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1.
Complement Ther Med ; 80: 103008, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38040096

RESUMO

BACKGROUND: We performed a systematic review and meta-analysis of all published clinical trial studies to provide a more accurate estimation of pomegranate effects on liver enzymes in different clinical conditions. METHODS: A systematic literature search was carried out using electronic databases, including PubMed, Web of Science, and Scopus, up to March 2023 to identify eligible randomized clinical trials (RCTs) evaluating the effect of pomegranate consumption on liver function enzymes. Heterogeneity tests of the selected trials were performed using the I2 statistic. Random effects models were assessed based on the heterogeneity tests, and pooled data were determined as the weighted mean difference with a 95% confidence interval. RESULTS: Out of 3811 records, 9 eligible RCTs were included in the current study. However, there are limitations in the included studies, which can be mentioned in the dose, duration, and type of interventions that are different among the studies, as well as the small number of included studies. All this causes heterogeneity among studies and this heterogeneity limits the consistency of the results. Our meta-analysis showed that pomegranate intake had a significant effect on lowering aspartate aminotransferase (AST) levels in long-term intervention (> 8 weeks), obese (BMI≥30) individuals, or patients with metabolic disorders. Furthermore, results showed a significant decrease in alanine aminotransferase (ALT) levels in the long-term intervention (> 8 weeks) or in patients with metabolic disorders following the pomegranate intake. Combined results from the random-effects model indicated a significant reduction in gamma-glutamyl transferase (GGT) levels (WMD: -5.43 IU/L 95% CI: -7.78 to -3.08; p < 0.001;) following the pomegranate intake. The results of Egger's test mentioned a significant publication bias for the trials examining the effect of pomegranate intake on AST (p = 0.007) and ALT (p = 0.036). CONCLUSION: Our results suggest that long-term pomegranate intake may be effective in ameliorating liver enzymes in adults with obesity and metabolic disorders who are more likely to have elevated baseline liver enzymes due to some degree of liver injury or tissue damage. However, some studies failed to conduct independent biochemical characterization of the product used, including the presence and quantity of polyphenols, antioxidants, and proanthocyanidins.


Assuntos
Hepatopatias , Doenças Metabólicas , Punica granatum , Adulto , Humanos , Alanina Transaminase , Fígado , Hepatopatias/tratamento farmacológico , Testes de Função Hepática
2.
Front Pharmacol ; 14: 1234300, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37927606

RESUMO

Objectives: Non-alcoholic fatty liver disease (NAFLD) and its progression to non-alcoholic steatohepatitis (NASH) and hepatocarcinoma is a serious and growing problem. However, the development of new therapies is severely hindered by a lack of high-throughput assays for drug testing. Methods: We have developed a simple transwell assay comprised of HepG2 hepatocytes, hepatic LX-2 stellate cells, and differentiated THP-1 cells. The cells were incubated with an activating mixture containing the NASH-associated risk factors, glucose, insulin, free fatty acids (FFAs), and lipopolysaccharide (LPS) for 72 h. We compared different combinations of culture conditions to obtain a model system that recapitulates the main features of NAFLD/NASH, i.e., increased steatosis, reactive oxygen species (ROS), secretion of pro-inflammatory cytokines/chemokines, and presence of fibrosis. To confirm the usefulness of the optimized model system, we screened for compounds that inhibit steatosis in the hepatocytes and evaluated the most effective compound in the triculture model system. Results: The activating mixture stimulated HepG2 cells in this triculture to accumulate more fat and produce higher levels of reactive oxygen species (ROS) than HepG2 cells in monocultures. As well, higher levels of inflammatory cytokines and chemokines (IL-8, IL-6, MIP-1α, etc.) were produced in this triculture compared to monocultures. In addition, in all LX-2 monocultures and cocultures, exposure to the activating mixture increased markers of fibrosis. A major strength of our triculture system is that it makes possible the simultaneous monitoring of 4 main features of NASH, i.e., steatosis, oxidative stress, inflammation and fibrosis. Screening potential modulators that may reduce steatosis in HepG2 cells revealed the protective effects of the isoalkaloid, berberine. Tested using this novel triculture assay, treatment with 5 µM berberine decreased steatosis and ROS in HepG2 hepatocytes, reduced inflammatory cytokine production and inhibited collagen production from LX-2 cells. Conclusion: This simple triculture model recapitulates the main features of NAFLD/NASH and should be useful for high-throughput preclinical drug discovery. In this model, berberine showed promising results in decreasing steatosis and ROS and protection against fibrosis.

