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1.
Life Sci ; 258: 118232, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32781066

RESUMO

AIMS: To elucidate the mechanism by which (-)-epigallocatechin-3-gallate (EGCG) mediates intracellular Ca2+ increase in androgen-independent prostate cancer (PCa) cells. MAIN METHODS: Following exposure to different doses of EGCG, viability of DU145 and PC3 PCa cells was evaluated by MTT assay and the intracellular Ca2+ dynamics by the fluorescent Ca2+ chelator Fura-2. The expression of different channels was investigated by qPCR analysis and sulfhydryl bonds by Ellman's assay. KEY FINDINGS: EGCG inhibited DU145 and PC3 proliferation with IC50 = 46 and 56 µM, respectively, and induced dose-dependent peaks of internal Ca2+ that were dependent on extracellular Ca2+. The expression of TRPC4 and TRPC6 channels was revealed by qPCR in PC3 cells, but lack of effect by modulators and blockers ruled out an exclusive role for these, as well as for voltage-dependent T-type Ca2+ channels. Application of dithiothreitol and catalase and sulfhydryl (SH) measurements showed that EGCG-induced Ca2+ rise depends on SH oxidation, while the effect of EGTA, dantrolene, and the PLC inhibitor U73122 suggested that EGCG-induced Ca2+ influx acts as a trigger for Ca2+-induced Ca2+ release, involving both ryanodine and IP3 receptors. Different from EGCG, ATP caused a rapid Ca2+ increase, which was independent of external Ca2+, but sensitive to U73122. SIGNIFICANCE: EGCG induces an internal Ca2+ increase in PCa cells by a multi-step mechanism. As dysregulation of cytosolic Ca2+ is directly linked to apoptosis in PCa cells, these data confirm the possibility of using EGCG as a synergistic adjuvant in combined therapies for recalcitrant malignancies like androgen-independent PCa.


Assuntos
Antioxidantes/farmacologia , Cálcio/metabolismo , Catequina/análogos & derivados , Líquido Intracelular/metabolismo , Neoplasias da Próstata/metabolismo , Catequina/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Humanos , Líquido Intracelular/efeitos dos fármacos , Masculino , Células PC-3
2.
Arch Biochem Biophys ; 690: 108505, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32679195

RESUMO

Obesity has major adverse consequences on human health contributing to the development of, among others, insulin resistance and type 2 diabetes, cardiovascular disease, non-alcoholic fatty liver disease, altered behavior and cognition, and cancer. Changes in dietary habits and lifestyle could contribute to mitigate the development and/or progression of these pathologies. This review will discuss current evidence on the beneficial actions of the flavan-3-ol (-)-epicatechin (EC) on obesity-associated comorbidities. These benefits can be in part explained through EC's capacity to mitigate several common events underlying the development of these pathologies, including: i) high circulating levels of glucose, lipids and endotoxins; ii) chronic systemic inflammation; iii) tissue endoplasmic reticulum and oxidative stress; iv) insulin resistance; v) mitochondria dysfunction and vi) dysbiosis. The currently known underlying mechanisms and cellular targets of EC's beneficial effects are discussed. While, there is limited evidence from human studies supplementing with pure EC, other studies involving cocoa supplementation in humans, pure EC in rodents and in vitro studies, support a potential beneficial action of EC on obesity-associated comorbidities. This evidence also stresses the need of further research in the field, which would contribute to the development of human dietary strategies to mitigate the adverse consequences of obesity.


Assuntos
Catequina/farmacologia , Obesidade/tratamento farmacológico , Animais , Glicemia/efeitos dos fármacos , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/tratamento farmacológico , Comorbidade , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Disbiose/metabolismo , Dislipidemias/metabolismo , Retículo Endoplasmático/metabolismo , Endotoxinas/metabolismo , Flavonoides/farmacologia , Humanos , Inflamação/metabolismo , Resistência à Insulina , Metabolismo dos Lipídeos , Transtornos Mentais/complicações , Transtornos Mentais/tratamento farmacológico , Mitocôndrias/metabolismo , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Estresse Oxidativo
3.
Life Sci ; 258: 118136, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32726662

