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International Journal of Molecular... Aug 2023Numerous basic studies have reported on the neuroprotective properties of several purine derivatives such as caffeine and uric acid (UA). Epidemiological studies have... (Review)
Review
Numerous basic studies have reported on the neuroprotective properties of several purine derivatives such as caffeine and uric acid (UA). Epidemiological studies have also shown the inverse association of appropriate caffeine intake or serum urate levels with neurodegenerative diseases such as Alzheimer disease (AD) and Parkinson's disease (PD). The well-established neuroprotective mechanisms of caffeine and UA involve adenosine A receptor antagonism and antioxidant activity, respectively. Our recent study found that another purine derivative, paraxanthine, has neuroprotective effects similar to those of caffeine and UA. These purine derivatives can promote neuronal cysteine uptake through excitatory amino acid carrier protein 1 (EAAC1) to increase neuronal glutathione (GSH) levels in the brain. This review summarizes the GSH-mediated neuroprotective effects of purine derivatives. Considering the fact that GSH depletion is a manifestation in the brains of AD and PD patients, administration of purine derivatives may be a new therapeutic approach to prevent or delay the onset of these neurodegenerative diseases.
Topics: Humans; Adenosine A2 Receptor Antagonists; Alzheimer Disease; Brain; Cysteine; Excitatory Amino Acid Transporter 3; Glutathione; Neuroprotection; Neuroprotective Agents; Parkinson Disease; Purines; Receptor, Adenosine A2A; Theophylline; Uric Acid; Caffeine
PubMed: 37685879
DOI: 10.3390/ijms241713067 -
Drug Design, Development and Therapy 2018Theophylline has been used for decades to treat both acute and chronic asthma. Despite its longevity in the practitioner's formulary, no detailed meta-analysis has been... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVE
Theophylline has been used for decades to treat both acute and chronic asthma. Despite its longevity in the practitioner's formulary, no detailed meta-analysis has been performed to determine the conditions, including concomitant medications, under which theophylline should be used for acute exacerbations of asthma. We aimed to quantify the usefulness and side effects of theophylline with or without ethylene diamine (aminophylline) in acute asthma, with particular emphasis on patient subgroups, such as children, adults, and concomitant medications.
METHODS
We searched PubMed, EMBASE, The Cochrane Library, ClinicalTrials.gov, and the WHO Clinical Trials Registry for randomized, controlled clinical trials. We planned a priori subgroup analyses by time post-medication, concomitant medication, control type, and age.
RESULTS
We included 52 study arms from 42 individual trials. Of these, 29 study arms included an active control, such as adrenaline, beta-2 agonists, or leukotriene receptor antagonists, and 23 study arms compared theophylline (with or without ethylene diamine) with placebo or no drug. Theophylline significantly reduced heart rate when compared with active control (=0.01) and overall duration of stay (=0.002), but beta-2 agonists were superior to theophylline at improving forced expiratory volume in one second (FEV1) (=0.002). Theophylline was not significantly different from other drugs in its effects on respiratory rate, forced vital capacity (FVC), peak expiratory flow rate, admission rate, use of rescue medication, oxygen saturation, or symptom score. Closer examination of the data revealed that the medications given in addition to theophylline or control significantly changed the effectiveness of theophylline (subgroup difference: <0.00001).
CONCLUSION
Given the low cost of theophylline, and its similar efficacy and rate of side effects compared with other drugs, we suggest that theophylline, when given with bronchodilators with or without steroids, is a cost-effective and safe choice for acute asthma exacerbations.
Topics: Acute Disease; Administration, Intravenous; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Humans; Theophylline
PubMed: 29391776
DOI: 10.2147/DDDT.S156509 -
Analytical Sciences : the International... Feb 2008Recent progress in analytical terahertz (THz) spectroscopy is reviewed with illustrative examples showing that it is an effective method for detecting and identifying... (Review)
Review
Recent progress in analytical terahertz (THz) spectroscopy is reviewed with illustrative examples showing that it is an effective method for detecting and identifying intermolecular interactions in chemical compounds, such as hydrogen bonds. The unique and characteristic properties of THz waves, their significance to both science and industry, and the bases of one of the successful fields of analytical THz spectroscopy, namely THz time-domain spectroscopy and THz imaging for chemical analysis, are described. Preliminary quantitative studies are presented to show the potential of THz spectroscopy for the detection and identification of intermolecular hydrogen bonds in unknown mixture samples. The selective detection of intramolecular hydrogen bonds and the detection of intramolecular interactions in ice are also introduced. Some brief remarks are provided on future developments, the main issues, and the prospects for analytical THz spectroscopy.