3.
Inflammopharmacology ; 31(5): 2283-2301, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37507609

RESUMO

BACKGROUND: Several studies have shown the effects of pomegranate on oxidative stress and inflammation biomarkers, while some studies showed no effects of pomegranate on these biomarkers. Therefore, we aimed to evaluate the effects of pomegranate consumption on C-reactive protein (CRP), interlukin-6 (IL-6), tumor necrosis factor α (TNF-α), total antioxidant capacity (TAC), and malondialdehyde (MDA) in adults. METHODS: A systematic literature search was performed using databases, including PubMed, Web of Science, and Scopus, up to May 2023 to identify eligible randomized controlled trials (RCTs). Heterogeneity tests of the included trials were performed using the I2 statistic. Random effects models were assessed based on the heterogeneity tests, and pooled data were determined as the weighted mean difference with a 95% confidence interval. RESULTS: Of 3811 records, 33 eligible RCTs were included in the current study. Our meta-analysis of the pooled findings showed that pomegranate consumption significantly reduced CRP (WMD: -0.50 mg/l; 95% CI -0.79 to -0.20; p = 0.001), IL-6 (WMD: -1.24 ng/L 95% CI -1.95 to -0.54; p = 0.001), TNF-α (WMD: -1.96 pg/ml 95%CI -2.75 to -1.18; p < 0.001), and MDA (WMD: -0.34 nmol/ml 95%CI -0.42 to -0.25; p < 0.001). Pooled analysis of 13 trials revealed that pomegranate consumption led to a significant increase in TAC (WMD: 0.26 mmol/L 95%CI 0.03 to 0.49; p = 0.025). CONCLUSION: Overall, the results demonstrated that pomegranate consumption has beneficial effects on oxidative stress and inflammatory biomarkers in adults. Therefore, pomegranate can be consumed as an effective dietary approach to attenuate oxidative stress and inflammation in patients with cardiovascular diseases. PROSPERO REGISTRATION CODE: CRD42023406684.


Assuntos
Punica granatum , Adulto , Humanos , Punica granatum/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Biomarcadores/metabolismo , Proteína C-Reativa/metabolismo , Inflamação/tratamento farmacológico , Estresse Oxidativo , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Suplementos Nutricionais
4.
Front Nutr ; 9: 1051418, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36532545

RESUMO

Objectives: Given the current controversy concerning the efficacy of omega 3 supplements at reducing inflammation, we evaluated the safety and efficacy of omega 3 on reducing inflammation in people with a 6-year lung cancer risk >1.5% and a C reactive protein (CRP) level >2 mg/L in a phase IIa cross-over study. Materials and methods: Forty-nine healthy participants ages 55 to 80, who were still smoking or had smoked in the past with ≥30 pack-years smoking history, living in British Columbia, Canada, were randomized in an open-label trial to receive 2.4 g eicosapentaenoic acid (EPA) + 1.2 g docosahexaenoic acid (DHA)/day for 6 months followed by observation for 6 months or observation for 6 months first and then active treatment for the next 6 months. Blood samples were collected over 1 year for measurement of plasma CRP, plasma and red blood cell (RBC) membrane levels of EPA, DHA and other fatty acids, Prostaglandin E2 (PGE2), Leukotriene B4 (LTB4) and an inflammatory marker panel. Results: Twenty one participants who began the trial within the active arm completed the trial while 20 participants who started in the control arm completed the study. Taking omega 3 resulted in a significant decrease in plasma CRP and PGE2 but not LTB4 levels. Importantly, the effect size for the primary outcome, CRP values, at the end of the intervention relative to baseline was medium (Cohen's d = 0.56). DHA, but not EPA levels in RBC membranes inversely correlated with PGE2 levels. Omega 3 also led to a significant reduction in granulocytes and an increase in lymphocytes. These high-dose omega 3 supplements were well tolerated, with only minor gastrointestinal symptoms in a subset of participants. Conclusion: Omega 3 fatty acids taken at 3.6 g/day significantly reduce systemic inflammation with negligible adverse health effects in people who smoke or have smoked and are at high risk of lung cancer.ClinicalTrials.gov, NCT number: NCT03936621.

