EGCG encapsulation efficiency was 96%. A reduction of almost 15-fold in the MIC and MBC against the strains was observed when EGCG was encapsulated in LCHNP, indicating the potential of EGCG encapsulation in lipid-polymer hybrid nanoparticles. Taking the results together, the LCHNP-EGCG could be an interesting system to use in dental care due to their nanometric size, mucoadhesive properties high antibacterial activity against relevant planktonic microorganisms.


Assuntos
Antibacterianos , Catequina , Catequina/análogos & derivados , Quitosana , Testes de Sensibilidade Microbiana , Nanopartículas , Streptococcus mutans , Catequina/farmacologia , Catequina/química , Quitosana/química , Quitosana/farmacologia , Streptococcus mutans/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Nanopartículas/química , Streptococcus sobrinus/efeitos dos fármacos , Lacticaseibacillus casei/efeitos dos fármacos , Lipídeos/química , Plâncton/efeitos dos fármacos , Cárie Dentária/microbiologia , Cárie Dentária/prevenção & controle , Portadores de Fármacos/química , Tamanho da Partícula , Emulsões , Sonicação
5.
Sci Rep ; 14(1): 10424, 2024 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-38710752

RESUMO

The storage process has a significant impact on tea quality. Few is known about effect of storage on quality of oolong tea. This study aimed to assess the effect of different storage times on the key chemical components of oolong tea by measuring changes in catechin, free amino acid, and alkaloid content. Variation in the main substances was determined by principal component analysis and heat map analysis. The results revealed notable effects of the storage process on the levels of theanine, epigallocatechin gallate (EGCG), and glutamine. These findings suggest that these compounds could serve as indicators for monitoring changes in oolong tea quality during storage. Additionally, the study observed an increase in the antibacterial ability of tea over time. Correlation analysis indicated that the antibacterial ability against Micrococcus tetragenus and Escherichia coli was influenced by metabolites such as aspartic acid, threonine, serine, gamma-aminobutyric acid, ornithine, alanine, arginine, and EGCG. Overall, this study presents an approach for identifying key metabolites to monitor tea quality effectively with relatively limited data.


Assuntos
Alcaloides , Aminoácidos , Antibacterianos , Catequina , Chá , Catequina/análogos & derivados , Catequina/farmacologia , Catequina/química , Catequina/análise , Chá/química , Aminoácidos/análise , Antibacterianos/farmacologia , Antibacterianos/química , Alcaloides/farmacologia , Alcaloides/análise , Alcaloides/química , Armazenamento de Alimentos/métodos , Escherichia coli/efeitos dos fármacos , Camellia sinensis/química
6.
Molecules ; 29(9)2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38731582

RESUMO

Clinicians often have to face infections caused by microorganisms that are difficult to eradicate due to their resistance and/or tolerance to antimicrobials. Among these pathogens, Pseudomonas aeruginosa causes chronic infections due to its ability to form biofilms on medical devices, skin wounds, ulcers and the lungs of patients with Cystic Fibrosis. In this scenario, the plant world represents an important reservoir of natural compounds with antimicrobial and/or antibiofilm properties. In this study, an extract from the leaves of Combretum micranthum G. Don, named Cm4-p, which was previously investigated for its antimicrobial activities, was assayed for its capacity to inhibit biofilm formation and/or to eradicate formed biofilms. The model strain P. aeruginosa PAO1 and its isogenic biofilm hyperproducer derivative B13 were treated with Cm4-p. Preliminary IR, UV-vis, NMR, and mass spectrometry analyses showed that the extract was mainly composed of catechins bearing different sugar moieties. The phytocomplex (3 g/L) inhibited the biofilm formation of both the PAO1 and B13 strains in a significant manner. In light of the obtained results, Cm4-p deserves deeper investigations of its potential in the antimicrobial field.


Assuntos
Antibacterianos , Biofilmes , Catequina , Combretum , Testes de Sensibilidade Microbiana , Extratos Vegetais , Pseudomonas aeruginosa , Biofilmes/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Antibacterianos/farmacologia , Antibacterianos/química , Catequina/farmacologia , Catequina/química , Combretum/química , Folhas de Planta/química , Açúcares , Humanos
7.
Int J Mol Sci ; 25(9)2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38732012

