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1.
Molecules ; 26(12)2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34208050

RESUMO

Potential effects of tea and its constituents on SARS-CoV-2 infection were assessed in vitro. Infectivity of SARS-CoV-2 was decreased to 1/100 to undetectable levels after a treatment with black tea, green tea, roasted green tea, or oolong tea for 1 min. An addition of (-) epigallocatechin gallate (EGCG) significantly inactivated SARS-CoV-2, while the same concentration of theasinensin A (TSA) and galloylated theaflavins including theaflavin 3,3'-di-O-gallate (TFDG) had more remarkable anti-viral activities. EGCG, TSA, and TFDG at 1 mM, 40 µM, and 60 µM, respectively, which are comparable to the concentrations of these compounds in tea beverages, significantly reduced infectivity of the virus, viral RNA replication in cells, and secondary virus production from the cells. EGCG, TSA, and TFDG significantly inhibited interaction between recombinant ACE2 and RBD of S protein. These results suggest potential usefulness of tea in prevention of person-to-person transmission of the novel coronavirus.


Assuntos
Antivirais/farmacologia , Biflavonoides/química , Catequina/química , Ácido Gálico/análogos & derivados , SARS-CoV-2/fisiologia , Chá/química , Replicação Viral/efeitos dos fármacos , Enzima de Conversão de Angiotensina 2/química , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , Antivirais/química , Biflavonoides/farmacologia , COVID-19/patologia , COVID-19/virologia , Catequina/análogos & derivados , Catequina/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Ácido Gálico/química , Ácido Gálico/farmacologia , Humanos , Mapas de Interação de Proteínas/efeitos dos fármacos , SARS-CoV-2/isolamento & purificação , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/metabolismo , Chá/metabolismo , Células Vero
2.
Molecules ; 26(12)2021 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-34204433

RESUMO

Catechins are a part of the chemical family of flavonoids, a naturally occurring antioxidant, and a secondary metabolite in certain plants. Green tea catechins are well recognized for their essential anti-inflammatory, photo-protective, antioxidant, and chemo-preventive functions. Ultraviolet radiation is a principal cause of damage to the skin. Studies observed that regular intake of green tea catechins increased the minimal dose of radiation required to induce erythema. The objectives of this systematic review and meta-analysis are to determine the effectiveness of green tea catechins in cutaneous erythema and elucidate whether green tea catechin consumption protects against erythema (sunburn) inflammation. A comprehensive literature search was conducted to identify the relevant studies. Two researchers carried out independent screening, data extraction, and quality assessment according to the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). The pooled effect of green tea catechins on protection against erythema was assessed using approaches fixed-effects or random-effects model to quantify the effectiveness of green tea catechins in the erythema dose-response. Studies not be included in meta-analyses were summarized narratively. Six randomized controlled studies of enrolled studies regularly administrated green tea catechins orally for 6 to 12 weeks involving healthy volunteers comprising a total of 100 participants were included in the analysis. The results revealed green tea catechins have favorable protection against erythema inflammation even at increased minimal erythema dose (MED) of ultraviolet radiation. Meta-analysis results confirm oral supplementation of green tea catechins is highly effective at low-intensity ultraviolet radiation-induced erythema response (MED range; 1.25-1.30) compared to placebo, showing a significant pooling difference (p = 0.002) in erythema index (SMD: -0.35; 95% CI, -0.57 to -0.13; I2 = 4%, p = 0.40) in the random-effects model. The pro-inflammatory signaling pathways through oral supplementation with green tea catechins are an attractive strategy for photo-protection in healthy human subjects and could represent a complementary approach to topical sunscreens. Therefore, studies that involved green tea catechin in topical applications to human subjects were also evaluated separately, and their meta-analysis is presented as a reference. The evidence indicates that regular green tea catechin supplementation is associated with protection against UV-induced damage due to erythema inflammation.


Assuntos
Catequina/farmacologia , Eritema/tratamento farmacológico , Chá/química , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Catequina/química , Eritema/metabolismo , Eritema/prevenção & controle , Flavonoides/metabolismo , Flavonoides/farmacologia , Humanos , Inflamação/tratamento farmacológico , Pele/metabolismo , Protetores Solares/farmacologia , Chá/metabolismo , Raios Ultravioleta/efeitos adversos
3.
Int J Mol Sci ; 22(13)2021 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-34206850

