Showing papers on "Theobromine published in 2022"

Selection of Aptamers for Sensing Caffeine and Discrimination of Its Three Single Demethylated Analogues.

Abstract: With the growing consumption of caffeine-containing beverages, detection of caffeine has become an important biomedical, bioanalytical, and environmental topic. We herein isolated four high-quality aptamers for caffeine with dissociation constants ranging from 2.2 to 14.6 μM as characterized using isothermal titration calorimetry. Different binding patterns were obtained for the three single demethylated analogues: theobromine, theophylline, and paraxanthine, highlighting the effect of the molecular symmetry of the arrangement of the three methyl groups in caffeine. A structure-switching fluorescent sensor was designed showing a detection limit of 1.2 μM caffeine, which reflected the labeled caffeine concentration within 6.1% difference for eight commercial beverages. In 20% human serum, a detection limit of 4.0 μM caffeine was achieved. With the four aptamer sensors forming an array, caffeine and the three analogues were well separated from nine other closely related molecules.

Pharmacokinetics of Caffeine: A Systematic Analysis of Reported Data for Application in Metabolic Phenotyping and Liver Function Testing

Abstract: Caffeine is by far the most ubiquitous psychostimulant worldwide found in tea, coffee, cocoa, energy drinks, and many other beverages and food. Caffeine is almost exclusively metabolized in the liver by the cytochrome P-450 enzyme system to the main product paraxanthine and the additional products theobromine and theophylline. Besides its stimulating properties, two important applications of caffeine are metabolic phenotyping of cytochrome P450 1A2 (CYP1A2) and liver function testing. An open challenge in this context is to identify underlying causes of the large inter-individual variability in caffeine pharmacokinetics. Data is urgently needed to understand and quantify confounding factors such as lifestyle (e.g., smoking), the effects of drug-caffeine interactions (e.g., medication metabolized via CYP1A2), and the effect of disease. Here we report the first integrative and systematic analysis of data on caffeine pharmacokinetics from 141 publications and provide a comprehensive high-quality data set on the pharmacokinetics of caffeine, caffeine metabolites, and their metabolic ratios in human adults. The data set is enriched by meta-data on the characteristics of studied patient cohorts and subjects (e.g., age, body weight, smoking status, health status), the applied interventions (e.g., dosing, substance, route of application), measured pharmacokinetic time-courses, and pharmacokinetic parameters (e.g., clearance, half-life, area under the curve). We demonstrate via multiple applications how the data set can be used to solidify existing knowledge and gain new insights relevant for metabolic phenotyping and liver function testing based on caffeine. Specifically, we analyzed 1) the alteration of caffeine pharmacokinetics with smoking and use of oral contraceptives; 2) drug-drug interactions with caffeine as possible confounding factors of caffeine pharmacokinetics or source of adverse effects; 3) alteration of caffeine pharmacokinetics in disease; and 4) the applicability of caffeine as a salivary test substance by comparison of plasma and saliva data. In conclusion, our data set and analyses provide important resources which could enable more accurate caffeine-based metabolic phenotyping and liver function testing.

