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

RESUMO

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


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


Assuntos
Humanos , Neoplasias Colorretais/tratamento farmacológico , Catequina/análogos & derivados , Catequina/farmacologia , Quercetina/farmacologia , Ciclo Celular , Anexina A5 , Linhagem Celular Tumoral , Proliferação de Células
2.
Front Immunol ; 13: 943321, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35935939

RESUMO

Quercetin, a naturally non-toxic flavonoid within the safe dose range with antioxidant, anti-apoptotic and anti-inflammatory properties, plays an important role in the treatment of aging-related diseases. Sirtuin 1 (SIRT1), a member of NAD+-dependent deacetylase enzyme family, is extensively explored as a potential therapeutic target for attenuating aging-induced disorders. SIRT1 possess beneficial effects against aging-related diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Depression, Osteoporosis, Myocardial ischemia (M/I) and reperfusion (MI/R), Atherosclerosis (AS), and Diabetes. Previous studies have reported that aging increases tissue susceptibility, whereas, SIRT1 regulates cellular senescence and multiple aging-related cellular processes, including SIRT1/Keap1/Nrf2/HO-1 and SIRTI/PI3K/Akt/GSK-3ß mediated oxidative stress, SIRT1/NF-κB and SIRT1/NLRP3 regulated inflammatory response, SIRT1/PGC1α/eIF2α/ATF4/CHOP and SIRT1/PKD1/CREB controlled phosphorylation, SIRT1-PINK1-Parkin mediated mitochondrial damage, SIRT1/FoxO mediated autophagy, and SIRT1/FoxG1/CREB/BDNF/Trkß-catenin mediated neuroprotective effects. In this review, we summarized the role of SIRT1 in the improvement of the attenuation effect of quercetin on aging-related diseases and the relationship between relevant signaling pathways regulated by SIRT1. Moreover, the functional regulation of quercetin in aging-related markers such as oxidative stress, inflammatory response, mitochondrial function, autophagy and apoptosis through SIRT1 was discussed. Finally, the prospects of an extracellular vesicles (EVs) as quercetin loading and delivery, and SIRT1-mediated EVs as signal carriers for treating aging-related diseases, as well as discussed the ferroptosis alleviation effects of quercetin to protect against aging-related disease via activating SIRT1. Generally, SIRT1 may serve as a promising therapeutic target in the treatment of aging-related diseases via inhibiting oxidative stress, reducing inflammatory responses, and restoring mitochondrial dysfunction.


Assuntos
Quercetina , Sirtuína 1 , Senescência Celular , Glicogênio Sintase Quinase 3 beta/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Quercetina/farmacologia , Quercetina/uso terapêutico , Sirtuína 1/metabolismo
3.
Oxid Med Cell Longev ; 2022: 2710607, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35936216

RESUMO

The presented study was performed to verify whether rutin and/or quercetin can inhibit liver injury induced by doxorubicin (DXR) in male Wistar rats. In this study, male Wistar rats were treated via the oral route with rutin and quercetin (50 mg/kg) either alone or in combination every other day for five weeks concomitant with receiving intraperitoneal DXR (2 mg/kg) two times a week for five successive weeks. Quercetin, rutin, and their combination significantly improved the deteriorated serum AST, ALT, and ALP activities and total bilirubin level, as well as albumin, AFP, and CA 19.9 levels in DXR-injected rats. Treatments of the DXR-injected group with quercetin and rutin prevented the elevation in liver lipid peroxidation and the reduction in superoxide dismutase, glutathione-S-transferase and glutathione peroxidase activities, and glutathione content. Treatments with quercetin and rutin significantly repressed the elevated expression of liver p53 and TNF-α and enhanced Nrf2 expression. Furthermore, the treatments significantly reduced DXR-induced liver histological changes. In conclusion, rutin and quercetin either alone or in combination may have potential preventive effects against DXR-induced hepatotoxicity through inhibiting oxidative stress, inflammation, and apoptosis as well as modulating the Nrf2 expression.


