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1.
Food Funct ; 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38757391

RESUMO

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

2.
Biomed Pharmacother ; 166: 115437, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37677966

RESUMO

Polyphenols have been widely used to treat various chronic skin diseases because they are beneficial in wound healing and show anti-inflammatory effects, however, the mechanism of action remains ambiguous. Previously, we reported the wound healing capability of tea polyphenols (TPP), the major functional component of tea, in vivo. The current study aimed to address the mechanisms of TPP in wound healing during different phases (inflammation, proliferation and remodeling). During the inflammation phase, TPP reduced the production of proinflammatory cytokines (IL-1ß, IL-6 and TNF-α) and inhibited infiltration of neutrophils; during the proliferation phase, TPP promoted the expression of growth factor VEGF-A, which can promote vascular endothelial cell division and induce angiogenesis; TPP improved the morphology of the wound and restored the ratio of type III/I collagens during the remodeling phase, as determined by Masson-trichrome staining and Sirius red staining assays. By tracking the changes in the wound area, TPP and recombinant human epidermal growth factor (rhEGF), rather than povidone-iodine (PVP-I), were able to promote wound healing. These results suggest that TPP plays a pivotal role in all the key stages of wound healing and displays distinct mechanisms from rhEGF, suggesting clinical significance for the future application of TPP as a natural wound healing agent.


Assuntos
Bioensaio , Relevância Clínica , Humanos , Animais , Camundongos , Modelos Animais de Doenças , Colágeno Tipo I , Colágeno Tipo III , Fator de Crescimento Epidérmico , Inflamação , Chá
3.
Molecules ; 28(9)2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-37175254

RESUMO

L-theanine (N-ethyl-γ-glutamine) is the main amino acid in tea leaves. It not only contributes to tea flavor but also possesses several health benefits. Compared with its sedative and calming activities, the immunomodulatory effects of L-theanine have received less attention. Clinical and epidemiological studies have shown that L-theanine reduces immunosuppression caused by strenuous exercise and prevents colds and influenza by improving immunity. Numerous cell and animal studies have proven that theanine plays an immunoregulatory role in inflammation, nerve damage, the intestinal tract, and tumors by regulating γδT lymphocyte function, glutathione (GSH) synthesis, and the secretion of cytokines and neurotransmitters. In addition, theanine can be used as an immunomodulator in animal production. This article reviews the research progress of L-theanine on immunoregulation and related mechanisms, as well as its application in poultry and animal husbandry. It is hoped that this work will be beneficial to future related research.


Assuntos
Citocinas , Glutamatos , Animais , Glutamatos/química , Imunidade , Chá/química
4.
Nutrients ; 14(16)2022 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-36014921

RESUMO

Glucose-dependent insulinotropic polypeptide (GIP) is one of the important incretins and possesses lots of physiological activities such as stimulating insulin secretion and maintaining glucose homeostasis. The pentacyclic triterpenoid saponins are the major active ingredients in tea (Camellia sinensis) seeds. This study aimed to investigate the effect of tea seed saponins on the GIP secretion and related mechanisms. Our data showed that the total tea seed saponins (TSS, 65 mg/kg BW) and theasaponin E1 (TSE1, 2-4 µM) could increase the GIP mRNA and protein levels in mice and STC-1 cells. Phlorizin, the inhibitor of Sodium/glucose cotransporter 1 (SGLT1), reversed the TSE1-induced increase in Ca2+ and GIP mRNA level. In addition, TSE1 upregulated the protein expression of Takeda G protein-coupled receptor 5 (TGR5), and TGR5 siRNA significantly decreased GIP expression in TSE1-treated STC-1 cells. Network pharmacology analysis revealed that six proteins and five signaling pathways were associated with SGLT1, TGR5 and GIP regulated by TSE1. Taken together, tea seed saponins could stimulate GIP expression via SGLT1 and TGR5, and were promising natural active ingredients for improving metabolism and related diseases.