RESUMO

Treating postoperative (PO) pain is a clinical challenge. Inadequate PO pain management can lead to worse outcomes, for example chronic post-surgical pain. Therefore, acquiring new information on the PO pain mechanism would increase the therapeutic options available. In this paper, we evaluated the role of a natural substance, epigallocatechin-3-gallate (EGCG), on pain and neuroinflammation induced by a surgical procedure in an animal model of PO pain. We performed an incision of the hind paw and EGCG was administered for five days. Mechanical allodynia, thermal hyperalgesia, and motor dysfunction were assessed 24 h, and three and five days after surgery. At the same time points, animals were sacrificed, and sera and lumbar spinal cord tissues were harvested for molecular analysis. EGCG administration significantly alleviated hyperalgesia and allodynia, and reduced motor disfunction. From the molecular point of view, EGCG reduced the activation of the WNT pathway, reducing WNT3a, cysteine-rich domain frizzled (FZ)1 and FZ8 expressions, and both cytosolic and nuclear ß-catenin expression, and the noncanonical ß-catenin-independent signaling pathways, reducing the activation of the NMDA receptor subtype NR2B (pNR2B), pPKC and cAMP response element-binding protein (pCREB) expressions at all time points. Additionally, EGCG reduced spinal astrocytes and microglia activation, cytokines overexpression and nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB) pathway, downregulating inducible nitric oxide synthase (iNOS) activation, cyclooxygenase 2 (COX-2) expression, and prostaglandin E2 (PGE2) levels. Thus, EGCG administration managing the WNT/ß-catenin signaling pathways modulates PO pain related neurochemical and inflammatory alterations.


Assuntos
Analgésicos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Catequina/análogos & derivados , Dor Pós-Operatória/tratamento farmacológico , Analgésicos/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Catequina/farmacologia , Catequina/uso terapêutico , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Receptores Frizzled/genética , Receptores Frizzled/metabolismo , Masculino , NF-kappa B/genética , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Proteína Quinase C/genética , Proteína Quinase C/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/genética , Receptores de N-Metil-D-Aspartato/metabolismo , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo , Proteínas Wnt/genética , Proteínas Wnt/metabolismo , Via de Sinalização Wnt , beta Catenina/genética , beta Catenina/metabolismo
4.
Molecules ; 26(13)2021 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-34206736

RESUMO

Green tea can influence the gut microbiota by either stimulating the growth of specific species or by hindering the development of detrimental ones. At the same time, gut bacteria can metabolize green tea compounds and produce smaller bioactive molecules. Accordingly, green tea benefits could be due to beneficial bacteria or to microbial bioactive metabolites. Therefore, the gut microbiota is likely to act as middle man for, at least, some of the green tea benefits on health. Many health promoting effects of green tea seems to be related to the inter-relation between green tea and gut microbiota. Green tea has proven to be able to correct the microbial dysbiosis that appears during several conditions such as obesity or cancer. On the other hand, tea compounds influence the growth of bacterial species involved in inflammatory processes such as the release of LPS or the modulation of IL production; thus, influencing the development of different chronic diseases. There are many studies trying to link either green tea or green tea phenolic compounds to health benefits via gut microbiota. In this review, we tried to summarize the most recent research in the area.


Assuntos
Bactérias/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Microbiota/efeitos dos fármacos , Fenóis/farmacologia , Extratos Vegetais/farmacologia , Chá , Animais , Antioxidantes/farmacologia , Catequina/farmacologia , Disbiose/complicações , Disbiose/tratamento farmacológico , Humanos , Inflamação/metabolismo , Neoplasias/complicações , Neoplasias/metabolismo , Obesidade/complicações , Obesidade/metabolismo , Fenóis/química , Fenóis/metabolismo , Polifenóis/farmacologia , Chá/química
5.
Nutrients ; 13(7)2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34209677

RESUMO

In recent years, neurological and neurodegenerative disorders research has focused on altered molecular mechanisms in search of potential pharmacological targets, e.g., imbalances in mechanisms of response to oxidative stress, inflammation, apoptosis, autophagy, proliferation, differentiation, migration, and neuronal plasticity, which occur in less common neurological and neurodegenerative pathologies (Huntington disease, multiple sclerosis, fetal alcohol spectrum disorders, and Down syndrome). Here, we assess the effects of different catechins (particularly of epigalocatechin-3-gallate, EGCG) on these disorders, as well as their use in attenuating age-related cognitive decline in healthy individuals. Antioxidant and free radical scavenging properties of EGCG -due to their phenolic hydroxyl groups-, as well as its immunomodulatory, neuritogenic, and autophagic characteristics, makes this catechin a promising tool against neuroinflammation and microglia activation, common in these pathologies. Although EGCG promotes the inhibition of protein aggregation in experimental Huntington disease studies and improves the clinical severity in multiple sclerosis in animal models, its efficacy in humans remains controversial. EGCG may normalize DYRK1A (involved in neural plasticity) overproduction in Down syndrome, improving behavioral and neural phenotypes. In neurological pathologies caused by environmental agents, such as FASD, EGCG enhances antioxidant defense and regulates placental angiogenesis and neurodevelopmental processes. As demonstrated in animal models, catechins attenuate age-related cognitive decline, which results in improvements in long-term outcomes and working memory, reduction of hippocampal neuroinflammation, and enhancement of neuronal plasticity; however, further studies are needed. Catechins are valuable compounds for treating and preventing certain neurodegenerative and neurological diseases of genetic and environmental origin. However, the use of different doses of green tea extracts and EGCG makes it difficult to reach consistent conclusions for different populations.