CsMYB184 regulates caffeine biosynthesis in tea plants

Abstract: As the most well-known and globally consumed central nervous system stimulant, caffeine is a purine alkaloid natural product usually derived from tea and coffee. Caffeine has a wide range of health benefits on the human body, and plays crucial roles in pollination, resistance to herbivore attacks, and pathogen infections in plants (Zhao et al., 2020). While caffeine biosynthetic pathways have been extensively studied in tea (Camellia sinensis L) and coffee plants, the regulation of caffeine biosynthesis is not understood (Zhao et al., 2020). Tea Caffeine Synthase1 (TCS1) is the first N-methyltransferase gene reported in the tea plant, possessing the 1-N methyltransferase activity responsible for converting theobromine to caffeine (Kato et al., 2000). Studies on the structure–activity of TCS1 and genetic variations in the TCS1 gene of tea plant populations have supported that TCS1 is a determination enzyme for caffeine content (Jin et al., 2016). To explore the regulation of caffeine biosynthesis, 23 candidate transcription factors (TFs) from Weighted Gene Co-expression Network Analysis were screened in a luciferase reporter gene activation system driven by the TCS1 promoter (Figure S1). MYB184 (TEA029017) showed the highest TCS1 promoter activation with 4.7-fold (Figure 1a). Yeast one-hybrid assay showed that the 828 to 1670 bp region of TCS1 promoter, which contains an MYBCORE and a fused MYB1AT-MYBPLANT, was critically required for MYB184 recognition (Figure 1b). In planta promoter, trans-activation assays further confirmed the regions required for binding to and activating of the TCS1 promoter by MYB184 to be between 1596 and 1670 bp (Figure 1c). EMSA assay was performed to further validate the binding of MYB184 to the fused MYB1AT-MYBPLANT motif in vitro (Figure 1d–f). We then examined the function of MYB184 in regulating caffeine synthesis in tea plants. An antisense oligodeoxynucleotide (asODN) interference experiment was performed with tea plant shoot tips to knock down MYB184 expression (MYB184-KD) (Figure 1g). Accordingly, caffeine contents and the expression of TCS1 were significantly reduced in MYB184-KD shoot tips compared with the senseODN control (Figure 1h–i). However, overexpression of MYB184 (MYB184OE) in tea plant transgenic hairy root lines significantly up-regulated TCS1 transcription and thereby increased the caffeine contents as compared with wildtype root controls (Figure 1j–m). KeKecha (Camellia ptilophylla, KKC in short), belonging to the Thea section, had significantly lower caffeine but higher theobromine (Figure 1n). Although a previous study showed that TCS1 in KKC had lower NMT activity compared with TCS1 in modern tea cultivars (Jin et al., 2016), we detected a significantly lower expression level of TCS1 in KKC than in other tea cultivars (Figure 1o). To understand why TCS1 in KKC is downregulated, we cloned and compared the promoter sequences of TCS1 from KKC and from SCZ. However, the alignment of the promoter sequences did not show critical Indels or SNPs on MYB binding sites (Figure 1p). On the other hand, transcriptome analyses showed that only MYB184 expression level was significantly lower by ~14-fold in KKC than in other tea cultivars (Figure 1q,r). We thus proposed that the lower MYB184 transcript level in KKC might be the cause of the reduced TCS1 expression level. We further cloned the promoter of the MYB184 gene from KKC (proMYB184), and compared it with those from other tea cultivars. A 437-bp long terminal repeat (LTR) insertion was identified only in the proMYB184 at the site of 982 bp, but not in these promoters from other tea cultivars, as verified with both MYB184 promoter cloning and detection with PCR primers specific for the LTR insertion (Figure 1s). In tea plants, LTR insertion in a gene usually leads to suppression of the gene expression (Xia et al., 2020), which may explain the lower expression level of MYB184 in KKC than in other tea cultivars. Indeed, GUS reporter assays showed that the proMYB184 with the LTR insertion exhibited clearly lower promoter activity than four representative promoters without the LTR insertion from tea cultivars (Figure 1t). We thus concluded that the LTR insertion in the promoter of MYB184 resulted in suppressed MYB184 expression, leading to the lower TCS1 transcript level and thereby lower caffeine contents in KKC. To expand MYB184 activation of TCS1 to other Camellia species, we examined several other wild tea relatives that are known to contain significantly lower levels of caffeine compared with modern tea cultivars (Figure 1u). They also have lower TCS1 and MYB184 expression levels compared with modern tea cultivars containing higher levels of caffeine (Figures 1v,w and S2). This further supports the indispensable role of MYB184 in activation of TCS1 gene expression and caffeine biosynthesis in C. sinensis. In summary, we characterized MYB184 as the major activator of TCS1 and caffeine production in tea plants. An LTR insertion in the MYB184 promoter in wild tea C. ptilophylla explained its low TCS1 expression level and caffeine content. Our study may offer a

Tea and its components reduce the production of uric acid by inhibiting xanthine oxidase