5.
Cancer Cell Int ; 21(1): 66, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33478512

RESUMO

Gastric cancer (GC) is one of the most common cancers with high malignancy. In spite of the great development in diagnostic tools and application of anti-tumor drugs, we have not witnessed a significant increase in the survival time of patients with GC. Multiple studies have revealed that Wnt, Nrf2, MAPK, and PI3K/Akt signaling pathways are involved in GC invasion. Besides, long non-coding RNAs and microRNAs function as upstream mediators in GC malignancy. GC cells have acquired resistance to currently applied anti-tumor drugs. Besides, combination therapy is associated with higher anti-tumor activity. Resveratrol (Res) is a non-flavonoid polyphenol with high anti-tumor activity used in treatment of various cancers. A number of studies have demonstrated the potential of Res in regulation of molecular pathways involved in cancer malignancy. At the present review, we show that Res targets a variety of signaling pathways to induce apoptotic cell death and simultaneously, to inhibit the migration and metastasis of GC cells.

6.
Br J Nurs ; 29(22): S27-S30, 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33325291

RESUMO

AIM: The family plays a key role in supporting and caring for patients who have a gastrointestinal stoma because of cancer. This study investigated the quality of life of family members caring for such patients. METHODS: A descriptive study was conducted in 2020 in Iran. The study sample consisted of 250 family members caring for cancer patients with an intestinal stoma. The Caregiver Quality of Life Index-Cancer scale was used to measure quality of life. This scale has 35 questions, which are categorised into four subscales: mental/emotional burden; lifestyle disruption; positive adaptation; and financial concerns. The highest possible total score is 140 (35 in each subscale), and a high score indicates a poor quality of life. RESULTS: A total of 250 carers took part in the study. Of these, 143 (57.2%) were men and the average age was 35.1 years. Mean scores of mental/emotional burden, lifestyle disruption, positive adaptation, and financial concerns were 28.4±41, 17.3±3.2, 19.8±28, and 8.6±1.2 respectively. No significant relationship was found between participants' quality of life and demographic variables. CONCLUSION: Carers' quality of life is relatively poor. Carers' quality of life need to be improved and support programmes, devised and delivered by nurses, could have a role in this.


Assuntos
Cuidadores , Estomas Cirúrgicos , Adulto , Estudos Transversais , Família , Humanos , Irã (Geográfico) , Masculino , Qualidade de Vida
7.
Int J Chronic Dis ; 2020: 5742569, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32724791

RESUMO

BACKGROUND: The aim of this study was to investigate the psychosocial adjustment to illness and its relation with spiritual health in cancer patients. METHODS: This study was conducted in 2019 in Iran. It was a descriptive study with a sample of 124 cancer patients. Data were collected using two questionnaires of the psychosocial adjustment to illness scale (PAIS) with 46 questions and the Paloutzian and Ellison spiritual health scale with 20 questions. RESULTS: The mean age of the participants in this study was 52.4 ± 13.2 (range 18 to 87 years). The mean months of life with cancer were 16.5 months. The mean score of psychosocial adjustment to illness was 30.7 ± 15.5. The mean score of spiritual wellbeing in the studied patients was 71.4 ± 17.1. The results of the Pearson correlation test showed a significant inverse relationship between the mean score of psychosocial adjustment to illness and the mean score of spiritual wellbeing (p > 0.001, rr = -.355). CONCLUSION: Cancer patients in this study had relatively good psychosocial adjustment with their illness. Spiritual wellbeing can increase psychosocial adjustment to illness in this group of patients.

9.
Phytother Res ; 34(8): 1745-1760, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32157749

RESUMO

Curcumin is a naturally occurring nutraceutical compound with a number of therapeutic and biological activities such as antioxidant, anti-inflammatory, anti-diabetic, antitumor, and cardioprotective. This plant-derived chemical has demonstrated great potential in targeting various signaling pathways to exert its protective effects. Signal transducers and activator of transcription (STAT) is one of the molecular pathways involved in a variety of biological processes such as cell proliferation and cell apoptosis. Accumulating data demonstrates that the STAT pathway is an important target in treatment of a number of disorders, particularly cancer. Curcumin is capable of affecting STAT signaling pathway in induction of its therapeutic impacts. Curcumin is able to enhance the level of anti-inflammatory cytokines and improve inflammatory disorders such as colitis by targeting STAT signaling pathway. Furthermore, studies show that inhibition of JAK/STAT pathway by curcumin is involved in reduced migration and invasion of cancer cells. Curcumin normalizes the expression of JAK/STAT signaling pathway to exert anti-diabetic, renoprotective, and neuroprotective impacts. At the present review, we provide a comprehensive discussion about the effect of curcumin on JAK/STAT signaling pathway to direct further studies in this field.