Assuntos
Hepatite , Quercetina , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Apoptose , Doxorrubicina/toxicidade , Fator de Transcrição de Proteínas de Ligação GA/metabolismo , Glutationa/metabolismo , Hepatite/metabolismo , Inflamação/patologia , Fígado/metabolismo , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Quercetina/farmacologia , Quercetina/uso terapêutico , Ratos , Ratos Wistar , Rutina/farmacologia , Rutina/uso terapêutico
4.
J Exp Clin Cancer Res ; 41(1): 235, 2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-35918767

RESUMO

BACKGROUND: Radiation therapy (RT) with androgen deprivation therapy (ADT) is an effective therapy to suppress the locally advanced prostate cancer (PCa). However, we unexpectedly found that RT could also induce the androgen receptor splice variant 7 (ARv7) expression to decrease the radiosensitivity. METHODS: The study was designed to target ARv7 expression with Quercetin or ARv7-shRNA that leads to enhancing and increasing the radiation sensitivity to better suppress the PCa that involved the modulation of the circNHS/miR-512-5p/XRCC5 signaling. RESULTS: Mechanism studies revealed that RT-induced ARv7 may function via altering the circNHS/miR-512-5p/XRCC5 signaling to decrease the radiosensitivity. Results from preclinical studies using multiple in vitro cell lines and in vivo mouse models concluded that combining RT with the small molecule of Quercetin to target full-length AR and ARv7 could lead to better efficacy to suppress PCa progression. CONCLUSION: Together, these results suggest that ARv7 may play key roles to alter the PCa radiosensitivity, and targeting this newly identified ARv7 mediated circNHS/miR-512-5p/XRCC5 signaling with Quercetin may help physicians to develop a novel RT to better suppress the progression of PCa.


Assuntos
MicroRNAs , Neoplasias da Próstata , Antagonistas de Androgênios , Animais , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Humanos , Autoantígeno Ku/genética , Autoantígeno Ku/metabolismo , Masculino , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Neoplasias da Próstata/radioterapia , Quercetina/farmacologia , Tolerância a Radiação , Receptores Androgênicos/metabolismo
5.
Biomed Res Int ; 2022: 9709365, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35915797

RESUMO

Background: Parkia clappertoniana Keay (Family: Fabaceae) (P. clappertoniana) fruit husk is commonly used in northern Ghana for wound treatment. However, this folk claim remains to be confirmed scientifically. Objective: This study investigated wound healing and antimicrobial effects of P. clappertoniana fruit husk extract (PCFHE) by using excision wound model in rats. Materials and Methods: After preparation and phytochemical analysis of PCFHE, it was reconstituted in purified water and emulsifying ointment yielding a wound healing formula (0.3, 1, and 3%). Excision wounds were established in healthy male Sprague-Dawley rats (aged 8-10 weeks; weighing 150-200 g). Rats were randomly assigned into six groups (model, 1% silver sulfadiazine [SSD], vehicle, and PCFHE [0.3, 1, and 3%, respectively]) and topically treated daily until complete wound healing. The endpoints (period of epithelialization, wound contraction, collagen content, erythema index, oedema index, inflammatory cell infiltration, and antimicrobial activity) were assessed for all groups. Minimum fungicidal concentration (MFC), minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and time-kill were assessed. Results: Quercetin and catechin were detected in PCFHE. Compared to model and vehicle groups, PCFHE-treatment groups improved wound healing and antimicrobial (MBC, MFC, and MIC) endpoints. PCFHE demonstrated bacteriostatic and fungicidal effects against identified wound contaminants (Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, and Candida albicans). Conclusion: P. clappertoniana fruit husk possesses wound healing and antimicrobial effects in excisional wounds in rats that confirms its folk use, and the reported pharmacological properties of PCFHE are attributable to its quercetin and catechin phyto-constituents.


Assuntos
Anti-Infecciosos , Fabaceae , Extratos Vegetais , Cicatrização , Animais , Anti-Infecciosos/farmacologia , Catequina/farmacologia , Fabaceae/química , Frutas , Masculino , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Quercetina/farmacologia , Ratos , Ratos Sprague-Dawley , Cicatrização/efeitos dos fármacos
6.
Cell Mol Biol (Noisy-le-grand) ; 67(5): 151-156, 2022 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-35818258

RESUMO

Antibiotic resistance in pathogenic bacteria to various types of antibiotics has resulted in the necessity of new effective strategies to get around this problem. In recent investigations, metal or metal oxide nanoparticles specifically silver nanoparticles (AgNPs) have been employed successfully to hinder antibiotic-resistant Gram-negative and Gram-positive bacteria. However, AgNPs at high concentrations have cytotoxicity for eukaryotic cells which, application of other biocompatible materials particularly plant secondary metabolites of curcumin and quercetin to reduce cytotoxicity is a critical affair. These compounds may be used directly or indirectly to produce AgNPs. In this regard, modified NPs by curcumin and quercetin have shown an increased therapeutic effect and biocompatibility and biodegredibility properties. Therefore, here, recent advances and challenges about antibacterial and biocompatibility properties of nanoformulation of AgNPs with curcumin and quercetin are presented.