Assuntos
Antioxidantes/farmacologia , Catequina/farmacologia , Doenças do Sistema Nervoso/tratamento farmacológico , Doenças Neurodegenerativas/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Envelhecimento Cognitivo/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Plasticidade Neuronal/efeitos dos fármacos
6.
Molecules ; 26(13)2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34209485

RESUMO

(-)-Epigallocatechin-3-O-gallate (EGCG), the most abundant component of catechins in tea (Camellia sinensis (L.) O. Kuntze), plays a role against viruses through inhibiting virus invasiveness, restraining gene expression and replication. In this paper, the antiviral effects of EGCG on various viruses, including DNA virus, RNA virus, coronavirus, enterovirus and arbovirus, were reviewed. Meanwhile, the antiviral effects of the EGCG epi-isomer counterpart (+)-gallocatechin-3-O-gallate (GCG) were also discussed.


Assuntos
Antivirais/farmacologia , COVID-19/tratamento farmacológico , Catequina/análogos & derivados , Chá/química , Animais , Antivirais/uso terapêutico , Catequina/farmacologia , Catequina/uso terapêutico , Humanos , Internalização do Vírus/efeitos dos fármacos , Vírus/efeitos dos fármacos
7.
Molecules ; 26(12)2021 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-34203004

RESUMO

Green tea and its bioactive components, especially polyphenols, possess many health-promoting and disease-preventing benefits, especially anti-inflammatory, antioxidant, anticancer, and metabolic modulation effects with multi-target modes of action. However, the effect of tea polyphenols on immune function has not been well studied. Moreover, the underlying cellular and molecular mechanisms mediating immunoregulation are not well understood. This review summarizes the recent studies on the immune-potentiating effects and corresponding mechanisms of tea polyphenols, especially the main components of (-)-epigallocatechin-3-gallate (EGCG) and (-)-epicatechin-3-gallate (ECG). In addition, the benefits towards immune-related diseases, such as autoimmune diseases, cutaneous-related immune diseases, and obesity-related immune diseases, have been discussed.


Assuntos
Antioxidantes/farmacologia , Imunidade/efeitos dos fármacos , Fatores Imunológicos/farmacologia , Polifenóis/farmacologia , Chá/química , Animais , Antioxidantes/química , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Catequina/análogos & derivados , Catequina/química , Catequina/farmacologia , Flavonoides/química , Flavonoides/farmacologia , Humanos , Fatores Imunológicos/química , Polifenóis/química
8.
PLoS One ; 16(6): e0253489, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34138966

RESUMO

In the pursuit of suitable and effective solutions to SARS-CoV-2 infection, we investigated the efficacy of several phenolic compounds in controlling key cellular mechanisms involved in its infectivity. The way the SARS-CoV-2 virus infects the cell is a complex process and comprises four main stages: attachment to the cognate receptor, cellular entry, replication and cellular egress. Since, this is a multi-part process, it creates many opportunities to develop effective interventions. Targeting binding of the virus to the host receptor in order to prevent its entry has been of particular interest. Here, we provide experimental evidence that, among 56 tested polyphenols, including plant extracts, brazilin, theaflavin-3,3'-digallate, and curcumin displayed the highest binding with the receptor-binding domain of spike protein, inhibiting viral attachment to the human angiotensin-converting enzyme 2 receptor, and thus cellular entry of pseudo-typed SARS-CoV-2 virions. Both, theaflavin-3,3'-digallate at 25 µg/ml and curcumin above 10 µg/ml concentration, showed binding with the angiotensin-converting enzyme 2 receptor reducing at the same time its activity in both cell-free and cell-based assays. Our study also demonstrates that brazilin and theaflavin-3,3'-digallate, and to a still greater extent, curcumin, decrease the activity of transmembrane serine protease 2 both in cell-free and cell-based assays. Similar pattern was observed with cathepsin L, although only theaflavin-3,3'-digallate showed a modest diminution of cathepsin L expression at protein level. Finally, each of these three compounds moderately increased endosomal/lysosomal pH. In conclusion, this study demonstrates pleiotropic anti-SARS-CoV-2 efficacy of specific polyphenols and their prospects for further scientific and clinical investigations.