RESUMO

Neuroblastoma (NB) is the most commonly diagnosed extracranial solid tumor in children, accounting for 15% of all childhood cancer deaths. Although the 5-year survival rate of patients with a high-risk disease has increased in recent decades, NB remains a challenge in pediatric oncology, and the identification of novel potential therapeutic targets and agents is an urgent clinical need. The RNA-binding protein LIN28B has been identified as an oncogene in NB and is associated with a poor prognosis. Given that LIN28B acts by negatively regulating the biogenesis of the tumor suppressor let-7 miRNAs, we reasoned that selective interference with the LIN28B/let-7 miRNA interaction would increase let-7 miRNA levels, ultimately leading to reduced NB aggressiveness. Here, we selected (-)-epigallocatechin 3-gallate (EGCG) out of 4959 molecules screened as the molecule with the best inhibitory activity on LIN28B/let-7 miRNA interaction and showed that treatment with PLC/PLGA-PEG nanoparticles containing EGCG (EGCG-NPs) led to an increase in mature let-7 miRNAs and a consequent inhibition of NB cell growth. In addition, EGCG-NP pretreatment reduced the tumorigenic potential of NB cells in vivo. These experiments suggest that the LIN28B/let-7 miRNA axis is a good therapeutic target in NB and that EGCG, which can interfere with this interaction, deserves further preclinical evaluation.


Assuntos
Catequina , MicroRNAs , Neuroblastoma , Proteínas de Ligação a RNA , Catequina/análogos & derivados , Catequina/farmacologia , Neuroblastoma/genética , Neuroblastoma/patologia , Neuroblastoma/metabolismo , Neuroblastoma/tratamento farmacológico , MicroRNAs/genética , MicroRNAs/metabolismo , Humanos , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Animais , Camundongos , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos Nus
8.
Life Sci ; 348: 122677, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38702026

RESUMO

AIMS: Epidemiological evidence indicates that there is a substantial association between body mass index (BMI) and at least ten forms of cancer, including melanoma, and BMI imbalance contributes to the poor survival rate of cancer patients before and after therapy. Nevertheless, few pharmacological studies on models of obesity and cancer have been reported. In this study, we administered epigallocatechin gallate (EGCG) to B16BL6 tumor-bearing mice that received a high-fat diet (HFD) to examine its impact. METHODS: B16BL6 tumor-bearing mice were fed a HFD. Body weight and food intake were documented every week. We conducted a Western blot analysis to examine the protein levels in the tumor, gastrocnemius (GAS), and tibialis anterior (TA) muscles, as well as the inguinal and epididymal white adipose tissues (iWAT and eWAT). KEY FINDINGS: EGCG has been shown to have anti-cancer effects equivalent to those of cisplatin, a chemotherapy drug. Furthermore, EGCG protected against the loss of epidydimal white adipose tissue by regulating protein levels of lipolysis factors of adipose triglyceride lipase and hormone-sensitive lipase as well as WAT browning factors of uncoupling protein 1, as opposed to cisplatin. EGCG was shown to reduce the protein levels of muscular atrophy factors of muscle RING-finger protein-1, whereas cisplatin did not contribute to rescuing the atrophy of TA and GAS muscles. CONCLUSION: Taken together, our findings indicate that EGCG has a preventive effect against cachexia symptoms and has anti-cancer effects similar to those of cisplatin in tumor-bearing mice fed a high-fat diet.


Assuntos
Catequina , Dieta Hiperlipídica , Melanoma Experimental , Camundongos Endogâmicos C57BL , Atrofia Muscular , Animais , Catequina/análogos & derivados , Catequina/farmacologia , Catequina/uso terapêutico , Dieta Hiperlipídica/efeitos adversos , Camundongos , Masculino , Atrofia Muscular/prevenção & controle , Atrofia Muscular/metabolismo , Atrofia Muscular/tratamento farmacológico , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/metabolismo , Melanoma Experimental/patologia , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Obesidade/metabolismo , Obesidade/tratamento farmacológico , Músculo Esquelético/metabolismo , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/patologia
9.
J Hazard Mater ; 472: 134602, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38749242

