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1.
Braz. j. biol ; 83: e248746, 2023. graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1339351

RESUMO

Abstract Colorectal cancer (CRC) is one of the most common cancers leading to comorbidities and mortalities globally. The rational of current study was to evaluate the combined epigallocatechin gallate and quercetin as a potent antitumor agent as commentary agent for therapeutic protocol. The present study investigated the effect of epigallocatechin Gallate (EGCG) (150mg) and quercetin (200mg) at different proportions on proliferation and induction of apoptosis in human colon cancer cells (HCT-116). Cell growth, colonogenic, Annexin V in addition cell cycle were detected in response to phytomolecules. Data obtained showed that, the colony formation was inhibited significantly in CRC starting from the lowest concentration tested of 10 µg/mL resulting in no colonies as visualized by a phase-contrast microscope. Data showed a significant elevation in the annexin V at 100 µg/mL EGCG(25.85%) and 150 µg/mL quercetin (48.35%). Moreover, cell cycle analysis showed that this combination caused cell cycle arrest at the G1 phase at concentration of 100 µg/mL (72.7%) and 150 µg/mL (75.25%). The combined effect of epigallocatechin Gallate and quercetin exert antiproliferative activity against CRC, it is promising in alternative conventional chemotherapeutic agent.


Resumo O câncer colorretal (CCR) é um dos cânceres mais comuns, levando a comorbidades e mortalidade em todo o mundo. O racional do presente estudo foi avaliar a combinação de galato de epigalocatequina e quercetina como um agente antitumoral potente como agente de comentário para protocolo terapêutico. O presente estudo investigou o efeito de galato de epigalocatequina (EGCG) (150 mg) e quercetina (200 mg) em diferentes proporções na proliferação e indução de apoptose em células de câncer de cólon humano (HCT-116). O crescimento celular, colonogênico, anexina V, além do ciclo celular foram detectados em resposta a fitomoléculas. Os dados obtidos mostraram que a formação de colônias foi inibida significativamente no CRC a partir da concentração mais baixa testada de 10 µg/mL, resultando em nenhuma colônia conforme visualizado por um microscópio de contraste de fase. Os dados mostraram uma elevação significativa na anexina V a 100 µg/mL de EGCG (25,85%) e 150 µg/mL de quercetina (48,35%). Além disso, a análise do ciclo celular mostrou que essa combinação causou parada do ciclo celular na fase G1 na concentração de 100 µg/mL (72,7%) e 150 µg/mL (75,25%). O efeito combinado da epigalocatequina galato e quercetina exerce atividade antiproliferativa contra o CCR, é promissor como agente quimioterápico alternativo convencional.


Assuntos
Humanos , Neoplasias Colorretais/tratamento farmacológico , Catequina/análogos & derivados , Catequina/farmacologia , Quercetina/farmacologia , Ciclo Celular , Anexina A5 , Linhagem Celular Tumoral , Proliferação de Células
2.
J Mol Model ; 28(10): 319, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36109366

RESUMO

Human parainfluenza viruses (HPIVs) are ( -)ssRNA viruses belonging to Paramyoviridaie family. They are one of the leading causes of mortality in infants and young children and can cause ailments like croup, bronchitis, and pneumonia. Currently, no antiviral medications or vaccines are available to effectively treat parainfluenza. This necessitates the search for a novel and effective treatment. Computer-aided drug design (CADD) methodology can be utilized to discover target-based inhibitors with high accuracy in less time. A library of 45 phytocompounds with immunomodulatory properties was prepared. Thereafter, molecular docking studies were conducted to characterize the binding behavior of ligand in the binding pocket of HPIV3 HN protein. The physicochemical properties for screened compounds were computed, and the top hits from docking studies were further analyzed and validated using molecular dynamics simulation studies using the Desmond module of Schrodinger Suite 2021-1, followed by MM/GBSA analysis. The compounds CID:72276 (1) and CID:107905 (2) emerged as lead compounds of our in silico investigation. Further in vitro studies will be required to prove the efficacy of lead compounds as inhibitors and to determine the exact mechanism of their inhibition. Computational studies predict three natural flavonoids to inhibit the HN protein of HPIV3.