Assuntos
Curcumina , Nanopartículas Metálicas , Antibacterianos/farmacologia , Bactérias , Curcumina/farmacologia , Testes de Sensibilidade Microbiana , Quercetina/farmacologia , Prata/farmacologia
7.
Ann Parasitol ; 68(2): 263-273, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35809560

RESUMO

Trichomonosis, caused by infection with a motile protozoan parasite called Trichomonas vaginalis, is the most common non-viral sexually transmitted disease worldwide. Since the 1960s, metronidazole has been used as a drug of choice. Considering increased resistance to anti-trichomonial drugs, alternative treatments are urgently needed. In this study, the standard strain of T. vaginalis was cultured in TYM medium. Curcumin and quercetin loaded with hyaluronic acid niosomes were prepared by the thin film hydration method. The mean vesicle size, polydispersity index, and zeta potential of each prepared formulation were characterized, and its anti-Trichomonas activity was assessed by concentrations of 0.01, 0.1, 1, 10 and 100 mg/ml. The cytotoxicity effects of the mentioned drugs were determined using a MTT assay on L929 fibroblast cell viability. The particle sizes of curcumin, quercetin, and curcumin-quercetin entrapped modified nano-niosomes were characterised as 243 ± 5.28, 223 ± 7.21 and 266 ± 4.81 nm. The results showed that quercetin and curcumin at a concentration of 100 mg/ml after 24 h had anti-T. vaginalis activity. However, curcumin at a concentration of 100 at time 3h with 97% growth inhibition had better performance than positive control (metronidazole). According to the results of the MTT assay, all drugs, even at the highest concentration (400 mg/ml), had no toxic effect on the fibroblast cell line. According to potent in vitro activity of curcumin and quercetin nanoniosomes against T. vaginalis in comparison with metronidazole, it can be concluded these compounds could be promising therapeutic candidates for trichomonosis in future.


Assuntos
Curcumina , Tricomoníase , Trichomonas vaginalis , Curcumina/farmacologia , Curcumina/uso terapêutico , Humanos , Lipossomos/farmacologia , Lipossomos/uso terapêutico , Metronidazol/farmacologia , Metronidazol/uso terapêutico , Quercetina/farmacologia , Quercetina/uso terapêutico , Trichomonas vaginalis/fisiologia
8.
Oxid Med Cell Longev ; 2022: 4591134, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35879991

RESUMO

Alcoholic liver disease (ALD) is a multifaceted process that involves excessive lipid, reactive oxygen species (ROS) production, unbalanced mitochondrial homeostasis, and ultimate cell death. Quercetin is a dietary phytochemical presented in various fruits and vegetables, which has anti-inflammatory and antioxidant effects. According to recent advances in pharmanutritional management, the effects of quercetin on various mitochondrial processes have attracted attention. In the study, we explored whether quercetin could attenuate ethanol-induced hepatocyte pyroptosis by maintaining mitochondrial homeostasis and studied its hepatoprotective effect and the underlying mechanism. We chose L02 cells to establish an in vitro model with ethanol-induced hepatocyte pyroptosis. Then, the cells at approximately 80% confluence were treated with quercetin (80, 40, and 20 µM). The cell viability (CCK-8) was used to investigate the effect of quercetin on ethanol-induced L02 cell proliferation. Relative assay kits were used to measure oxidative stress index (OSI = TOS/TAS), lipid peroxidation (LPO) release, and mitochondrial membrane potential (δΨm). The morphology of mitochondria was characterized by transmission electron microscopy- (TEM-) based analysis. Mitochondrial dynamics (Mito Tracker Green), mitROS (MitoSOX Red Mitochondrial Superoxide) production, and nuclear DNA (nDNA) damage (γH2AX) markers were detected by immunofluorescence. The mRNA levels of mitochondrial function (including mitochondrial DNA (mtDNA) transcription genes TWNK, MTCO1, and MFND) and pyroptosis-related genes were detected by RT-qPCR, and the protein levels of NLRP3, ASC, caspase1, cleaved-caspase1, IL-18, IL-1ß, and GSDMD-N were detected by western blot. The results showed that quercetin treatment downregulated redox status, lipid droplets, and LPO release, restored damaged mitochondrial membrane potential, and repaired mtDNA damage, PGC-1α nuclear transfer, and mitochondrial dynamics. The gene and protein expressions of NLRP3, ASC, cleaved-caspase1, IL-18, IL-1ß, and GSDMD-N were decreased, which effectively inhibited cell pyroptosis. Therefore, the results indicated that quercetin protected ethanol-induced hepatocyte pyroptosis via scavenging mitROS and promoting PGC-1α-mediated mitochondrial homeostasis in L02 cells.


