Showing papers on "Theobromine published in 2010"

Natural Compounds in the Human Diet and their Ability to Bind Mutagens Prevents DNA–Mutagen Intercalation

Abstract: Human diet may contain many mutagenic or carcinogenic aromatic compounds as well as some beneficial physiologically active dietary components, especially plant food phytochemicals, which act as mutagenesis or carcinogenesis inhibitors. This study compared the binding properties of natural compounds in the human diet (caffeine, theophylline, theobromine, and resveratrol) with a water-soluble derivative of chlorophyll to bind to acridine orange, a known mutagen. An analysis was conducted to determine which substances were effective binding agents and may thus be useful in prevention of chemical-induced mutagenesis and carcinogenesis. Data indicated that in order to bind 50% of the mutagen in a complex, less than twice the concentration of chlorophyllin was needed, the resveratrol concentration was 20-fold higher, while a 1000-fold or even 10,000-fold excess of xanthines were required to bind acridine orange.

Effects of Paraxanthine and Caffeine on Sleep, Locomotor Activity, and Body Temperature in Orexin/Ataxin-3 Transgenic Narcoleptic Mice

Abstract: CAFFEINE, IN THE FORM OF CAFFEINE-CONTAINING BEVERAGES OR OVER-THE-COUNTER CAFFEINE TABLETS (100 MG OR 200 MG), IS A WIDELY USED WAKE-promoting substance, used to reduce sleepiness in normal people.1,2 Caffeine is also widely used for patients with primary (such as narcolepsy) and secondary hypersomnia (hypersomnia associated with neurological diseases); these patients self-medicate with caffeine before they visit the sleep clinic to receive more potent medication.2 Caffeine is a non-selective antagonist for adenosine receptors (A1 and A2a receptors), and blockade of these receptors is believed to mediate its stimulant effects.1 One of the limitations of caffeine for treating hypersomnia is its low wake-promoting potency, while high doses may induce side effects such as anxiety, tremors, headache, and gastrointestinal irritation. Caffeine is demethylated to 3 active metabolites, paraxanthine, theobromine, and theophylline, and C-8 hydroxylated to 1,3,7-trimethyluric acid (TMU).3–5 The interspecies variations in caffeine metabolism, related to cytochrome P4501A enzyme, exist; and the percentages of the production of these 4 metabolites are reported to be 59.9%, 8.7%, 5.0%, and 26.4% in humans, and 19.1%, 10.8%, 21.7%, and 47.8% in mice.5 Like caffeine, paraxanthine is a central nervous stimulant. In addition, caffeine and paraxanthine have similar anti-adenosine actions, though the literature has consistently reported that paraxanthine exhibits slightly higher binding potencies for adenosine A1 and A2a receptors6 and both lower toxicity and lesser anxiogenic effects than caffeine.7 This may be explained by the pharmacological properties of other caffeine metabolites, such as theophylline, which often induce nausea, diarrhea, tachycardia, and arrhythmias.8 A recent study demonstrated that paraxanthine provides protection against dopaminergic cell death via ryanodine receptor stimulation.9 Therefore, paraxanthine may be more effective than caffeine for wake-promotion in normal people and treatment of hypersomnia in those with cardiovascular and neurological diseases. Therefore, we evaluated the wake-promoting efficacy of paraxanthine in wild-type (WT) and narcoleptic mice models and compared it with those of caffeine and modafinil. Effects of these compounds on locomotor activity, core body temperature and anxiety levels were also compared. Narcoleptic mice were included since narcolepsy is the prototypical primary hypersomnia, and orexin/ataxin-3 narcoleptic mice share the major pathophysiology of human narcolepsy (hypocretin cell ablation).10,11 As such, the observed efficacy in narcoleptic mice is an accurate predictor of efficacy for treatment of pathological sleepiness.

Induction of neutral endopeptidase (NEP) activity of SK-N-SH cells by natural compounds from green tea.

Abstract: Deposition of amyloid beta-peptide as senile plaques in the brain is one of the neuropathological hallmarks of Alzheimer's disease, which is the most prevalent progressive neurodegenerative disease leading to dementia. Neutral endopeptidase is one of the major beta-amyloid-degrading enzymes in the brain. To examine the influence of different polyphenols and other natural products from green tea extract (from Camellia sinensis, Theaceae), we used the neuroblastoma cell line SK-N-SH and studied the changes in the specific cellular neutral endopeptidase activity after long-term treatment with these substances. We have shown that caffeine leads to an increase in specific cellular neutral endopeptidase activity more than theophylline, theobromine or theanine. We have also shown that the combination of epicatechin, epigallocatechin and epigallocatechingallate with caffeine, theobromine or theophylline induced cellular neutral endopeptidase activity. It is suggested that the enhancement of cellular neutral endopeptidase activity by green tea extract and its natural products might be correlated with an elevated level of intracellular cyclic adenosine monophosphate.