Assuntos
Camellia sinensis , Polipeptídeo Inibidor Gástrico , Saponinas , Animais , Polipeptídeo Inibidor Gástrico/metabolismo , Glucose/metabolismo , Camundongos , RNA Mensageiro/genética , Receptores Acoplados a Proteínas G/genética , Saponinas/farmacologia , Sementes/metabolismo , Chá
5.
Metabolites ; 12(5)2022 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-35629970

RESUMO

Previously, we found that three types of Tieguanyin tea (Tgy-Q, Tgy-N and Tgy-C) extracts could alleviate Alzheimer's disease (AD) in a mouse model among which Tgy-C was more effective. In this study, APP/PS1 transgenic mice were used to investigate the metabolomic changes in the feces of mice treated with Tieguanyin tea extracts. Results showed that the profile of fecal metabolites was obviously changed in AD mice. Metabolomics analysis found the effects of Tgy-C, especially its decreasing effect on the fecal metabolites in AD mice-132 of the 155 differential metabolites were decreased. KEGG enrichment revealed that differential metabolites could participate in functional pathways including protein digestion and absorption, biosynthesis of amino acids and ABC transporters. Further comparisons of the metabolites between groups showed that although Tgy-N and Tgy-Q exerted a decreasing effect on the fecal metabolites, Tgy-C was more effective. Moreover, correlation analysis found that the levels of the fecal metabolites were highly correlated with the contents of functional components in tea extracts. Finally, 16S rDNA sequencing presented that Tieguanyin extracts modified the gut microbiota by targeting diverse bacteria. In this study, we investigated the differences of three types of Tieguanyin tea extracts on the fecal metabolites as well as the bacterial community of the gut microbiota in AD mice. The identified differential metabolites and the changed intestinal bacteria might provide potential diagnostic biomarkers for the occurrence and progression of AD.

6.
Nutrients ; 14(7)2022 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-35406003

RESUMO

Theaflavin-3,3'-digallate (TF3) is a representative theaflavin of black tea and is remarkable for the anti-coronary heart disease effect. As an adaptive response to heart failure, pathological cardiac hypertrophy (PCH) has attracted great interest. In this study, the PCH cell model was established with H9c2 cells by angiotensin II, and the prevention effect and mechanisms of TF3 were investigated. The results showed that the cell size and fetal gene mRNA level were significantly reduced as pretreated with TF3 at the concentration range of 1-10 µM, also the balance of the redox system was recovered by TF3 at the concentration of 10 µM. The intracellular Ca2+ level decreased, Calcineurin (CaN) expression was down-regulated and the p-NFATc3 expression was up-regulated. These results indicated that TF3 could inhibit the activation of the CaN-NFAT signal pathway to prevent PCH, and TF3 may be a potentially effective natural compound for PCH and heart failure.


Assuntos
Biflavonoides , Catequina , Insuficiência Cardíaca , Angiotensina II/farmacologia , Antioxidantes/farmacologia , Biflavonoides/farmacologia , Calcineurina , Cardiomegalia/induzido quimicamente , Cardiomegalia/tratamento farmacológico , Cardiomegalia/prevenção & controle , Catequina/análogos & derivados , Catequina/farmacologia , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/prevenção & controle , Humanos , Miócitos Cardíacos , Transdução de Sinais
7.
Metabolites ; 12(3)2022 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-35323647