Assuntos
Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/prevenção & controle , Polifenóis/farmacologia , SARS-CoV-2/efeitos dos fármacos , Glicoproteína da Espícula de Coronavírus/metabolismo , Internalização do Vírus/efeitos dos fármacos , Células A549 , Benzopiranos/farmacologia , Biflavonoides/farmacologia , COVID-19/virologia , Catequina/análogos & derivados , Catequina/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Curcumina/farmacologia , Humanos , Ligação Proteica/efeitos dos fármacos , SARS-CoV-2/metabolismo , SARS-CoV-2/fisiologia , Vírion/efeitos dos fármacos , Vírion/metabolismo , Vírion/fisiologia , Ligação Viral/efeitos dos fármacos
9.
Nutrients ; 13(5)2021 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-34063322

RESUMO

Preservation of vascular endothelium integrity and functionality represents an unmet medical need. Indeed, endothelial dysfunction leads to decreased nitric oxide biosynthesis, which is prodromic of hypertension and hypercoagulability. In this panorama, the nutraceutical supplement Taurisolo®, a polyphenolic extract from Aglianico cultivar grape, rich in catechin and procyanidins, was evaluated as a vasoprotective, vasorelaxing, anti-hypertensive and anti-coagulant agent in: cell lines, isolated vessels, in vivo models of chronic hypertension and hypercoagulability, and in clinical tests of endothelial reactivity. Taurisolo® demonstrated to fully protect vascular cell viability from oxidative stimulus at 100 µg/mL and evoke vasorelaxing effects (Emax = 80.6% ± 1.9 and pEC50 = 1.19 ± 0.03) by activation of the Sirtuins-AMPK-pathway. Moreover, Taurisolo®, chronically administered at 20 mg/Kg/die in in vivo experiments, inhibited the onset of cardiac hypertrophy (heart weight/rat weight = 3.96 ± 0.09 vs. 4.30 ± 0.03), hypercoagulability (decrease of fibrinogen vs. control: p < 0.01) and hypertension (mean of Psys: 200 ± 2 vs. control 234 ± 2 mmHg) and improved endothelial function (Emax = 88.9% ± 1.5 vs. control 59.6% ± 3.6; flow-mediated dilation in healthy volunteers after 400 mg twice daily for 8 weeks vs. baseline: p = 0.019). In conclusion, Taurisolo® preserves the vascular function against ox-inflamm-ageing process and the consequent cardiovascular accidents.


Assuntos
Suplementos Nutricionais , Endotélio Vascular/efeitos dos fármacos , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Vitis/química , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Anticoagulantes/farmacologia , Anti-Hipertensivos/farmacologia , Catequina/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Humanos , Hipertensão/tratamento farmacológico , Masculino , Estresse Oxidativo/efeitos dos fármacos , Proantocianidinas/farmacologia , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Sirtuínas/metabolismo , Trombofilia/tratamento farmacológico , Vasodilatadores/farmacologia
10.
Gene ; 794: 145774, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34126197

RESUMO

BACKGROUND: Transforming growth factor-ß (TGF-ß)-induced Epithelial-to-mesenchymal transition (EMT) process is a fundamental target for preventing cervical cancer cells' progression and invasion. Green tea and its principal active substance, Epigallocatechin-3-gallate (EGCG), demonstrate anti-tumor activities in various tumor cells. METHODS: The cell viability of two cervical cancer cell lines, Hela and SiHa, in the experimental groups was examined employing the MTT method, and ROS generation was probed applying 2',7'-dichlorofluorescein diacetate-based assay. The Smad signaling and EMT process was evaluated utilizing western blot analysis and quantitative real-time polymerase chain reaction (qRT-PCR). Chromatin immunoprecipitation (ChIP) and Smad binding element (SBE)-luciferase assays were employed to measure Smad-DNA interaction and Smad transcriptional activity, respectively. RESULTS: EGCG (0-100 µmol/L) and green tea extract (0-250 µg/ml) suppressed the viability of cancer cells in a dose-dependent manner (p < 0.01). Our conclusions affirmed that pre-incubation with green tea extract (80 µg/ml) and EGCG (60 µmol/L) significantly reversed the impacts of TGF-ß in Hela and SiHa cells by decreasing Vimentin, ZEB, Slug, Snail, and Twist and increasing E-cadherin expression. The molecular mechanism of green tea extract and EGCG for TGF-ß-induced EMT inhibition interfered with ROS generation and Smad signaling. Green tea extract and EGCG could significantly decrease ROS levels, the phosphorylation of Smad2/3, the translocation, DNA binding, and activity of Smads in cervical cancer cell lines treated with TGF-ß1 (p < 0.01). CONCLUSION: EGCG and green tea extract suppressed TGF-ß-induced EMT in Hela and SiHa cells, and the underlying molecular mechanism may be related to the ROS generation and Smad signaling pathway.