Phenolic Acids and Methylxanthines Composition and Antioxidant Properties of Mate (Ilex paraguariensis) Residue

Abstract: UNLABELLED Ilex paraguariensis is known to contain compounds with antioxidant properties, such as phenolic acids, and its stimulant properties are attributed to methylxanthines, such as caffeine. The aims of this study were to evaluate the phenolic, methylxanthinic, and tannin composition of a mate residue (mate powder), to compare the quali-quantitative phenolic composition and the antioxidant potential of extracts obtained from distinct solvent systems. Among the extracts prepared with different solvents, the 80% methanol extract showed the highest total polyphenol content (11.51 g/100 g) and antioxidant activity. HPLC analysis showed that 4,5 dicaffeoylquinic acid is the major component of the phenolic fraction of mate powder. The caffeine, theobromine, and tannin contents in mate powder were 1.01, 0.10, and 0.29 g/100 g, respectively. Consumption of mate powder would significantly contribute to antioxidant and stimulant intake, providing high amounts of phenolic acids, tannins, and methylxanthines with biological effects potentially beneficial for human health. PRACTICAL APPLICATION This article contributes to the minimization of residues in yerba-mate processing.

Supramolecular Assembly of Protonated Xanthine Alkaloids in Their Perchlorate Salts

Abstract: Single crystal X-ray structures of new perchlorate salts of a series of four xanthine alkaloids, for example, xanthine (xt), caffeine (cf), theophylline (tp), and theobromine (tb) are reported. The treatment of xanthine derivatives with 70% of HClO4 afforded their salts Hxt·ClO4·2(H2O), 1; Htp·ClO4, 2; Htb·ClO4, 3; and Hcf·ClO4·H2O, 4. Xanthine form dimers via N(9)−H···O−C(6) hydrogen bond in the crystal structure. Of the two possible resonance structures of the protonated imidazoles, one of the structures was found to be major in xanthine, theobromine, and caffeine salts, while both structures are of equal contribution in theophylline salts. These observations also have been verified by using the structural information available in the Cambridge Structural Database. Interestingly, xanthine 1 is present as a dihydrate and 4 as a monohydrate, whereas 2 and 3 are crystallized without any water. Thus, proton transfer from the strong acid HClO4 to the weakly basic imidazole ring of xanthines occurs which lead...

Studies on the coordination chemistry of methylated xanthines and their imidazolium salts. Part 1: benzyl derivatives

Abstract: New imidazolium salts derived from the natural methylated xanthines theophylline, theobromine and caffeine, namely 1,3-dimethyl-9-benzylxanthinium bromide (tphBzBr, 1a), 3,7-dimethyl-9-benzylxanthinium bromide (tbrBzBr, 2a) and 1,3,7-trimethyl-9-benzylxanthinium bromide (caffBzBr, 3a), are reported. Also, the disubstituted analog of 1a, 1,3-dimethyl-7,9-dibenzylxanthinium bromide (tphBz2Br, 1a′) was identified and characterized by NMR. The coordination chemistry of ligands 1a–3a toward palladium, and some theoretical aspects of the unmodified theophylline, theobromine and caffeine are studied. Our results prove that the theophylline derivative has the thermodynamic tendency to form N-bonded species, even when an equilibrium between the Pd–NHC and the “theophyllinate” was observed spectroscopically, due to the anisotropy of the NHC ligand. To confirm the N-coordination, the solid state structure of the new “theophyllinate” species PdBr2(tphBz-H)2 (4), derived from 1a, was determined by X-ray diffraction. The analog with theobromine, ligand 2a, coordinates to palladium via N1, in an analogous manner to 1a, and a mixture of the cis/trans isomers of its palladium complex is obtained. On the other hand, since there is no possibility of N-coordination in 3a, this caffeine derivative forms a Pd-NHC compound after deprotonation with a strong base. Both the theoretical results and the experimental evidence are in accordance, in terms of the predicted coordination sites or possibility of modification of the selected methylated xanthines to obtain new ligands.

Hydrotropic extraction of theobromine from cocoa bean shell.