Abstract: Background The health benefits of tea are as diverse including the reduction of uric acid levels. Xanthine oxidase is the most directly mediated enzyme in the production of uric acid. Objective To explore the inhibitory effects of different teas and its main bioactive components on the production of uric acid. Design Experimental study. The experiments were conducted in vitro using human immortalized normal liver cell line HL-7702 (L-02). Results The inhibition of the xanthine oxidase activities and the expression level of xanthine dehydrogenase mRNA stimulated in the hyperuric hepatocyte cell model showed that the unfermented green tea and th1e lightly fermented yellow tea, white tea, and oolong tea significantly stronger than the highly fermented black tea and dark tea. The main bioactive compound, gallic acid, showed the strongest inhibitory effect on uric acid production, followed by tea polyphenols and theaflavins. Discussion All teas exhibited significant inhibition of xanthine oxidase activities, and the degree of fermentation of tea may be inversely proportional to its ability to inhibit the production of uric acid. Compared with tea polyphenols rich in tea, gallic acid may be a more potential uric acid-lowering component. Conclusion In this article, we first compared the effects of six traditional Chinese tea made from a single variety in stabilizing the synthesis of uric acid and found that the lighter the fermentation, the greater the potential for inhibiting the production of uric acid. Furthermore, we analyzed the inhibitory effects of its main biochemical active ingredients and found that the inhibitory effects of polyphenols rich in lightly fermented tea were significantly stronger than caffeine rich in highly fermented tea. Our findings will be helpful for people to choose a proper tea for alleviating hyperuricemia and provide a scientific basis for uric acid-lowering tea processing.

New Anticancer Theobromine Derivative Targeting EGFRWT and EGFRT790M: Design, Semi-Synthesis, In Silico, and In Vitro Anticancer Studies

Abstract: Based on the pharmacophoric features of EGFR inhibitors, a new semisynthetic theobromine-derived compound was designed to interact with the catalytic pocket of EGFR. Molecular docking against wild (EGFRWT; PDB: 4HJO) and mutant (EGFRT790M; PDB: 3W2O) types of EGFR-TK indicated that the designed theobromine derivative had the potential to bind to that pocket as an antiangiogenic inhibitor. The MD and MM-GBSA experiments identified the exact binding with optimum energy and dynamics. Additionally, the DFT calculations studied electrostatic potential, stability, and total electron density of the designed theobromine derivative. Both in silico ADMET and toxicity analyses demonstrated its general likeness and safety. We synthesized the designed theobromine derivative (compound XI) which showed an IC50 value of 17.23 nM for EGFR inhibition besides IC50 values of 21.99 and 22.02 µM for its cytotoxicity against A549 and HCT-116 cell lines, respectively. Interestingly, compound XI expressed a weak cytotoxic potential against the healthy W138 cell line (IC50 = 49.44 µM, 1.6 times safer than erlotinib), exhibiting the high selectivity index of 2.2. Compound XI arrested the growth of A549 at the G2/M stage and increased the incidence of apoptosis.

Therapeutic Properties of Green Tea: A Review

Abstract: The most consumed beverage in the world is tea after water. Till today the consumption of black tea is 70% while that of green tea is only 20%. One reason for this percentage is lack of awareness about green tea and invested research. Green tea along with caffeine which imparts characteristic taste, bitterness and stimulating effect, is also rich in a group of chemicals, called Catechin Polyphenols (Commonly known as Tannins, which contribute to bitter taste and astringency) and deliver antioxidant properties. Furthermore, green tea also comprises of amino acids such as Theanine along with alkaloids such as Adenine, Dimethylxanthine, Theobromine, Theophylline and Xanthine. Some vitamins, like vitamin A, vitamin B1, vitamin B2, vitamin B3, vitamin C and vitamin E are also found in green tea. The present review gives the study of various constituents of green tea and their impact on human health. Studies provide strong evidence that owing to antioxidant properties daily intake of green tea may be used as a preventive measure for different types of cancer and other diseases. This review gives a detailed analysis of constituents of green tea and highlighting it's potential as a natural nutraceutical. However, although much of the documented literature mentions positive effect yet much had to be explored on correlation between concentration of green tea and toxicity.