Assuntos
Curcumina/uso terapêutico , Janus Quinases/metabolismo , Fatores de Transcrição STAT/metabolismo , Transdução de Sinais/efeitos dos fármacos , Produtos Biológicos , Curcumina/farmacologia , Humanos
10.
Life Sci ; 250: 117547, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32173311

RESUMO

Gastric cancer (GC) is responsible for high morbidity and mortality worldwide. This cancer claims fifth place among other cancers. There are a number of factors associated with GC development such as alcohol consumption and tobacco smoking. It seems that genetic factors play significant role in GC malignancy and progression. MicroRNAs (miRs) are short non-coding RNA molecules with negative impact on the expression of target genes. A variety of studies have elucidated the potential role of miRs in GC growth. Investigation of molecular pathways has revealed that miRs function as upstream modulators of Wnt signaling pathway. This signaling pathway involves in important biological processes such as cell proliferation and differentiation, and its dysregulation is associated with GC invasion. At the present review, we demonstrate that how miRs regulate Wnt signaling pathway in GC malignancy.


Assuntos
Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , Neoplasias Gástricas/metabolismo , Via de Sinalização Wnt , Apoptose , Diferenciação Celular , Linhagem Celular Tumoral , Movimento Celular/genética , Núcleo Celular/metabolismo , Proliferação de Células , Citoplasma/metabolismo , Humanos , Ligantes , Transporte Proteico , Transdução de Sinais , Neoplasias Gástricas/patologia , beta Catenina/metabolismo
11.
Artigo em Inglês | MEDLINE | ID: mdl-32021369

RESUMO

INTRODUCTION AND AIM: Prevention of pressure injuries in patients hospitalized in intensive care units is significantly important. Therefore, in the present study, the effect of using olive oil and fish oil prophylactic dressings on the development of heel pressure injuries was investigated. METHODS: The present study was a clinical trial conducted in the intensive care unit of Shahid Beheshti Hospital, in Yasuj. Fifty patients, who were at moderate to high risk of pressure injuries development, were randomly divided into two groups based on the mean score of the Braden scale. In one group, patients' heels were dressed using olive oil prophylactic dressing, and in the other group, patients' heels were dressed using fish oil prophylactic dressing. The dressings were changed 3 times a day. Collected data were then analyzed using SPSS v16. RESULTS: No significant difference was determined in demographic variables among the two groups (p<0.05). In terms of the development of heel pressure injuries, none of the patients in the olive oil and fish oil groups had pressure injuries. CONCLUSION: There were no statistically significant differences in either treatment group related to heel pressure injuries outcomes during the 7 days observed in the study. Additionally, both dressings had the same effects. Further studies are recommended in this regard.

12.
Free Radic Biol Med ; 152: 767-775, 2020 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-31972341

RESUMO

Dietary polyphenols act in cancer prevention and may inhibit carcinogenesis. A possible mitochondrial mechanism for carcinogen-induced neoplastic transformation and chemoprevention by polyphenols, however, is largely unexplored. Using the Bhas 42 cell model of carcinogen-induced neoplastic transformation, we investigated benzo[a]pyrene (B[a]P) along with different polyphenols for their effects on mitochondrial content and function, and on mitochondrial and intracellular ROS generation. Bhas 42 cells were either co-treated with 5 µM polyphenol starting 2 h before exposure to 4 µM B[a]P for 24 or 72 h, or pre-treated with polyphenol for 24 h and removed prior to B[a]P exposure. Exposure to B[a]P decreased mitochondrial content (by 46% after 24 h and 30% after 72 h), decreased mitochondrial membrane potential and cellular ATP, and increased generation of mitochondrial superoxide and intracellular ROS. Polyphenol co-treatments protected against the decreased mitochondrial content, with resveratrol being the most effective (increasing the mitochondrial content after 72 h by 75%). Measurements after 24 h of mRNA for mitochondria-related proteins and of SIRT1 enzyme activity suggested an involvement of increased mitochondrial biogenesis in the polyphenol effects. The polyphenol co-treatments also ameliorated B[a]P-induced deficits in mitochondrial function (most strongly resveratrol), and increases in generation of mitochondrial superoxide and intracellular ROS. Notably, 24 h pre-treatments with polyphenols strongly suppressed subsequent B[a]P-induced increases, after 24 and 72 h, in mitochondrial superoxide and intracellular ROS generation, with resveratrol being the most effective. In conclusion, the results support a mechanism for B[a]P carcinogenesis involving impaired mitochondrial function and increased mitochondria-derived ROS, that can be ameliorated by dietary polyphenols. The evidence supports an increase in mitochondrial biogenesis behind the strong chemoprevention by resveratrol, and a mitochondrial antioxidant effect in chemoprevention by quercetin.