Assuntos
Catequina/análogos & derivados , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Extratos Vegetais/farmacologia , Chá/química , Fator de Crescimento Transformador beta/farmacologia , Neoplasias do Colo do Útero/metabolismo , Catequina/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HeLa , Humanos , Extratos Vegetais/química , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas Smad/genética , Proteínas Smad/metabolismo , Neoplasias do Colo do Útero/tratamento farmacológico
11.
Molecules ; 26(9)2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-34063635

RESUMO

Tea is one of the most widely consumed beverages worldwide after water, and green tea accounts for 20% of the total tea consumption. The health benefits of green tea are attributed to its natural antioxidants, namely, catechins, which are phenolic compounds with diverse beneficial effects on human health. The beneficial effects of green tea and its major bioactive component, (-)-epigallocatechin-3-gallate (EGCG), on health include high antioxidative, osteoprotective, neuroprotective, anti-cancer, anti-hyperlipidemia and anti-diabetic effects. However, the review of green tea's benefits on female reproductive disorders, including polycystic ovary syndrome (PCOS), endometriosis and dysmenorrhea, remains scarce. Thus, this review summarises current knowledge on the beneficial effects of green tea catechins on selected female reproductive disorders. Green tea or its derivative, EGCG, improves endometriosis mainly through anti-angiogenic, anti-fibrotic, anti-proliferative and proapoptotic mechanisms. Moreover, green tea enhances ovulation and reduces cyst formation in PCOS while improving generalised hyperalgesia, and reduces plasma corticosterone levels and uterine contractility in dysmenorrhea. However, information on clinical trials is inadequate for translating excellent findings on green tea benefits in animal endometriosis models. Thus, future clinical intervention studies are needed to provide clear evidence of the green tea benefits with regard to these diseases.


Assuntos
Catequina/farmacologia , Dismenorreia/tratamento farmacológico , Endometriose/tratamento farmacológico , Síndrome do Ovário Policístico/tratamento farmacológico , Chá/química , Inibidores da Angiogênese/farmacologia , Animais , Antioxidantes/uso terapêutico , Apoptose , Camellia sinensis , Catequina/análogos & derivados , Proliferação de Células , Corticosterona/sangue , Estudos Transversais , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Extratos Vegetais/farmacologia , Útero/patologia
12.
Nucleic Acids Res ; 49(12): 6893-6907, 2021 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-34142161

RESUMO

Selenoprotein P (SELENOP) is a major plasma selenoprotein that contains 10 Sec residues, which is encoded by the UGA stop codon. The mRNA for SELENOP has the unique property of containing two Sec insertion sequence (SECIS) elements, which is located in the 3' untranslated region (3'UTR). Here, we coincidentally identified a novel gene, CCDC152, by sequence analysis. This gene was located in the antisense region of the SELENOP gene, including the 3'UTR region in the genome. We demonstrated that this novel gene functioned as a long non-coding RNA (lncRNA) that decreased SELENOP protein levels via translational rather than transcriptional, regulation. We found that the CCDC152 RNA interacted specifically and directly with the SELENOP mRNA and inhibited its binding to the SECIS-binding protein 2, resulting in the decrease of ribosome binding. We termed this novel gene product lncRNA inhibitor of SELENOP translation (L-IST). Finally, we found that epigallocatechin gallate upregulated L-IST in vitro and in vivo, to suppress SELENOP protein levels. Here, we provide a new regulatory mechanism of SELENOP translation by an endogenous long antisense ncRNA.


Assuntos
Regulação da Expressão Gênica , Biossíntese de Proteínas , RNA Longo não Codificante/metabolismo , Selenoproteína P/genética , Catequina/análogos & derivados , Catequina/farmacologia , Linhagem Celular Tumoral , Regulação para Baixo , Humanos , RNA Longo não Codificante/genética , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/antagonistas & inibidores , Selenoproteína P/biossíntese
13.
Int J Mol Sci ; 22(9)2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-34068829

