Showing papers on "Theobromine published in 2019"

Metabolic Profiling of Dietary Polyphenols and Methylxanthines in Normal and Malignant Mammary Tissues from Breast Cancer Patients

Abstract: Scope Dietary polyphenols may protect against breast cancer. However, it is unknown whether polyphenols reach human malignant breast tumors in molecular forms and(or) at concentrations likely to act against cancer. Methods and results Ninteen breast cancer patients consumed three capsules daily from biopsy-confirmed diagnosis to surgery (6 ± 2 days). The capsules contained pomegranate, orange, lemon, olive, cocoa, and grapeseed extracts plus resveratrol, providing 37 different phenolics (473.7 mg), theobromine and caffeine (19.7 mg). A total of 101 metabolites are identified in urine, 69 in plasma, 39 in normal (NT), and 33 in malignant (MT) tissues by UPLC-ESI-QTOF-MS. Eight control patients did not consume extracts. Phenolic-derived metabolites in MT and NT are mainly glucuronidated and(or) sulfated. Some representative metabolites detected in MT (median and range, pmol g-1 ) are urolithin-A-3-O-glucuronide (26.2; 3.2-66.5), 2,5-dihydroxybenzoic acid (40.2; 27.7-52.2), resveratrol-3-O-sulfate (86.4; 7.8-224.4), dihydroresveratrol-3-O-glucuronide (109.9; 10.3-229.4), and theobromine (715.0; 153.9-3,216). Metabolites, as detected in breast tissues, do not exert antiproliferative or estrogenic/antiestrogenic activities in MCF-7 breast cancer cells. Conclusion This is the first study that describes the metabolic profiling of dietary phenolics and methylxanthines in MT and NT comprehensively. Although phase-II conjugation might hamper a direct anticancer activity, long-term tumor-senescent chemoprevention cannot be discarded.

Impact of Coffee and Cacao Purine Metabolites on Neuroplasticity and Neurodegenerative Disease

Abstract: Increasing evidence suggests that regular consumption of coffee, tea and dark chocolate (cacao) can promote brain health and may reduce the risk of age-related neurodegenerative disorders. However, the complex array of phytochemicals in coffee and cacao beans and tea leaves has hindered a clear understanding of the component(s) that affect neuronal plasticity and resilience. One class of phytochemicals present in relatively high amounts in coffee, tea and cacao are methylxanthines. Among such methylxanthines, caffeine has been the most widely studied and has clear effects on neuronal network activity, promotes sustained cognitive performance and can protect neurons against dysfunction and death in animal models of stroke, Alzheimer's disease and Parkinson's disease. Caffeine's mechanism of action relies on antagonism of various subclasses of adenosine receptors. Downstream xanthine metabolites, such as theobromine and theophylline, may also contribute to the beneficial effects of coffee, tea and cacao on brain health.

Caffeine Content and Related Gene Expression: Novel Insight into Caffeine Metabolism in Camellia Plants Containing Low, Normal, and High Caffeine Concentrations.

Abstract: Caffeine is a crucial secondary metabolic product in tea plants. Although the presence of caffeine in tea plants has been identified, the molecular mechanisms regulating relevant caffeine metabolism remain unclear. For the elucidation of the caffeine biosynthesis and catabolism in Camellia plants, fresh, germinated leaves from four Camellia plants with low (2), normal (1), and high (1) caffeine concentrations, namely, low-caffeine tea 1 (LCT1, Camellia crassicolumna), low-caffeine tea 2 (LCT2, C. crassicolumna), Shuchazao (SCZ, C. sinensis), and Yunkang 43 (YK43, C. sinensis) were used in this research. Transcriptome and purine alkaloids analyses of these Camellia leaves were performed using RNA-Seq and liquid chromatography-mass spectrometry (LC-MS). Moreover, 15N-caffeine tracing was performed to determine the metabolic fate of caffeine in leaves of these plants. Caffeine content was correlated with related gene expression levels, and a quantitative real-time (qRT) PCR analysis of specific genes showed a consistent tendency with the obtained transcriptomic analysis. On the basis of the results of stable isotope-labeled tracer experiments, we discovered a degradation pathway of caffeine to theobromine. These findings could assist researchers in understanding the caffeine-related mechanisms in Camellia plants containing low, normal, and high caffeine content and be applied to caffeine regulation and breeding improvement in future research.

Exploring cocoa properties: is theobromine a cognitive modulator?