RESUMO

Sulfamethoxazole (SMZ) is a commonly used antibiotic in aquaculture, and its residues in water bodies pose a significant threat to aquatic organisms in the water environment. In the present study, epigallocatechin-3-gallate (EGCG), a catecholamine, was used to mitigate the immunotoxicity caused by SMZ exposure in Procambarus clarkii. EGCG reduced the apoptosis rate, which was elevated by SMZ exposure, and increased the total hemocyte count. Simultaneously, EGCG enhanced the activities of enzymes related to antibacterial and antioxidant activities, such as superoxide dismutase (SOD), catalase (CAT), lysozyme (LZM), acid phosphatase (ACP), and GSH, which were decreased following SMZ exposure. Hepatopancreatic histology confirmed that EGCG ameliorated SMZ-induced tissue damage caused by SMZ exposure. In addition to EGCG attenuating SMZ-induced immunotoxicity in crayfish, we determined that EGCG can effectively reduce SMZ residues in crayfish exposed to SMZ. In addition, at the genetic level, the expression levels of genes related to the immune response in hemocytes were disrupted after SMZ exposure, and EGCG promoted their recovery and stimulated an increase in the expression levels of metabolism-related transcripts in hemocytes. The transcriptome analysis was conducted, and "phagosome" and "apoptosis" pathways were shown to be highlighted using Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. To the best of our knowledge, this is the first study to confirm that EGCG attenuates SMZ-induced immunotoxicity in aquatic animals and reduces SMZ residues in aquatic animals exposed to SMZ. Our study contributes to the understanding of the mechanisms by which EGCG reduces the immunotoxicity of antibiotic residues in aquatic animals.


Assuntos
Astacoidea , Catequina , Hemócitos , Sulfametoxazol , Poluentes Químicos da Água , Animais , Catequina/análogos & derivados , Catequina/farmacologia , Astacoidea/efeitos dos fármacos , Astacoidea/imunologia , Sulfametoxazol/toxicidade , Poluentes Químicos da Água/toxicidade , Hemócitos/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Antioxidantes/farmacologia , Antibacterianos/toxicidade , Muramidase/metabolismo , Resíduos de Drogas
10.
Curr Gene Ther ; 24(4): 292-306, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38783529

RESUMO

BACKGROUND: Many studies have suggested that tea has antidepressant effects; however, the underlying mechanism is not fully studied. As the main anti-inflammatory polyphenol in tea, catechin may contribute to the protective role of tea against depression. OBJECTIVE: The objective of this study is to prove that catechin can protect against lipopolysaccharide (LPS)-induced depressive-like behaviours in mice, and then explore the underlying molecular mechanisms. METHODS: Thirty-one C57BL/6J mice were categorized into the normal saline (NS) group, LPS group, catechin group, and amitriptyline group according to their treatments. Elevated Plus Maze (EPM), Tail Suspension Test (TST), and Open Field Test (OFT) were employed to assess depressive- like behaviours in mice. RNA sequencing (RNA-seq) and subsequent Bioinformatics analyses, such as differential gene analysis and functional enrichment, were performed on the four mouse groups. RESULTS: In TST, the mice in the LPS group exhibited significantly longer immobility time than those in the other three groups, while the immobility times for the other three groups were not significantly different. Similarly in EPM, LPS-treated mice exhibited a significantly lower percentage in the time/path of entering open arms than the mice in the other three groups, while the percentages of the mice in the other three groups were not significantly different. In OFT, LPS-treated mice exhibited significantly lower percentages in the time/path of entering the centre area than those in the other three groups. The results suggested that the LPS-induced depression models were established successfully and catechin can reverse (LPS)-induced depressive-like behaviours in mice. Finally, RNA-seq analyses revealed 57 differential expressed genes (DEGs) between LPS and NS with 19 up-regulated and 38 down-regulated. Among them, 13 genes were overlapped with the DEGs between LPS and cetechin (in opposite directions), with an overlapping p-value < 0.001. The 13 genes included Rnu7, Lcn2, C4b, Saa3, Pglyrp1, Gpx3, Lyz2, S100a8, S100a9, Tmem254b, Gm14288, Hbb-bt, and Tmem254c, which might play key roles in the protection of catechin against LPS-induced depressive-like behaviours in mice. The 13 genes were significantly enriched in defense response and inflammatory response, indicating that catechin might work through counteracting changes in the immune system induced by LPS. CONCLUSION: Catechin can protect mice from LPS-induced depressive-like behaviours through affecting inflammatory pathways and neuron-associated gene ontologies.


Assuntos
Comportamento Animal , Catequina , Depressão , Lipopolissacarídeos , Camundongos Endogâmicos C57BL , Animais , Lipopolissacarídeos/toxicidade , Lipopolissacarídeos/efeitos adversos , Catequina/farmacologia , Camundongos , Depressão/tratamento farmacológico , Depressão/induzido quimicamente , Depressão/genética , Masculino , Comportamento Animal/efeitos dos fármacos , Modelos Animais de Doenças , Inflamação/tratamento farmacológico , Inflamação/genética , Inflamação/induzido quimicamente , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos
11.
Cancer Lett ; 592: 216934, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38710299