Assuntos
Catequina , Infecções por Paramyxoviridae , Catequina/farmacologia , Catequina/uso terapêutico , Criança , Pré-Escolar , Proteína HN/química , Proteína HN/genética , Proteína HN/metabolismo , Hemaglutininas/farmacologia , Hemaglutininas/uso terapêutico , Humanos , Ligantes , Simulação de Acoplamento Molecular , Neuraminidase , Vírus da Parainfluenza 1 Humana/metabolismo , Vírus da Parainfluenza 3 Humana/genética , Infecções por Paramyxoviridae/tratamento farmacológico , Proteínas Virais
3.
Pharm Biol ; 60(1): 1762-1770, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36086802

RESUMO

CONTEXT: (-)-Epicatechin (EPI) is a crucial substance involved in the protective effects of flavanol-rich foods. Previous studies have indicated EPI has a cardioprotective effect, but the molecular mechanisms in inhibition of cardiac fibrosis are unclear. OBJECTIVE: We evaluated the effect of EPI in preventing cardiac fibrosis and the underlying molecular mechanism related to the SIRT1-SUMO1/AKT/GSK3ß pathway. MATERIALS AND METHODS: Cardiac fibrosis mice model was established with transaortic constriction (TAC). Male C57BL/6 mice were randomly separated into 4 groups. Mice received 1 mg/kg/day of EPI or vehicle orally for 4 weeks. The acutely isolated cardiac fibroblasts were induced to myofibroblasts with 1 µM angiotensin II (Ang II). The cardiac function was measured with the ultrasonic instrument. Histological analysis of mice's hearts was determined with H&E or Masson method. The protein level of fibrosis markers, SUMOylation of SIRT1, and AKT/GSK3ß pathway were quantified by immunofluorescence and western blot. RESULTS: EPI treatment (1 mg/kg/day) could reverse the TAC-induced decline in LVEF (TAC, 61.28% ± 1.33% vs. TAC + EPI, 74.00% ± 1.64%), LVFS (TAC, 28.16% ± 0.89% vs. TAC + EPI, 37.18% ± 1.29%). Meantime, we found that 10 µM EPI blocks Ang II-induced transformation of cardiac fibroblasts into myofibroblasts. The underlying mechanism of EPI-inhibited myofibroblasts transformation involves activation of SUMOylation of SIRT1 through SP1. Furthermore, SUMOylation of SIRT1 inhibited Ang II-induced fibrogenic effect via the AKT/GSK3ß pathway. CONCLUSION: EPI plays a protective effect on cardiac fibrosis by regulating the SUMO1-dependent modulation of SIRT1, which provides a theoretical basis for use in clinical therapies.


Assuntos
Catequina , Miofibroblastos , Angiotensina II/toxicidade , Animais , Catequina/farmacologia , Fibroblastos/patologia , Fibrose , Glicogênio Sintase Quinase 3 beta , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miofibroblastos/metabolismo , Miofibroblastos/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sirtuína 1/metabolismo , Ubiquitina
4.
Int J Mol Sci ; 23(17)2022 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-36077157

RESUMO

Sexual dysfunction is a common problem for men with diabetes. Epigallocatechin gallate (EGCG) is known to ameliorate erectile function in aging rats. However, there has not yet been a report to evaluate its effects on diabetic male rat sexual behavior in the literature. In this study, we investigated the effects of EGCG on male sexual behavior in diabetic rats. Diabetic rats were induced by a single intraperitoneal injection of 65 mg/kg of streptozotocin. After streptozotocin injection for one week, animals were then orally treated with 40 mg/kg of EGCG or vehicle. Copulatory behavior and fasting blood glucose levels were recorded before treatment, as well as 7 and 14 days after treatment. Serum LH, testosterone, and PDE5a levels were measured by EIA assay after the last behavioral test. Data showed that diabetic rats who had diminished sexual functions demonstrated significantly increased latencies in mount, intromission, and ejaculation, as well as significant decreases in frequencies of intromission and ejaculation, compared to non-diabetic controls, indicating sexual function recovery. Lower blood glucose levels were also found in diabetic rats after EGCG treatment. Additionally, the lower LH and higher PDE5a levels in diabetic rats than controls were also noted. The findings declared that EGCG had a protective effect on male sexual behavior in diabetic rats.