RESUMO

The endothelium is a critical regulator of vascular homeostasis, controlling vascular tone and permeability as well as interactions of leukocytes and platelets with blood vessel walls. Consequently, endothelial dysfunction featuring inflammation and reduced vasodilation are considered central to cardiovascular disease (CVD) pathogenesis and have become a therapeutic area of focus. Type II endothelial cell (EC) activation by stress-related stimuli such as tumor necrosis factor-α (TNF-α) initiates the nuclear factor-κB (NF-κB) signaling pathway, a master regulator of inflammatory responses. Because dysregulated NF-κB signaling has been tightly linked to several CVDs, EC-specific inhibition of NF-κB represents an attractive pharmacological strategy. As accumulating evidence highlights the clinical benefits of tea catechin for multiple diseases including CVDs, we sought to determine whether the tea catechin epigallocatechin gallate (EGCG) that displays antioxidative, anti-inflammatory, hypolipidemic, anti-thrombogenic, and anti-hypertensive properties offers protection against CVDs by suppressing the canonical NF-κB pathway. Our findings indicate that EGCG downregulates multiple components of the TNF-α-induced NF-κB signaling pathway and thereby reduces the consequent increase in inflammatory gene transcription and protein expression. Furthermore, EGCG blocked type II EC activation, evidenced by diminished EC leakage and monocyte adhesion in EGCG-treated cells. In summary, our study advances knowledge of EGCG's anti-inflammatory effects on the NF-κB pathway and hence its benefits on endothelial health, supporting its therapeutic potential for CVDs.


Assuntos
Catequina/análogos & derivados , Vasos Coronários/patologia , Células Endoteliais/patologia , Inflamação/tratamento farmacológico , Catequina/farmacologia , Catequina/uso terapêutico , Adesão Celular/efeitos dos fármacos , Permeabilidade da Membrana Celular/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Humanos , Inflamação/genética , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Monócitos/efeitos dos fármacos , Monócitos/patologia , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
5.
Toxicol Appl Pharmacol ; 401: 115100, 2020 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-32512070

RESUMO

(-)-Epigallocatechin-3-gallate (EGCG) is the main bioactive component in tea (Camellia sinensis) catechins, and exhibits potential antitumor activity against colorectal cancer (CRC). However, the underlying mechanisms are largely unclear. We investigated the effects of EGCG on activities of CRC cells and the exact molecular mechanism. We used human colon cancer cells (HT-29) and exposed them to EGCG at various concentrations. The MTT assay, flow cytometry, and TUNEL staining were used to study the underlying mechanisms of EGCG (proliferation, apoptosis, autophagy). Western blotting was used to measure expression of marker proteins of the cell cycle, apoptosis, and autophagy. Using a combined microarray-based transcriptomic and ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight tandem mass spectrometry (UHPLC-QTOF/MS)-based metabolomic approach, we investigated the perturbed pathways induced by EGCG treatment at transcript and metabolite levels. Transcriptomic analyses showed that 486 genes were differentially expressed between untreated and EGCG-treated cells. Also, 88 differentially expressed metabolites were identified between untreated and EGCG-treated cells. The altered metabolites were involved in the metabolism of glutathione, glycerophospholipids, starch, sucrose, amino sugars, and nucleotide sugars. There was substantial agreement between the results of transcriptomics and metabolomics analyses. Our data indicate that the anticancer activity of EGCG against HT-29 cells is mediated by induction of cell-cycle arrest, apoptosis, and autophagy. EGCG modulates cancer-cell metabolic pathways. These results provide a platform for future molecular mechanistic studies of EGCG.


Assuntos
Anticarcinógenos/farmacologia , Catequina/análogos & derivados , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Metabolômica/métodos , Transcriptoma/efeitos dos fármacos , Anticarcinógenos/uso terapêutico , Catequina/farmacologia , Catequina/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Neoplasias do Colo/tratamento farmacológico , Células HT29 , Humanos , Transcriptoma/fisiologia
6.
Am J Chin Med ; 48(4): 1005-1019, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32468825

RESUMO

Harboring insulin-producing cells, the pancreas has more interstitial insulin than any other organ. In vitro, insulin activates both insulin receptor (IR) and insulin-like growth factor-1 receptor (IGF1R) to stimulate pancreatic cancer cells. Whether intra-pancreatic insulin nourishes pancreatic cancer cells in vivo remains uncertain. In the present studies, we transplanted human pancreatic cancer cells orthotopically in euglycemic athymic mice whose intra-pancreatic insulin was intact or was decreased following pretreatment with streptozotocin (STZ). In the next eight weeks, the tumor carriers were treated with one of the IR/IGF1R antagonists penta-O-galloyl-[Formula: see text]-D-glucose (PGG) and epigallocatechin gallate (EGCG) or treated with vehicle. When pancreatic tumors were examined, their fraction occupied with living cells was decreased following STZ pretreatment and/or IR/IGF1R antagonism. Using Western blot, we examined tumor grafts for IR/IGF1R expression and activity. We also determined proteins that were downstream to IR/IGF1R and responsible for signal transduction, glycolysis, angiogenesis, and apoptosis. We demonstrated that STZ-induced decrease in intra-pancreatic insulin reduced IR/IGF1R expression and activity, decreased the proteins that promoted cell survival, and increased the proteins that promoted apoptosis. These suggest that intra-pancreatic insulin supported local cancer cells. When tumor carriers were treated with PGG or EGCG, the results were similar to those seen following STZ pretreatment. Thus, the biggest changes in examined proteins were usually seen when STZ pretreatment and PGG/EGCG treatment concurred. This suggests that intra-pancreatic insulin normally combated pharmacologic effects of PGG and EGCG. In conclusion, intra-pancreatic insulin nourishes pancreatic cancer cells and helps the cells resist IR/IGF1R antagonism.