RESUMO

The Staphylococcal nuclease and Tudor domain containing 1 (SND1) has been identified as an oncoprotein. Our previous study demonstrated that SND1 impedes the major histocompatibility complex class I (MHC-I) assembly by hijacking the nascent heavy chain of MHC-I to endoplasmic reticulum-associated degradation. Herein, we aimed to identify inhibitors to block SND1-MHC-I binding, to facilitate the MHC-I presentation and tumor immunotherapy. Our findings validated the importance of the K490-containing sites in SND1-MHC-I complex. Through structure-based virtual screening and docking analysis, (-)-Epigallocatechin (EGC) exhibited the highest docking score to prevent the binding of MHC-I to SND1 by altering the spatial conformation of SND1. Additionally, EGC treatment resulted in increased expression levels of membrane-presented MHC-I in tumor cells. The C57BL/6J murine orthotopic melanoma model validated that EGC increases infiltration and activity of CD8+ T cells in both the tumor and spleen. Furthermore, the combination of EGC with programmed death-1 (PD-1) antibody demonstrated a superior antitumor effect. In summary, we identified EGC as a novel inhibitor of SND1-MHC-I interaction, prompting MHC-I presentation to improve CD8+ T cell response within the tumor microenvironment. This discovery presents a promising immunotherapeutic candidate for tumors.


Assuntos
Apresentação de Antígeno , Linfócitos T CD8-Positivos , Catequina , Endonucleases , Camundongos Endogâmicos C57BL , Animais , Linfócitos T CD8-Positivos/imunologia , Camundongos , Humanos , Apresentação de Antígeno/imunologia , Endonucleases/metabolismo , Catequina/análogos & derivados , Catequina/farmacologia , Linhagem Celular Tumoral , Antígenos de Histocompatibilidade Classe I/imunologia , Antígenos de Histocompatibilidade Classe I/metabolismo , Simulação de Acoplamento Molecular , Melanoma Experimental/imunologia , Melanoma Experimental/patologia , Melanoma Experimental/metabolismo , Melanoma Experimental/terapia , Antígenos de Neoplasias/imunologia , Antígenos de Neoplasias/metabolismo
12.
Colloids Surf B Biointerfaces ; 239: 113971, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38759296

RESUMO

The optimal material for repairing skull defects should exhibit outstanding biocompatibility and mechanical properties. Specifically, hydrogel scaffolds that emulate the microenvironment of the native bone extracellular matrix play a vital role in promoting osteoblast adhesion, proliferation, and differentiation, thereby yielding superior outcomes in skull reconstruction. In this study, a composite network hydrogel comprising sodium alginate (SA), epigallocatechin gallate (EGCG), and zinc ions (Zn2+) was developed to establish an ideal osteogenic microenvironment for bone regeneration. Initially, physical entanglement and hydrogen bonding between SA and EGCG resulted in the formation of a primary network hydrogel known as SA-EGCG. Subsequently, the inclusion of Zn2+ facilitated the creation of a composite network hydrogels named SA-EGCG-Zn2+ via dynamic coordination bonds with SA and EGCG. The engineered SA-EGCG2 %-Zn2+ hydrogels offered an environment mimicking the native extracellular matrix (ECM). Moreover, the sustained release of Zn2+ from the hydrogel effectively enhanced cell adhesion, promoted proliferation, and stimulated osteoblast differentiation. In vitro experiments have shown that SA-EGCG2 %-Zn2+ hydrogels greatly enhance the attachment and growth of osteoblast precursor cells (MC3T3-E1), while also increasing the expression of genes related to osteogenesis in these cells. Additionally, in vivo studies have confirmed that SA-EGCG2 %-Zn2+ hydrogels promote new bone formation and accelerate the regeneration of bone in situ, indicating promising applications in the realm of bone tissue engineering.


Assuntos
Alginatos , Catequina , Proliferação de Células , Hidrogéis , Crânio , Alicerces Teciduais , Zinco , Zinco/química , Zinco/farmacologia , Alginatos/química , Alginatos/farmacologia , Catequina/química , Catequina/análogos & derivados , Catequina/farmacologia , Crânio/efeitos dos fármacos , Crânio/lesões , Crânio/patologia , Animais , Camundongos , Hidrogéis/química , Hidrogéis/farmacologia , Alicerces Teciduais/química , Proliferação de Células/efeitos dos fármacos , Osteoblastos/efeitos dos fármacos , Osteoblastos/citologia , Osteoblastos/metabolismo , Diferenciação Celular/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Regeneração Óssea/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos
13.
Biomed Mater ; 19(4)2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38815600