RESUMO

Triterpene saponins exhibit various biological and pharmacological activities. However, the knowledge on saponin biosynthesis in tea plants (Camellia sinensis L.) is still limited. In this work, tea flower and seed samples at different developmental stages and leaves were collected and analyzed with UPLC-PDA-MS and RNA sequencing for saponin determination and transcriptome comparison. The saponin content reached around 19% in the freshly mature seeds and 7% in the green flower buds, and decreased with the fruit ripeness and flower blooming. Almost no saponins were detected in leaf samples. PCA and KEGG analysis suggested that the gene expression pattern and secondary metabolism in TF1 and TS2 vs. leaf samples were significantly different. Weighted gene coexpression network analysis (WGCNA) uncovered two modules related to saponin content. The mevalonate (MVA) instead of 2-C-methyl-d-erythritol-4-phospate (MEP) pathway was responsible for saponin accumulation in tea plants, and 3-hydroxy-3-methylglutaryl-CoA synthase (HMGS), diphosphomevalonate decarboxylase (MVD) and isopentenyl diphosphate isomerase (IDI) may be the key enzymes involved in saponin biosynthesis in tea seeds and flowers. Moreover, ten transcription factors (TFs) were predicted to regulate saponin biosynthesis in the tea plant. Taken together, our study provides a global insight into the saponin biosynthesis and accumulation in the tea plant.

8.
Food Funct ; 13(4): 2033-2043, 2022 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-35106523

RESUMO

Black tea exhibits potential to improve hyperglycemia and insulin resistance, where theaflavins (TFs) are its characteristic components. The aim of this study was to explore the anti-diabetic mechanism of TFs. High-fat diet and streptozotocin-induced type 2 diabetes (T2D) mice were administered with TFs by gavage daily for 5 weeks. The biochemical analysis suggested that TFs possess potential anti-diabetic activity, which is comparable to that of metformin. RNA-sequencing analysis showed that TFs had a significant influence on the hepatic transcriptional profile of the T2D mice. The nine significantly enriched KEGG pathways were mainly associated with pancreatic secretion, digestion and metabolism of fat, protein and glycerolipid, and tight junctions. Quantitative real-time PCR and immunohistochemistry analysis verified that TFs improved pancreas function and intestine tight junction, with an increase in the expression of carboxyl ester lipase (Cel), chymotrypsinogen B (Ctrb1), pancreatic triglyceride lipase (Pnlip) and chymotrypsin-like elastase 3B (Cela3b) in the pancreas and cingulin and claudin-1 in the intestine. TFs improved mitochondrial biogenesis with the downregulation of peroxisome proliferator-activated receptor coactivator (PGC) 1α and 1ß in the liver, but had less effect on the muscle. This work revealed the comprehensive mechanism of TFs against T2D, suggesting that TFs are a potential natural agent for improving type 2 diabetes.


Assuntos
Antioxidantes/uso terapêutico , Biflavonoides/uso terapêutico , Catequina/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Chá , Animais , Antioxidantes/farmacologia , Biflavonoides/farmacologia , Glicemia , Catequina/farmacologia , Dieta Hiperlipídica , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Resistência à Insulina , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estreptozocina
9.
Plant Foods Hum Nutr ; 77(1): 105-111, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35138518

RESUMO

Obesity is a worldwide epidemic and increases the risk of metabolic syndrome through chronic inflammation. Tea polyphenols (TP), the major functional component of tea, has shown preventive effects on obesity and obesity-related disease, but the underlying mechanism is complicated and remains obscure. The present study was aimed to elucidate the anti-inflammation effect of TP in high-fat-diet (HFD)-induced obese mice. Results showed that TP reduced obesity-induced inflammation and systemic lipopolysaccharides (LPS) level. The decrease of LPS level in circulation was followed by the downregulation of LPS specific receptor, toll-like receptor 4 (TLR4), and its co-receptor cluster of differentiation 14 (CD14) and adaptor protein differentiation factor 88 (MyD88) in hepatic and adipose tissues. That further inhibited the activation of nuclear factor κB (NF-κB). The serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-1-beta (IL-1ß) and interleukin-6 (IL-6) were significantly decreased by TP in HFD-fed mice. TP also maintained the intestinal barrier integrity by increasing intestinal tight junction proteins and reversed gut dysbiosis in obese mice. These results suggested that TP attenuated obesity-induced inflammation by reducing systemic LPS level and inhibiting LPS-activated TLR4/NF-κB pathway.