Assuntos
Catequina/análogos & derivados , Taninos Hidrolisáveis/farmacologia , Insulina/fisiologia , Neoplasias Pancreáticas/patologia , Receptor de Insulina/antagonistas & inibidores , Animais , Catequina/farmacologia , Linhagem Celular Tumoral , Expressão Gênica/efeitos dos fármacos , Humanos , Insulina/metabolismo , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Camundongos Nus , Receptor de Insulina/genética , Receptor de Insulina/metabolismo , Estreptozocina/farmacologia
7.
Biomed Environ Sci ; 33(4): 238-247, 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-32438961

RESUMO

Objective: This study aimed to explore the protective effect of procyanidin B2 (PCB2) on acute liver injury induced by aflatoxin B 1 (AFB 1) in rats. Methods: Forty Sprague Dawley rats were randomly divided into control, AFB 1, AFB 1 + PCB2, and PCB2 groups. The latter two groups were administrated PCB2 intragastrically (30 mg/kg body weight) for 7 d, whereas the control and AFB 1 groups were given the same dose of double distilled water intragastrically. On the sixth day of treatment, the AFB 1 and AFB 1 + PCB2 groups were intraperitoneally injected with AFB 1 (2 mg/kg). The control and PCB2 groups were intraperitoneally administered the same dose of dimethyl sulfoxide (DMSO). On the eighth day, all rats were euthanized: serum and liver tissue were isolated for further examination. Hepatic histological features were assessed by hematoxylin and eosin-stained sections. Weight, organ coefficient (liver, spleen, and kidney), liver function (serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, and direct bilirubin), oxidative index (catalase, glutathione, superoxide dismutase, malondialdehyde, and 8-hydroxy-2'-deoxyguanosine), inflammation factor [hepatic interleukin-6 (IL-6) mRNA expression and serum IL-6], and bcl-2/bax ratio were measured. Results: AFB 1 significantly caused hepatic histopathological damage, abnormal liver function, oxidative stress, inflammation, and bcl-2/bax ratio reduction compared with DMSO-treated controls. Our results indicate that PCB2 treatment can partially reverse the adverse liver conditions induced by AFB 1. Conclusion: Our findings indicate that PCB2 exhibits a protective effect on acute liver injury induced by AFB 1.


Assuntos
Aflatoxina B1/toxicidade , Biflavonoides/farmacologia , Catequina/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Venenos/toxicidade , Proantocianidinas/farmacologia , Substâncias Protetoras/farmacologia , Animais , Biflavonoides/administração & dosagem , Catequina/administração & dosagem , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Masculino , Proantocianidinas/administração & dosagem , Substâncias Protetoras/administração & dosagem , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
8.
Proc Natl Acad Sci U S A ; 117(21): 11788-11798, 2020 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-32393630

RESUMO

Down syndrome (DS) is the most common form of intellectual disability. The cognitive alterations in DS are thought to depend on brain regions critical for learning and memory such as the prefrontal cortex (PFC) and the hippocampus (HPC). Neuroimaging studies suggest that increased brain connectivity correlates with lower intelligence quotients (IQ) in individuals with DS; however, its contribution to cognitive impairment is unresolved. We recorded neural activity in the PFC and HPC of the trisomic Ts65Dn mouse model of DS during quiet wakefulness, natural sleep, and the performance of a memory test. During rest, trisomic mice showed increased theta oscillations and cross-frequency coupling in the PFC and HPC while prefrontal-hippocampal synchronization was strengthened, suggesting hypersynchronous local and cross-regional processing. During sleep, slow waves were reduced, and gamma oscillations amplified in Ts65Dn mice, likely reflecting prolonged light sleep. Moreover, hippocampal sharp-wave ripples were disrupted, which may have further contributed to deficient memory consolidation. Memory performance in euploid mice correlated strongly with functional connectivity measures that indicated a hippocampal control over memory acquisition and retrieval at theta and gamma frequencies, respectively. By contrast, trisomic mice exhibited poor memory abilities and disordered prefrontal-hippocampal functional connectivity. Memory performance and key neurophysiological alterations were rescued after 1 month of chronic administration of a green tea extract containing epigallocatequin-3-gallate (EGCG), which improves executive function in young adults with DS and Ts65Dn mice. Our findings suggest that abnormal prefrontal-hippocampal circuit dynamics are candidate neural mechanisms for memory impairment in DS.