Abstract: Nutritional qualities of cocoa have been acknowledged by several authors; a particular focus has been placed on its high content of flavanols, known for their excellent antioxidant properties and subsequent protective effect on cardio- and cerebrovascular systems as well as for neuromodulatory and neuroprotective actions. Other active components of cocoa are methylxanthines (caffeine and theobromine). Whereas the effects of caffeine are extensively researched, the same is not the case for theobromine; this review summarizes evidence on the effect of theobromine on cognitive functions. Considering animal studies, it can be asserted that acute exposition to theobromine has a reduced and delayed nootropic effect with respect to caffeine, whereas both animal and human studies suggested a potential neuroprotective action of long-term assumption of theobromine through a reduction of Aβ amyloid pathology, which is commonly observed in Alzheimer's disease patients' brains. Hence, the conceivable action of theobromine alone and associated with caffeine or other cocoa constituents on cognitive modulation is yet underexplored and future studies are needed to shed light on this promising molecule.

Pro-oxidant and lifespan extension effects of caffeine and related methylxanthines in Caenorhabditis elegans.

Abstract: Caffeine and related purine alkaloids are common ingredients of many stimulating drinks. Studies have shown that lower concentrations of caffeine have a protective role in aging-related disorders. However, the associated mode of action of caffeine and its related methylxanthines is still not clear. In this study, we demonstrated that caffeine and theophylline promote longevity in Caenorhabditis elegans. Lifespan studies with the wild type, DAF-16 and SKN-1 mutant strains indicated that the methylxanthines-mediated lifespan extension in C. elegans was independent of DAF-16/FOXO and SKN-1. All the tested methylxanthines could protect C. elegans against acute oxidative stress. At early stages of life, an increase of ROS (reactive oxygen species) induced the translocation of DAF-16 and SKN-1, resulting in upregulation of several antioxidant genes, for example, sod-3p::GFP, gst-4p::GFP, gcs-1p::GFP; and downregulation of hsp-16.2p::GFP. RT-PCR corroborates the upregulation of gst-4 and skn-1 genes. The expression of DAF-16 decreased although its nuclear translocation was induced.

Inflammatory Microenvironment and Adipogenic Differentiation in Obesity: The Inhibitory Effect of Theobromine in a Model of Human Obesity In Vitro

Abstract: Objective. Obesity is considered a clinic condition characterized by a state of chronic low-grade inflammation. The role of macrophages and adipocytokines in adipose tissue inflammation is in growing investigation. The physiopathological mechanisms involved in inflammatory state in obesity are not fully understood though the adipocytokines seem to characterize the biochemical link between obesity and inflammation. The aim of this work is to analyze the effect of theobromine, a methylxanthine present in the cocoa, on adipogenesis and on proinflammatory cytokines evaluated in a model of fat tissue inflammation in vitro. Methods. In order to mimic in vitro this inflammatory condition, we investigated the interactions between human-like macrophages U937 and human adipocyte cell lines SGBS. The effect of theobromine on in vitro cell growth, cell cycle, adipogenesis, and cytokines release in the supernatants has been evaluated. Results. Theobromine significantly inhibits the differentiation of preadipocytes in mature adipocytes and reduces the levels of proinflammatory cytokines as MCP-1 and IL-1β in the supernatants obtained by the mature adipocytes and macrophages interaction. Conclusion. Theobromine reduces adipogenesis and proinflammatory cytokines; these data suggest its potential therapeutic effect for treating obesity by control of macrophages infiltration in adipose tissue and inflammation.

Caffeine metabolism during cultivation of oyster mushroom (Pleurotus ostreatus) with spent coffee grounds.

Abstract: In coffee-producing countries, waste products from coffee production are useful substrates for cultivation of Pleurotus ostreatus. This species is relatively easy to grow, coffee waste substrates are readily available and the mushroom fruiting bodies are a valuable source of nutrition and income. In developed countries, cultivation of P. ostreatus on spent coffee grounds (SCG) from coffee consumption is a novel way to recycle this urban waste product. Here, we studied the effect of SCG and caffeine on growth of a commercial strain of P. ostreatus in liquid and solid cultures, and on a commercial scale. The presence of caffeine inhibited mycelial growth on agar and in liquid culture in the laboratory. Increased levels of SCG in an SCG/sawdust substrate also delayed mycelial growth and delayed or prevented fruiting during commercial cultivation. Despite growth inhibition, partial degradation of caffeine to xanthine by P. ostreatus mycelium was observed in all SCG-containing substrate mixtures. Degradation of caffeine proceeded mainly via sequential N-demethylation to theophylline (1,3-dimethylxanthine) and 3-methylxanthine, although both paraxanthine and theobromine also accumulated in the substrate. Caffeine and its demethylated metabolites were also detected in fruiting bodies, but it was not clear whether caffeine metabolism occurred in the fruiting bodies themselves or whether caffeine metabolites were translocated there from the mycelium. Based on the caffeine concentrations measured in fruiting bodies after growth with SCG, it would be necessary to consume ~ 250 kg of fresh oyster mushrooms to obtain the amount of caffeine equivalent to one cup of espresso coffee, suggesting that the health impact of caffeine in these mushrooms is low. However, the ability of P. ostreatus to degrade caffeine indicates that this and other species in this genus may have potential applications in detoxification of coffee production wastes.