Methylxanthines as Potential Inhibitor of SARS-CoV-2: an In Silico Approach

Abstract: The aim of the present study was to test the binding affinity of methylxanthines (caffeine/theine, methylxanthine, theobromine, theophylline and xanthine) to three potential target proteins namely Spike protein (6LZG), main protease (6LU7) and nucleocapsid protein N-terminal RNA binding domain (6M3M) of SARS-CoV-2. Proteins and ligand were generated using AutoDock 1.5.6 software. Binding affinity of methylxanthines with SARS-CoV-2 target proteins was determined using Autodock Vina. MD simulation of the best interacting complexes was performed using GROMACS 2018.3 (in duplicate) and Desmond program version 2.0 (academic version) (in triplicate) to study the stabile interaction of protein-ligand complexes. Among the selected methylxanthines, theophylline showed the best binding affinity with all the three targets of SARS-CoV-2 (6LZG - 5.7 kcal mol-1, 6LU7 - 6.5 kcal mol-1, 6M3M - 5.8 kcal mol-1). MD simulation results of 100 ns (in triplicate) showed that theophylline is stable in the binding pockets of all the selected SARS-CoV-2 proteins. Moreover, methylxanthines are safer and less toxic as shown by high LD50 value with Protox II software as compared to drug chloroquine. This research supports the use of methylxanthines as a SARS-CoV-2 inhibitor. It also lays the groundwork for future studies and could aid in the development of a treatment for SARS-CoV-2 and related viral infections.The online version contains supplementary material available at 10.1007/s40495-021-00276-3.

Methylxanthines as Potential Inhibitor of SARS-CoV-2: an In Silico Approach

Abstract: The aim of the present study was to test the binding affinity of methylxanthines (caffeine/theine, methylxanthine, theobromine, theophylline and xanthine) to three potential target proteins namely Spike protein (6LZG), main protease (6LU7) and nucleocapsid protein N-terminal RNA binding domain (6M3M) of SARS-CoV-2. Proteins and ligand were generated using AutoDock 1.5.6 software. Binding affinity of methylxanthines with SARS-CoV-2 target proteins was determined using Autodock Vina. MD simulation of the best interacting complexes was performed using GROMACS 2018.3 (in duplicate) and Desmond program version 2.0 (academic version) (in triplicate) to study the stabile interaction of protein-ligand complexes. Among the selected methylxanthines, theophylline showed the best binding affinity with all the three targets of SARS-CoV-2 (6LZG - 5.7 kcal mol-1, 6LU7 - 6.5 kcal mol-1, 6M3M - 5.8 kcal mol-1). MD simulation results of 100 ns (in triplicate) showed that theophylline is stable in the binding pockets of all the selected SARS-CoV-2 proteins. Moreover, methylxanthines are safer and less toxic as shown by high LD50 value with Protox II software as compared to drug chloroquine. This research supports the use of methylxanthines as a SARS-CoV-2 inhibitor. It also lays the groundwork for future studies and could aid in the development of a treatment for SARS-CoV-2 and related viral infections.The online version contains supplementary material available at 10.1007/s40495-021-00276-3.

Antioxidant and sensory evaluation of cocoa (Theobroma cacao L.) tea formulated with cocoa bean hull of different origins

Abstract: Cocoa nibs are the main ingredient for chocolate production while cocoa bean hulls are the major by-product. Uniqueness of this study is that we investigate the antioxidant content and activity of single origin cocoa bean hulls compared to nibs based on their total phenolic content (TPC), total flavonoid content (TFC), free radical scavenging activity (DPPH Assay), ferric reducing powder (FRAP), and ferrous ion chelating (FIC) ability, thus highlighting regional differences. Venezuela raw cocoa bean hull had the highest antioxidant properties and these properties can tolerate roasting up to 100 ⁰C. Roasting temperature influences both the antioxidant properties and the flavor profile of the resulting cocoa tea. Of the 105 respondents of the hedonic survey, 67.64% indicated that they would buy our cocoa tea. Cocoa tea made from Malaysia and Venezuela origin had a higher theobromine content and a much lower caffeine content compared to green tea. In all cases, cocoa tea made primarily from the cocoa bean hull is safe for consumption as the Aflatoxin (B1, B2, G1, G2), Ochratoxin A, and pesticides residues were not detected within the detection limits (0.001 mg/kg and 0.005 mg/kg). It can be concluded that regional differences give a unique flavor profile to the cocoa bean hull and there were differences in terms of antioxidant properties.