Assuntos
Síndrome de Down/fisiopatologia , Hipocampo/fisiologia , Córtex Pré-Frontal/fisiologia , Reconhecimento Psicológico/fisiologia , Animais , Catequina/análogos & derivados , Catequina/farmacologia , Modelos Animais de Doenças , Função Executiva/efeitos dos fármacos , Feminino , Hipocampo/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Rede Nervosa/efeitos dos fármacos , Rede Nervosa/fisiologia , Fármacos Neuroprotetores/farmacologia , Córtex Pré-Frontal/efeitos dos fármacos , Reconhecimento Psicológico/efeitos dos fármacos
9.
PLoS One ; 15(4): e0224853, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32298262

RESUMO

Diets rich in flavonoids have been related with low obesity rates, which could be related with their potential to inhibit pancreatic lipase, the main enzyme of fat assimilation. Some flavonoids can aggregate in aqueous medium suggesting that the inhibition mechanism could occur on both molecular and colloidal levels. This study investigates the interaction of two flavonoid aggregates, quercetin and epigallocatechin gallate (EGCG), with pancreatic lipase under simplified intestinal conditions. The stability and the morphology of these flavonoid aggregates were studied in four different solutions: Control (water), salt, low lipase concentration and high lipase concentration. Particles were found by optical microscopy in almost all the solutions tested, except EGCG-control. The results show that the precipitation rate decreases for quercetin and increases for EGCG in salt solution and that lipase stabilize quercetin aggregates. In addition, both flavonoids were shown to precipitate together with pancreatic lipase resulting in a sequestering of the enzyme.


Assuntos
Antioxidantes/farmacologia , Catequina/análogos & derivados , Mucosa Intestinal/metabolismo , Lipase/metabolismo , Quercetina/farmacologia , Animais , Antioxidantes/metabolismo , Catequina/metabolismo , Catequina/farmacologia , Dimerização , Inibidores Enzimáticos/metabolismo , Inibidores Enzimáticos/farmacologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/enzimologia , Lipase/antagonistas & inibidores , Quercetina/metabolismo , Suínos
10.
J Oleo Sci ; 69(5): 479-486, 2020 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-32281563

RESUMO

EGCG is a major pharmacological compound in green tea. Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide. Inflammation and insulin resistance are involved in the development of the disease. In this study, we investigated the beneficial effect of EGCG on the liver tissue of NAFLD rats induced by a high-fat diet and its underlying mechanism. Thirty Sprague-Dawley rats received a normal diet, a HFD and a HFD+EGCG. The expression levels of inflammatory signaling pathway genes (e.g., TLR4, TRAF6, IKKß, NF-κB, TNF-α) and insulin signaling transduction pathway genes (e.g., PI3K, AKT, IRS-1, IRS-2) were detected in the liver. We observed that EGCG decreased the triglyceride (TG) concentration in rat livers and suppressed TLR4, TRAF6, IKKß, p-IKKß, p-NF-κB, and TNF-α levels compared with those in the HFD group, whereas PI3K, AKT, IRS-1, and IRS-2 indicators were improved. EGCG improves obesity-associated subacute hepatic inflammation states, probably through the TLR4 signaling pathway. Furthermore, EGCG also alleviated hepatic insulin resistance. These data indicate that EGCG improves NAFLD from two ways: inhibition of inflammation and improvement of insulin resistance in liver tissues.


Assuntos
Anti-Inflamatórios , Catequina/análogos & derivados , Dieta Hiperlipídica/efeitos adversos , Resistência à Insulina , Hepatopatias/tratamento farmacológico , Hepatopatias/metabolismo , Fígado/metabolismo , Fitoterapia , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Animais , Catequina/isolamento & purificação , Catequina/farmacologia , Catequina/uso terapêutico , Inflamação , Hepatopatias/etiologia , Ratos Sprague-Dawley , Chá/química
11.
Biofouling ; 36(3): 256-265, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32326756

RESUMO

This study aimed to evaluate the effects of tea extracts on oral biofilm colonization depending on steeping temperature. S. mutans and S. sobrinus were cultured and treated with green or black tea extracts prepared under different steeping conditions. Biofilm formation, glucosyltransferase (GTF) levels, bacterial growth, and acidogenicity were evaluated. Biofilms were also assessed by gas chromatography-mass spectrometry and confocal laser scanning microscopy. All extracts with hot steeping showed higher inhibitory effects on biofilm formation and cell viability and lower GTF levels compared with those with cold steeping (p < 0.05). Hot steeping significantly reduced bacterial growth (p < 0.05) and maintained the pH. Catechins were only identified from hot steeping extracts. Within the limits of this study, extracts with cold steeping showed lower inhibitory effects on oral biofilms. The different effects between steeping extracts may be attributed to the difference in catechins released from tea extracts under the different steep conditions.