Role of Theobromine in Cocoa's Metabolic Properties in Healthy Rats.

Abstract: Cocoa is rich in polyphenols and methylxanthines, and it has been reported that its consumption, among other properties, has beneficial effects on metabolism. This study aimed to investigate the role of theobromine in cocoa’s metabolic properties in healthy rats. In addition to morphometric measurements, biochemical markers of lipids and glucose metabolism and gene expression of molecules related to immune cells in adipose and hepatic tissues were assessed after 7 or 18 days of diet. Additionally, a metabolomic analysis was carried out at day 7. This study revealed the presence of six discriminant metabolites in plasma due to the diets. Moreover, the results showed that theobromine is the main responsible factor for cocoa’s effects on body weight gain as well as on lipid and glucose metabolism. The effects on body weight and lipids appeared as early as after 7 days of diet, whereas those affecting glucose metabolism required a longer intervention.

More than just caffeine: psychopharmacology of methylxanthine interactions with plant-derived phytochemicals.

Abstract: In general, preparations of coffee, teas, and cocoa containing high levels of polyphenols, L-theanine and other bioactive compounds selectively enhance mood and cognition effects of caffeine. This review summarizes the bioactive components of commonly consumed natural caffeine sources (e.g. guayusa, mate and camellia teas, coffee and cocoa) and analyzes the psychopharmacology of constituent phytochemicals: methylxanthines, polyphenols, and L-theanine. Acute and chronic synergistic effects of these compounds on mood and cognition are compared and discussed. Specific sets of constituent compounds such as polyphenols, theobromine and L-theanine appear to enhance mood and cognition effects of caffeine and alleviate negative psychophysiological effects of caffeine. However, more research is needed to identify optimal combinations and ratios of caffeine and phytochemicals for enhancement of cognitive performance.

Effect of Caffeine and Other Methylxanthines on Aβ-Homeostasis in SH-SY5Y Cells.

Abstract: Methylxanthines (MTX) are alkaloids derived from the purine-base xanthine. Whereas especially caffeine, the most prominent known MTX, has been formerly assessed to be detrimental, this point of view has changed substantially. MTXs are discussed to have beneficial properties in neurodegenerative diseases, however, the mechanisms of action are not completely understood. Here we investigate the effect of the naturally occurring caffeine, theobromine and theophylline and the synthetic propentofylline and pentoxifylline on processes involved in Alzheimer's disease (AD). All MTXs decreased amyloid-β (Aβ) level by shifting the amyloid precursor protein (APP) processing from the Aβ-producing amyloidogenic to the non-amyloidogenic pathway. The α-secretase activity was elevated whereas β-secretase activity was decreased. Breaking down the molecular mechanism, caffeine increased protein stability of the major α-secretase ADAM10, downregulated BACE1 expression and directly decreased β-secretase activity. Additionally, APP expression was reduced. In line with literature, MTXs reduced oxidative stress, decreased cholesterol and a decreased in Aβ1-42 aggregation. In conclusion, all MTXs act via the pleiotropic mechanism resulting in decreased Aβ and show beneficial properties with respect to AD in neuroblastoma cells. However, the observed effect strength was moderate, suggesting that MTXs should be integrated in a healthy diet rather than be used exclusively to treat or prevent AD.

Effects of Maturity at Harvest and Fermentation Conditions on Bioactive Compounds of Cocoa Beans.