Assuntos
NF-kappa B , Receptor 4 Toll-Like , Animais , Inflamação/tratamento farmacológico , Inflamação/prevenção & controle , Interleucina-6 , Lipopolissacarídeos , Camundongos , Camundongos Obesos , NF-kappa B/metabolismo , Obesidade/tratamento farmacológico , Polifenóis/farmacologia , Chá , Receptor 4 Toll-Like/metabolismo
10.
Food Chem ; 383: 132463, 2022 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-35183969

RESUMO

Two major green leaf volatiles (GLVs) in tea that contribute greatly to tea aroma, particularly the green odor, are (E)-2-hexenal and (Z)-3-hexenal. Until now, their formation and related mechanisms during tea manufacture have remained unclear. Our data showed that the contents of (E)-2-hexenal and (Z)-3-hexenal increased more than 1000-fold after live tea leaves were torn. Subsequently, a new (Z)-3:(E)-2-hexenal isomerase (CsHI) was identified in Camellia sinensis. CsHI irreversibly catalyzed the conversion of (Z)-3-hexenal to (E)-2-hexenal. Abiotic stresses including low temperature, dehydration, and mechanical wounding, did not influence the (E)-2-hexenal content in intact tea leaves during withering, but regulated the proportions of (Z)-3-hexenal and (E)-2-hexenal in torn leaves by modulating CsHI at the transcript level. For the first time, this work reveals the formation of (E)-2-hexenal during tea processing and suggests that CsHI may play a pivotal role in tea flavor development as well as in plant defense against abiotic stresses.


Assuntos
Camellia sinensis , Aldeídos , Isomerases , Folhas de Planta , Chá
11.
Nutrients ; 13(12)2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34959930

RESUMO

Theaflavin-3,3'-digallate (TF3) is the most important theaflavin monomer in black tea. TF3 was proved to reduce blood glucose level in mice and rats. However, the elaborate anti-diabetic mechanism was not well elucidated. In this work, human hepatoma G2 (HepG2) cells and zebrafish (Danio rerio) were used simultaneously to reveal anti-diabetic effect of TF3. The results showed that TF3 could effectively rise glucose absorption capacity in insulin-resistant HepG2 cells and regulate glucose level in diabetic zebrafish. The hypoglycemic effect was mediated through down-regulating phosphoenolpyruvate carboxykinase and up-regulating glucokinase. More importantly, TF3 could significantly improve ß cells regeneration in diabetic zebrafish at low concentrations (5 µg/mL and 10 µg/mL), which meant TF3 had a strong anti-diabetic effect. Obviously, this work provided the potential benefit of TF3 on hypoglycemic effect, regulating glucose metabolism enzymes, and protecting ß cells. TF3 might be a promising agent for combating diabetes.


Assuntos
Biflavonoides/farmacologia , Catequina/análogos & derivados , Avaliação Pré-Clínica de Medicamentos/métodos , Hipoglicemiantes , Animais , Biflavonoides/isolamento & purificação , Catequina/isolamento & purificação , Catequina/farmacologia , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Glucoquinase/metabolismo , Glucose/metabolismo , Células Hep G2 , Humanos , Fosfoenolpiruvato Carboxiquinase (ATP)/metabolismo , Chá/química , Regulação para Cima/efeitos dos fármacos , Peixe-Zebra
12.
Molecules ; 26(6)2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33802884