Assuntos
Piroptose , Quercetina , DNA Mitocondrial/metabolismo , Etanol/farmacologia , Hepatócitos/metabolismo , Homeostase , Interleucina-18/metabolismo , Mitocôndrias/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Quercetina/farmacologia , Espécies Reativas de Oxigênio/metabolismo
9.
Theriogenology ; 189: 262-269, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35809360

RESUMO

The present study was designed to investigate the effects of Quercetin on the developmental competence of bovine oocytes and cumulus-granulosa cells (CGs). Two groups of immature cumulus-oocyte complexes (COCs) were subjected to IVM with or without Quercetin. The viability, nuclear status, early and late apoptosis of oocytes and CGs were evaluated using gene expression analysis and staining methods. Embryonic development was assessed morphologically by recording Post-IVF survival, cleavage, and blastocyst rates. The proportion of oocytes reaching the MII stage was greater and the number of early-apoptotic oocytes was lower in the group matured with Quercetin compared to the Control (p < 0.05). Relative upregulation of OCT-4, IGF2R and Bcl-2, and downregulation of CHOP was seen in treated oocytes. Also, downregulation of Bax and upregulation of Glut-4 was detected in treated CGs. The treated oocytes experienced higher post-IVF survival and cleavage rates compared to the untreated group (p < 0.05); more cleaved embryos reached ≥16-cell stage and blastocyst at days 4th and 7th respectively. In addition, total blastocyst rate was significantly improved. It is concluded that supplementing maturation media with Quercetin can enhance the quality of bovine oocytes and endow them with protective potential against early apoptotic damage possibly through CHOP regulation of BCL2 gene family, triggering expression of a gene in CGs to maintain the intactness of oocyte against apoptotic signals and providing oocytes with more energy substrates. It also boosts the subsequent development of oocyte to blastocyst and improves the efficacy of bovine embryo production in vitro.


Assuntos
Fertilização In Vitro , Quercetina , Animais , Blastocisto/fisiologia , Bovinos , Células do Cúmulo/fisiologia , Desenvolvimento Embrionário , Feminino , Fertilização In Vitro/veterinária , Técnicas de Maturação in Vitro de Oócitos/métodos , Técnicas de Maturação in Vitro de Oócitos/veterinária , Oócitos/fisiologia , Gravidez , Quercetina/farmacologia
10.
Soft Matter ; 18(30): 5645-5653, 2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-35861218

RESUMO

In this work, we report the development of nitrogen-doped carbon dots (NDCDs) as a drug carrier using quercetin (QC) as a model drug for anti-cancer drug delivery application. NDCDs were prepared by a simple hydrothermal method using Luffa acutangula as a carbon source. The characterization of QC-NDCDs was done by UV-vis spectroscopy, fluorescence spectroscopy, zeta potential measurements, high-resolution transmission electron microscopy (HR-TEM), Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), and Raman spectroscopy. The as-synthesized NDCDs have a small particle size with hydroxyl and nitrogen-containing groups (pyridinic and amide groups), enhancing the fluorescence properties, and were obtained in a good quantum yield (14%). Furthermore, the in vitro alamarBlue® assay revealed that the NDCDs-QC conjugate was nontoxic to colon cancer cells. This NDCDs-QC conjugate is able to kill cancer cells in the NDCDs-QC form compared to free QC as confirmed by in vitro MTT assay results. Thus, the developed NDCDs conjugate can be used as a promising drug delivery and bio-imaging vehicle in cancer therapy.