Assuntos
Benzo(a)pireno , Estilbenos , Benzo(a)pireno/toxicidade , Flavonoides/metabolismo , Potencial da Membrana Mitocondrial , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Resveratrol/metabolismo , Estilbenos/farmacologia
13.
Phytother Res ; 34(4): 721-728, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31972874

RESUMO

Effective management and treatment of cancer depend on developing novel antitumor drugs with the capability of targeting various molecular pathways. Identification and subsequent targeting of these pathways are of importance in cancer therapy. MicroRNAs (miRNAs) are small noncoding RNA molecules responsible for post-transcriptional regulation of genes. Notably, miRNAs participate in a number of biological processes such as proliferation, apoptosis, differentiation, and cell cycle regulation. So, any impairment in the expression and function of miRNAs is associated with development of disorders, particularly cancer. Naturally occurring nutraceutical compounds have attracted much attention due to their great antitumor activity. Among them, sulforaphane isolated from Brassica oleracea (broccoli) is of interest due to its therapeutic and biological activities such as antidiabetic, antioxidant, anti-inflammatory, hepatoprotection, and cardiprotection. Sulforaphane has demonstrated great antitumor activity and is able to significantly inhibit proliferation, viability, migration, malignancy, and epithelial-to-mesenchymal transition of cancer cells. These antitumor effects have widely been investigated, and it appears that there is a need for a precise review to demonstrate the molecular pathway that sulforaphane follows to exert its antitumor activity. At the present review, we focus on the modulatory impact of sulforaphane on miRNAs and exhibit that how various miRNAs in different cancers are regulated by sulforaphane.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Isotiocianatos/farmacologia , MicroRNAs/fisiologia , Neoplasias/tratamento farmacológico , Neoplasias/genética , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Brassica/química , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Isotiocianatos/isolamento & purificação , MicroRNAs/metabolismo , Neoplasias/patologia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Sulfóxidos
14.
APMIS ; 127(10): 681-687, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31274211

RESUMO

Ulcerative colitis (UC) is a chronic recurrent inflammation of the colon. It has been proposed that the UC pathogenesis may be related to vitamin D deficiency and/or vitamin D administration in UC patients may have an ameliorating effect on the intestinal inflammation. The aim of this study was to assess the effect of vitamin D on the serum levels of immune cytokines in UC patients. In this double-blind randomized controlled trial, 90 mild-to-moderate UC patients were assigned to get either a single muscular injection of 7.5 mg vitamin D3 or 1 mL normal saline as placebo. Three months later serum levels of IL-4, IL-10, IL-12p70, IFN-γ, and TNF-α were measured. Two group variables were compared using independent t-test and analysis of covariance (ANCOVA). There was a significant increase in vitamin D only in the vitamin D group. Compared to placebo, vitamin D had significant decreasing effects on serum TNF-α, IFN-γ, and IL12p70 levels, but it had no significant effect on serum levels of IL4 and IL10. Vitamin D seems to inhibit Th1 immune responses and have no effect on Th2 responses. The findings of this study support several in vitro studies, which suggest a therapeutic immunomodulatory potential of vitamin D.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Citocinas/sangue , Vitamina D/administração & dosagem , Adolescente , Adulto , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placebos/administração & dosagem , Soro/química , Células Th1/efeitos dos fármacos , Resultado do Tratamento , Adulto Jovem
15.
Clin Cosmet Investig Dermatol ; 12: 347-354, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31190942