From Cocoa to Chocolate: Effect of Processing on Flavanols and Methylxanthines and Their Mechanisms of Action

Abstract: Despite the health benefits associated with the ingestion of the bioactive compounds in cocoa, the high concentrations of polyphenols and methylxanthines in the raw cocoa beans negatively influence the taste, confer the astringency and bitterness, and affect the stability and digestibility of the cocoa products. It is, therefore, necessary to process cocoa beans to develop the characteristic color, taste, and flavor, and reduce the astringency and bitterness, which are desirable in cocoa products. Processing, however, affects the composition and quantities of the bioactive compounds, resulting in the modification of the health-promoting properties of cocoa beans and chocolate. In this advanced review, we sought to better understand the effect of cocoa’s transformational process into chocolate on polyphenols and methylxanthine and the mechanism of action of the original flavanols and methylxanthines. More data on the cocoa processing effect on cocoa bioactives are still needed for better understanding the effect of each processing step on the final polyphenolic and methylxanthine composition of chocolate and other cocoa products. Regarding the mechanisms of action, theobromine acts through the modulation of the fatty acid metabolism, mitochondrial function, and energy metabolism pathways, while flavanols mainly act though the protein kinases and antioxidant pathways. Both flavanols and theobromine seem to be involved in the nitric oxide and neurotrophin regulation.

Vertical Transfer of Metabolites Detectable from Newborn’s Dried Blood Spot Samples Using UPLC-MS: A Chemometric Study

Abstract: The pregnancy period and first days of a newborn’s life is an important time window to ensure a healthy development of the baby. This is also the time when the mother and her baby are exposed to the same environmental conditions and intake of nutrients, which can be determined by assessing the blood metabolome. For this purpose, dried blood spots (DBS) of newborns are a valuable sampling technique to characterize what happens during this important mother-child time window. We used metabolomics profiles from DBS of newborns (age 2–3 days) and maternal plasma samples at gestation week 24 and postpartum week 1 from n=664 mother-child pairs of the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC2010) cohort, to study the vertical mother-child transfer of metabolites. Further, we investigated how persistent the metabolites are from the newborn and up to 6 months, 18 months, and 6 years of age. Two hundred seventy two metabolites from UPLC-MS (Ultra Performance Liquid Chromatography-Mass Spectrometry) analysis of DBS and maternal plasma were analyzed using correlation analysis. A total of 11 metabolites exhibited evidence of transfer (R>0.3), including tryptophan betaine, ergothioneine, cotinine, theobromine, paraxanthine, and N6-methyllysine. Of these, 7 were also found to show persistence in their levels in the child from birth to age 6 years. In conclusion, this study documents vertical transfer of environmental and food-derived metabolites from mother to child and tracking of those metabolites through childhood, which may be of importance for the child’s later health and disease.

Purine alkaloids in tea plants: component, biosynthetic mechanism and genetic variation

Abstract: The purine alkaloids, including caffeine, theobromine, and theacrine, are one of the most important quality and functional components of tea plants and commercial teas. In this paper, we review the component, biosynthetic mechanism and genetic variation of purine alkaloids in tea plants. The content of caffeine and theobromine in 403 accessions Chinese tea germplasms core collection preserved in the National Germplasm Hangzhou Tea Repository were analyzed using High Performance Liquid Chromatography (HPLC). The purine alkaloid profiles of different tea varieties, germplasm types, geographical origin, seasons, were highlighted. Some naturally low caffeine or caffeine-free, high theobromine or high theacrine germplasms were identified and the possible biosynthetic mechanism of hypernormal purine alkaloid content in tea plants were partially revealed. Some Cleaved Amplified Polymorphic Sequences (CAPS) DNA markers were developed for the identification of purine alkaloid content. The potential application of genetic engineering and DNA markers developed based on the low caffeine TCS1 (tea caffeine synthesis gene) alleles for marker assisted selection (MAS), and cocoa tea and kucha in low caffeine/high theacrine tea cultivar breeding programs were also reviewed.