Abstract: Cocoa beans and cocoa products contain considerable amounts of bioactive compounds. Harvesting cocoa fruit too early or too late may have effects on the phenolic and alkaloid concentrations of the cocoa powder. Fermentation, a primary processing used to transform cocoa beans to cocoa powder, may also influence the contents of bioactive compounds. In this study, proanthocyanidins, the major compounds in cocoa polyphenols, caffeine and theobromine of cocoa beans, were evaluated at different maturities at harvest, and with different fermentation durations, with and without the addition of a commercial enzyme, Pectinex® Ultra SP-L. The amounts of proanthocyanidins, caffeine and theobromine, and the antioxidant capacities of the unfermented cocoa beans increased as the fruits matured. The values ranged from 16.12–27.28 g catechin equivalents (CE)/100 g dry weight (DW); 99.66–173.61 mg/100 g DW; 556.39–948.84 mg/100 g DW; 23.23–26.32 mol Trolox equivalents (TE)/100 g DW, respectively. Prolonged fermentation with or without the addition of pectinase, from three to seven days, significantly reduced the amounts of these compounds present. Fermentation using the enzyme significantly reduced the proanthocyanidin content and antioxidant capacity of the cocoa powder, with the overall means decreasing from 8.93–4.93 g CE/100 g DW and from 15.81–12.95 g mol TE/100 g DW, respectively. Two-way ANOVA analyses showed that the proanthocyanidins, caffeine, theobromine contents and the antioxidant capacity of cocoa beans were strongly dependet to their stages of maturity, fermentation methods and fermentation duration.

Isolation, analysis and in vitro assessment of CYP3A4 inhibition by methylxanthines extracted from Pu-erh and Bancha tea leaves

Abstract: Methylxanthines, purine alkaloids found in plants, are found in beverages (coffee, tea, cocoa) and foods (chocolate and other cocoa-containing foods) commonly consumed worldwide. Members of this family include caffeine, theophylline and theobromine. Methylxanthines have a variety of pharmacological effects, and caffeine and theophylline are used as pharmaceuticals. Methylxanthines are metabolized in the liver predominantly by the enzyme CYP1A2. Their co-administration with CYP1A2 inhibitors may lead to pharmacokinetic interactions. Little is known about the possible drug interactions between caffeine and substrates of other CYP450 enzymes. In our study, methylxanthine fractions inhibited CYP3A4 in a concentration-dependent manner. Concomitant consumption of green tea with CYP3A4 substrates could increase the possibility of interactions, and this requires further clarification. The inhibition of CYP3A4 is not only due to the presence of catechin derivatives but methylxanthines may also contribute to this effect.

Chronic administration of theobromine inhibits mTOR signal in rats

Abstract: Theobromine is a caffeine derivative and the primary methylxanthine in Theobroma cacao. We have shown previously that theobromine inhibits the Akt-mammalian target of rapamycin (mTOR) signal in vitro. In this study, we investigated whether orally administered theobromine could inhibit mTOR activity in rats. mTOR is phosphorylated by Akt. Thus, the level of phosphorylated mTOR was used as an index of mTOR activity. Male Wistar rats were divided into two groups. The control group (CN) was fed a normal diet, while the theobromine group (TB) was fed a diet supplemented with 0.05% theobromine for 40 days. We measured body-weights and tissue weights, food and water intake, blood count, concentrations of theobromine in the plasma, liver and brain, and the levels of phosphorylated mTOR in the liver and brain. Orally administered theobromine did not affect the body-weights and tissue weights, food and water intake, and blood count as determined by comparison with levels in rats that were fed standard chow. Theobromine was detected in the plasma, liver and brain obtained from TB rats, but was not detected in tissues obtained from CN rats. The phosphorylated mTOR levels in the liver and brain were significantly lower in TB rats than in CN rats. The results suggest that oral theobromine inhibits mTOR signalling in vivo.

Rapid and Sensitive Determination of Methylxanthines in Commercial Brands of Tea Using Ultra-High-Performance Liquid Chromatography-Mass Spectrometry.

Abstract: Recently, chromatographic techniques have the potential to be greener in order to reduce the environmental impact. In this work, a new simple, sensitive, efficient, and green analytical method based on UHPLC-MS has been developed for a quick determination of methylxanthines including caffeine, theobromine, and theophylline in tea. Under the optimum conditions, a baseline separation has been achieved within 30 seconds, using isocratic elution consisting of 90% water and only 10% acetonitrile at 0.5 mL/min flow rate (3 mL acetonitrile per hour). The mass spectrometer was operated with the SIR mode in ESI+. The developed method was found to be linear in the range of 0.03–5 μg/mL, with correlation coefficients greater than 0.9995 for the three compounds. The respective values of LOD were found to be 0.025, 0.015, and 0.01 μg/mL for caffeine, theobromine, and theophylline, respectively. The proposed assay was applied to 30 commercial tea samples of different brands. Both caffeine and theobromine were found in all tea samples with maximum concentration in sample no. 15, corresponding to 32.6 and 2.72 mg/g of caffeine and theobromine, respectively. On the contrary, theophylline was not detected at all in most samples. When compared with all previous studies that dealt with the same compounds in different matrices, the developed method was found to be the fastest, allowing high-throughput analyses with more than 100 samples/h. The results prove that the method is suitable for routine analysis of methylxanthines and to distinguish the quality of tea samples of various brands.