RESUMO

Novel therapeutic strategies for ovarian cancer treatment are in critical need due to the chemoresistance and adverse side effects of platinum-based chemotherapy. Theasaponin E1 (TSE1) is an oleanane-type saponin from Camellia sinensis seeds. Its apoptosis-inducing, cell cycle arresting and antiangiogenesis activities against platinum-resistant ovarian cancer cells were elucidated in vitro and using the chicken chorioallantoic membrane (CAM) assay. The results showed that TSE1 had more potent cell growth inhibitory effects on ovarian cancer OVCAR-3 and A2780/CP70 cells than cisplatin and was lower in cytotoxicity to normal ovarian IOSE-364 cells. TSE1 significantly induced OVCAR-3 cell apoptosis via the intrinsic and extrinsic apoptotic pathways, slightly arresting cell cycle at the G2/M phase, and obviously inhibited OVCAR-3 cell migration and angiogenesis with reducing the protein secretion and expression of vascular endothelial growth factor (VEGF). Western bolt assay showed that Serine/threonine Kinase (Akt) signaling related proteins including Ataxia telangiectasia mutated kinase (ATM), Phosphatase and tensin homolog (PTEN), Akt, Mammalian target of rapamycin (mTOR), Ribosome S6 protein kinase (p70S6K) and e IF4E-binding protein 1(4E-BP1) were regulated, and Hypoxia inducible factor-1α (HIF-1α) protein expression was decreased by TSE1 in OVCAR-3 cells. Moreover, TSE1 treatment potently downregulated protein expression of the Notch ligands including Delta-like protein 4 (Dll4) and Jagged1, and reduced the protein level of the intracellular domain (NICD) of Notch1. Combination treatment of TSE1 with the Notch1 signaling inhibitor tert-butyl (2S)-2-[[(2S)-2-[[2-(3,5-difluorophenyl)acetyl]amino]propanoyl]amino]-2-phenylacetate (DAPT), or the Akt signaling inhibitor wortmannin, showed a stronger inhibition toward HIF-1α activation compared with single compound treatment. Taken together, TSE1 might be a potential candidate compound for improving platinum-resistant ovarian cancer treatment via Dll4/Jagged1-Notch1-Akt-HIF-1α axis.


Assuntos
Inibidores da Angiogênese/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neovascularização Patológica/tratamento farmacológico , Ácido Oleanólico/análogos & derivados , Neoplasias Ovarianas/tratamento farmacológico , Saponinas/farmacologia , Animais , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Camellia sinensis/química , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Membrana Corioalantoide/efeitos dos fármacos , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos , Feminino , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Ácido Oleanólico/farmacologia , PTEN Fosfo-Hidrolase/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sementes/química , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Serina-Treonina Quinases TOR/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
13.
RSC Adv ; 11(20): 12074-12085, 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-35423741

RESUMO

Wuyi rock tea is a typical and famous oolong tea in China and roasting is an important manufacturing procedure for its flavor formation. This work aimed to explore the effect of roasting on non-volatiles and volatiles of 12 Wuyi rock tea samples at three roasting levels (low, moderate and sufficient), made from four tea cultivars (Shuixian, Qizhong, Dahongpao, Rougui). Results show that different roasting had not caused significant difference on contents of soluble solids, total polyphenols, flavonoids, soluble sugar, thearubigins and theabrownins, while it slightly regulated caffeine, proteins and theaflavins, and remarkably reduced catechins and free amino acids. The ratio of polyphenol content/amino acid content, a negative-correlated indicator of fresh and brisk taste, significantly increased with the increase of roasting degree. High-level roasting not only decreased the fresh and brisk taste of the tea infusion, but also reduced the amount of bioactive ingredients including catechins and theanine. A total of 315 volatiles were detected and analyzed with OPLS-DA and HCA methods, in which 99 volatiles were found with variable importance in the projection (VIP) values greater than 1.00. Tea samples at different roasting degrees were successfully separated by this model of roasting-level discrimination. 'Naphthalene, 1,2,3,4-tetrahydro-1,6,8-trimethyl-', '1,1,5-trimethyl-1,2-dihydronaphthalene', 'p-Xylene', 'alpha.-methyl-.alpha.-[4-methyl-3-pentenyl]oxiranemethanol', 'hydrazinecarboxylic acid, phenylmethyl ester', and '3-buten-2-one, 4-(2,6,6-trimethyl-2-cyclohexen-1-yl)-' might be key characteristic markers for the roasting process of Wuyi rock tea.