Topics: Carbohydrates; Dinitrobenzenes; Glass; Glutamic Acid; Hydrogen Bonding; Ice; Infrared Rays; Spectrum Analysis; Theophylline; Time Factors; Triazines
PubMed: 18270407
DOI: 10.2116/analsci.24.185 -
Exercise Immunology Review 2014Plant alkaloids are found in foods, beverages, and supplements consumed by athletes for daily nutrition, performance enhancement, and immune function improvement. This... (Review)
Review
Plant alkaloids are found in foods, beverages, and supplements consumed by athletes for daily nutrition, performance enhancement, and immune function improvement. This paper examined possible immunomodulatory roles of alkaloids in exercise contexts, with a focus on human studies. Four representative groups were scrutinized: (a) caffeine (guaranine, mateine); (b) theophylline and its isomers, theobromine and paraxanthine; (c) ginger alkaloids including gingerols and shogaol; and (d) ephedra alkaloids such as ephedrine and pseudoephedrine. Emerging or prospective alkaloid sources (Goji berry, Noni berry, and bloodroot) were also considered. Human in vitro and in vivo studies on alkaloids and immune function were often conflicting. Caffeine may be immunomodulatory in vivo depending on subject characteristics, exercise characteristics, and immune parameters measured. Caffeine may exhibit antioxidant capacities. Ginger may exert in vivo anti-inflammatory effects in certain populations, but it is unclear whether these effects are due to alkaloids or other biochemicals. Evidence for an immunomodulatory role of alkaloids in energy drinks, cocoa, or ephedra products in vivo is weak to nonexistent. For alkaloid sources derived from plants, variability in the reviewed studies may be due to the presence of unrecognized alkaloids or non-alkaloid compounds (which may themselves be immunomodulatory), and pre-experimental factors such as agricultural or manufacturing differences. Athletes should not look to alkaloids or alkaloid-rich sources as a means of improving immune function given their inconsistent activities, safety concerns, and lack of commercial regulation.
Topics: Alkaloids; Anti-Inflammatory Agents; Antioxidants; Athletes; Beverages; Caffeine; Catechols; Diet; Dietary Supplements; Ephedrine; Exercise; Fatty Alcohols; Food; Food Analysis; Humans; Immune System; Immunologic Factors; Molecular Structure; Phytotherapy; Plants, Medicinal; Theophylline
PubMed: 24974722
DOI: No ID Found -
Microbial Cell Factories Mar 2020Caffeine, theobromine and theophylline are main purine alkaloid in tea. Theophylline is the downstream metabolite and it remains at a very low level in Camellia...
BACKGROUND
Caffeine, theobromine and theophylline are main purine alkaloid in tea. Theophylline is the downstream metabolite and it remains at a very low level in Camellia sinensis. In our previous study, Aspergillus sydowii could convert caffeine into theophylline in solid-state fermentation of pu-erh tea through N-demethylation. In this study, tea-derived fungi caused theophylline degradation in the solid-state fermentation. The purpose of this study is identify and isolate theophylline-degrading fungi and investigate their application in production of methylxanthines with theophylline as feedstock through microbial conversion.
RESULTS
Seven tea-derived fungi were collected and identified by ITS, β-tubulin and calmodulin gene sequences, Aspergillus ustus, Aspergillus tamarii, Aspergillus niger and A. sydowii associated with solid-state fermentation of pu-erh tea have shown ability to degrade theophylline in liquid culture. Particularly, A. ustus and A. tamarii could degrade theophylline highly significantly (p < 0.01). 1,3-dimethyluric acid, 3-methylxanthine, 3-methyluric acid, xanthine and uric acid were detected consecutively by HPLC in A. ustus and A. tamarii, respectively. The data from absolute quantification analysis suggested that 3-methylxanthine and xanthine were the main degraded metabolites in A. ustus and A. tamarii, respectively. 129.48 ± 5.81 mg/L of 3-methylxanthine and 159.11 ± 10.8 mg/L of xanthine were produced by A. ustus and A. tamarii in 300 mg/L of theophylline liquid medium, respectively.