Assuntos
Neoplasias , Pontos Quânticos , Carbono/química , Corantes Fluorescentes/química , Humanos , Nitrogênio/química , Pontos Quânticos/química , Quercetina/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier
11.
Viruses ; 14(7)2022 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-35891437

RESUMO

Despite the fast development of vaccines, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still circulating and generating variants of concern (VoC) that escape the humoral immune response. In this context, the search for anti-SARS-CoV-2 compounds is still essential. A class of natural polyphenols known as flavonoids, frequently available in fruits and vegetables, is widely explored in the treatment of different diseases and used as a scaffold for the design of novel drugs. Therefore, herein we evaluate seven flavonoids divided into three subclasses, isoflavone (genistein), flavone (apigenin and luteolin) and flavonol (fisetin, kaempferol, myricetin, and quercetin), for COVID-19 treatment using cell-based assays and in silico calculations validated with experimental enzymatic data. The flavonols were better SARS-CoV-2 inhibitors than isoflavone and flavones. The increasing number of hydroxyl groups in ring B of the flavonols kaempferol, quercetin, and myricetin decreased the 50% effective concentration (EC50) value due to their impact on the orientation of the compounds inside the target. Myricetin and fisetin appear to be preferred candidates; they are both anti-inflammatory (decreasing TNF-α levels) and inhibit SARS-CoV-2 mainly by targeting the processability of the main protease (Mpro) in a non-competitive manner, with a potency comparable to the repurposed drug atazanavir. However, fisetin and myricetin might also be considered hits that are amenable to synthetic modification to improve their anti-SARS-CoV-2 profile by inhibiting not only Mpro, but also the 3'-5' exonuclease (ExoN).


Assuntos
COVID-19 , Flavonas , Isoflavonas , COVID-19/tratamento farmacológico , Flavonas/farmacologia , Flavonoides/farmacologia , Flavonóis/farmacologia , Humanos , Isoflavonas/farmacologia , Quempferóis , Simulação de Acoplamento Molecular , Inibidores de Proteases , Quercetina/farmacologia , SARS-CoV-2
12.
Cell Mol Biol Lett ; 27(1): 60, 2022 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-35883021

RESUMO

The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway is involved in many immunological processes, including cell growth, proliferation, differentiation, apoptosis, and inflammatory responses. Some of these processes can contribute to cancer progression and neurodegeneration. Owing to the complexity of this pathway and its potential crosstalk with alternative pathways, monotherapy as targeted therapy has usually limited long-term efficacy. Currently, the majority of JAK-STAT-targeting drugs are still at preclinical stages. Meanwhile, a variety of plant polyphenols, especially quercetin, exert their inhibitory effects on the JAK-STAT pathway through known and unknown mechanisms. Quercetin has shown prominent inhibitory effects on the JAK-STAT pathway in terms of anti-inflammatory and antitumor activity, as well as control of neurodegenerative diseases. This review discusses the pharmacological effects of quercetin on the JAK-STAT signaling pathway in solid tumors and neurodegenerative diseases.


Assuntos
Inibidores de Janus Quinases , Neoplasias , Doenças Neurodegenerativas , Humanos , Inibidores de Janus Quinases/farmacologia , Janus Quinases/antagonistas & inibidores , Janus Quinases/metabolismo , Janus Quinases/farmacologia , Neoplasias/tratamento farmacológico , Doenças Neurodegenerativas/tratamento farmacológico , Quercetina/farmacologia , Quercetina/uso terapêutico , Fatores de Transcrição STAT/antagonistas & inibidores , Fatores de Transcrição STAT/metabolismo , Fatores de Transcrição STAT/farmacologia , Transdução de Sinais
13.
Nutrients ; 14(14)2022 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-35889819

RESUMO

Regulatory T cells (Tregs) and CD4+/CD25+ T cells play an important role in the suppression of excessive immune responses, homeostasis of immune function, and oral tolerance. In this study, we screened for food-derived polyphenols that induce Tregs in response to retinaldehyde dehydrogenase (RALDH2) activation using macrophage-like THP-1 cells. THP-1 cells were transfected with an EGFP reporter vector whose expression is regulated under the control of mouse Raldh2 promoter and named THP-1 (Raldh2p-EGFP) cells. The THP-1 (Raldh2p-EGFP) cells were treated with 33 polyphenols after inducing their differentiation into macrophage-like cells using phorbol 12-myristate 13-acetate. Of the 33 polyphenols, five (kaempferol, quercetin, morin, luteolin and fisetin) activated Raldh2 promoter activity, and both quercetin and luteolin activated the endogenous Raldh2 mRNA expression and enzymatic activity. Furthermore, these two polyphenols increased transforming growth factor beta 1 and forkhead box P3 mRNA expression, suggesting that they have Treg-inducing ability. Finally, we verified that these polyphenols could induce Tregs in vivo and consequently induce IgA production. Oral administration of quercetin and luteolin increased IgA production in feces of mice. Therefore, quercetin and luteolin can induce Tregs via RALDH2 activation and consequently increase IgA production, suggesting that they can enhance intestinal barrier function.