14.
Foods ; 11(1)2021 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-35010207

RESUMO

Alzheimer's disease (AD) is a common neurodegenerative disease; tea components have important neuroprotective effects. This article explores the effects and mechanisms of Qingxiang Tiguanyin (Tgy-Q), Nongxiang Tieguanyin (Tgy-N), and Chenxiang Tieguanyin (Tgy-C) extracts on APP/PS1 AD model mice. Morris water maze and new object recognition experiments show that Tieguanyin extracts can effectively enhance the cognitive ability of APP/PS1 mice. H&E staining, Nissl staining, and immunohistochemical staining show that Tieguanyin extracts make nerve cell boundaries and nucleoli become clearer, relieve nucleus pyknosis, and effectively reduce Aß1-40 and Aß1-42 in the hippocampus and cortex. They also restore the morphology of microglia and astrocytes. In addition, Tieguanyin extracts can balance the oxidative stress level in the brain of APP/PS1 mice by improving the antioxidant capacity. Western blot results show that Tieguanyin extracts can reduce the expression of NF-κB p65, TNF-α, IL-1ß, IL-6, COX-2, and iNOS in mouse brain, which demonstrates that Tieguanyin extracts improves cognitive ability by alleviating inflammation. This article demonstrates for the first time that Tieguanyin extracts can inhibit the excessive activation of the NF-κB p65 signaling pathway and improve the antioxidant capacity in the cerebral cortex and hippocampus, to improve the cognitive ability of APP/PS1 mice. Our results shed light into the beneficial of Tieguanyin tea extracts on preventing and alleviating AD diseases.

15.
Molecules ; 25(22)2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33187244

RESUMO

Tea flower saponins (TFS) possess effective anticancer properties. The diversity and complexity of TFS increases the difficulty of their extraction and purification from tea flowers. Here, multiple methods including solvent extraction, microporous resin separation and preparative HPLC separation were used to obtain TFS with a yield of 0.34%. Furthermore, we revealed that TFS induced autophagy-as evidenced by an increase in MDC-positive cell populations and mCherry-LC3B-labeled autolysosomes and an upregulation of LC3II protein levels. 3-MA reversed the decrease in cell viability induced by TFS, showing that TFS induced autophagic cell death. TFS-induced autophagy was not dependent on the Akt/mTOR/p70S6K signaling pathway. TFS-induced autophagy in OVCAR-3 cells was accompanied by ERK pathway activation and reactive oxygen species (ROS) generation. This paper is the first report of TFS-mediated autophagy of ovarian cancer cells. These results provide new insights for future studies of the anti-cancer effects of TFS.


Assuntos
Apoptose/efeitos dos fármacos , Autofagia , Camellia sinensis/química , Neoplasias Ovarianas/patologia , Saponinas/farmacologia , Adenina/análogos & derivados , Adenina/farmacologia , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular , Cromatografia Líquida de Alta Pressão , Feminino , Flores/química , Humanos , Lisossomos/química , Proteínas Associadas aos Microtúbulos/química , Extratos Vegetais/farmacologia , Espécies Reativas de Oxigênio/química , Transdução de Sinais
16.
Molecules ; 25(15)2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32752095