Assuntos
Catequina , Diabetes Mellitus Experimental , Animais , Glicemia , Catequina/análogos & derivados , Catequina/farmacologia , Catequina/uso terapêutico , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Humanos , Masculino , Ratos , Estreptozocina
5.
Molecules ; 27(17)2022 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-36080195

RESUMO

Tea contains high levels of the compound epigallocatechin gallate (EGCG). It is considered an important functional component in tea and has anti-cancer, antioxidant, and anti-inflammatory effects. The eight phenolic hydroxyl groups in EGCG's chemical structure are the basis for EGCG's multiple biological effects. At the same time, it also leads to poor chemical stability, rendering EGCG prone to oxidation and isomerization reactions that change its original structure and biological activity. Learning how to maintain the activity of EGCG has become an important goal in understanding the biological activity of EGCG and the research and development of tea-related products. Metal-organic frameworks (MOFs) are porous materials with a three-dimensional network structure that are composed of inorganic metals or metal clusters together with organic complexes. MOFs exploit the porous nature of the material itself. When a drug is an appropriate size, it can be wrapped into the pores by physical or chemical methods; this allows the drug to be released slowly, and MOFs can also reduce drug toxicity. In this study, we used MOF Zn(BTC)4 materials to load EGCG and investigated the sustained release effect of EGCG@MOF Zn(BTC)4 and the biological effects on wound healing in a diabetic mouse model.


Assuntos
Catequina , Diabetes Mellitus , Animais , Catequina/análogos & derivados , Catequina/química , Catequina/farmacologia , Camundongos , Chá/química , Cicatrização , Zinco
6.
Cells ; 11(17)2022 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-36078067

RESUMO

In the current study, for the first time, we study mitophagy enhancer urolithin A and a combination of urolithin A+green tea extract EGCG against human Aß peptide-induced mitochondrial and synaptic, dendritic, inflammatory toxicities and behavioral changes in humanized homozygous amyloid beta knockin (hAbKI) mice of late-onset Alzheimer's disease (AD). Our findings reveal significantly increased positive effects of urolithin A and a combination treatment of urolithin A+EGCG in hAbKI mice for phenotypic behavioral changes including motor coordination, locomotion/exploratory activity, spatial learning and working memory. mRNA and protein levels of mitochondrial fusion, synaptic, mitophagy and autophagy genes were upregulated, and mitochondrial fission genes are downregulated in urolithin A and combine treatment in hAbKI mice; however, the effect is stronger in combined treatment. Immunofluorescence analysis of hippocampal brain sections shows similar findings of mRNA and protein levels. Mitochondrial dysfunction is significantly reduced in both treatment groups, but a stronger reduction is observed in combined treatment. Dendritic spines and lengths are significantly increased in both treatment groups, but the effect is stronger in combined treatment. The fragmented number of mitochondria is reduced, and mitochondrial length is increased, and mitophagosomal formations are increased in both the groups, but the effect is stronger in the combined treatment. The levels of amyloid beta (Aß) 40 and Aß42 are reduced in both treatments, however, the reduction is higher for combined treatment. These observations suggest that urolithin A is protective against human Aß peptide-induced toxicities; however, combined treatment of urolithin A+EGCG is effective and stronger, indicating that combined therapy is promising to treat late-onset AD patients.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Catequina/análogos & derivados , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Catequina/farmacologia , Cumarínicos , Humanos , Camundongos , Dinâmica Mitocondrial , RNA Mensageiro/metabolismo
7.
J Agric Food Chem ; 70(36): 11353-11366, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36044725

RESUMO

Epigallocatechin gallate (EGCG) is easily oxidized by environmental stress elements, including light, heat, and oxygen; thus, its biological activities can be reduced or even lost when exposed to a natural environment. Here, soluble soybean polysaccharide (SSPS) was successfully etherized by 3-chloro-2-hydroxypropyl trimethylammonium chloride (CHPTAC), positively charged to extract cationic SSPS (CSSPS). Nanoparticles based on CSSPS can improve the encapsulation efficiency (EE) and sustained bioactivity of EGCG. The EE of EGCG by CSSPS was improved significantly as compared with that of SSPS due to the electrostatic interactions. Furthermore, the protective and sustained-release effects of CSSPS on EGCG in the EGCG-CSSPS nanoparticles (EGCG-CSSPS-NPs) markedly improved the sustained antioxidant and antimicrobial activities of EGCG, which was confirmed by the results of a salmon-preservation experiment. In addition, cytotoxicity tests showed that EGCG-CSSPS-NPs could effectively inhibit the proliferation of tumor cells but had no obvious toxicity to normal cells.