Assuntos
Polifenóis , Linfócitos T Reguladores , Aldeído Oxirredutases/metabolismo , Animais , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Imunoglobulina A/metabolismo , Luteolina/farmacologia , Camundongos , Polifenóis/farmacologia , Quercetina/farmacologia , RNA Mensageiro/metabolismo
14.
Food Res Int ; 158: 111502, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35840209

RESUMO

Intestinal epithelial barrier dysfunction can cause several intestinal diseases. Flavonoids have been shown to be beneficial to the intestinal epithelial barrier function. However, the effects of taxifolin (TAX), a naturally occurring flavonoid, on the intestinal epithelial barrier function are unclear. Thus, the aims of this study were to investigate the protective effect and potential mechanism of TAX against lipopolysaccharide (LPS)-induced intestinal epithelial barrier dysfunction in a Caco-2 cell monolayer model. Our results showed that TAX increased the transepithelial electrical resistance (TEER) and decreased the fluorescein isothiocyanate (FITC)-dextran (4 kDa) flux in the damaged intestinal epithelial barrier. Meanwhile, TAX inhibited an LPS-induced decrease in mRNA and protein expression of tight junction (TJ) proteins (claudin-1, zonula occludens [ZO]-1, and occludin), and ameliorating the continuous distribution pattern disrupted of TJs. These results suggested that TAX ameliorated intestinal epithelial barrier dysfunction. Regarding the underlying mechanism, TAX reduced the LPS-induced secretion of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 in Caco-2 cell monolayers. In addition, TAX suppressed the phosphorylation of nuclear factor kappa-B (NF-κB), inhibitor protein of NF-κBα (IκBα), and myosin light chain (MLC), and downregulated the expression of myosin light chain kinase (MLCK) in LPS-treated Caco-2 cells. In summary, TAX can maintain TJ proteins by inhibiting the NF-κB/MLCK pathway and pro-inflammatory factor secretion to ameliorate LPS-induced intestinal epithelial barrier dysfunction. Thus, TAX is a promising candidate agent for use in functional food to ameliorate intestinal barrier dysfunction.


Assuntos
Mucosa Intestinal , Quinase de Cadeia Leve de Miosina , NF-kappa B , Quercetina , Células CACO-2 , Humanos , Enteropatias/induzido quimicamente , Enteropatias/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Lipopolissacarídeos/farmacologia , Quinase de Cadeia Leve de Miosina/efeitos dos fármacos , Quinase de Cadeia Leve de Miosina/metabolismo , NF-kappa B/efeitos dos fármacos , NF-kappa B/metabolismo , Quercetina/análogos & derivados , Quercetina/farmacologia , Proteínas de Junções Íntimas/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
15.
Molecules ; 27(14)2022 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-35889348

RESUMO

Polycystic ovary syndrome (PCOS) is a common multisystem disease with reproductive, metabolic and psychological abnormalities. It is characterized by a high prevalence rate in women of childbearing age and highly heterogeneous clinical manifestations, which seriously harm women's physical and mental health. Quercetin (QUR) is a natural compound of flavonoids found in a variety of foods and medicinal plants. It can intervene with the pathologic process of PCOS from multiple targets and channels and has few adverse reactions. It is mentioned in this review that QUR can improve ovulation disorder, relieve Insulin resistance (IR), reduce androgen, regulate lipid metabolism, regulate gut microbiota and improve vascular endothelial function, which is of great significance in the treatment of PCOS.


Assuntos
Resistência à Insulina , Síndrome do Ovário Policístico , Androgênios , Feminino , Humanos , Ovulação , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/metabolismo , Quercetina/farmacologia , Quercetina/uso terapêutico
16.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 38(8): 714-720, 2022 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-35851085