Assuntos
Biofilmes/efeitos dos fármacos , Extratos Vegetais/farmacologia , Streptococcus mutans/efeitos dos fármacos , Streptococcus sobrinus/efeitos dos fármacos , Chá/química , Temperatura , Biofilmes/crescimento & desenvolvimento , Catequina/farmacologia , Extratos Vegetais/isolamento & purificação , Streptococcus mutans/crescimento & desenvolvimento , Streptococcus sobrinus/crescimento & desenvolvimento
12.
PLoS One ; 15(4): e0231815, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32348327

RESUMO

Reducing carbohydrates digestion by having a low glycaemic index (GI) foods has been linked to weight loss. Inhibiting related enzymes is an alternative way to decrease carbohydrate digestion. RCM-107 (Slimming Plus), an eight-herb formula that is modified from RCM-104, indicated significant weight-loss action in clinical trials. However, no published research has studied its mechanism of action on reducing carbohydrate absorption via suppressing the activities of porcine pancreatic alpha-amylase (PPA). In this paper, we used fluorescence PPA inhibition assay to investigate the inhibitory effects of RCM-107 and the individual herbs present in this herbal mixture on amylase activity. Subsequently, molecular docking predicted the key active compounds that may be responsible for the enzyme inhibition. According to our results, both the RCM-107 formula and several individual herbs displayed α-amylase inhibitory effects. Also, marginal synergistic effects of RCM-107 were detected. In addition, alisol B, (-)-epigallocatechin-3-gallate (EGCG) and plantagoside have been predicted as the key active compounds that may be responsible for the α-amylase inhibition effect of RCM-107 according to inter-residue contact analysis. Finally, Glu233, Gln63, His305, Asp300 and Tyr151 are predicted to be markers of important areas with which potential amylase inhibitors would interact. Therefore, our data has provided new knowledge on the mechanisms of action of the RCM-107 formula and its individual herbal ingredients for weight loss, in terms of decreasing carbohydrate digestion via the inhibition of pancreatic alpha-amylase.


Assuntos
Fármacos Antiobesidade/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Obesidade/tratamento farmacológico , alfa-Amilases Pancreáticas/antagonistas & inibidores , Perda de Peso/efeitos dos fármacos , Animais , Fármacos Antiobesidade/química , Metabolismo dos Carboidratos/efeitos dos fármacos , Catequina/análogos & derivados , Catequina/química , Catequina/farmacologia , Colestenonas/química , Colestenonas/farmacologia , Medicamentos de Ervas Chinesas/química , Ensaios Enzimáticos , Flavanonas/química , Flavanonas/farmacologia , Glucosídeos/química , Glucosídeos/farmacologia , Humanos , Simulação de Acoplamento Molecular , Obesidade/metabolismo , alfa-Amilases Pancreáticas/química , alfa-Amilases Pancreáticas/metabolismo , Suínos
13.
Food Chem ; 324: 126847, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32344340

RESUMO

This study aimed to investigate the inhibitory effect of chestnut inner skin extract (CISE) on the activity of postprandial blood sugar-related enzymes. In total, 12 flavonoids were identified by HPLC-TOF-MS. CISE showed strong and weak inhibition on α-amylase and α-glucosidase, with the IC50 of 27.2 and 2.3 µg/mL, respectively. The inhibition modes of CISE against α-amylase and α-glucosidase were mixed-type and non-competitive type, respectively. Epicatechin gallate noncompetitively inhibited α-amylase, α-glucosidase and dipeptidyl peptidase IV (DPP-IV). Analysis by ultraviolet-visible spectroscopy, fluorescence spectroscopy and circular dichroism suggested that flavonoids altered the hydrophobicity and microenvironment of these enzymes. CISE decreased the starch bioavailability by reducing the enzymatic hydrolysis rate and increasing the fraction of undigested starch. The extract reduced the rapidly digestible starch and increased the resistant starch after incorporation into A-, B- or C- crystallinity starch. Thus, the chestnut inner skin is a useful resource for regulating postprandial blood sugar level.


Assuntos
Inibidores da Dipeptidil Peptidase IV/farmacologia , Fagaceae/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Extratos Vegetais/farmacologia , Disponibilidade Biológica , Catequina/análogos & derivados , Catequina/farmacologia , Dipeptidil Peptidase 4/química , Dipeptidil Peptidase 4/metabolismo , Inibidores da Dipeptidil Peptidase IV/química , Flavonoides/análise , Inibidores de Glicosídeo Hidrolases/química , Nozes/química , Extratos Vegetais/química , Amido/farmacocinética , alfa-Amilases/antagonistas & inibidores , alfa-Amilases/química , alfa-Glucosidases/química
14.
J Med Virol ; 92(6): 693-697, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32167173

