RESUMO
AIM: This systematic review and meta-analysis evaluated theobromine's (Theobroma cacao) potential in remineralizing white spot lesions in dental enamel. Methods: This study is reported according to the PRISMA checklist and was registered in PROSPERO (CRD42023414371). In vitro tests that evaluated the remineralizing potential of theobromine compared to fluoride ion after demineralization for the formation of white spot lesions on enamel were selected, with no limitation on the year of publication. Electronic searches were performed in PubMed/MEDLINE, Scopus, and Web of Science by two independent researchers. Thirty articles were received of which six were selected according to the inclusion criteria. RESULTS: The selected studies evaluated the Enamel Surface Microhardness (SMH), Vickers or Knoop, before and after treatment with theobromine and fluoride solutions. For the SMH Vickers, there were no differences between groups at baseline (p=1.00; mean difference: -0.00; CI: -11.36 to 11.36) and after treatment (p=0.51; mean difference: 4.12; CI: -8.16 to 16.41). The results of SMH Knoop showed differences between groups at baseline, favoring the experimental group (p=0.002; mean difference: 9.84; CI: 3.65 to 16.02) and after treatment favoring the control group (p=0.00001; mean difference: -5.45; CI: -7.62 to -3.27). CONCLUSION: The use of theobromine increases the microhardness of dental enamel subjected to a demineralization process, thus being effective in the remineralization of this tissue with success equivalent to that obtained with the use of fluoride.
Assuntos
Esmalte Dentário , Teobromina , Remineralização Dentária , Remineralização Dentária/métodos , Humanos , Teobromina/uso terapêutico , Teobromina/farmacologia , Esmalte Dentário/efeitos dos fármacos , Cárie Dentária , Fluoretos/uso terapêutico , Cariostáticos/uso terapêuticoRESUMO
Natural products have been studied to reveal new therapies against human dysfunctions since they present several medicinal properties. Caffeine, theobromine and (+)-catechin are remarkable natural agents in the class of methylxanthines and flavonoids. These bioactive molecules have several biological activities, for instance, antioxidant, anti-inflammatory, and antitumor capacity. In this sense, studies focusing on these molecules have been performed to discover new treatments against diseases, such as cancer. Cancer is a serious public health problem worldwide responsible for more than 70% of all deaths globally. Industrialized products associated with a sedentary lifestyle and a diet low in antioxidants are related to neoplasms development. Unfortunately, many types of cancers are extremely aggressive and untreatable since, in many cases, they are resistant to chemotherapy. Therefore, revealing new strategies to block cancer growth is one of the biggest challenges to science. In this context, despite the known anticancer actions of caffeine, theobromine and (+)-catechin, it is still essential to elucidate the causal antitumor mechanism of these molecules by analyzing the dysfunctional cancer pathways associated with the hallmarks of cancer. Hence, this review aims to describe the anticancer activity of caffeine, theobromine, and (+)-catechin against the different hallmarks and enabling characteristics of cancer.
Assuntos
Produtos Biológicos , Catequina , Neoplasias , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Cafeína/farmacologia , Catequina/farmacologia , Catequina/uso terapêutico , Humanos , Neoplasias/tratamento farmacológico , Teobromina/farmacologiaRESUMO
Hyperlipidemia causes lipotoxicity which prompts an inflammatory response linked to the development of cardiovascular diseases. Natural compounds have been receiving special attention for its potential to treat diseases, inexpensiveness, and safety. Guarana (Paullinia cupana) has demonstrated notable anti-inflammatory and antioxidant effects, which may prevent chronic diseases caused by changes in lipid profile. Thus, this study aims to evaluate the effect of guarana powder (Paullinia cupana) in the purine metabolism and inflammatory profile in lymphocytes and serum of rats with Poloxamer-407-induced hyperlipidemia. Pretreatment with guarana 12.5, 25, and 50 mg/kg/day or caffeine (0.2 mg/kg/day) by gavage was applied to adult male Wistar rats for a period of 30 days. As a comparative standard, we used simvastatin (0.04 mg/kg) post-induction. Hyperlipidemia was acutely induced with intraperitoneally injection of Poloxamer-407 (500 mg/kg). Guarana powder and caffeine increased the activity of the E-NTPDase (ecto-apyrase), and all pretreatments decreased the E-ADA (ecto-adenosine deaminase) activity, reducing the inflammatory process caused by lipotoxicity. In hyperlipidemic rats, ATP levels were increased while adenosine levels were decreased, guarana and caffeine reverted these changes. Guarana powder, caffeine, and simvastatin also prevented the increase in INF-γ and potentiated the increase in IL-4 levels, promoting an anti-inflammatory profile. Guarana promoted a more robust effect than caffeine. Our results show that guarana powder and caffeine have an anti-inflammatory as seen by the shift from a proinflammatory to an anti-inflammatory profile. The effects of guarana were more pronounced, suggesting that guarana powder may be used as a complementary therapy to improve the lipotoxicity-associated inflammation.