Effect of Hydroxybenzoic Acids on Caffeine Detection Using Taste Sensor with Lipid/Polymer Membranes

Abstract: A taste sensor with lipid/polymer membranes can objectively evaluate taste. As previously reported, caffeine can be detected electrically using lipid/polymer membranes modified with hydroxybenzoic acids (HBAs). However, a systematic understanding of how HBAs contribute to caffeine detection is still lacking. In this study, we used various HBAs such as 2,6–dihydroxybenzoic acid (2,6–DHBA) to modify lipid/polymer membranes, and we detected caffeine using a taste sensor with the modified membranes. The effect of the concentrations of the HBAs on caffeine detection was also discussed. The results of the caffeine detection indicated that the response to caffeine and the reference potential measured in a reference solution were affected by the log P and pKa of HBAs. Furthermore, the taste sensor displayed high sensitivity to caffeine when the reference potential was adjusted to an appropriate range by modification with 2,6–DHBA, where the slope of the change in reference potential with increasing 2,6–DHBA concentration was steep. This is helpful in order to improve the sensitivity of taste sensors to other taste substances, such as theophylline and theobromine, in the future.

The association between caffeine intake and testosterone: NHANES 2013–2014

Abstract: Abstract Background Caffeine is one of the most commonly used psychoactive drugs in the world, and provides many health benefits including alertness, improved memory, and reducing inflammation. Despite these benefits, caffeine has been implicated in a number of adverse health outcomes possibly due to effects within the endocrine system, effects that may contribute to impaired reproductive function and low testosterone in men. Previous studies have investigated associations between caffeine consumption and testosterone levels in men, although the quantity and generalizability of these studies is lacking, and the results between studies are conflicting and inconclusive. Methods Using data from a cross-sectional study of 372 adult men in the 2013–2014 NHANES survey cycle, the researchers set out to characterize the association between serum testosterone levels, caffeine, and 14 caffeine metabolites. Results Multivariable, weighted linear regression revealed a significant inverse association between caffeine and testosterone. Multivariable, linear regression revealed significant, inverse associations between 6 xanthine metabolic products of caffeine and testosterone. Inverse associations were observed between 5-methyluric acid products and testosterone, as well as between 5-acetlyamino-6-amino-3-methyluracil and testosterone. A significant, positive association was observed for 7-methyl xanthine, 3,7-dimethyluric acid, and 7-methyluric acid. Logistic regression models to characterize the association between 2 biologically active metabolites of caffeine (theobromine and theophylline) and odds of low testosterone (< 300 ng/dL) were non-significant. Conclusions These findings suggest a potential role for caffeine’s contribution to the etiology of low testosterone and biochemical androgen deficiency. Future studies are warranted to corroborate these findings and elucidate biological mechanisms underlying this association.

Immunostimulatory Activities of Theobromine on Macrophages via the Activation of MAPK and NF-κB Signaling Pathways

Abstract: Theobromine is mainly found in plant foods, such as tea; the primary source of theobromine is the seeds of the Theobroma cacao tree. Theobromine is an alkaloid belonging to the methylxanthine class of drugs, and it is similar to theophylline and caffeine. Theobromine is known for its efficacy and role in health and disorder prevention. We evaluated the effects of theobromine on macrophage function, including the phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB). Theobromine significantly stimulated the production of nitric oxide (NO) and prostaglandin E2 through immune responses, which relate to the increased expression of inducible nitric oxide synthase and cyclooxygenase-2. Additionally, theobromine increased the production of inflammatory cytokines, including tumor necrosis factor-α and interleukin-6 in macrophages. Additionally, theobromine induced the translocation and activity of NF-κB in a concentration-dependent manner. Consistent with these results, the phosphorylation level of MAPKs was increased in theobromine-stimulated macrophages. Collectively, these data revealed that theobromine acts as an immune response stimulator via the NF-κB and MAPKs signaling pathways. Thus, theobromine might have protective effects against inflammatory disorders.