RESUMO

Ovarian cancer is considered to be one of the most serious malignant tumors in women. Natural compounds have been considered as important sources in the search for new anti-cancer agents. Saponins are characteristic components of tea (Camellia sinensis) flower and have various biological activities, including anti-tumor effects. In this study, a high purity standardized saponin extract, namely Baiye No.1 tea flower saponin (BTFS), which contained Floratheasaponin A and Floratheasaponin D, were isolated from tea (Camellia sinensis cv. Baiye 1) flowers by macroporous resin and preparative liquid chromatography. Then, the component and purity were detected by UPLC-Q-TOF/MS/MS. This high purity BTFS inhibited the proliferation of A2780/CP70 cancer cells dose-dependently, which is evidenced by the inhibition of cell viability, reduction of colony formation ability, and suppression of PCNA protein expression. Further research found BTFS induced S phase cell cycle arrest by up-regulating p21 proteins expression and down-regulating Cyclin A2, CDK2, and Cdc25A protein expression. Furthermore, BTFS caused DNA damage and activated the ATM-Chk2 signaling pathway to block cell cycle progression. Moreover, BTFS trigged both extrinsic and intrinsic apoptosis-BTFS up-regulated the expression of death receptor pathway-related proteins DR5, Fas, and FADD and increased the ratio of pro-apoptotic/anti-apoptotic proteins of the Bcl-2 family. BTFS-induced apoptosis seems to be related to the AKT-MDM2-p53 signaling pathway. In summary, our results demonstrate that BTFS has the potential to be used as a nutraceutical for the prevention and treatment of ovarian cancer.


Assuntos
Apoptose/efeitos dos fármacos , Camellia sinensis/química , Extratos Vegetais/química , Pontos de Checagem da Fase S do Ciclo Celular/efeitos dos fármacos , Saponinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Camellia sinensis/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ciclina A2/genética , Ciclina A2/metabolismo , Inibidor de Quinase Dependente de Ciclina p27/genética , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Feminino , Flores/química , Flores/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/isolamento & purificação , Ácido Oleanólico/farmacologia , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Antígeno Nuclear de Célula em Proliferação/genética , Antígeno Nuclear de Célula em Proliferação/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Saponinas/química , Saponinas/isolamento & purificação , Proteína Supressora de Tumor p53/metabolismo
17.
Int J Mol Sci ; 21(12)2020 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-32560563

RESUMO

Ovarian cancer is currently ranked at fifth in cancer deaths among women. Patients who have undergone cisplatin-based chemotherapy can experience adverse effects or become resistant to treatment, which is a major impediment for ovarian cancer treatment. Natural products from plants have drawn great attention in the fight against cancer recently. In this trial, purified tea (Camellia sinensis (L.) Kuntze) flower saponins (PTFSs), whose main components are Chakasaponin I and Chakasaponin IV, inhibited the growth and proliferation of ovarian cancer cell lines A2780/CP70 and OVCAR-3. Flow cytometry, caspase activity and Western blotting analysis suggested that such inhibitory effects of PTFSs on ovarian cancer cells were attributed to the induction of cell apoptosis through the intrinsic pathway rather than extrinsic pathway. The p53 protein was then confirmed to play an important role in PTFS-induced intrinsic apoptosis, and the levels of its downstream proteins such as caspase families, Bcl-2 families, Apaf-1 and PARP were regulated by PTFS treatment. In addition, the upregulation of p53 expression by PTFSs were at least partly induced by DNA damage through the ATM/Chk2 pathway. The results help us to understand the mechanisms underlying the effects of PTFSs on preventing and treating platinum-resistant ovarian cancer.


Assuntos
Apoptose/efeitos dos fármacos , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos , Flores/química , Saponinas/farmacologia , Chá/química , Proteína Supressora de Tumor p53/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA , Feminino , Humanos , Espectrometria de Massas , Estrutura Molecular , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Saponinas/química , Transdução de Sinais/efeitos dos fármacos
18.
Molecules ; 24(20)2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31652500

RESUMO

Saponins in the Camellia sinensis seeds have a broad spectrum of biological properties and application potentials. However, up to now, no chromatographic methods have been developed to provide full fingerprinting and quality assurance for these saponins. This research aimed to develop a novel method to tentatively identify and quantify saponins in C. sinensis seeds by ultra-high-performance liquid chromatography coupled with photo-diode array detector and quadrupole time-of-flight mass spectrometry (UPLC-PDA-QTOF-MS/MS), and compare it with the classic vanillin-sulfuric acid assay. Fifty-one triterpene saponins, including six potentially new compounds, were simultaneously detected by UPLC-PDA-MS/MS, and their chemical structures were speculated according to the retention behavior and fragmentation pattern. The total saponin content in the crude extract and the purified saponin fraction of C. sinensis seeds were quantified to be 19.57 ± 0.05% (wt %) and 41.68 ± 0.09% (wt %) respectively by UPLC-PDA at 210 nm, while the corresponding values were determined to be 43.11 ± 3.17% (wt %) and 56.60 ± 5.79% (wt %) respectively by the vanillin-sulfuric acid assay. The developed UPLC-PDA -MS/MS method could determine specified saponins, and is more reliable for quantifying the C. sinensis seed saponins than the classic spectrophotometric method. It is of great significance for the future investigations and applications of these saponins.