Assuntos
Anti-Inflamatórios/farmacologia , Cafeína/farmacologia , Hiperlipidemias/tratamento farmacológico , Inflamação/prevenção & controle , Teobromina/farmacologia , Teofilina/farmacologia , Adenosina/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Anti-Inflamatórios/administração & dosagem , Cafeína/administração & dosagem , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Hiperlipidemias/fisiopatologia , Inflamação/etiologia , Linfócitos/efeitos dos fármacos , Linfócitos/metabolismo , Masculino , Ratos , Ratos Wistar , Sinvastatina/farmacologia , Teobromina/administração & dosagem , Teofilina/administração & dosagemRESUMO
The Brazilian Food Supplement Law recently recognized that guarana (Paullinia cupana) contains bioactive substances, hence supporting its role as a functional food ingredient. The health benefits of guarana are associated, at least in part, to its phenolic compounds. However, to the best of our knowledge, there is no literature addressing the presence of phenolic compounds in the fraction containing insoluble-bound compounds and its contribution in terms of alpha-glucosidase inhibition. The concentration of phenolic extracts released from the insoluble-bound fraction required to inhibit 50% of alpha-glucosidase (IC50) activity was 5.8-fold lower than that present in the soluble counterpart. Both fractions exhibited a mixed inhibition mode. Fourteen proanthocyanidins (dimers to tetramers) present in the insoluble-bound fraction were tentatively identified by MALDi-TOF-MS. Future studies aiming at increasing the concentration of the soluble counterpart are deemed necessary. The results presented here enhance the phenolic database of guarana and have a practical impact on the procurement of nutraceuticals and functional ingredients related to the prevention and/or management of type 2 diabetes. The Brazilian normative on food supplements has been recently revised. This study lends support to the future inclusion of guarana powder in the list of sources of proanthocyanidins for the industry of food supplements.
Assuntos
Cafeína/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores de Glicosídeo Hidrolases/farmacologia , Polifenóis/farmacologia , Proantocianidinas/farmacologia , Teobromina/farmacologia , Teofilina/farmacologia , Brasil , Cafeína/química , Suplementos Nutricionais , Humanos , Medicina Tradicional/métodos , Paullinia/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Teobromina/química , Teofilina/química , alfa-Glucosidases/efeitos dos fármacosRESUMO
Microbiota alterations are observed in pathological conditions, and their regulation is a subject of great interest. Gut microbes are affected by diet, and plant polyphenols may have positive effect on gut microbiota; however, plant-derived extracts may have toxic effects. Guarana (Paullinia cupana Mart.) is a nontraditional medicinal plant applied worldwide. Guarana yields an alkaloid and polyphenol-rich seed with antimicrobial, antioxidant, and anti-inflammatory properties, where caffeine is the major compound. We evaluated the effects of guarana seed powder (GSP) and purified caffeine on gut microbial composition and redox and inflammatory parameters in Wistar rats after 21 days of treatment. Fecal microbiota was analyzed utilizing 16S rDNA sequencing. Antioxidant enzymes activities from liver, kidney, and colon, as well as oxidative damage markers, were evaluated. Total nonenzymatic antioxidant potential was also evaluated. Microbiota was altered by both treatments, GSP and caffeine, without loss of diversity. In the liver, the kidney, and the colon, we observed a decrease in the antioxidant enzymes activities in the GSP group with no increase in the expression of oxidative damage markers, although some enzymes were also regulated by caffeine. Taken together, these results suggested that GSP ameliorates redox parameters but negatively affected gut microbiota, partially via caffeine.