Assuntos
Anti-Infecciosos , Catequina , Nanopartículas , Antioxidantes/farmacologia , Catequina/análogos & derivados , Catequina/farmacologia , Cátions , Polissacarídeos/farmacologia , Soja
8.
Int J Mol Sci ; 23(16)2022 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-36012227

RESUMO

(-)-Epicatechin (EC) is part of a large family of biomolecules called flavonoids and is widely distributed in the plant kingdom. Several studies have shown the beneficial effects of EC consumption. Many of these reported effects are exerted by activating the signaling pathways associated with the activation of two specific receptors: the G protein-coupled estrogen receptor (GPER), a transmembrane receptor, and the pregnane X receptor (PXR), which is a nuclear receptor. However, the effects of EC are so diverse that these two receptors cannot describe the complete phenomenon. The apelin receptor or APLNR is classified within the G protein-coupled receptor (GPCR) family, and is capable of activating the G protein canonical pathways and the ß-arrestin transducer, which participates in the phenomenon of receptor desensitization and internalization. ß-arrestin gained interest in selective pharmacology and mediators of the so-called "biased agonism". With molecular dynamics (MD) and in vitro assays, we demonstrate how EC can recruit the ß-arrestin in the active conformation of the APLN receptor acting as a biased agonist.


Assuntos
Catequina , Receptores de Apelina/metabolismo , Catequina/farmacologia , Proteínas de Ligação ao GTP/metabolismo , Ligantes , Receptores Acoplados a Proteínas G/metabolismo , beta-Arrestinas/metabolismo
9.
Nutrients ; 14(16)2022 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-36014899

RESUMO

(-)-Epigallocatechin gallate (EGCG) has been associated with multiple beneficial effects. However, EGCG is known to be degraded by the gut microbiota. The present study investigated the hypothesis that microbial metabolism would create major catechol-moiety-containing microbial metabolites with different ability from EGCG to induce nuclear factor-erythroid 2-related factor 2 (Nrf2)-mediated gene expression. A reporter gene bioassay, label-free quantitative proteomics and reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) were combined to investigate the regulation of Nrf2-related gene expression after exposure of U2OS reporter gene or Hepa1c1c7 cells in vitro to EGCG or to its major microbial catechol-moiety-containing metabolites: (-)-epigallocatechin (EGC), gallic acid (GA) and pyrogallol (PG). Results show that PG was a more potent inducer of Nrf2-mediated gene expression than EGCG, with a 5% benchmark dose (BMD5) of 0.35 µM as compared to 2.45 µM for EGCG in the reporter gene assay. EGC and GA were unable to induce Nrf2-mediated gene expression up to the highest concentration tested (75 µM). Bioinformatical analysis of the proteomics data indicated that Nrf2 induction by PG relates to glutathione metabolism, drug and/or xenobiotics metabolism and the pentose phosphate pathway. Taken together, our findings demonstrate that the microbial metabolite PG is a more potent inducer of Nrf2-associated gene expression than its parent compound EGCG.


Assuntos
Catequina , Microbioma Gastrointestinal , Catequina/análogos & derivados , Catequina/farmacologia , Catecóis , Ácido Gálico , Expressão Gênica , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Pirogalol/farmacologia , Chá
10.
Food Chem ; 397: 133792, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-35917785

RESUMO

The active coatings supplemented with epigallocatechin gallate (EGCG) (0.16 %, 0.32 %, and 0.64 %, respectively) combined with superchilling storage (-3 ± 0.2 °C) were used to reduce hydrogen peroxide (H2O2) content, and inhibit lipid and protein oxidations of large yellow croaker during 42 days of superchilling storage. EGCG coatings delayed lipid and protein oxidations by inhibiting the generation of H2O2, malondialdehyde (MDA) and carbonyl groups, and maintaining a higher Ca2+-ATPase activity and sulfhydryl content. We also observed that EGCG treatments maintained myofibrillar organized secondary structure by keeping higher α-helix content, and also stabilized tertiary structure during superchilling storage. Low-field nuclear magnetic resonance (LF-NMR) revealed that EGCG treatments might improve the association of water molecules with protein for fixed water. In addition, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and scanning electron microscope (SEM) images both showed that these treatments could delay the myofibrillar degradation of fresh fish. Overall, we report that the active coatings containing EGCG treatments protect the lipid and protein of large yellow croaker during superchilling storage.