Assuntos
Camellia sinensis/química , Cromatografia Líquida de Alta Pressão/métodos , Saponinas/análise , Espectrometria de Massas por Ionização por Electrospray/métodos , Triterpenos/análise , Estrutura Molecular , Extratos Vegetais/química , Saponinas/química , Sementes/química , Espectrometria de Massas em Tandem/métodos , Triterpenos/química
19.
Molecules ; 24(4)2019 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-30769778

RESUMO

Theaflavin-3,3'-digallate (TF3) is a unique polyphenol in black tea. Epidemiological studies have proved that black tea consumption decreases the incidence rate of ovarian cancer. Our former research demonstrated that TF3 inhibited human ovarian cancer cells. Nevertheless, the roles of checkpoint kinase 2 (Chk2) and p27 kip1 (p27) in TF3-mediated inhibition of human ovarian cancer cells have not yet been investigated. In the current study, TF3 enhanced the phosphorylation of Chk2 to modulate the ratio of pro/anti-apoptotic Bcl-2 family proteins to initiate intrinsic apoptosis in a p53-independent manner and increased the expression of death receptors to activate extrinsic apoptosis in OVCAR-3 human ovarian carcinoma cells. In addition, TF3 up-regulated the expression of p27 to induce G0/G1 cell cycle arrest in OVCAR-3 cells. Our study indicated that Chk2 and p27 were vital anticancer targets of TF3 and provided more evidence that TF3 might be a potent agent to be applied as adjuvant treatment for ovarian cancer.


Assuntos
Biflavonoides/farmacologia , Carcinoma/tratamento farmacológico , Catequina/análogos & derivados , Quinase do Ponto de Checagem 2/genética , Inibidor de Quinase Dependente de Ciclina p27/genética , Neoplasias Ovarianas/tratamento farmacológico , Antioxidantes/química , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Biflavonoides/química , Camellia sinensis/química , Carcinoma/genética , Carcinoma/patologia , Catequina/química , Catequina/farmacologia , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Transdução de Sinais/efeitos dos fármacos , Chá/química , Proteína Supressora de Tumor p53/genética
20.
J Agric Food Chem ; 67(19): 5361-5373, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30612424

RESUMO

During the past 20 years, many studies have focused on polyphenol compounds for their potential beneficial health effects. Flavonoids represent a large class of phenolic compounds found in fruits, vegetables, nuts, grains, cocoa, tea, and other beverages. Flavonoids have shown antioxidant and anti-inflammatory activities. Given the putative relationship between inflammation and insulin resistance, the consumption of flavonoids or flavonoid-rich foods has been suggested to reduce the risk of diabetes by targeting inflammatory signals. This is the first comprehensive review summarizing the current research progress on the inhibition of inflammation and alleviation of insulin resistance by flavonoids as well as the mechanistic link between these disorders. Laboratory and human studies on the activities of major flavonoids (flavones, isoflavones, flavonols, etc.) are discussed.


Assuntos
Flavonoides/administração & dosagem , Inflamação/tratamento farmacológico , Resistência à Insulina , Extratos Vegetais/administração & dosagem , Animais , Flavonoides/química , Humanos , Inflamação/genética , Inflamação/imunologia , Estrutura Molecular , Extratos Vegetais/química , Transdução de Sinais/efeitos dos fármacos
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