Abstract: Cocoa bean shell (CBS) is a waste product from chocolate and cocoa milling industries CBS is high in nutritive value but it is of limited use in animal feeds because of its toxic theobromine content Though its theobromine content limited the use of CBS, its amino acid profile of CBS compares favourably with palm kernel cake suggesting that it could be utilized as a medium protein source to substitute grain protein in livestock diets Theobromine is also possesed many farmacological function such as anti cancer, diuretics, cardiac stimulants, hypocholesterolemic, smooth-muscle relaxants, atshma and coronary vasodilators Considering that Indonesia is the third largest producer of cocoa in the, the potential usage of both protein and theobromine content of cocoa bean shell, thus it is neccesary to separate theobromine from cocoa bean shell A new developed separation process is the extraction process using aqueous hydrotropes solution for recovery of naturally occurring secondary metabolites The solubility of the secondary metabolites extracted are increased sharply and easily recovered Recently several researches demonstrated that high solubilization capacity and selectivity in solubilization by hydrotropy could be used for extraction of water insoluble bioactive compound such as piperin, limonin, curcuminoids and forskolin Based on the promising result by hydrotropic extraction of natural product, thus it is a promising method in administering theobromine from cocoa bean shell Keywords: hydrotropic, extraction, theobromine, cocoa bean shell

Cacao to cocoa to chocolate: healthy food?

Abstract: Chocolate is derived from cocoa beans - the fruit of the cacao tree or Theobroma cacao (the latin term: food of the gods). Recent published articles demonstrate that the quality and quantity of the antioxidants in cocoa and chocolate are very high and their flavonoids are believed to reduce the number of free radicals in the body that contribute to medical problems, such as cardiovascular disease and cancer and also to offer some anti-aging health benefits. Cocoa can lower the leukotriene/ prostacyclin ratio and is shown to have beneficial effects on platelets and possibly inflammation and vessel dilation. They inhibit low-density lipoprotein (LDL) oxidation, raise the high-density lipoprotein (HDL) level and reduce the thrombotic tendency. Their antioxidant catechin content is four times that of tea. They help the body process nitric oxide. Their flavanols and procyanidins have inhibitory effects on hemolysis, they can also attribute as a defense against reactive oxygen species (ROS) and can inhibit their carcinogenic processes. Also they are shown to inhibit growth and polyamine biosynthesis of human colonic cancer cells. They contain tryptophan and anandamide, which lessen anxiety, promote relaxation and trigger the production of endorphins. Cocoa can prevent dental caries and may play a regulating role in the function of the immune system and prevent infectious and autoimmune diseases. It stimulates lactase enzyme activity. Although caffeine may be harmful in large dose, chocolate contains it in small amount in comparison to coffee and tea. Negative effects of chocolate on childhood hyperactivity and migraine as well as tension headaches are controversial. Since the theobromine content of chocolate relaxes the esophageal sphincter, patients suffering from heartburn should avoid it. Cocoa can trigger some allergic reactions such as atopic dermatitis. This article reviews the potential health benefits and disadvantages of cocoa & chocolate and suggests that their flavonoid-rich types are health beneficial and when consumed in moderation, along with other plant foods, can be part of a healthy diet.

First artificial acidic fluorescent receptors for caffeine and other xanthine alkaloids

Abstract: Recognition of three xanthine alkaloids caffeine, theobromine and theophylline with acidic fluorescent receptors has been achieved for the first time through the host–guest interaction. The designed receptors are based on the choice of different fluorophores as spacers which can accommodate the bicyclic xanthine guests in between the binding phenolic hydroxyl or carboxyl groups. Among all the xanthine alkaloids, caffeine being the strongest base, its binding constants were maximum though all the nitrogens of caffeine are methylated. Photochemically the trans isomers were converted to the cis isomers which generated cavities for better binding of the xanthine alkaloids. Receptor 4-{4-[4′-(3-Carboxypropoxy)phynylazo]phenoxy}butyric acid (5) has been shown to be most effective in enhancement of fluorescence intensity with caffeine complexation. The binding properties have been studied by a combination of experimental techniques such as UV-visible and fluorescence spectroscopy. Also solid state binding performance between receptor 4,4′-Diazenyldiphenol (4) and caffeine has been described.