RESUMO

Cassia abbreviata is widely used in Sub-Saharan Africa for treating many diseases, including HIV-1 infection. We have recently described the chemical structures of 28 compounds isolated from an alcoholic crude extract of barks and roots of C. abbreviata, and showed that six bioactive compounds inhibit HIV-1 infection. In the present study, we demonstrate that the six compounds block HIV-1 entry into cells: oleanolic acid, palmitic acid, taxifolin, piceatannol, guibourtinidol-(4α→8)-epiafzelechin, and a novel compound named as cassiabrevone. We report, for the first time, that guibourtinidol-(4α→8)-epiafzelechin and cassiabrevone inhibit HIV-1 entry (IC50 of 42.47 µM and 30.96 µM, respectively), as well as that piceatannol interacts with cellular membranes. Piceatannol inhibits HIV-1 infection in a dual-chamber assay mimicking the female genital tract, as well as HSV infection, emphasizing its potential as a microbicide. Structure-activity relationships (SAR) showed that pharmacophoric groups of piceatannol are strictly required to inhibit HIV-1 entry. By a ligand-based in silico study, we speculated that piceatannol and norartocarpetin may have a very similar mechanism of action and efficacy because of the highly comparable pharmacophoric and 3D space, while guibourtinidol-(4α→8)-epiafzelechin and cassiabrevone may display a different mechanism. We finally show that cassiabrevone plays a major role of the crude extract of CA by blocking the binding activity of HIV-1 gp120 and CD4.


Assuntos
Cassia/química , Infecções por HIV/tratamento farmacológico , Extratos Vegetais/farmacologia , Internalização do Vírus/efeitos dos fármacos , Catequina/farmacologia , Proteína gp120 do Envelope de HIV/genética , Infecções por HIV/genética , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/patogenicidade , Humanos , Ácido Oleanólico/farmacologia , Ácido Palmítico/farmacologia , Extratos Vegetais/química , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/genética , Raízes de Plantas/virologia , Quercetina/análogos & derivados , Quercetina/farmacologia , Estilbenos/farmacologia
14.
Int J Mol Sci ; 22(10)2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34065602

RESUMO

Resistance to anticancer therapeutics occurs in virtually every type of cancer and becomes a major difficulty in cancer treatment. Although 5-fluorouracil (5FU) is the first-line choice of anticancer therapy for gastric cancer, its effectiveness is limited owing to drug resistance. Recently, altered cancer metabolism, including the Warburg effect, a preference for glycolysis rather than oxidative phosphorylation for energy production, has been accepted as a pivotal mechanism regulating resistance to chemotherapy. Thus, we investigated the detailed mechanism and possible usefulness of antiglycolytic agents in ameliorating 5FU resistance using established gastric cancer cell lines, SNU620 and SNU620/5FU. SNU620/5FU, a gastric cancer cell harboring resistance to 5FU, showed much higher lactate production and expression of glycolysis-related enzymes, such as lactate dehydrogenase A (LDHA), than those of the parent SNU620 cells. To limit glycolysis, we examined catechin and its derivatives, which are known anti-inflammatory and anticancer natural products because epigallocatechin gallate has been previously reported as a suppressor of LDHA expression. Catechin, the simplest compound among them, had the highest inhibitory effect on lactate production and LDHA activity. In addition, the combination of 5FU and catechin showed additional cytotoxicity and induced reactive oxygen species (ROS)-mediated apoptosis in SNU620/5FU cells. Thus, based on these results, we suggest catechin as a candidate for the development of a novel adjuvant drug that reduces chemoresistance to 5FU by restricting LDHA.


Assuntos
Catequina/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Fluoruracila/farmacologia , Lactato Desidrogenase 5/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Apoptose/efeitos dos fármacos , Catequina/análogos & derivados , Linhagem Celular Tumoral , Glicólise/efeitos dos fármacos , Humanos , Espécies Reativas de Oxigênio/metabolismo , Estômago/efeitos dos fármacos , Neoplasias Gástricas/metabolismo
15.
Int J Mol Sci ; 22(9)2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-34066609

RESUMO

Pseudomonas aeruginosa (P. aeruginosa), one of the dangerous multidrug resistance pathogens, orchestrates virulence factors production through quorum sensing (QS). Since the exploration of QS inhibitors, targeting virulence to circumvent bacterial pathogenesis without causing significant growth inhibition is a promising approach to treat P. aeruginosa infections. The present study has evaluated the anti-QS and anti-infective activity of epigallocatechin-3-gallate (EGCG), a bioactive ingredient of the traditional green tea, against P. aeruginosa. EGCG showed significant inhibitory effects on the development of biofilm, protease, elastase activity, swimming, and swarming motility, which was positively related to the production of C4-AHL. The expression of QS-related and QS-regulated virulence factors genes was also evaluated. Quantitative PCR analysis showed that EGCG significantly reduced the expression of las, rhl, and PQS genes and was highly correlated with the alterations of C4-AHL production. In-vivo experiments demonstrated that EGCG treatment reduced P. aeruginosa pathogenicity in Caenorhabditis elegans (C. elegans). EGCG increased the survival of C. elegans by 23.25%, 30.04%, and 36.35% in a dose-dependent manner. The findings of this study strongly suggest that EGCG could be a potential candidate for QS inhibition as an anti-virulence compound against bacterial infection.