RESUMO

Excessive reactive oxygen species (ROS) in the microenvironment of osteoporosis (OP) not only accelerate the bone absorption, but also affect the osteogenic and mineralized effect of osteoblasts. Procyanidins (PC) have been reported to have anti-oxidation effects, but low bioavailability. This study aimed to explore the effect of magnesium oxide nanoparticles (MgO-PC NPs)-loaded PC on the osteogenesis and mineralization of osteoblasts that stimulated by H2O2. PC was loaded onto MgO NPs and characterized by transmission electron microscopy, energy dispersive spectroscopy, dynamic light scattering, and Fourier transform infrared spectroscopy. After primary screening by cytotoxicity assay, MgO-PC NPs containing 20 µM of PC were chosen for further studies. In H2O2-stimulated osteoblasts, dichlorodihydrofluorescein diacetate probe, Cell Counting Kit-8, quantitative real-time polymerase chain reaction, alkaline phosphatase staining/activity and Alizarin red staining were used to detect the ROS production, cell viability and osteogenic and mineralized markers of osteoblasts. PC was loaded onto MgO NPs to successfully receive MgO-PC NPs with a diameter of about 144 nm and negative potential. PC can sustain release from MgO-PC NPs for at least 16 d. The controlled release of PC from MgO-PC NPs can effectively eliminate ROS and thereby promoted the cell activity. Most importantly, the osteogenesis and mineralization of osteoblasts under oxidative stress were also significantly reversed by MgO-PC NPS. Thus, these findings indicate that MgO-PC NPs may be developed as a potential therapeutic strategy for OP.


Assuntos
Biflavonoides , Catequina , Sobrevivência Celular , Peróxido de Hidrogênio , Óxido de Magnésio , Nanopartículas , Osteoblastos , Osteogênese , Estresse Oxidativo , Proantocianidinas , Espécies Reativas de Oxigênio , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteoblastos/citologia , Proantocianidinas/farmacologia , Proantocianidinas/química , Catequina/química , Catequina/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Óxido de Magnésio/química , Espécies Reativas de Oxigênio/metabolismo , Animais , Sobrevivência Celular/efeitos dos fármacos , Biflavonoides/farmacologia , Biflavonoides/química , Osteogênese/efeitos dos fármacos , Peróxido de Hidrogênio/química , Nanopartículas/química , Preparações de Ação Retardada/química , Camundongos , Calcificação Fisiológica/efeitos dos fármacos , Espectroscopia de Infravermelho com Transformada de Fourier
14.
FEBS Open Bio ; 14(6): 955-967, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38711215

RESUMO

Patterned hair loss (PHL) or androgenetic alopecia is a condition affecting about 50% of people worldwide. Several pharmacological medications have been developed over the years, but few studies have investigated their effectiveness. Therefore, new, safer and more effective strategies are required. Recent investigations showed that Annurca apple extract application could induce keratin production and promote hair growth thanks to the high amount of procyanidin B2 contained in. Hence, this study aimed to investigate the role of an Annurca apple extract in preventing PHL by testing it on human follicle dermal papilla cells (HFDPCs) for the first time. Treatment of HFDPCs with Annurca apple extract counteracted intracellular reactive oxygen species accumulation by increasing the activity of antioxidant enzymes such as superoxide dismutase 2 and catalase. Furthermore, treatment with Annurca apple extract increased ß-catenin and fibroblast growth factor 2, which are involved in hair growth stimulation. These data suggest that Annurca apple extract may be a potential therapeutically useful nutraceutical product for preventing or treating hair loss by reducing oxidative stress and inducing the expression of hair growth-related factors.


Assuntos
Alopecia , Malus , Estresse Oxidativo , Extratos Vegetais , Espécies Reativas de Oxigênio , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Alopecia/tratamento farmacológico , Alopecia/metabolismo , Humanos , Malus/química , Espécies Reativas de Oxigênio/metabolismo , Antioxidantes/farmacologia , Folículo Piloso/efeitos dos fármacos , Folículo Piloso/metabolismo , Proantocianidinas/farmacologia , Catequina/farmacologia , Superóxido Dismutase/metabolismo , Células Cultivadas , Biflavonoides/farmacologia , Catalase/metabolismo
15.
Arch Oral Biol ; 164: 105990, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38749386