RESUMO

An outbreak of coronavirus disease 2019 (COVID-19) occurred in Wuhan and it has rapidly spread to almost all parts of the world. For coronaviruses, RNA-dependent RNA polymerase (RdRp) is an important polymerase that catalyzes the replication of RNA from RNA template and is an attractive therapeutic target. In this study, we screened these chemical structures from traditional Chinese medicinal compounds proven to show antiviral activity in severe acute respiratory syndrome coronavirus (SARS-CoV) and the similar chemical structures through a molecular docking study to target RdRp of SARS-CoV-2, SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV). We found that theaflavin has a lower idock score in the catalytic pocket of RdRp in SARS-CoV-2 (-9.11 kcal/mol), SARS-CoV (-8.03 kcal/mol), and MERS-CoV (-8.26 kcal/mol) from idock. To confirm the result, we discovered that theaflavin has lower binding energy of -8.8 kcal/mol when it docks in the catalytic pocket of SARS-CoV-2 RdRp by using the Blind Docking server. Regarding contact modes, hydrophobic interactions contribute significantly in binding and additional hydrogen bonds were found between theaflavin and RdRp. Moreover, one π-cation interaction was formed between theaflavin and Arg553 from the Blind Docking server. Our results suggest that theaflavin could be a potential SARS-CoV-2 RdRp inhibitor for further study.


Assuntos
Antivirais/química , Betacoronavirus/efeitos dos fármacos , Biflavonoides/química , Catequina/química , Medicamentos de Ervas Chinesas/química , RNA Replicase/química , Proteínas Virais/química , Sequência de Aminoácidos , Antivirais/farmacologia , Betacoronavirus/enzimologia , Betacoronavirus/genética , Biflavonoides/farmacologia , Domínio Catalítico , Catequina/farmacologia , Biologia Computacional/métodos , Medicamentos de Ervas Chinesas/farmacologia , Expressão Gênica , Humanos , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , Coronavírus da Síndrome Respiratória do Oriente Médio/enzimologia , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Simulação de Acoplamento Molecular , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Estrutura Secundária de Proteína , RNA Replicase/antagonistas & inibidores , RNA Replicase/genética , RNA Replicase/metabolismo , Vírus da SARS/efeitos dos fármacos , Vírus da SARS/enzimologia , Vírus da SARS/genética , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Termodinâmica , Proteínas Virais/antagonistas & inibidores , Proteínas Virais/genética , Proteínas Virais/metabolismo
15.
Enzyme Microb Technol ; 135: 109496, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32146939

RESUMO

Catechins in green tea possess various health benefits. Enzymatic treatment improves physiological activities by inducing bioconversion of catechins. Here, we investigated the effect of green tea infusion (GT) after tannase treatment, which transforms (-)-epigallocatechin gallate (EGCG) to gallic acid (GA) and (-)-epigallocatechin (EGC), on adipocyte differentiation and mature adipocyte metabolism. The optimal conditions for tannase-mediated improvement in GA and EGC yields in GT were investigated using response surface methodology. Yields of GA and EGC were 43-fold (0.43 mg/mL) and 1.66-fold higher (1.11 mg/mL), respectively, compared to GT without tannase treatment. The optimal reaction conditions for tannase-mediated biotransformation were observed on 0.54 mg mL-1 of tannase, reaction time (86.79 min), and reaction temperature at 22.59 °C. GT and tannase-treated GT (TANs) upregulated adiponectin, uncoupling protein 1, adipose triglyceride lipase, and hormone-sensitive lipase gene expression in differentiated 3T3-L1 adipocytes, with TAN inducing better effects than GT, which implies that tannase treatment improved the beneficial effect of GT on adipocyte metabolism. Thus, tannase-mediated bio-transformation is an attractive candidate for preparing GT with enhanced anti-obesity properties.


Assuntos
Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Hidrolases de Éster Carboxílico/química , Catequina/análogos & derivados , Proteínas Fúngicas/química , Extratos Vegetais/química , Adipócitos/citologia , Adiponectina/genética , Adiponectina/metabolismo , Animais , Aspergillus/enzimologia , Biocatálise , Camellia sinensis/química , Catequina/química , Catequina/farmacologia , Diferenciação Celular , Manipulação de Alimentos , Ácido Gálico/química , Ácido Gálico/farmacologia , Camundongos , Células NIH 3T3 , Extratos Vegetais/farmacologia , Folhas de Planta/química , Chá/química , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismo
16.
Artigo em Inglês | MEDLINE | ID: mdl-32171165