Assuntos
Catequina , Perciformes , Tragacanto , Alginatos/química , Animais , Catequina/análogos & derivados , Catequina/química , Catequina/farmacologia , Peróxido de Hidrogênio/metabolismo , Lipídeos , Perciformes/metabolismo , Água
11.
Methods Mol Biol ; 2538: 145-163, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35951299

RESUMO

Amyloid inhibitors, such as the green tea compound epigallocatechin gallate EGCG, apomorphine or curlicide, have antibacterial properties. Conversely, antibiotics such as tetracycline derivatives or rifampicin also affect eukaryotic amyloids formation and may be used to treat neurodegenerative diseases. This opens the possibility for existing drugs to be repurposed in view of new therapy, targeting amyloid-like proteins from eukaryotes to prokaryotes and conversely. Here we present how to evaluate the effect of these amyloid-forming inhibitors on bacterial amyloid self-assemblies in vitro and on bacterial survival. The different approaches possible are presented.


Assuntos
Amiloidose , Catequina , Amiloide/metabolismo , Proteínas Amiloidogênicas , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias/metabolismo , Catequina/farmacologia , Humanos
12.
J Mater Chem B ; 10(36): 6965-6973, 2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36000287

RESUMO

Bioinspired and biosafety antioxidant nanoparticle assemblies from natural occurring molecules have been regarded as a class of effective therapeutic nanomaterials for addressing current inflammatory diseases such as acute kidney injury. In this study, a series of epicatechin-assembled nanoparticles have been developed via one-pot enzymatic polymerization of epicatechin. The prepared poly (epicatechin) (PEC) nanoparticles (NPs) showed excellent antioxidant capacity to scavenge multiple toxic free radicals, thus being able to effectively protect cells under oxidative stress conditions in vitro. Furthermore, in the renal ischemia/reperfusion model, blood renal function testing and renal tissue staining revealed a prominent therapeutic effect of PEC NPs. All these findings suggested that this class of bioinspired antioxidant nanoparticles provided a new therapeutic strategy for human ischemia/reperfusion-related diseases.


Assuntos
Injúria Renal Aguda , Catequina , Nanopartículas , Traumatismo por Reperfusão , Injúria Renal Aguda/tratamento farmacológico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Catequina/farmacologia , Catequina/uso terapêutico , Humanos , Rim/fisiologia , Traumatismo por Reperfusão/tratamento farmacológico
13.
Int J Med Sci ; 19(7): 1131-1137, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35919819

RESUMO

Although melanogenesis is a defense mechanism against ultraviolet (UV)-induced skin damage, abnormally excessive melanin production causes pigmentation disorders. Tyrosinase, as a key factor for melanin synthesis, plays an important role in inducing skin pigmentation. Therefore, the inhibition of tyrosinase is crucial in preventing skin pigmentation in the cosmetics and medicine fields. However, the majority of well-known tyrosinase inhibitors have been discontinued due to toxic effects on the skin or lack of selectivity and/or stability. In this study, we evaluated possible anti-melanogenic effects of catechin-7-O-α-L-rhamnopyranoside (C7R) isolated from the stem bark of Ulmus parvifolia, to discover a new tyrosinase inhibitor that has both safety and stability. When C7R was pretreated in B16F10 melanoma cells stimulated by α-melanocyte-stimulating hormone, this compound reduced melanin accumulation and murine tyrosinase activity. In line with these results, C7R inhibits tyrosinase purified from a mushroom in vitro like kojic acid and arbutin. Furthermore, C7R exhibited a competitive inhibition on a Lineweaver-Burk plot. Next, the underlying mechanisms of the C7R-mediated tyrosinase inhibitory effect were sought through docking simulation and pharmacophore analysis between tyrosinase residues and C7R. The results of these analyses showed that C7R had binding energy of -14.5kcal/mol, and indicated that C7R interacts with tyrosinase through an aromatic ring and various hydrophobic and hydrogen bonds. Together, our results suggest that C7R can be applied as a novel natural anti-melanogenic agent that inhibits tyrosinase.