RESUMO

INTRODUCTION: There have been reports on the effects of epigallocatechin gallate (EGCG) against Streptococcus mutans viability and acidogenesis. However, the effects of EGCG on the virulence of S. mutans biofilm development have yet to be fully investigated using validated cariogenic biofilm models. OBJECTIVE: Thus, this study aimed to evaluate the effects of EGCG on S. mutans biofilm virulence using a validated cariogenic model and clinically relevant treatment regimens, twice a day for 1.5 min. METHODS: Effects of EGCG on bacterial viability, polyssacharide synthesis and biofilm acidogenesis were evaluated. The morphology and 3D structure of the biofilms were evaluated by scanning electron (SEM) and confocal laser scanning microscopy, respectively. RESULTS: No significant change in S. mutans viability or culture medium pH were observed when comparing EGCG-treated and NaCl-treated biofilms. EGCG significantly reduced the accumulation of soluble and insoluble polysaccharides, resulting in the formation of a biofilm with interspaced exopolysaccharide-microcolony complexes unevenly distributed on enamel. The SEM images of the biofilm treated with EGCG depict multilayers of cells arranged in short chains of microorganisms adhered to an unstructured matrix, which is not continuous and does not enmesh or protect the microorganisms entirely. Importantly, confocal images demonstrated that treatment with EGCG affected the 3D structure and organization of S. mutans biofilm, which presented a biofilm matrix more confined to the location of the microcolonies. CONCLUSION: In conclusion, EGCG lowered the virulence of S. mutans matrix-rich biofilm by reducing the synthesis of biofilm matrix components, altering the biofilm matrix structure, organization, and distribution.


Assuntos
Biofilmes , Catequina , Microscopia Confocal , Microscopia Eletrônica de Varredura , Streptococcus mutans , Biofilmes/efeitos dos fármacos , Streptococcus mutans/efeitos dos fármacos , Catequina/farmacologia , Catequina/análogos & derivados , Virulência/efeitos dos fármacos , Cárie Dentária/microbiologia , Concentração de Íons de Hidrogênio , Viabilidade Microbiana/efeitos dos fármacos , Polissacarídeos Bacterianos , Esmalte Dentário/efeitos dos fármacos , Esmalte Dentário/microbiologia
16.
Food Funct ; 15(11): 6068-6081, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38757391

RESUMO

Epigallocatechin gallate (EGCG), a prominent bioactive compound found in tea, offers numerous health benefits. Previous studies have highlighted its potential in mitigating hyperuricemia. In this study, hyperuricemic mice induced by potassium oxonate (PO) were treated with EGCG or the anti-hyperuricemia medication allopurinol (AP) to investigate the mechanisms underlying their anti-hyperuricemic effects. The results demonstrated that both EGCG and AP significantly reduced serum uric acid (UA) levels. Further analysis revealed that EGCG promoted the expression of UA secretion transporter genes (Oat1 and Oct1) while inhibiting the expression of UA reabsorption transporter genes (Urat1 and Glut9) in the kidney. By 16S rDNA sequencing, EGCG, but not AP, was found to alter the composition of the gut microbiota. Notably, EGCG induced significant changes in the relative abundance of specific bacteria such as Lactobacillus, Faecalibaculum, and Bifidobacterium, which displayed high correlations with serum UA levels and UA-related gene expression. Metabolomic analysis suggested that EGCG-induced modifications in bacterial metabolites might contribute to the alleviation of hyperuricemia. Transcriptomic analysis of the intestinal epithelium identifies 191 differentially expressed genes (DEGs) in EGCG-treated mice, including 8 purine-related genes. This study elucidates the anti-hyperuricemic mechanisms of EGCG, particularly its influence on the gut microbiota and gene expression in the intestinal epithelium.


Assuntos
Catequina , Modelos Animais de Doenças , Microbioma Gastrointestinal , Hiperuricemia , Ácido Úrico , Animais , Hiperuricemia/tratamento farmacológico , Catequina/análogos & derivados , Catequina/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Camundongos , Masculino , Ácido Úrico/sangue , Ácido Úrico/metabolismo , Camundongos Endogâmicos C57BL , Alopurinol/farmacologia , Rim/efeitos dos fármacos , Rim/metabolismo , Transportadores de Ânions Orgânicos/metabolismo , Transportadores de Ânions Orgânicos/genética , Ácido Oxônico , Intestinos/efeitos dos fármacos , Intestinos/microbiologia , Bactérias/classificação , Bactérias/genética , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação , Proteínas Facilitadoras de Transporte de Glucose
17.
Carbohydr Polym ; 338: 122205, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38763727