RESUMO

Tobacco mosaic virus (TMV) is one of the most damaging plant viruses from an economic and research point of view. Epigallocatechin-3-Gallate (EGCG), a flavonoid type secondary metabolite can selectively improve plant defense against pathogens; however, the effect of EGCG on plant defense against TMV and the underlying mechanism(s) remain elusive. In this study, exogenous EGCG application increased plant resistance to TMV as revealed by significantly decreased transcript levels of TMV-coat protein (CP) in tomato leaves. A time-course of H2O2 concentrations in tomato leaves showed that TMV inoculation rapidly increased the H2O2 accumulation, reaching its peak at 3 days post-inoculation (dpi) which remained the highest until 6 dpi. However, the combined treatment of EGCG and TMV remarkably decreased the concentrations of H2O2 at 3 and 6 dpi. Meanwhile, the transcript levels of RESPIRATORY BURST OXIDASE HOMOLOG 1 (SlRBOH1) were significantly increased by either EGCG or TMV inoculation, but the EGCG treatment along with TMV caused a further upregulation in the SlRBOH1 transcripts compared with that in only TMV-inoculated plants. Chemical scavenging of H2O2 or silencing SlRBOH1 both compromised the EGCG-induced enhanced resistance to TMV. Furthermore, EGCG-induced elevation in the activity of antioxidant enzymes was abolished by SlRBOH1 silencing, suggesting that EGCG enhanced defense against TMV by increasing the antioxidant enzyme activity via RBOH1-dependent H2O2 signaling. Taken together, our results suggest that EGCG functioned to maintain a delicate balance between ROS signaling and ROS scavenging via RBOH1, which enhanced tomato resistance to TMV.


Assuntos
Catequina/análogos & derivados , Resistência à Doença , Lycopersicon esculentum , Transdução de Sinais , Vírus do Mosaico do Tabaco , Catequina/farmacologia , Resistência à Doença/efeitos dos fármacos , Peróxido de Hidrogênio/metabolismo , Lycopersicon esculentum/virologia , Proteínas de Plantas/metabolismo , Transdução de Sinais/efeitos dos fármacos
17.
Am J Chin Med ; 48(2): 341-356, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32138537

RESUMO

MicroRNA 145 (miR-145) is a critical modulator of cardiovascular diseases. The downregulation of myocardial miR-145 is followed by an increase in disabled-2 (Dab2) expression in cardiomyocytes. (-)-epigallocatechin gallate (EGCG) is a flavonoid that has been evaluated extensively due to its diverse pharmacological properties including anti-inflammatory effects. The aim of this study was to investigate the cardioprotective effects of EGCG under hypoxia-induced stress in vitro and in vivo. The hypoxic insult led to the suppression of miR-145 expression in cultured rat cardiomyocytes in a concentration-dependent manner. Western blotting and real-time PCR were performed. In rat myocardial infarction study, in situ hybridization, and immunofluorescent analyses were adopted. The western blot and real-time PCR data revealed that hypoxic stress with 2.5% O2 suppressed the expression of miR-145 and Wnt3a/ß-catenin in cultured rat cardiomyocytes but augmented Dab2. Treatment with EGCG attenuated Dab2 expression, but increased Wnt3a and ß-catenin in hypoxic cultured cardiomyocytes. Following in vivo myocardial infarction (MI) study, the data revealed the myocardial infarct area reduced by 48.5%, 44.6%, and 48.5% in EGCG (50mg/kg) or miR-145 dominant or Dab2 siRNA groups after myocardial infarction for 28 days, respectively. This study demonstrated that EGCG increased miR-145, Wnt3a, and ß-catenin expression but attenuated Dab2 expression. Moreover, EGCG ameliorated myocardial ischemia in vivo. The novel suppressive effect was mediated through the miR-145 and Dab2/Wnt3a/ß-catenin pathways.


Assuntos
Proteínas Adaptadoras de Transporte Vesicular/genética , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Catequina/análogos & derivados , Expressão Gênica/efeitos dos fármacos , MicroRNAs/genética , MicroRNAs/metabolismo , Isquemia Miocárdica/tratamento farmacológico , Isquemia Miocárdica/genética , Miócitos Cardíacos/metabolismo , Fitoterapia , Proteína Wnt3A/genética , Proteína Wnt3A/metabolismo , beta Catenina/genética , beta Catenina/metabolismo , Animais , Catequina/farmacologia , Catequina/uso terapêutico , Células Cultivadas , Relação Dose-Resposta a Droga , Ratos
18.
J Agric Food Chem ; 68(9): 2673-2683, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32050765