Assuntos
Catequina/análogos & derivados , Glicosídeos , Melanoma Experimental , Animais , Catequina/farmacologia , Linhagem Celular Tumoral , Glicosídeos/farmacologia , Melaninas , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/metabolismo , Camundongos , Monofenol Mono-Oxigenase/metabolismo , alfa-MSH/farmacologia
14.
Microvasc Res ; 144: 104408, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35878868

RESUMO

BACKGROUND: Venous thrombosis (VT) is one of the most frequent cardiovascular diseases, which seriously endangers people's health. Recently, the protective role of epigallocatechin-3-gallate (EGCG) against multiple cardiovascular diseases has been well studied. Nevertheless, whether EGCG is implicated in the progression of VT is still unclear. METHODS: Rat models of VT were established by inferior vena cava (IVC) ligation. Histological characterization of the IVC tissues was examined by hematoxylin-eosin (H&E) staining. TUNEL assay was utilized to detect cell apoptosis in IVC tissues. The concentrations of the oxidative stress biomarkers, malondialdehyde (MDA) and superoxide dismutase (SOD), were estimated by corresponding kits. In addition, the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-8 in rat plasma were estimated by ELISA. Further, the expression levels of apoptosis markers (Bax, Bcl-2, and Cleaved-caspase 3) as well as key molecules p-PI3K and p-AKT in phosphoinositide 3-kinase (PI3K)/AKT signaling pathway were assessed by western blot. RESULTS: Compared to the sham group, the model group showed obvious thrombus formation in IVC tissues, while the EGCG treatment significantly repressed thrombosis. EGCG inhibited cell apoptosis in IVC tissues of VT rat models. The decreased SOD concentration and increased MDA concentration in the plasma of VT rats were reversed by EGCG treatment. Additionally, the elevated levels of TNF-α, IL-6 and IL-8 in the plasma of VT rats can be partially reduced by the treatment of EGCG. Finally, we also found that EGCG reduced the levels of phosphorylated (p)-PI3K and p-AKT in IVC tissues of VT rat models, indicating that the hyperactivation of the PI3K/AKT signaling pathway was inhibited by EGCG. CONCLUSION: This study proves that EGCG alleviates thrombosis, cell apoptosis, inflammatory response, and oxidative stress injury in VT by inactivating PI3K/AKT signaling pathway.


Assuntos
Catequina , Traumatismo por Reperfusão Miocárdica , Trombose , Animais , Apoptose , Catequina/análogos & derivados , Catequina/farmacologia , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Transdução de Sinais , Superóxido Dismutase/metabolismo , Trombose/prevenção & controle , Fator de Necrose Tumoral alfa/metabolismo
15.
FASEB J ; 36(8): e22426, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35779042

RESUMO

As a major tea component, theabrownin represents a promising anti-cancer candidate. However, its effect on the melanoma is unknown. To evaluate the in vitro and in vivo anti-melanoma efficacy of TB, we conducted cell viability, immunostaining, comet, and TUNEL assays on human A375 melanoma cells, and employed a zebrafish xenograft model of A375 cells. Real-time PCR (qPCR) and western blot were conducted to explore the molecular mechanisms of TB. In vitro, TB significantly inhibited the proliferation of A375 cells, and A375 cells showed the highest inhibitory rate among the other melanoma cell line (A875) and human dermal fibroblasts. TB triggered DNA damage and induced apoptosis of A375 cells and significantly inhibited the growth of A375 xenograft tumors in zebrafishes. Several key molecular events were activated by TB, including DNA damage-associated p53 and NF-κB pathways, through up-regulation of GADD45α, γ-H2A.X, phospho-ATM(p-ATM), phospho-ATR (p-ATR), phospho-p53 (p-p53), phospho-IKKα/ß (p-IKKα/ß), phospho-p65 (p-p65), etc. However, the TB-activated molecular events were counteracted by either knockdown of p53 or p65, and only dual knockdown of both p53 and p65 completed counteracted the anti-melanoma efficacy of TB. In conclusion, TB triggered DNA damage and thereby inhibited proliferation and induced cellular senescence and apoptosis of melanoma cells through mechanisms mediated by p53/NF-κB signaling crosstalk. This is the first report on the efficacy and mechanisms of TB on melanoma cells, making TB a promising candidate for anti-melanoma agent development.