RESUMO

Objective To investigate the effect of quercetin on cell proliferation and apoptosis of MCF-7 human breast cancer cells, and effects of signaling pathways of PTEN/PI3K/AKT and c-Jun N-terminal kinase (JNK) signaling pathway. Methods MCF-7 cells were treated with quercetin (0, 20, 40, 60, 80, 100 µmol/L) CCK-8 assay was used to detect the cell proliferation, and cell apoptosis was assayed by flow cytometry. Hochesst33342 staining was used to observe the changes of nuclear number and karyotype, and flow cytometry was employed to detect cell apoptosis. The expression of PTEN and phosphorylated JNK (p-JNK) were detected by immunofluorescence cytochemistry, and the protein levels of PTEN, phosphorylated PI3K (p-PI3K), p-JNK and phosphorylated AKT (p-AKT) were detected by Western blot analysis. After treated with PI3K/AKT pathway inhibitor LY294002, the cell apoptosis and related protein expression were detected by the above methods again. Results With increased quercetin concentration, cell activity decreased and cell growth was inhibited in a concentration dependent manner; the nuclear concentration and apoptosis also increased. High concentration of quercetin significantly enhanced the expression and distribution of PTEN protein, decreased the levels of p-PI3K and p-AKT protein, and inhibited the expression of p-JNK protein. After adding LY294002 to inhibit PI3K/AKT, the apoptosis rate increased for cells treated with both LY294002 and quercetin; the expression of PTEN protein also showed an increase. Quercetin could significantly enhance the effect of LY294002 on p-PI3K/AKT/PTEN protein. Conclusion Quercetin can signeristically inhibit cell viability and induce cell apoptosis on MCF-7 cells, by up-regulating the expression of PTEN and down-regulating PI3K/AKT and JNK pathways.


Assuntos
Neoplasias da Mama , Fosfatidilinositol 3-Quinases , Apoptose , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Humanos , Sistema de Sinalização das MAP Quinases , PTEN Fosfo-Hidrolase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Proteínas Proto-Oncogênicas c-akt/metabolismo , Quercetina/farmacologia
17.
Int J Mol Sci ; 23(13)2022 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-35806418

RESUMO

Fluorescent materials based on aggregation-induced emission luminogens (AIEgens) have unique advantages for in situ and real-time monitoring of biomolecules and biological processes because of their high luminescence intensity and resistance to photobleaching. Unfortunately, many AIEgens require time-consuming and expensive syntheses, and the presence of residual toxic reagents reduces their biocompatibility. Herein, silver@quercetin nanoparticles (Ag@QCNPs), which have a clear core-shell structure, were prepared by redox reaction of quercetin (QC), a polyphenolic compound widely obtained from plants, including those used as foods, and silver ions. Ag@QCNPs show both aggregation-induced luminescence and the distinct plasma scattering of silver nanoparticles, as well as good resistance to photobleaching and biocompatibility. The Ag@QCNPs were successfully used for cytoplasmic labeling of living cells and for computerized tomography imaging in tumor-bearing mice, demonstrating their potential for clinical applications.


Assuntos
Nanopartículas Metálicas , Nanopartículas , Animais , Corantes Fluorescentes/química , Camundongos , Fotodegradação , Quercetina/farmacologia , Prata
18.
Molecules ; 27(13)2022 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-35807260

RESUMO

Moringa oleifera (M. oleifera) leaves are rich in nutrients and antioxidant compounds that can be consumed to prevent and overcome malnutrition. The water infusion of its leaf is the easiest way to prepare the herbal drink. So far, no information is available on the antioxidant, antimutagenic, and antivirus capacities of this infusion. This study aimed to determine the composition of the bioactive compounds in M. oleifera leaf infusion, measuring for antioxidant and antimutagenic activity, and evaluating any ability to inhibit the SARS-CoV-2 main protease (Mpro). The first two objectives were carried out in vitro. The third objective was carried out in silico. The phytochemical analysis of M. oleifera leaf infusion was carried out using liquid chromatography-mass spectrometry (LC-MS). Antioxidant activity was measured as a factor of the presence of the free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH). The antimutagenicity of M. oleifera leaf powder infusion was measured using the plasmid pBR322 (treated free radical). The interaction between bioactive compounds and Mpro of SARS-CoV-2 was analyzed via molecular docking. The totals of phenolic compound and flavonoid compound from M. oleifera leaf infusion were 1.780 ± 5.00 µg gallic acid equivalent/g (µg GAE/g) and 322.91 ± 0.98 µg quercetin equivalent/g (µg QE/g), respectively. The five main bioactive compounds involved in the infusion were detected by LC-MS. Three of these were flavonoid glucosides, namely quercetin 3-O-glucoside, kaempferol 3-O-neohesperidoside, and kaempferol 3-α-L-dirhamnosyl-(1→4)-ß-D-glucopyranoside. The other two compounds were undulatoside A, which belongs to chromone-derived flavonoids, and gentiatibetine, which belongs to alkaloids. The antioxidant activity of M. oleifera leaf infusion was IC50 8.19 ± 0.005 µg/mL, which is stronger than the standard butylated hydroxytoluene (BHT) IC50 11.60 ± 0.30 µg/mL. The infusion has an antimutagenic effect and therefore protects against deoxyribonucleic acid (DNA) damage. In silico studies showed that the five main bioactive compounds have an antiviral capacity. There were strong energy bonds between Mpro molecules and gentiatibetine, quercetin, undulatoside A, kaempferol 3-o-neohesperidoside, and quercetin 3-O-glucoside. Their binding energy values are -5.1, -7.5, -7.7, -5.7, and -8.2 kcal/mol, respectively. Their antioxidant activity, ability to maintain DNA integrity, and antimutagenic properties were more potent than the positive controls. It can be concluded that leaf infusion of M. oleifera does provide a promising herbal drink with good antioxidant, antimutagenic, and antivirus capacities.