Assuntos
Biofilmes/crescimento & desenvolvimento , Catequina/análogos & derivados , Pseudomonas aeruginosa/fisiologia , Percepção de Quorum/efeitos dos fármacos , Acil-Butirolactonas/metabolismo , Animais , Biofilmes/efeitos dos fármacos , Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/microbiologia , Catequina/farmacologia , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Glicolipídeos/biossíntese , Testes de Sensibilidade Microbiana , Movimento , Peptídeo Hidrolases/metabolismo , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/crescimento & desenvolvimento , Piocianina/biossíntese , Percepção de Quorum/genética
16.
J Food Biochem ; 45(6): e13758, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33997996

RESUMO

The incidence of bladder cancer in traditional green tea-consuming countries was dramatically lower than low green tea-consuming countries. Epigallocatechin-3-gallate (EGCG), an active ingredient extracted from green tea, showed effective inhibition of formation and progression of many tumors. However, whether autophagy involved in this tumor-suppression mechanism of EGCG on bladder cancer was still unclear. In this study, we demonstrated low concentration of EGCG-induced proliferation inhibition and increased apoptosis in bladder cancer cell lines (5,637 and T24 cells) indicated by the increased expression of apoptosis-related protein (caspase9, caspase3 and BAX). In addition, low dose of EGCG also regulated autophagy pathway associated protein (LC3B II and Beclin) expression and this autophagy pathway was blocked by PI3K/AKT inhibitor; moreover, knockdown of ATG5 reversed EGCG-induced apoptosis in 5,637 cells, indicating that EGCG might inhibit the bladder cancer through autophagy pathway. Our findings indicated that EGCG should be considered as a novel therapy for bladder cancer treatment by regulating autophagy pathway. PRACTICAL APPLICATIONS: Our research proved EGCG from green tea could be used as an effective anti-tumor ingredient by revealing another mechanism that epigallocatechin-3-Gallate inhibited bladder cancer cells via inducing autophagy-related apoptosis. And green tea could be considered as a kind of tumor-preventing beverage.


Assuntos
Catequina , Neoplasias da Bexiga Urinária , Apoptose , Autofagia , Catequina/análogos & derivados , Catequina/farmacologia , Linhagem Celular Tumoral , Humanos , Fosfatidilinositol 3-Quinases , Neoplasias da Bexiga Urinária/tratamento farmacológico
17.
Food Chem ; 361: 130047, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34029903

RESUMO

Inhibition of maltase, sucrase, isomaltase and glucoamylase activity by acarbose, epigallocatechin gallate, epicatechin gallate and four polyphenol-rich tea extract from white, green, oolong, black tea, were investigated by using rat intestinal enzymes and human Caco-2 cells. Regarding rat intestinal enzyme mixture, all four tea extracts were very effective in inhibiting maltase and glucoamylase activity, but only white tea extract inhibited sucrase and isomaltase activity and the inhibition was limited. Mixed-type inhibition on rat maltase activity was observed. Tea extracts in combination with acarbose, produced a synergistic inhibitory effect on rat maltase activity. Caco-2 cells experiments were conducted in Transwells. Green tea extract and epigallocatechin gallate show dose-dependent inhibition on human sucrase activity, but no inhibition on rat sucrase activity. The opposite was observed on maltase activity. The results highlighted the different response in the two investigated model systems and show that tea polyphenols are good inhibitors for α-glucosidase activity.


Assuntos
Glicosídeo Hidrolases/antagonistas & inibidores , Intestinos/enzimologia , Extratos Vegetais/química , Polifenóis/farmacologia , Chá/química , Acarbose/farmacologia , Animais , Células CACO-2 , Catequina/análogos & derivados , Catequina/farmacologia , Glucana 1,4-alfa-Glucosidase/antagonistas & inibidores , Inibidores de Glicosídeo Hidrolases/farmacologia , Humanos , Cinética , Oligo-1,6-Glucosidase/antagonistas & inibidores , Ratos , Sacarase/antagonistas & inibidores , alfa-Glucosidases/efeitos dos fármacos
18.
Caries Res ; 55(3): 205-214, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34010838