CONCLUSIONS
For the first time, we confirmed that isolated A. ustus, A. tamarii degrade theophylline through N-demethylation and oxidation. We were able to biologically produce 3-methylxanthine and xanthine efficiently from theophylline through a new microbial synthesis platform with A. ustus and A. tamarii as appropriate starter strains.
Topics: Aspergillus; Biotransformation; Fermentation; Theophylline; Xanthine; Xanthines
PubMed: 32192512
DOI: 10.1186/s12934-020-01333-0 -
Journal of Nutritional Science and... 2023Skeletal muscle mass is maintained by a balance between the synthesis and degradation of muscle proteins, the collapse of which causes muscle wasting. The prevention of...
Skeletal muscle mass is maintained by a balance between the synthesis and degradation of muscle proteins, the collapse of which causes muscle wasting. The prevention of muscle wasting improves the quality of life and extends a healthy life. The methyl xanthine theophylline showed strong preventive activity against dexamethasone-induced muscle atrophy, as determined using the expression level of myosin heavy chain in C2C12 myotubes. Mechanistically, theophylline inhibited the expression of ubiquitin ligases MuRF1 and Cbl-b, but not that of atrogin-1. Furthermore, theophylline inhibits glucocorticoid receptor translocation to the nucleus. A pull-down assay using a theophylline probe revealed that theophylline and dexamethasone competitively interacted with the glucocorticoid receptor, suggesting an antagonistic activity of theophylline on glucocorticoid receptors. Additionally, theophylline inhibited the dexamethasone-induced phosphorylation of p38 and FoxO3a in C2C12 myotubes. These findings suggest that theophylline is an effective food ingredient in the prevention of glucocorticoid-induced skeletal muscle atrophy.
Topics: Humans; Theophylline; Quality of Life; Receptors, Glucocorticoid; Muscular Atrophy; Muscle Fibers, Skeletal; Dexamethasone
PubMed: 37648515
DOI: 10.3177/jnsv.69.284 -
The Cochrane Database of Systematic... 2001Bronchiectasis is characterised by chronic sputum production,bronchial wall dilation,recurrent infection and airflow limitation. Methylxanthines are used in the... (Review)
Review
BACKGROUND
Bronchiectasis is characterised by chronic sputum production,bronchial wall dilation,recurrent infection and airflow limitation. Methylxanthines are used in the management of airflow limitation associated with asthma and COPD, where they are also purported to have anti-inflammatory properties. In theory they may be of use in bronchiectasis.
OBJECTIVES
To determine the efficacy of methylxanthines in the treatment of bronchiectasis.
SEARCH STRATEGY
The Cochrane Airways Group clinical trials register derived from MEDLINE,EMBASE and hand searches using the terms bronchiectasis, aminophylline, theophylline and methyl- xanthine
SELECTION CRITERIA
Only randomised controlled trials were to be considered.
DATA COLLECTION AND ANALYSIS
The results of the searches were reviewed by two authors. Searches yielded seven trials none of which met the inclusion criteria.
MAIN RESULTS
No randomised controlled trials were identified.
REVIEWER'S CONCLUSIONS
Further research is required to establish if the methylxanthines have a role in the treatment of bronchiectasis.
Topics: Administration, Oral; Aminophylline; Bronchiectasis; Bronchodilator Agents; Humans; Randomized Controlled Trials as Topic; Theophylline
PubMed: 11279764
DOI: 10.1002/14651858.CD002734 -
European Respiratory Review : An... Jun 2018Theophylline can still have a role in the management of stable chronic obstructive pulmonary disease (COPD), but its use remains controversial, mainly due to its narrow... (Meta-Analysis)
Meta-Analysis Review
Theophylline can still have a role in the management of stable chronic obstructive pulmonary disease (COPD), but its use remains controversial, mainly due to its narrow therapeutic window. Doxofylline, another xanthine, is an effective bronchodilator and displays a better safety profile than theophylline. Therefore, we performed a quantitative synthesis to compare the efficacy and safety profile of different xanthines in COPD.The primary end-point of this meta-analysis was the impact of xanthines on lung function. In addition, we assessed the risk of adverse events by normalising data on safety as a function of person-weeks. Data obtained from 998 COPD patients were selected from 14 studies and meta-analysed using a network approach.The combined surface under the cumulative ranking curve (SUCRA) analysis of efficacy (change from baseline in forced expiratory volume in 1 s) and safety (risk of adverse events) showed that doxofylline was superior to aminophylline (comparable efficacy and significantly better safety), bamiphylline (significantly better efficacy and comparable safety), and theophylline (comparable efficacy and significantly better safety).Considering the overall efficacy/safety profile of the investigated agents, the results of this quantitative synthesis suggest that doxofylline seems to be the best xanthine for the treatment of COPD.