RESUMO

Developing multifunctional films with antibacterial, antioxidant, and sustained-release properties is a robust strategy for preventing contamination of perishable fruits by foodborne microorganisms. This study engineered a sustained-release biodegradable antibacterial film loaded with EGCG (Pickering emulsion (PE)/α-Cyclodextrin (α-CD)/Konjac glucomannan (KGM)) through multi-strategy cross-linking for fruit preservation. EGCG is stabilized using PE and incorporated into the α-CD/KGM inclusion compound; the unique structure of α-CD enhances EGCG encapsulation, while KGM provides the film toughness and surface adhesion. The composite film's physicochemical properties, antioxidant, bacteriostatic and biodegradability were studied. Results showed that Pickering emulsions with 3 % oil phase exhibited excellent stability. Moreover, α-CD introduction increased the loading and sustained release of EGCG from the film, and its concentration significantly affected the light transmission, thermal stability, mechanical strength, mechanical characteristics and antioxidant capacity of the composite membrane. Antioxidant and antimicrobial activities of the composite film increased significantly with increasing α-CD concentration. Application of the film to tomatoes and strawberries effectively inhibited Escherichia coli and Staphylococcus aureus growth, prolonging the shelf-life of the fruits. Notably, the composite film exhibits superior biodegradability in soil. This EGCG-loaded PE/α-CD/KGM composite film is anticipated to be a multifunctional antimicrobial preservation material with sustained-release properties and biodegradable for perishable food applications.


Assuntos
Antibacterianos , Antioxidantes , Catequina , Emulsões , Escherichia coli , Frutas , Mananas , alfa-Ciclodextrinas , alfa-Ciclodextrinas/química , Catequina/análogos & derivados , Catequina/química , Catequina/farmacologia , Mananas/química , Mananas/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Frutas/química , Emulsões/química , Antioxidantes/química , Antioxidantes/farmacologia , Escherichia coli/efeitos dos fármacos , Conservação de Alimentos/métodos , Staphylococcus aureus/efeitos dos fármacos , Embalagem de Alimentos/métodos , Testes de Sensibilidade Microbiana , Reagentes de Ligações Cruzadas/química , Liberação Controlada de Fármacos
18.
Birth Defects Res ; 116(5): e2350, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38761027

RESUMO

BACKGROUND: Cyprodinil is a widely used fungicide with broad-spectrum activity, but it has been associated with cardiac abnormalities. (-)-Epicatechin gallate (ECG), a natural polyphenolic compound, has been shown to possess protective properties in cardiac development. METHODS: In this study, we investigated whether ECG could mitigate cyprodinil-induced heart defects using zebrafish embryos as a model. Zebrafish embryos were exposed to cyprodinil with or without ECG. RESULTS: Our results demonstrated that ECG significantly improved the survival rate, embryo movement, and hatching delay induced by cyprodinil. Furthermore, ECG effectively ameliorated cyprodinil-induced cardiac developmental toxicity, including pericardial anomaly and impairment of cardiac function. Mechanistically, ECG attenuated the cyprodinil-induced alterations in mRNA expression related to cardiac development, such as amhc, vmhc, tbx5, and gata4, as well as calcium ion channels, such as ncx1h, atp2a2a, and cdh2. Additionally, ECG was found to inhibit the activity of the aryl hydrocarbon receptor (AhR) signaling pathways induced by cyprodinil. CONCLUSIONS: In conclusion, our findings provide evidence for the protective effects of ECG against cyprodinil-induced cardiac developmental toxicity, mediated through the inhibition of AhR activity. These findings contribute to a better understanding of the regulatory mechanisms and safe utilization of pesticide, such as cyprodinil.


Assuntos
Catequina , Coração , Receptores de Hidrocarboneto Arílico , Peixe-Zebra , Animais , Receptores de Hidrocarboneto Arílico/metabolismo , Coração/efeitos dos fármacos , Catequina/análogos & derivados , Catequina/farmacologia , Cardiopatias Congênitas/metabolismo , Embrião não Mamífero/efeitos dos fármacos , Embrião não Mamífero/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fungicidas Industriais/farmacologia , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos
19.
Int J Nanomedicine ; 19: 4299-4317, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38766654