RESUMO

Background: This study aimed 1) to examine the impact of honey on diabetic foot; 2) to examine the effect of olive oil on diabetic foot; and 3) to compare the impact of honey and olive oil in the healing of diabetic foot. Methods: In this randomized controlled trial, 45 patients took part. Patients were randomly assigned to three groups. In the honey group, the wound was dressed using gauzes with honey daily for 1 month. In the olive oil group, the wound was dressed using gauzes with olive oil (4 mL) daily for 1 month. Patients in the control group received usual dressing. Wounds were assessed before and after intervention using the Wagner scoring system and the checklist of diabetic foot healing (where a higher score indicates better wound healing). Results: Demographic characteristics of patients in the three groups were similar. Mean scores of tissue around the wound, wound grade, wound drainage, and wound healing were similar before intervention in all three groups. After intervention, means score of tissue around the wound, wound grade, wound drainage, and wound healing were significantly higher in patients in the honey and olive oil groups compared to patients in the control group. Conclusion: The results of this study reveal that honey is as effective as olive oil in the treatment of diabetic foot. Given the few studies on this topic, further investigation is needed.

16.
J Agric Food Chem ; 67(22): 6241-6247, 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31117508

RESUMO

A question in cell culture and dietary studies on protection by flavonoids against conditions such as hepatocyte steatosis is whether effects might be due to phenolic breakdown/digestion products. In HepG2 hepatocytes, treatment with quercetin, cyanidin, or their phenolic breakdown/digestion products (protocatechuic acid, 2,4,6-trihydroxybenzaldehyde, and caffeic acid), starting 2 h prior to oleic acid for 24 h, protected similarly against increases in intracellular lipid and reactive oxygen species and decreased mitochondrial membrane potential. Cyanidin or the phenolic products also protected against decreased mitochondrial content. After preincubation for only 1 h (to limit spontaneous degradation) and removal prior to oleic acid, only the phenolic products protected against decreased mitochondrial content, and without adding oleic acid, only protocatechuic acid and caffeic acid, and less so cyanidin, induced mitochondrial content. The results suggest that phenolic breakdown/digestion products of cyanidin and quercetin contribute to the protective effects in vitro, and perhaps in vivo.


Assuntos
Antocianinas/farmacologia , Fígado Gorduroso/tratamento farmacológico , Mitocôndrias/efeitos dos fármacos , Fenóis/metabolismo , Quercetina/farmacologia , Antocianinas/química , Antocianinas/metabolismo , Fígado Gorduroso/metabolismo , Flavonoides/química , Flavonoides/metabolismo , Flavonoides/farmacologia , Células Hep G2 , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Mitocôndrias/metabolismo , Modelos Biológicos , Estresse Oxidativo/efeitos dos fármacos , Fenóis/química , Fenóis/farmacologia , Quercetina/química , Quercetina/metabolismo , Espécies Reativas de Oxigênio/metabolismo
17.
Nutrients ; 11(3)2019 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-30832407

RESUMO

In this study, we aimed to determine the relative effectiveness of common dietary polyphenols or the isoquinoline alkaloid berberine in protecting against molecular mechanisms underlying non-alcoholic fatty liver disease (NAFLD) involving changes to cellular lipid metabolism and bioenergetics. In a model of steatosis using HepG2 hepatocytes, exposure of the cells to 1.5 mM oleic acid (OA) for 24 h caused steatosis and distorted cell morphology, induced the expression of mRNA for enzymes that are involved in lipogenesis and fatty acid oxidation (FAS and CPT1A), and impaired indices of aerobic energy metabolism (PPARγ mRNA expression, mitochondrial membrane potential (MMP), and galactose-supported ATP production). Co-treatment with 10 µM of selected polyphenols all strongly protected against the steatosis and changes in cell morphology. All polyphenols, except cyanidin, inhibited the effects on FAS and PPARγ and further increased CPT1A1 expression, suggesting a shift toward increased ß-oxidation. Resveratrol, quercetin, catechin, and cyanidin, however not kuromanin or berberine, ameliorated the decreases in MMP and galactose-derived ATP. Berberine was unique in worsening the decrease in galactose-derived ATP. In further investigations of the mechanisms involved, resveratrol, catechin, and berberine increased SIRT1 enzyme activity and p-AMPKαThr172 protein, which are involved in mitochondrial biogenesis. In conclusion, selected polyphenols all protected against steatosis with similar effectiveness, however through different mechanisms that increased aerobic lipid metabolism and mitochondrial function.