RESUMO

It has been suggested that green tea-derived epigallocatechin gallate (EGCG), which has antimicrobial properties, might help prevent dental caries. However, the detailed properties of EGCG remain unclear. In this study, the antimicrobial properties of EGCG were evaluated by examining its bactericidal activity, its inhibitory effects against bacterial growth, acid production, acidic end-product formation, and sugar uptake (phosphoenolpyruvate-dependent phosphotransferase system, PEP-PTS activity), and its effects on bacterial aggregation, using monocultured planktonic cells of Streptococcus mutans and non-mutans streptococci. Coincubating S. mutans with EGCG (1 mg/mL) for 4 h had no bactericidal effects, while it decreased the growth and acid production of S. mutans by inhibiting the activity of the PEP-PTS. EGCG (2 mg/mL) caused rapid bacterial cell aggregation and had reduced the optical density of S. mutans cell suspension by 86.7% at pH 7.0 and 90.7% at pH 5.5 after 2 h. EGCG also reduced the acid production of non-mutans streptococci, including S. sanguinis, S. gordonii, and S. salivarius, and promoted the aggregation of these non-mutans streptococci. Furthermore, these antimicrobial effects of short-term EGCG treatment persisted in the presence of saliva. These results suggest that EGCG might have short-term antibacterial effects on caries-associated streptococci in the oral cavity.


Assuntos
Catequina , Cárie Dentária , Biofilmes , Catequina/análogos & derivados , Catequina/farmacologia , Cárie Dentária/prevenção & controle , Humanos , Streptococcus mutans , Chá
19.
Oxid Med Cell Longev ; 2021: 5599997, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33953830

RESUMO

Nonalcoholic fatty liver disease (NAFLD) represents one of the most common chronic liver diseases in the world. It has been reported that epigallocatechin-3-gallate (EGCG) plays important biological and pharmacological roles in mammalian cells. Nevertheless, the mechanism underlying the beneficial effect of EGCG on the progression of NAFLD has not been fully elucidated. In the present study, the mechanisms of action of EGCG on the growth, apoptosis, and autophagy were examined using oleic acid- (OA-) treated liver cells and the high-fat diet- (HFD-) induced NAFLD mouse model. Administration of EGCG promoted the growth of OA-treated liver cells. EGCG could reduce mitochondrial-dependent apoptosis and increase autophagy possibly via the reactive oxygen species- (ROS-) mediated mitogen-activated protein kinase (MAPK) pathway in OA-treated liver cells. In line with in vitro findings, our in vivo study verified that treatment with EGCG attenuated HFD-induced NAFLD through reduction of apoptosis and promotion of autophagy. EGCG can alleviate HFD-induced NAFLD possibly by decreasing apoptosis and increasing autophagy via the ROS/MAPK pathway. EGCG may be a promising agent for the treatment of NAFLD.


Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Catequina/análogos & derivados , Dieta Hiperlipídica/efeitos adversos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Animais , Catequina/farmacologia , Catequina/uso terapêutico , Modelos Animais de Doenças , Progressão da Doença , Humanos , Masculino , Camundongos , Hepatopatia Gordurosa não Alcoólica/fisiopatologia
20.
J Food Sci ; 86(6): 2445-2456, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33963549

RESUMO

The interactions between polysaccharides and phenolics in foods affect their physicochemical properties and bioactivity. Pectin and catechin/procyanidin present in plants ubiquitously and attracting more attentions for the potential health benefits. This work investigates the interactions between high methoxyl pectin and catechin/procyanidin in a simulative juice model using multiple microscopic and spectroscopic approaches and their influences on the antioxidant activity of phenolics were evaluated in the Caco-2 cells model. The results showed that pectin with either of phenolic compunds exhibited lower transmittance, zeta potential, viscosity, and larger particle size than it alone. The morphology of pectin complexes with either of phenolics under experimental conditions (pH = 3.5) was observed. The ΔH° (-6.821 kJ mol-1 ) and ΔS° (6.357×10-2  kJ mol-1 ) indicated that pectin interacts with procyanidin via electrostatic interaction, whereas hydrophobic interaction was the dominant drive force between pectin and catechin (ΔH° = 1.422 kJ mol-1 ; ΔS° = 13.048 × 10-2  kJ mol-1 ). The antioxidant activities of catechin/procyanidin decreased while binding with pectin based on indexes of glutathione peroxidase, total superoxide dismutase, total antioxidant capacity, and malondialdehyde. PRACTICAL APPLICATION: The findings of this work indicated that the physicochemical property of pectin and the antioxidant activity of catechin/procyanidin were influenced by the interactions between pectin and catechin/procyanidin in a simulative food system. This study provides insights into the molecular interactions between pectin and phenolics in a simulative food system.


Assuntos
Antioxidantes/farmacologia , Biflavonoides/farmacologia , Catequina/farmacologia , Interações Medicamentosas , Sucos de Frutas e Vegetais/análise , Pectinas/farmacologia , Proantocianidinas/farmacologia , Antioxidantes/química , Biflavonoides/química , Células CACO-2 , Catequina/química , Humanos , Pectinas/química , Proantocianidinas/química , Espectrometria de Fluorescência
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