Simultaneous determination of theobromine, paraxanthine, theophylline, and caffeine in urine by reversed-phase high-performance liquid chromatography with diode array uv detection

Abstract: A reversed-phase high performance liquid chromatographic method was improved for the simultaneous determination of theobromine, paraxanthine, theophylline, and caffeine in urine. The method includes a liquid-liquid extraction at alkaline pH with ethylacetate. The 7-(2,3-dihidroxypropyl) theophylline was used as an internal standard (ISTD). The separation was achieved on a C18 column using 14:86 methanol:buffer (25 mM KH2PO4 adjusted to pH 4 with ortho-phosphoric acid) solution as mobile phase under isocratic conditions at a flow rate 1 mL min−1. An ultraviolet absorption at 274 nm was monitored. In these conditions, the LOD was 0.03 μg mL−1 for theobromine, 0.02 μg mL−1 for paraxanthine, 0.04 μg mL−1 for theophylline, and 0.08 μg mL−1 for caffeine. The method has been applied to urine samples.

Essential region for 3-N methylation in N-methyltransferases involved in caffeine biosynthesis

Abstract: The caffeine biosynthetic pathway is composed of three methylation steps, and N-methyltransferase catalyzing each step has high substrate specificity. Since the amino acid sequences among coffee 7-methylxanthosine synthase (CmXRS1), theobromine synthase, and caffeine synthase are highly homologous to each other, these substrate specificities seem to be determined in a very restricted region. The analysis of site-directed mutants for CmXRS1 that naturally acts at the initial step, i.e., 7-N methylation of xanthosine, revealed that the activity of 3-N methylation needs a histidine residue at corresponding position 161 in the CmXRS1 sequence. We succeeded in producing the mutant enzyme which can catalyze the first and second methylation steps in caffeine biosynthesis.

Therapeutic combinations of theobromine and an antihistamine

Abstract: An agent comprises theobromine and an antihistamine, as a combined preparation for simultaneous, sequential or separate use in therapy, particularly in the therapy of cough.

Extraction and estimation of theobromine in marketed tea by hptlc and uv method

Abstract: A rapid, simple and sensitive chromatographic method (RP-HPTLC) has been developed for the extraction and quantitative estimation of Theobromine in different extract tea samples (Camellia sinensis). Separation was performed on Silica gel 60 f 254 HPTLC plates with ethyl acetate: methanol (27:3 v/v), as mobile phase. The determination was carried out in the UV region, using densitometric absorbance at 274 nm. The maximum concentration of Theobromine in tea samples was found to be 2.313 %. The theobromine response was found to be linear over range 3-15 µg per zone. Limit of detection and quantitation were found to be 30 and 140 ng/ spot respectively. The HPTLC method was validated in terms of precision, accuracy, sensitivity and robustness. The proposed method provided precise and accurate analysis for extraction and estimation of theobromine by HPTLC-UV.

Identification of Paraxanthine as the Most Potent Inhibitor of TGF-β Dependent Connective Tissue Growth Factor Expression Among the Three Primary Caffeine Metabolites - A New Approach in the Pharmacological Management of Chronic Fibrogenic Diseases?

Abstract: Several epidemiological studies suggest that coffee drinking is associated with a slower progression of fibrogenesis in patients with chronic, particularly alcoholic, liver disease. However, a causal, mechanistic explanation was pending. New results indicate that the methylxanthine caffeine, major component of coffee and the most widely consumed pharmacologically active substance in the world, might be responsible for this phenomenon as it inhibits the synthesis of Connective Tissue Growth Factor (CTGF/CCN2) in liver parenchymal and non-parenchymal cells, primarily by inducing degradation of Smad2 (and to a much lesser extent Smad3). In particular paraxanthine has been identified as the most potent inhibitor of CTGF synthesis among the three primary metabolites of caffeine, i.e. paraxanthine, theophylline, and theobromine. CTGF plays a crucial role in the fibrotic remodeling of various organs which has therefore frequently been proposed as therapeutic target in the management of fibrotic disorders. This article summarizes the clinical- epidemiological observations as well as the pathophysiological background and provides suggestions for the therapeutic use of methylxanthine derivatives in the management of fibrotic liver diseases.

Drug combination with theobromine and its use in therapy

Abstract: An agent comprises theobromine and another non-opiate antitussive, for simultaneous, sequential or separate use in therapy. Preferably, the therapy is of cough.