Assuntos
Catequina , Melanoma , NF-kappa B , Animais , Apoptose/efeitos dos fármacos , Catequina/análogos & derivados , Catequina/farmacologia , Humanos , Quinase I-kappa B , Melanoma/tratamento farmacológico , Melanoma/genética , Melanoma/metabolismo , Melanoma/patologia , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Peixe-Zebra
16.
J Parasitol ; 108(4): 301-305, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35877154

RESUMO

New antibabesial drugs are required to fight resistant parasites, and plant-derived natural products are a robust source. Six kinds of natural product extracts derived from herbal medicines that are traditionally used for the treatment of malaria were selected to test the antibabesial effect on Babesia gibsoni in vitro and in vivo. Parasitized blood was collected from dogs infected with B. gibsoni to evaluate the inhibitory effect of verbenalin, catechin hydrate, dihydrolycorine, embelin, ursolic acid, agrimol B, and bruceine H in vitro. The expression levels of the 18S rRNA gene in all drug-treated groups were determined by relative quantification using a real-time PCR method. Significant inhibition of the in vitro growth of B. gibsoni was observed after treatment by those natural product extracts (200 nM concentration) (P < 0.05). Catechin hydrate showed the highest activity in vitro due to the lowest expression levels of the 18S rRNA gene. The IC50 value of catechin hydrate against B. gibsoni was 273 nM. In B. gibsoni infected dogs, intravenous administrations of catechin hydrate and diminazene aceturate showed significant (P < 0.05) inhibition of B. gibsoni growth at a dose of 11 mg/kg and 10 mg/kg, respectively, compared to the control group. The results of our study may suggest that catechin hydrate may be a promising alternative to treat canine babesiosis caused by B. gibsoni.


Assuntos
Babesia , Babesiose , Produtos Biológicos , Catequina , Doenças do Cão , Animais , Babesia/genética , Babesiose/tratamento farmacológico , Babesiose/parasitologia , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Catequina/farmacologia , Catequina/uso terapêutico , Doenças do Cão/tratamento farmacológico , Doenças do Cão/parasitologia , Cães , RNA Ribossômico 18S/genética
17.
Plant Foods Hum Nutr ; 77(3): 390-398, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35781857

RESUMO

The inhibitory effects of procyanidins from lotus (Nelumbo nucifera Gaertn.) seedpods on the activities of α-amylase, α-glucosidase and protein tyrosine phosphatase 1B (PTP1B), were studied and compared with those of (+)-catechin, (-)-epicatechin, epigallocatechin gallate (EGCG), procyanidin dimer B2 and trimer C1. The results showed that Lotus procyanidin extract (LPE) significantly inhibited α-amylase, α-glucosidase and PTP1B with IC50 values of 5.5, 1.0, and 0.33 µg/mL, respectively. The inhibition increased with the degree of polymerization and the existence of galloyl or gallocatechin units. Kinetic analysis showed that LPE inhibited α-glucosidase activity in a mixed competitive and noncompetitive mode. Fluorescence quenching revealed that α-glucosidase interacted with LPE or EGCG in an apparent static mode, or the model of "sphere of action". The apparent static (K) and bimolecular (kq) constants were 4375 M-1 and 4.375 × 1011 M-1 s-1, respectively, for LPE and 1195 M-1 and 1.195 × 1011 M-1 s-1, respectively, for EGCG. Molecular docking analysis provided further information on the interactions of (+)-catechin, (-)-epicatechin, EGCG, B2 and C1 with α-glucosidase. It is hypothesized that LPE may bind to multiple sites of the enzyme through hydrogen bonding and hydrophobic interactions, leading to conformational changes in the enzyme and thus inhibiting its activity. These findings first elucidate the inhibitory effect of LPE on diabetes-related enzymes and highlight the usefulness of LPE as a dietary supplement for the prophylaxis of diabetes.


Assuntos
Catequina , Diabetes Mellitus , Lotus , Nelumbo , Proantocianidinas , Biflavonoides , Catequina/análise , Catequina/farmacologia , Cinética , Lotus/química , Lotus/metabolismo , Simulação de Acoplamento Molecular , Nelumbo/química , Nelumbo/metabolismo , Proantocianidinas/análise , Sementes/química , alfa-Amilases/metabolismo , alfa-Glucosidases/metabolismo
18.
Bioelectrochemistry ; 147: 108199, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35841647