Assuntos
Cafeína/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Teobromina/farmacologia , Teofilina/farmacologia , Animais , Antioxidantes/farmacologia , Cafeína/química , Disbiose/induzido quimicamente , Disbiose/microbiologia , Disbiose/patologia , Masculino , Oxirredução/efeitos dos fármacos , Paullinia/química , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Ratos , Ratos Wistar , Sementes , Teobromina/química , Teofilina/químicaRESUMO
Hypercholesterolemia is a metabolic disorder characterized by high levels of low-density lipoprotein and blood cholesterol, causing inflammatory lesion. Purinergic signaling modulates the inflammatory and immune responses through adenine nucleotides and nucleoside. Guaraná has hypocholesterolemic and antiinflammatory properties. Considering that there are few studies demonstrating the effects of guaraná powder on the metabolism of adenine nucleotides, we investigated its effects on the activity of ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase) and ecto-adenosine deaminase activity in lymphocytes of rats with diet-induced hypercholesterolemia. The rats were divided into hypercholesterolemic and normal diet groups. Each group was subdivided by treatment: saline, guaraná powder 12.5, 25, or 50 mg/kg/day and caffeine concentration equivalent to highest dose of guaraná, fed orally for 30 days. An increase in adenosine triphosphate hydrolysis was observed in the lymphocytes of rats with hypercholesterolemia and treated with 25 or 50 mg/kg/day when compared with the other groups. The hypercholesterolemic group treated with the highest concentration of guaraná powder showed decreased ecto-adenosine deaminase activity compared with the normal diet groups. Guaraná was able to reduce the total cholesterol and low-density lipoprotein cholesterol to basal levels in hypercholesterolemic rats. High concentrations of guaraná associated with a hypercholesterolemic diet are likely to have contributed to the reduction of the inflammatory process.
Assuntos
Cafeína/farmacologia , Hipercolesterolemia/tratamento farmacológico , Paullinia/química , Teobromina/farmacologia , Teofilina/farmacologia , Adenosina Desaminase/metabolismo , Animais , Colesterol/sangue , LDL-Colesterol/sangue , Dieta Hiperlipídica , Linfócitos/enzimologia , Masculino , Preparações de Plantas/farmacologia , Ratos , Ratos WistarRESUMO
Reduction in sirtuin 1 (Sirt-1) is associated with extracellular matrix (ECM) accumulation in the diabetic kidney. Theobromine may reduce kidney ECM accumulation in diabetic rats. In the current study, we aimed to unravel, under diabetic conditions, the mechanism of kidney ECM accumulation induced by a reduction in Sirt-1 and the effect of theobromine in these events. In vitro, we used immortalized human mesangial cells (iHMCs) exposed to high glucose (HG; 30 mM), with or without small interfering RNA for NOX4 and Sirt-1. In vivo, spontaneously hypertensive rats (SHR) were rendered diabetic by means of streptozotocin and studied after 12 wk. The effects of treatment with theobromine were investigated under both conditions. HG leads to a decrease in Sirt-1 activity and NAD(+) levels in iHMCs. Sirt-1 activity could be reestablished by treatment with NAD(+), silencing NOX4, and poly (ADP-ribose) polymerase-1 (PARP-1) blockade, or with theobromine. HG also leads to a low AMP/ATP ratio, acetylation of SMAD3, and increased collagen IV, which is prevented by theobromine. Sirt-1 or AMPK blockade abolished these effects of theobromine. In diabetic SHR, theobromine prevented increases in albuminuria and kidney collagen IV, reduced AMPK, elevated NADPH oxidase activity and PARP-1, and reduced NAD(+) levels and Sirt-1 activity. These results suggest that in diabetes mellitus, Sirt-1 activity is reduced by PARP-1 activation and NAD(+) depletion due to low AMPK, which increases NOX4 expression, leading to ECM accumulation mediated by transforming growth factor (TGF)-ß1 signaling. It is suggested that Sirt-1 activation by theobromine may have therapeutic potential for diabetic nephropathy.
Assuntos
Diabetes Mellitus Experimental/metabolismo , Rim/metabolismo , NAD/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Sirtuína 1/metabolismo , Teobromina/farmacologia , Animais , Diabetes Mellitus Experimental/tratamento farmacológico , Modelos Animais de Doenças , Rim/efeitos dos fármacos , Masculino , Estresse Oxidativo/fisiologia , Poli(ADP-Ribose) Polimerase-1 , Ratos , Ratos Endogâmicos SHRRESUMO
The antioxidant effects of the hydro-alcoholic guaraná extract (Paullinia cupana var. sorbilis Mart.) on nitric oxide (NO) and other compounds generated from the degradation of sodium nitroprusside (SNP) in an embryonic fibroblast culture (NIH-3T3 cells) were evaluated. The guaraná bioactive compounds were initially determined by high-performance liquid chromatography: caffeine=12.240 mg/g, theobromine=6.733 mg/g and total catechins=4.336 mg/g. Cells were exposed to 10 µM SNP during a 6 h period because the cells exhibited >90% mortality at this concentration. Guaraná was added to the cultures in five concentrations (0.5, 1, 5, 10 and 20 mg/mL). The guaraná antioxidant effect was evaluated by viability assays, biochemical oxidation [lipid peroxidation, catalase and superoxide dismutase (SOD) activity] and genotoxicity (DNA Comet assay) analysis. Additionally, oxidative stress was evaluated by a 2,7-dihydrodichlorofluorescein diacetate fluorescence assay. Guaraná reverted the SNP toxicity mainly at lower concentrations (<5 mg), which decreased cell mortality, lipid peroxidation, DNA damage and cell oxidative stress as well as increased the SOD levels. These results demonstrate that guaraná has an antioxidant effect on NO metabolism in situations with higher cellular NO levels.