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming the leading cause of chronic liver diseases throughout the world. The deficit of pharmacotherapy for NAFLD calls for an urgent need for a new drug discovery and lifestyle management. Black tea is the most popular and functional drink consumed worldwide. Its main bioactive constituent theaflavin helps to prevent obesity-a major risk factor for NAFLD. To find new targets for the development of effective and safe therapeutic drugs from natural plants for NAFLD, we found a theaflavin monomer theaflavin-3,3'-digallate (TF3), which significantly reduced lipid droplet accumulation in hepatocytes, and directly bound and inhibited the activation of plasma kallikrein (PK), which was further proved to stimulate adenosine monophosphate activated protein kinase (AMPK) and its downstream targets. Taken together, we proposed that the TF3-PK-AMPK regulatory axis is a novel mechanism of lipid deposition mitigation, and PK could be a new target for NAFLD treatment.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Biflavonoides/farmacologia , Catequina/farmacologia , Hepatócitos/metabolismo , Gotículas Lipídicas/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Extratos Vegetais/farmacologia , Calicreína Plasmática/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Apoptose/efeitos dos fármacos , Camellia sinensis/química , Células Hep G2 , Hepatócitos/citologia , Hepatócitos/efeitos dos fármacos , Humanos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Transdução de Sinais/efeitos dos fármacos
19.
Chem Pharm Bull (Tokyo) ; 68(2): 140-149, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32009081

RESUMO

Previously, we reported that the c-Met inhibitory effect of Ephedra Herb extract (EHE) is derived from ingredients besides ephedrine alkaloids. Moreover, analgesic and anti-influenza activities of EHE and ephedrine alkaloids-free Ephedra Herb extract (EFE) have been reported recently. In this study, we examined the fractions containing c-Met kinase inhibitory activity from EHE and the fractions with analgesic and anti-influenza activities from EFE, and elucidated the structural characteristics of the active fractions. Significant c-Met kinase activity was observed in 30, 40, and 50% methanol (MeOH) eluate fractions obtained from water extract of EHE using Diaion HP-20 column chromatography. Similarly, 20 and 40% MeOH, and MeOH eluate fractions obtained from water extract of EFE were found to display analgesic and anti-influenza activities. Reversed phase-HPLC analysis of the active fractions commonly showed broad peaks characteristic of high-molecular mass condensed tannin. The active fractions were analyzed using 13C-NMR and decomposition reactions; the deduced structures of active components were high-molecular mass condensed tannins, which were mainly procyanidin B-type and partly procyanidin A-type, including pyrogallol- and catechol-type flavan 3-ols as extension and terminal units. HPLC and gel permeation chromatography (GPC) analyses estimated that the ratio of pyrogallol- and catechol-type was approximately 9 : 2, and the weight-average molecular weight based on the polystyrene standard was >45000. Furthermore, GPC-based analysis was proposed as the quality evaluation method for high-molecular mass condensed tannin in EHE and EFE.


Assuntos
Ephedra/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Alcaloides/química , Alcaloides/farmacologia , Analgésicos/química , Analgésicos/farmacologia , Animais , Antivirais/química , Antivirais/farmacologia , Biflavonoides/química , Biflavonoides/farmacologia , Catequina/química , Catequina/farmacologia , Linhagem Celular Tumoral , Cães , Efedrina/química , Efedrina/farmacologia , Humanos , Células Madin Darby de Rim Canino , Masculino , Camundongos , Proantocianidinas/química , Proantocianidinas/farmacologia , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores
20.
Biochemistry ; 59(10): 1093-1103, 2020 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-32100530

RESUMO

Epigallocatechin-3-gallate (EGCG) is a catechin found in green tea that can inhibit the amyloid formation of a wide variety of proteins. EGCG's ability to prevent or redirect the amyloid formation of so many proteins may reflect a common mechanism of action, and thus, greater molecular-level insight into how it exerts its effect could have broad implications. Here, we investigate the molecular details of EGCG's inhibition of the protein ß-2-microglobulin (ß2m), which forms amyloids in patients undergoing long-term dialysis treatment. Using size-exclusion chromatography and a collection of mass spectrometry-based techniques, we find that EGCG prevents Cu(II)-induced ß2m amyloid formation by diverting the normal progression of preamyloid oligomers toward the formation of spherical, redissolvable aggregates. EGCG exerts its effect by binding with a micromolar affinity (Kd ≈ 5 µM) to the ß2m monomer on the edge of two ß-sheets near the N-terminus. This interaction destabilizes the preamyloid dimer and prevents the formation of a tetramer species previously shown to be essential for Cu(II)-induced ß2m amyloid formation. EGCG's binding at the edge of the ß-sheets in ß2m is consistent with a previous hypothesis that EGCG generally prevents amyloid formation by binding cross-ß-sheet aggregation intermediates.


Assuntos
Amiloide/química , Catequina/análogos & derivados , Microglobulina beta-2/química , Amiloide/metabolismo , Proteínas Amiloidogênicas/química , Amiloidose/metabolismo , Catequina/metabolismo , Catequina/farmacologia , Catequina/fisiologia , Cromatografia em Gel/métodos , Cobre/metabolismo , Humanos , Espectrometria de Massas/métodos , Modelos Moleculares , Conformação Proteica em Folha beta/fisiologia , Multimerização Proteica/efeitos dos fármacos , Microglobulina beta-2/antagonistas & inibidores , Microglobulina beta-2/metabolismo
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