RESUMO

Catechin is a bioflavonoid known for its anti-cancer properties. In the present study, we combined theoretical and experimental approaches to reveal the potential of catechin application in the electroporation (EP) or electrochemotherapy (ECT) of pancreatic cancer cells. The molecular dynamics simulations were implemented to examine the interactions of catechin with a model of a membrane, its influence on the membrane's thickness, and the impact of the catechin-membrane interaction on the pore formation. The data were confronted with experimental measurement of the threshold electric field required for permeabilization of pancreatic cancer cells to a fluorescent dye YO-PRO-1. Further, we examined the influence of catechin on cell viability following electroporation with cisplatin or calcium ions. Finally, we investigated the catechin impact on four proteins associated with multidrug resistance: P-glycoprotein, MRP1, BCRP, and LRP. We demonstrated that catechin may boost the effects of electroporation through various mechanisms: i) increasing the cell permeability prior to electroporation ii) increasing the electroporation threshold iii) sensitization of cells to chemotherapeutic compounds. We showed that catechin incubation influences mRNA levels and mitigates the immunoreactivity of Pgp, MRP1, BCRP, and LRP but these changes did not translate to the efficacy of electrochemotherapy.


Assuntos
Catequina , Eletroquimioterapia , Neoplasias Pancreáticas , Subfamília B de Transportador de Cassetes de Ligação de ATP/uso terapêutico , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Catequina/farmacologia , Catequina/uso terapêutico , Linhagem Celular Tumoral , Eletroporação , Humanos , Proteínas de Neoplasias , Neoplasias Pancreáticas/tratamento farmacológico
19.
Nutrients ; 14(14)2022 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-35889906

RESUMO

Being in a prolonged depressed state increases the risk of developing depression. To investigate whether green tea intake is effective in improving depression-like moods, we used an experimental animal model of depression with lipopolysaccharide (LPS) and clarified the effects of green tea on the biological stress response and inflammation in the brain. Regarding the stress reduction effect of green tea, we found that the sum of caffeine (C) and epigallocatechin gallate (E) relative to the sum of theanine (T) and arginine (A), the major components of green tea, or the CE/TA ratio, is important. The results showed that depression-like behavior, adrenal hypertrophy as a typical stress response, and brain inflammation were suppressed in mice fed green tea components with CE/TA ratios of 2 to 8. In addition, the expression of Npas4, which is reduced in anxiety and depression, was maintained at the same level as controls in mice that consumed green tea with a CE/TA ratio of 4. In clinical human trials, the consumption of green tea with CE/TA ratios of 3.9 and 4.7 reduced susceptibility to subjective depression. These results suggest that the daily consumption of green tea with a CE/TA ratio of 4-5 is beneficial to improving depressed mood.


Assuntos
Catequina , Chá , Animais , Arginina/farmacologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Encéfalo , Cafeína/análise , Cafeína/farmacologia , Catequina/farmacologia , Humanos , Hipertrofia , Camundongos
20.
Food Chem Toxicol ; 167: 113306, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35863485

RESUMO

Although epigallocatechin-3-gallate (EGCG), the major polyphenol in green tea, has been shown to have many benefits, the effect of EGCG exposure in utero on adult uterine development is unclear. In this study, pregnant C57BL/6 mice were exposed to 1 mg/kg body weight (bw) EGCG dissolved in drinking water from gestational days 0.5-16.5. A significant decrease in uterine weight was observed in the adult female mice, accompanied by uterine atrophy, inflammation, and fibrosis in the endometrium. Uterine atrophy was attributed to the thinning of the endometrial stromal layer and a significant reduction in endometrial cell proliferation. The expression levels of related proteins in the NF-κB and RAF/MEK/ERK signaling pathways were significantly increased, which might be responsible for the occurrence of inflammation. Activation of the transforming growth factor beta (TGF-ß1)/Smad signaling pathway might be involved in the development of endometrial fibrosis. The changes in the expression of estrogen receptor α, ß (ERα, ERß), progesterone receptor (PGR), and androgen receptor (AR) might lead to changes in the aforementioned signaling pathways. The promoter region methylation level of Esr2 was increased, and the expression of DNMT3A was evaluated. Our study indicates a risk of EGCG intake during pregnancy affecting uterine development in offspring.


Assuntos
Catequina , Animais , Atrofia , Catequina/análogos & derivados , Catequina/farmacologia , Feminino , Fibrose , Inflamação , Camundongos , Camundongos Endogâmicos C57BL , Gravidez , Chá
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