Assuntos
Fibroblastos/efeitos dos fármacos , Nitroprussiato/efeitos adversos , Paullinia/química , Extratos Vegetais/farmacologia , Animais , Antioxidantes/farmacologia , Cafeína/análise , Cafeína/farmacologia , Catequina/análise , Catequina/farmacologia , Cromatografia Líquida de Alta Pressão , Ensaio Cometa , Dano ao DNA/efeitos dos fármacos , Fibroblastos/citologia , Fluoresceínas/análise , Camundongos , Células NIH 3T3 , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Teobromina/análise , Teobromina/farmacologiaRESUMO
AIM OF THE STUDY: Evaluate the potential inhibition of cough in a mouse model induced by sulfur dioxide gas of methanol and chloroform extracts of aerial parts of Chamaedorea tepejilote. MATERIAL AND METHODS: The antitussive effect was examined using the Ogyhara method. The extracts and theobromine were orally administered to mice. Each extract was administered to one group (400mg/Kg) and theobromine (2mg), and negative control received PVP. The frequency of cough was measured at 60, 90min after the administration of chloroform extract. RESULTS: The water extract of C. tepejilote had no effect on the pharmacological model used in this study. The effects of the methanol and chloroform extracts of this plant on sulfur-dioxide-induced cough in experimental animals show activity dose-dependently in the range between 100 to 500mg/Kg. At doses of 400mg/kg, the methanol and chloroform extracts inhibited cough by 41.72% and 49.1%, respectively; these results are comparable to the effect produced by the antitussive agent theobromine (53.4% inhibition). CONCLUSIONS: Both extracts exhibited significant antitussive activity, and the effect of the chloroform extract was dose dependent. The antitussive activity of this extract was comparable to that of theobromine. The effect of chloroform extract on the trachea was also tested; it did not relax pre-contractions in guinea pig trachealis induced KCl, carbachol or histamine.
Assuntos
Antitussígenos/farmacologia , Arecaceae/química , Tosse/tratamento farmacológico , Extratos Vegetais/farmacologia , Administração Oral , Animais , Antitussígenos/administração & dosagem , Antitussígenos/isolamento & purificação , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Cobaias , Masculino , Camundongos , Contração Muscular/efeitos dos fármacos , Componentes Aéreos da Planta , Extratos Vegetais/administração & dosagem , Dióxido de Enxofre , Teobromina/farmacologia , Fatores de Tempo , Traqueia/efeitos dos fármacosRESUMO
MTX is an effective therapy for autoimmune-inflammatory diseases. The mechanisms that mediate these actions are not completely clear. It is accepted that many of these effects are mediated through the release of adenosine with the activation of the adenosine receptor A2. MTX is used as a steroid sparing agent. An improved in vitro GC cell sensitivity in GC insensitive asthma patients has been demonstrated after MTX treatment. Most GC actions are mediated by the GCR. The effect of MTX on GCRs expression has not been previously evaluated. Therefore, we evaluate if MTX regulates the expression of glucocorticoid receptors, increasing the expression of the active receptor (GCR alpha) and/or decreasing the expression of the dominant negative receptor (GCR beta). We show that MTX increases the mRNA and protein levels of GCR alpha and decreases or leaves unchanged the protein expression of the GCR beta in CEM cells in culture. This effect was also observed in other lymphocytes (Jurkat and Raji) and in PBMNC from healthy volunteers. We also show that upon MTX treatment PBMC from normal volunteers exhibit a higher sensitivity to DEX inhibition on LPS-induced TNF alpha release. To explore if these actions are mediated by adenosine through the adenosine receptor A2 we evaluate the effect of adenosine on the GCRs expression and the effect of an A2 receptor blocker (DMPX) on MTX effects on GCRs expression. Our results show that adenosine does not mimic and DMPX can enhance MTX effects on these receptors. We conclude that MTX increases the GCR alpha/GCR beta ratio of expression in lymphocytes which could mediate its previously reported effects in improving cell glucocorticoid sensitivity. These actions are not mediated by the adenosine receptor A2.