Assuntos
COVID-19 , Moringa oleifera , Antioxidantes/química , Antivirais/análise , Antivirais/farmacologia , COVID-19/tratamento farmacológico , DNA/análise , Flavonoides/química , Glucosídeos/análise , Simulação de Acoplamento Molecular , Moringa oleifera/química , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Folhas de Planta/química , Quercetina/análise , Quercetina/farmacologia , SARS-CoV-2
19.
Drug Des Devel Ther ; 16: 2043-2053, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35791403

RESUMO

Rheumatoid arthritis (RA) is a chronic autoimmune disease that can lead to severe joint damage, disability and mortality. Quercetin (QUE) is a natural flavonoid that is ubiquitous in fruits and vegetables. This article reviews the effect of QUE on articular and extra-articular manifestations of RA in vitro and in vivo. In general, for articular manifestations, QUE inhibited synovial membrane inflammation by reducing inflammatory cytokines and mediators, decreasing oxidative stress, inhibiting proliferation, migration and invasion, and promoting apoptosis of fibroblast-like synoviocytes (FLS), regulated autoimmune response through modulating Th17/Treg imbalance and Th17 cells differentiation, reducing autoantibodies levels and regulating ectonucleoside triphosphate diphosphohydrolase (E-NTPDase)/ectoadenosine deaminase (E-ADA) activities, reduced bony damage via lowering matrix metalloproteinase (MMP)-1, MMP-3, receptor activator of nuclear factor kappa B ligand (RANKL) expression and osteoclasts formation. For extra-articular manifestations, QUE could reverse the neurodegenerative processes of the enteric nervous system (ENS) and exhibited cytoprotective, genoprotective and hepatoprotective effects. In addition, we also summarize some contradictory experimental results and explore the possibility for these differences to form a sound basis for the clinical application of QUE for RA.


Assuntos
Artrite Reumatoide , Sinoviócitos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Células Cultivadas , Humanos , Quercetina/farmacologia , Membrana Sinovial
20.
Genes (Basel) ; 13(7)2022 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-35885908

RESUMO

Background: Induced senescence could be exploited to selectively counteract the proliferation of cancer cells and target them for senolysis. We examined the cellular senescence induced by curcumin and whether it could be targeted by fisetin and quercetin, flavonoids with senolytic activity. Methods: Cell-cycle profiles, chromosome number and structure, and heterochromatin markers were evaluated via flow cytometry, metaphase spreads, and immunofluorescence, respectively. The activation of p21waf1/cip1 was assessed via RT-qPCR and immunoblotting. Senescent cells were detected via SA-ß-Galactosidase staining. Results: We report that curcumin treatment specifically triggers senescence in cancer cells by inducing mitotic slippage and DNA damage. We show that curcumin-induced senescence is p21waf1/cip1-dependent and characterized by heterochromatin loss. Finally, we found that flavonoids clear curcumin-induced senescent cancer cells. Conclusions: Our findings expand the characterization of curcumin-induced cellular senescence in cancer cells and lay the foundation for the combination of curcumin and flavonoids as a possible anti-cancer therapy.


Assuntos
Curcumina , Neoplasias , Pontos de Checagem do Ciclo Celular , Curcumina/farmacologia , Inibidor de Quinase Dependente de Ciclina p21/genética , Flavonoides/farmacologia , Flavonóis , Heterocromatina , Quercetina/farmacologia
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