Supercritical Fluid Extraction of Fat and Caffeine with Theobromine Retention in the Cocoa Shell

Abstract: The cocoa shell is a residue of low commercial value, which represents an alternative for obtaining substances of added value for the food and pharmaceutical industry. Substances of interest in the shell include fat and methylxanthines (theobromine and caffeine). In order to obtain the extraction behavior with supercritical CO2, a 23 factorial design was proposed with six central points, taking dynamic extraction into consideration. The following factors were involved: pressure (2,000–6,000 psi), temperature (313–333 K), and time (30–90 min). The obtained yield was between 3.66% and 15.30%. Fat was the substance that was extracted most effectively (94.73%). Caffeine demonstrated variability in the residue, with at least six treatments that exceeded a removal rate of more than 90%, while it was practically impossible to extract theobromine. The difference with regard to the extraction of theobromine may be attributed to its low solubility. Characterization using FT–IR showed the modifications before and after the process, providing clear evidence of the changes corresponding to the fat at 2,924, 2,854 and 1,745 cm−1. The results presented establish the basis for the extraction of substances such as fats and methylxanthines from a cocoa shell with the use of CO2.

CHAPTER 23:Caffeine and Minor Methylxanthines in Coffee

Abstract: Methylxanthines are the most consumed psychoactive substances in the world. Caffeine (1,3,7-trimethylxanthine) is the major methylxanthine in foods, followed by theobromine (3,7-dimethylxanthine), and, more scarcely, theophylline (1,3-dimethylxanthine). They are predominantly found in different parts of Coffea (coffee), Camelia sinensis (traditional tea), Ilex paraguariensis (mate), Theobroma cacao (cocoa), Paulinia cupana (guarana), and Cola (kola), among other plants. Caffeine and theobromine are also available in a number of commercial non-alcoholic beverages, supplements, and in association with therapeutic drugs. This chapter will approach chemical and compositional aspects of methylxanthines in coffee, including contents in the seeds and beverages, as well as factors that commonly affect them.

Methylxanthines in 100 Brazilian herbs and infusions: determination and consumption

Abstract: The contents of caffeine, theophylline and theobromine were studied in 100 plants commercialized in Brazil to investigate new sources of these compounds, and evaluate the consumption of these compounds when these plants are used as infusions (teas). Therefore, two extraction methods were performed, one used an ethanol solution and one used an aqueous infusion process. The extracts were analyzed by ultra-high-performance liquid chromatography. White, green, and black tea (Camellia sinensis) and yerba mate (Ilex paraguariensis) can be considered as potential sources of both caffeine and theobromine. Boldo (Peumus boldus) was a source of theobromine, and small-leaved lime (Tilia cordata), stonebreaker (Phylantus niruri), cow’s foot (Bauhinia forficata) and calendula (Calendula officinalis) presented the highest contents of theophylline. This study highlighted herbs not yet investigated for these compounds. The results obtained may be useful in future studies to evaluate the use of these plants as sources of methylxanthines in foods or drugs.

Revisiting the spectroscopy of xanthine derivatives: theobromine and theophylline

Abstract: We explore the influence of the relative position of the methyl substituent on the photophysics of theophylline and theobromine, two molecules that are structurally related to the DNA bases. Using a combination of spectroscopic techniques and quantum mechanical calculations, we show that moving the methyl group from N1 in theophylline to N7 in theobromine causes significant differences in their excited state properties, i.e., it produces pyramidalization of N7 in the excited state of the latter. Paradoxically, this modification seems to have little effect on the structural properties of the cation and the ionization process. It is suggested that similar effects may exist in the excited state properties of DNA bases.