Principaux effets neurotropes et psychotropes des méthylxanthines (caféine, théophylline, théobromine, paraxanthine) Main neurotropic and psychotropic effects of methylxanthines (caffeine, theophylline, theobromine, paraxanthine)

Abstract: RésuméLa caféine, alcaloïde principal du café, est la triméthyl 1-3-7 xanthine. Elle est présente en plus faible quantité dans le thé et le chocolat, au côté de diméthylxanthines: la théophylline, 1-3 diméthylxanthine, dans le thé, et la théobromine, 3-7 diméthylxanthine, dans le chocolat. La paraxanthine, 1-7 diméthylxanthine, est issue du métabolisme hépatique de la caféine par le cytochrome 1A2. Les effets de ces méthylxanthines sur l’éveil, l’anxiété, la neuroprotection dans les maladies d’Alzheimer et de Parkinson, l’humeur, la schizophrénie, l’épilepsie, la douleur sont ici brièvement considérés. Cette revue est conclue en soulignant que dans les café, thé, chocolat, l’effet de ces méthylxanthines est complété et parfois revisité par diverses substances associées, tels des polyphénols aux propriétés antioxydantes.AbstractCaffeine, the main alkaloid in coffee, corresponds to the 1-3-7 trimethylxanthine. Its concentration is lower in tea and chocolate, where it is associated with theophylline, 1-3 dimethylxanthine, in tea and with theobromine, 3-7 dimethylxanthine, in chocolate. Paraxanthine, 1-7dimethylxanthine, for its part, is produced by the hepatic metabolism of caffeine operated by a cytochrome of 1A2 type. The effects of these methylxanthines on awaking, anxiety, neuroprotection in Alzheimer’s and Parkinson’s diseases, mood, schizophrenia and nociception are briefly considered. This review is concluded by indicating that these effects of methylxanthines may be modified by various associated substances, such as polyphenols displaying antioxydant properties.

Methylxanthine content in hot drinks consumed in the State of Kuwait

Abstract: Apart from four major catechins present in Camellia sinensis (tea), four major methylxanthines are also present in tea aqueous extract. Caffeine with its structural similarity to uric acid is the predominant methylxanthine in tea and it is known to contribute to hypertension and obesity leading to diabetes. Caffeine intake from tea, soft drinks and candies may be contributing to high level of obesity and diabetes prevalent in Kuwait. There are a variety of hot drinks that are traditional to the culture of Kuwait and their caffeine content has not been established. In this study we have undertaken to establish caffeine content in traditional hot drinks used in Kuwait and have found that Arabic Gahwa, a very popular hot drink in Kuwait, has one of the lowest caffeine content among coffee drinks but its high frequency of consumption may have an additive effect on caffeine intake. Caffeine content of commercial brands and herbal teas used in Kuwait has also been established and found that Rabea black tea had the highest caffeine and theobromine content, while Red label black tea has the lowest caffeine. Reverse phase high performance liquid chromatography (HPLC) was used to establish methylxanthine content in different tea aqueous extracts. A comparison of caffeine content in various hot drinks is presented.

Theobromine for the treatment of cough

Abstract: The present invention is theobromine as an active agent to be delivered via the inhaled route, for the treatment of cough.

Effects of theobromine, a caffeine-like substance found in cocoa and chocolate, on mood and vigilance

Abstract: Like caffeine (CAF), theobromine (ThBr) is a methylxanthine found in foods such as cocoa and chocolate that might influence mood. ThBr crosses the blood-brain barrier and binds to adenosine recepto...

Interactions of xanthine and its derivatives with cyclodextrins in aqueous solutions

Abstract: Using calorimetry, 1H NMR, UV spectroscopy, and solubility methods, the interactions of natural and hydroxypropylated 6h-, β-, and γ-cyclodextrins with xanthine and its methylated derivatives (theophylline, theobromine, and caffeine) were studied in aqueous solutions at 298.15 K. Cyclodextrins revealed low complexation ability toward xanthine and its methylated derivatives. Hydroxypropyl-γ-cyclodextrin with the largest internal cavity is the most effective solubilizing agent for this type of compounds. The calculated thermodynamic parameters are discussed in terms of structural effects of cyclodextrins and purine alkaloids on the character of their intermolecular interactions in aqueous medium.

Use of combination of extract of lotus, extract of pomegranate (Punica granatum) and methylxanthine comprising e.g. caffeine and theophylline, or plant extract rich in methylxanthines, as agent to prevent signs of aging of skin or hair

Abstract: Use of a combination of at least two active ingredients comprising (i) an extract of lotus, (ii) an extract of pomegranate ( Punica granatum) and (iii) a methylxanthine comprising caffeine, theophylline, theobromine or paraxanthine, or plant extract rich in methylxanthines, as agent for preventing or reducing the signs of aging of the skin or hair, is claimed. ACTIVITY : Dermatological; Endocrine-Gen. MECHANISM OF ACTION : 5' Adenosine monophosphate activated protein kinase activator.