RESUMO

Background: Inhibition of amyloid ß protein fragment (Aß) aggregation is considered to be one of the most effective strategies for the treatment of Alzheimer's disease. (-)-Epigallocatechin-3-gallate (EGCG) has been found to be effective in this regard; however, owing to its low bioavailability, nanodelivery is recommended for practical applications. Compared to chemical reduction methods, biosynthesis avoids possible biotoxicity and cumbersome preparation processes. Materials and Methods: The interaction between EGCG and Aß42 was simulated by molecular docking, and green tea-conjugated gold nanoparticles (GT-Au NPs) and EGCG-Au NPs were synthesized using EGCG-enriched green tea and EGCG solutions, respectively. Surface active molecules of the particles were identified and analyzed using various liquid chromatography-tandem triple quadrupole mass spectrometry methods. ThT fluorescence assay, circular dichroism, and TEM were used to investigate the effect of synthesized particles on the inhibition of Aß42 aggregation. Results: EGCG as well as apigenin, quercetin, baicalin, and glutathione were identified as capping ligands stabilized on the surface of GT-Au NPs. They more or less inhibited Aß42 aggregation or promoted fibril disaggregation, with EGCG being the most effective, which bound to Aß42 through hydrogen bonding, hydrophobic interactions, etc. resulting in 39.86% and 88.50% inhibition of aggregation and disaggregation effects, respectively. EGCG-Au NPs were not as effective as free EGCG, whereas multiple thiols and polyphenols in green tea accelerated and optimized heavy metal detoxification. The synthesized GT-Au NPs conferred the efficacy of diverse ligands to the particles, with inhibition of aggregation and disaggregation effects of 54.69% and 88.75%, respectively, while increasing the yield, enhancing water solubility, and decreasing cost. Conclusion: Biosynthesis of nanoparticles using green tea is a promising simple and economical drug-carrying approach to confer multiple pharmacophore molecules to Au NPs. This could be used to design new drug candidates to treat Alzheimer's disease.


Assuntos
Peptídeos beta-Amiloides , Catequina , Ouro , Nanopartículas Metálicas , Simulação de Acoplamento Molecular , Fragmentos de Peptídeos , Chá , Peptídeos beta-Amiloides/antagonistas & inibidores , Peptídeos beta-Amiloides/metabolismo , Catequina/química , Catequina/farmacologia , Catequina/análogos & derivados , Chá/química , Nanopartículas Metálicas/química , Nanopartículas Metálicas/administração & dosagem , Ouro/química , Ligantes , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/antagonistas & inibidores , Humanos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Agregados Proteicos/efeitos dos fármacos
20.
Int J Pharm ; 656: 124095, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38588757

RESUMO

Reactive oxygen species (ROS) play a vital role in wound healing process by fighting against invaded bacteria. However, excess ROS at the wound sites lead to oxidative stress that can trigger deleterious effects, causing cell death, tissue damage and chronic inflammation. Therefore, we fabricated a core-shell structured nanomedicine with antibacterial and antioxidant properties via a facile and green strategy. Specifically, Prussian blue (PB) nanozyme was fabricated and followed by coating a layer of epigallocatechin-3-gallate (EGCG)-derived polymer via polyphenolic condensation reaction and self-assembly process, resulting in PB@EGCG. The introduction of PB core endowed EGCG-based polyphenol nanoparticles with excellent NIR-triggered photothermal properties. Besides, owing to multiple enzyme-mimic activity of PB and potent antioxidant capacity of EGCG-derived polymer, PB@EGCG exhibited a remarkable ROS-scavenging ability, mitigated intracellular ROS level and protected cells from oxidative damage. Under NIR irradiation (808 nm, 1.5 W/cm2), PB@EGCG (50 µg/mL) exerted synergistic EGCG-derived polymer-photothermal antibacterial activity against Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus). In vivo therapeutic effect was evaluated using a S. aureus-infected rat model indicated PB@EGCG with a prominent bactericidal ability could modulate the inflammatory microenvironment and accelerate wound healing. Overall, this dual-functional nanomedicine provides a promising strategy for efficient antibacterial therapy.


Assuntos
Antibacterianos , Antioxidantes , Catequina , Catequina/análogos & derivados , Escherichia coli , Ferrocianetos , Nanopartículas , Polímeros , Espécies Reativas de Oxigênio , Staphylococcus aureus , Catequina/química , Catequina/farmacologia , Catequina/administração & dosagem , Ferrocianetos/química , Animais , Espécies Reativas de Oxigênio/metabolismo , Antibacterianos/farmacologia , Antibacterianos/administração & dosagem , Antibacterianos/química , Staphylococcus aureus/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Ratos , Polímeros/química , Nanopartículas/química , Antioxidantes/farmacologia , Antioxidantes/administração & dosagem , Antioxidantes/química , Masculino , Ratos Sprague-Dawley , Humanos , Infecções Estafilocócicas/tratamento farmacológico , Camundongos , Terapia Fototérmica/métodos , Estresse Oxidativo/efeitos dos fármacos
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