Theobromine cocrystals with monohydroxybenzoic acids – synthesis, X-ray structural analysis, solubility and thermal properties

Abstract: Theobromine, an organic compound from the purine alkaloid group, is much less soluble in polar solvents than its analogues, i.e. caffeine and theophylline, that is why it has been used as an active pharmaceutical ingredient (API) model in cocrystal preparation. A series of theobromine (TBR) cocrystallization processes from solutions with such coformers as 2-hydroxybenzoic acid (2HBA), 3-hydroxybenzoic acid (3HBA) and 4-hydroxybenzoic acid (4HBA) were carried out. In addition, neat grinding and liquid-assisted grinding were performed. The obtained cocrystals TBR·2HBA and TBR·3HBA as well as TBR·2(4HBA)·H2O cocrystal monohydrate have been characterized by single crystal X-ray diffraction (SXRD), PXRD, UV-vis and STA (TGA/DSC) analyses. In all cases no proton transfer from the acid molecule to the imidazole nitrogen atom in theobromine was observed. TBR–acid heterosynthons are sustained by N⋯H–O interactions, where proton donors in TBR·2HBA and TBR·3HBA are carboxylic groups, and in TBR·2(4HBA)·H2O the proton donor is the hydroxyl group of the acid molecule. In each cocrystal, TBR–TBR homosynthon R22(8) formation by N–H⋯O hydrogen bonds was observed. Acid–acid dimers are created only in the crystal lattice of TBR·2(4HBA)·H2O. In the obtained cocrystals, similar supramolecular synthons were observed, such as in theophylline and caffeine cocrystals with the same coformers. C–H⋯O and π⋯π forces present in the described structures are responsible for 2D and 3D structure stabilization.

Determination of methylxanthines in tea samples by HPLC method

Abstract: Methylxanthines such as caffeine, theophylline, theobromine are significant and widespread psychoactive substances. We developed the isocratic method with optimum composition of the mobile phase 90 % water: 10 % acetonitrile and confirmed repeatability of retention times and peak areas. The developed HPLC method was applied to determine the content of methylxanthines in selected types of black and green teas available on the market. Of the black teas (tea bags), the highest concentration of theobromine was found in Ceylon tea (18.98 mg.L⁻¹). The highest concentration of caffeine was in a cup of Earl Gray tea (254.09 mg.L⁻¹). Among loose black teas, the highest content of both theobromine and caffeine was found in Pu Erh Superior tea, where the theobromine content was 24.62 mg.L⁻¹ and the caffeine content was 520.67 mg.L⁻¹. Of green powder teas, highest caffeine content (306.46 mg.L⁻¹) was in Shizuoka Matcha Premium and the highest content of theobromine (8.45 mg.L⁻¹) was found in GABA Midori. From the loose green tea, the highest concentration of theobromine (12.85 mg.L⁻¹) was in Lung Ching West Lake. The highest caffeine content (484.85 mg.L⁻¹) was in Gyokuro Shizuoka Premium Tea. In both types of teas the amount of theobromine and caffeine was quantified, but the presence of theophylline was not proven. Data on contents of these metabolites in tea products are highly informative for consumers.

Simultaneous estimation of xanthine alkaloids (Theophylline, Theobromine and Caffeine) by High-Performance Liquid Chromatography

Abstract: Methylxanthines are mainly a group of phytochemicals which are derived from purine base xanthine. These xanthines are obtained from plant as a result of secondary metabolism. There are various physiological actions that have been attributed to these derivatives in neurogenerative diseases, respiratory diseases, cancer and diabetes. The aim of this study is to develop a suitable qualitative and quantitative method for these xanthine derivatives. HPLC method is suitable for simultaneous estimation of methylxanthines, based on their physicochemical properties. Theobromine, Theophylline and Caffeine that belongs to alkaloids possess their economic effects. They have various stimulant effects on cardiovascular system, gastrointestinal system, respiratory system, central nervous system etc. that results in increased motivation to work, increased energy and increased alertness. High performance liquid chromatography is used for simultaneous determination of theophylline, theobromine and caffeine from different tea leaves.