Assuntos
Fígado Gorduroso/metabolismo , Mitocôndrias Hepáticas/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Polifenóis/farmacologia , Substâncias Protetoras/farmacologia , Carnitina O-Palmitoiltransferase/efeitos dos fármacos , Fígado Gorduroso/induzido quimicamente , Células Hep G2/efeitos dos fármacos , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipogênese/efeitos dos fármacos , Mitocôndrias Hepáticas/metabolismo , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Ácido Oleico , Oxirredução/efeitos dos fármacos
19.
Bioorg Med Chem Lett ; 27(16): 3669-3673, 2017 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-28716495

RESUMO

This study aims at investigating the cytotoxicity and some of the modes of action of 3,5-bis(3-dimethylamino-4-hydroxybenzylidene)-4-piperidone trihydrochloride 3 and two related compounds 2 (which lacks the dimethylaminomethyl groups) and 4 (which has an additional dimethylaminoethyl substituent in both aryl rings) in order to ascertain the contribution of dimethylaminoethyl substituent to bioactivity. The bioactivities of 2-4 were compared with curcumin 5. Both 2 and 3 displayed submicromolar GI50 values towards HCT-116 cells and were significantly more potent than 4, 5 and 5-fluorouracil (5-FU). All of the compounds displayed greater toxicity towards HCT-116 cells than human CRL-1790 non-malignant colon cells. In HCT-116 cells, the compounds 2, 3 and 5 increased the ratio of oxidised to reduced glutathione and destabilized the mitochondrial membrane potential. Both 2 and 5 produced an increase in mitochondrial superoxide and a burst in intracellular reactive oxygen species in HCT 116 cells. In addition, 2 and 4 stimulated respiration in rat liver mitochondria while 2 and 5 induced mitochondrial swelling. The results suggest that 2 and 5 cause oxidation or cross-linking of the thiols which control the mitochondrial permeability transition.


Assuntos
Apoptose/efeitos dos fármacos , Glutationa/química , Mitocôndrias/metabolismo , Piperidonas/química , Piperidonas/farmacologia , Linhagem Celular , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Curcumina/farmacologia , Glutationa/metabolismo , Células HCT116 , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Oxirredução/efeitos dos fármacos , Piperidonas/síntese química , Espécies Reativas de Oxigênio/metabolismo , Superóxidos/metabolismo
20.
Food Chem Toxicol ; 106(Pt A): 165-174, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28533128

RESUMO

While dietary polyphenols are widely recognized for cancer-preventing characteristics, the relative effectiveness and mechanisms of action of different polyphenols is not clear. In the present study, we investigated the protective effects of six different polyphenols against benzo[a]pyrene (B[a]P)-induced oxidative stress and neoplastic transformation in the Bhas 42 cell carcinogenesis assay. All of the polyphenols completely prevented the increased intracellular ROS generation by B[a]P at 12 h, and most inhibited after 3 days. B[a]P increased mitochondrial superoxide generation at 12 h, which was inhibited by the anthocyanins and berberine. B[a]P increased expression of genes related to oxidative stress and inflammation (Nrf2, UCP2, and TNF-α) after 24 h. Polyphenols strongly inhibited the increase in TNF-α and also several polyphenols inhibited the increase in UCP2. At 21 days after 72 h treatment, B[a]P produced a large increase in the number of neoplastic colonies. This transformation was inhibited by most polyphenols, and strongly by resveratrol. In summary, all tested polyphenols were able to inhibit B[a]P-induced increases in markers of oxidative stress and inflammation, and to inhibit cellular transformation, with resveratrol being notable for the strongest preventive effect on cell transformation. The results support a role for dietary polyphenols in protecting against B[a]P-induced carcinogenesis.


Assuntos
Benzo(a)pireno/toxicidade , Carcinogênese/efeitos dos fármacos , Transformação Celular Neoplásica/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Polifenóis/farmacologia , Animais , Linhagem Celular Tumoral , Humanos , Camundongos , Modelos Biológicos , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
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