Topics: Bronchodilator Agents; Forced Expiratory Volume; Humans; Lung; Pulmonary Disease, Chronic Obstructive; Recovery of Function; Theophylline; Treatment Outcome; Xanthines
PubMed: 29720510
DOI: 10.1183/16000617.0010-2018 -
Methods (San Diego, Calif.) Sep 2019Second-harmonic generation (SHG) is a biophysical tool that senses ligand-induced conformational changes in biomolecules. The Biodesy Delta™ has been developed as a... (Review)
Review
Second-harmonic generation (SHG) is a biophysical tool that senses ligand-induced conformational changes in biomolecules. The Biodesy Delta™ has been developed as a high-throughput screening platform to monitor conformational changes in proteins and oligonucleotides by SHG to support drug discovery efforts. This work will outline (1) an overview of this technology, (2) detailed protocols for optimizing screening-ready SHG assays on RNA targets, (3) practical considerations for developing robust and informative SHG measurements, and (4) a case study that demonstrates the application of these recommendations on an RNA target. The previously published theophylline aptamer SHG assay [1] was further optimized to maximize the assay window between the positive control (theophylline) and the negative control (caffeine). Optimization of this assay provides practical considerations for building a robust SHG assay on an RNA target, including testing for specific tethering of the conjugate to the surface as well as testing tool compound response stability, reversibility, and concentration-dependence/affinity. A more robust, better-performing theophylline aptamer SHG assay was achieved that would be more appropriate for conducting a screen.
Topics: Caffeine; Drug Discovery; High-Throughput Screening Assays; Humans; Ligands; Nucleic Acid Conformation; RNA; Theophylline
PubMed: 31116965
DOI: 10.1016/j.ymeth.2019.05.012 -
The Journal of Asthma : Official... Nov 2022Coffee intake has been inversely associated with asthma in adults. We examined the relation between urinary levels of caffeine or caffeine metabolites and asthma, lung...
OBJECTIVE
Coffee intake has been inversely associated with asthma in adults. We examined the relation between urinary levels of caffeine or caffeine metabolites and asthma, lung function, and fractional exhaled nitric oxide (FeNO) in adults.
METHODS
Cross-sectional study of 2,832 adults aged 18-79 years in the US National Health and Nutrition Examination Survey (NHANES). Multivariable logistic or linear regression was used for the analysis of urinary levels of caffeine or each of its three major metabolites (paraxanthine, theobromine, and theophylline) and current asthma, lung function, and FeNO.
RESULTS
Subjects with urinary paraxanthine levels in the fourth quartile (Q4) had 53% lower odds of current asthma than those whose urinary paraxanthine levels were in the first quartile (Q1; 95% confidence = 0.22 to 1.00). Among never and former smokers, subjects with urinary theophylline levels above Q1 had 49% lower odds of current asthma than those whose urinary theophylline level was in Q1 (95% CI = 0.31 to 0.85). Among subjects without current asthma, each log-unit increment in paraxanthine level was associated with a 0.83% increment in percent predicted (%pred) FEV and a 1.27% increment in %pred FVC, while each log-unit in theophylline was associated with a 1.24% increment in %pred FVC. Neither urinary caffeine nor any urinary caffeine metabolite was associated with bronchodilator response or FeNO.
CONCLUSIONS
Our findings suggest that two caffeine metabolites (theophylline and paraxanthine) may contribute to the previously reported inverse association between coffee intake and asthma in adults.
Topics: Adult; Asthma; Bronchodilator Agents; Caffeine; Coffee; Cross-Sectional Studies; Humans; Lung; Nutrition Surveys; Theobromine; Theophylline
PubMed: 34644210
DOI: 10.1080/02770903.2021.1993250