The impact of 2-aminoethanesulfonic acid, guaranine methyl theobromine 1, 3, 7-trimethylxanthine theine and/or isobutylphenyl propionic acid on masculine fecundity, and morphopathological disorders in rats

Abstract: Objectives: This study aims to evaluate the impact of caffeine (CAF), taurine (TUR), and ibuprofen (IBF) consumption on the masculine fecundity in rats and fetuses development. Methods: The 1st group was kept as a normal control received distilled water. The 2nd, 3rd, and 4th groups received orally 250 mg/kg, 40 mg/kg, and 270 mg/kg of TUR, CAF, and IBF, respectively. In addition, the 5th, 6th, 7th, and 8th groups received TUR with CAF, TUR with IBF, CAF with IBF, and TUR, CAF, IBF combination, for 45 days. Blood samples were taken to determine testosterone and follicle-stimulating hormone levels and oxidation levels. Moreover, in testes, malondialdehyde and nitrite/nitrate were estimated. Besides, the abnormality of sperms, sperm counts, and percentage of sperm motilities was characterized. These masculines were allowed to mate with untreated masculine rats to determine the rate of pregnancy and study any malformation in their fetuses. Results: The study revealed that each of CAF and/or IBF decreased the weights of fetuses, as well as sperm counts and motilities significantly. Besides, percentages of head and tail abnormalities were increased in CAF and/or IBF. The histopathological examination revealed the presence of marked degenerative changes in testes in CAF and/or IBF-treated groups. Conclusion: CAF and IBF have a teratogenic effect on spermatozoa and masculine fecundity, whereas TUR almost improved undesirable impacts induced by IBF or/and CAF.

Bacillus amyloliquefaciens HZ-12 heterologously expressing NdmABCDE with higher ability of caffeine degradation

Abstract: Caffeine is a major component of tea and coffee. Apart from the stimulatory effects, cumulative intake of caffeine has caused several diseases. In addition, the presence of caffeine brings out the deterioration of environmental pollution. Therefore, the demand for decaffeinated products, especially decaffeinated coffee and tea, is increasing. However, Pseudomonas putida as the most widely studied bacteria isn't suitable for producing decaffeinated tea and coffee due to the production of an unpleasant odor and endotoxins at the same time. A more appropriate system (Bacillus amyloliquefaciens HZ-12:ndmABCDE) is needed to produce decaffeinated products; and HZ-12:ndmABCDE was constructed by orderly integrating N-demethylase genes (ndmABCDE) in a safer strain HZ-12. Demethylases (NdmABCDE) in P. putida can degrade caffeine to xanthine, which was further degraded to CO2 and NH4+ by the purine metabolic pathway. Finally, HZ-12:ndmABCDE could degrade 52.6% of caffeine in the optimized medium, 31.5% higher than HZ-12; caffeine was demethylated in sequence to form theobromine, paraxanthine, 7-methylxanthine and xanthine; and there are no endotoxins and unpleasant odor. This study provides a safer strain (HZ-12:ndmABCDE) for producing decaffeinated tea and coffee and a new idea that B. amyloliquefaciens HZ-12 can heterologously express the demethylase genes in P. putida.

Synthesis and Biological Evaluation of Structurally Varied 5'-/6'-Isonucleosides and Theobromine-Containing N-Isonucleosidyl Derivatives

Abstract: Isonucleosides are rather stable regioisomeric analogs of nucleosides with broad therapeutic potential. We have previously demonstrated the ability of 5' and 6'-isonucleosides to inhibit the activity of acetylcholinesterase, a major target for Alzheimer's disease therapy. Continuing with our research on this topic, we report herein on the synthesis and biological evaluation of a variety of novel terminal isonucleosides and theobromine isonucleotide analogs. Xylofuranose-based purine or uracil 5'-isonucleosides and xylofuranos-5'-yl or glucos-6'-yl theobromine derivatives were accessed via Mitsunobu coupling between partially protected xylofuranose or glucofuranose derivatives with a nucleobase using conventional or microwave-assisted heating conditions. Theobromine-containing N-isonucleosidyl sulfonamide and phosphoramidate derivatives were synthesized from isonucleosidyl acetate precursors. The most active compounds in the cholinesterase inhibition assays were a glucopyranose-based theobromine isonucleosidyl acetate, acting as a dual inhibitor of acetylcholinesterase (AChE, Ki = 3.1 µM) and butyrylcholinesterase (BChE, Ki = 5.4 µM), and a 2-O,4-O-bis-xylofuranos-5'-yl uracil derivative, which displayed moderate inhibition of AChE (Ki = 17.5 µM). Docking studies revealed that the active molecules are positioned at the gorge entrance and at the active site of AChE. None of the compounds revealed cytoxic activity to cancer cells as well as to non-malignant mouse fibroblasts.

Functional and Medicinal Properties of Caffeine-Based Common Beverages

Abstract: Functional and medicinal beverages have been used to treat and cure diseases since the beginning of civilization. Among these beverages, coffee (Coffea arabica), black/green tea (Camellia sinensis), and yerba mate (Ilex paraguariensis), have been studied due to their important functional activities. These plants present several bioactive molecules in their chemical matrix that are responsible for therapeutic properties. For instance, coffee is mainly composed of caffeine, chlorogenic acid (CGA), cafestol, and kahweol, while black/green tea present principally polyphenols, caffeine, and theobromine. Moreover, yerba mate is predominantly composed of caffeine, theobromine, theophylline, aglycones, ursolic acid, oleoanolic, and CGA. Some studies reported important functional properties of these plants. Previous investigations described that these plants are able to increase neural activity and to promote health, besides presenting antiinflammatory, antitumor, thermogenic, and antioxidant capacities. In this sense, the frequent intake of these functional beverages can contribute to a healthier life.

Caffeine metabolite as a biomarker in carbon tetrachloride-induced hepatotoxicity in rats

Abstract: Liver injury is a form of trauma, also known as liver laceration, which represents 5% of all traumas of the abdomen. Caffeine, which is metabolized mainly in the liver, is a widely consumed stimulant that exists in many commonly consumed beverages. Glycyrrhizin (GZ) and boswellic acids (BA) are naturally occurring compounds and isolated from licorice and Olibanum gum, respectively. They proved to have both hepatoprotective and immunomodulatory activities and present potential drugs for liver disorders. The aim of this study is to investigate the effects of GZ and BA on hepatic intoxication in CCl4-induced hepatotoxicity and to investigate whether caffeine metabolites concentrations in serum can be used as biomarkers for liver function. Rats treated with CCl4 showed a significant increase in the average of all liver enzymes levels in serum in comparison with those in the control group which received only caffeine. On the other hand, rats treated with CCl4 and receiving BA and BA + GZ showed a slight reduction in enzymes levels. Theobromine concentration in rats’ sera which received CCl4 was significantly lower in comparison to the non-treated rats. Caffeine/theobromine (C/T) ratio could be accurately used as a biomarker for liver injury and/or early fibrosis without any interactions of false positive common liver function tests. Also, these results confirmed the hepatoprotective effect of both pentacyclic triterpenes, GZ and BA, tested in this model.

Degradation of Theobromine in Cocoa (Theobroma cacao) by-products by Fermentation with Aspergillus niger

Abstract: Aim: This study was carried out to determine the ability of Aspergillus niger to break down theobromine in cocoa by-products, for its possible use in animal feeds. Place and Duration of Study: Department of Biological Sciences, Wesley University, Ondo, Ondo State, Nigeria between January 2013 and June 2013. Methodology: Cocoa by-products (combination of cocoa bean shell (CBS) and cocoa bean meal (CBM)) was milled into fine particle size, sterilized and fermented with Aspergillus niger for 5 days. The theobromine content was monitored at 24 h interval during fermentation and proximate analyses were carried out before and after the fermentation process. Results: Significant reduction of theobromine content of 78.13% was observed after 5 days of fermentation. The crude protein and crude ash content increased by 2.7% and 51.9%, while the moisture content and crude fibre reduced by 21.3% and 23.8%, respectively. Conclusion: The study showed that Aspergillus niger has the potential to reduce the theobromine content and enhance the nutritive value of cocoa by-products, for possible use in animal feed.

Determination of Theobromine and Caffeine in Theobroma cacao Husk from Ethanolic Extract by GC-MS after CC Separation

Abstract: After CC separation of 21 samples from Theobroma cacao Husk was analyzed by GC-MS, from ethanolic extract at 90% was recovered a solid residue of 1 g after several days on the table of the Lab. This main residue (300 mg) was analyzed after successive separations with mixtures of CHCl3: MeOH (7:3) and CHCl3: MeOH (5:5) in CC using Silica Gel G 60-120 Mesh. All samples were analyzed by TLC on silica gel with fluorescent indicator 254 nm on aluminum cards (layer thickness 0.2 mm) (10 × 20 cm) using CHCl3: MeOH: n-propanol: water (5:6:1:4) as eluent (v/v/v). The presence of Caffeine (CF) and Theobromine (TB) was confirmed after several analyses of the samples by their characteristic fragmentation pattern but nevertheless was found the presence of Theophylline.

Synthesis and Properties of 8-Substituted 1-(2-Oxopropyl)Theobromine Derivatives

Abstract: A method for preparing previously unreported and potentially biologically active 1-(2-oxopropyl)theobromine derivatives was developed. Their physicochemical properties and antibacterial and antifungal activities were studied.