Comparative Analysis of Purine Alkaloids and Main Quality Components of the Three Camellia Species in China

Abstract: Tea (Camellia sinensis var. sinensis) is a widely consumed caffeine-containing beverage, however the Camellia genus also includes other species, which are consumed as tea in their local growing regions. Presently, HPLC analysis assessed 126 unique Camellia germplasms belonging to three Camellia species, C. sinensis var. pubilimba Chang (Csp), C. gymnogyna Chang (CgC) and C. crassicolumna Chang (CcC). Theobromine was the predominant purine alkaloid in all species, representing over 90% of purine alkaloids in Csp and CgC, and 50% in CcC. Significant variability existed in purine alkaloid patterns both between and within species, and some germplasms possessed highly unique alkaloid profiles. Sensory evaluation and quality composition analysis of green tea products produced from the three Camellia species suggested their unsuitability for use in tea production due to their unpalatable flavor. The results of this study revealed the differences in purine alkaloids and main quality components between Camellia species and tea, which contributed to understand why tea, rather than other Camellia species, has become a popular beverage in the world after long-term artificial selection. In addition, unique alkaloid profiles suggest usefulness of these germplasm resources in future breeding of decaffeinated tea plant varieties and alkaloid metabolism research.

The Effect of In Vitro Digestion on Matcha Tea (Camellia sinensis) Active Components and Antioxidant Activity

Abstract: This study investigates the effects of in vitro digestion on the antioxidant activity and release of phenolics, xanthine alkaloids, and L-theanine contents of matcha. It establishes digestibility values between 61.2–65.8%. Considering native matcha, the rutin content (303–479 µg/g) reached higher values than catechin (10.2–23.1 µg/g). Chlorogenic acid (2090–2460 µg/g) was determined as predominant. Rutin, quercetin, ferulic, ellagic, and caffeic acid were the least-released phenolics, and their remaining residues reached 76–84%. Protocatechuic, hydroxybenzoic acid, epigallocatechin, and epigallocatechin-3-gallate were the best-released phenolics, with the remaining residues under 1%. Caffeine, L-theanine, and theobromine contents in native matcha reached 16.1, 9.85, and 0.27 mg/g, respectively. Only caffeine (3.66–5.26 mg/g) and L-theanine (0.09–0.15 mg/g) were monitored in the undigested residue, representing 13 and 0.1% of the remaining part, respectively. A chemiluminescence assay showed that water-soluble antioxidants showed significant antioxidant activity in native matcha, while lipid-soluble compounds showed higher antioxidant activity in the undigested samples. Cinnamic and neochlorogenic acids were determined as the main contributors to the ACW values in the undigested matcha, epicatechin, and quercetin in the ACL fraction. The application of the digestion process reduced the antioxidant activity by more than 94%. SEM has proved specific digestion patterns of in vitro digestibility of matcha.

Methylxanthines Induce a Change in the AD/Neurodegeneration-Linked Lipid Profile in Neuroblastoma Cells

Abstract: Alzheimer’s disease (AD) is characterized by an increased plaque burden and tangle accumulation in the brain accompanied by extensive lipid alterations. Methylxanthines (MTXs) are alkaloids frequently consumed by dietary intake known to interfere with the molecular mechanisms leading to AD. Besides the fact that MTX consumption is associated with changes in triglycerides and cholesterol in serum and liver, little is known about the effect of MTXs on other lipid classes, which raises the question of whether MTX can alter lipids in a way that may be relevant in AD. Here we have analyzed naturally occurring MTXs caffeine, theobromine, theophylline, and the synthetic MTXs pentoxifylline and propentofylline also used as drugs in different neuroblastoma cell lines. Our results show that lipid alterations are not limited to triglycerides and cholesterol in the liver and serum, but also include changes in sphingomyelins, ceramides, phosphatidylcholine, and plasmalogens in neuroblastoma cells. These changes comprise alterations known to be beneficial, but also adverse effects regarding AD were observed. Our results give an additional perspective of the complex link between MTX and AD, and suggest combining MTX with a lipid-altering diet compensating the adverse effects of MTX rather than using MTX alone to prevent or treat AD.

Physicochemical characteristics and bioactive compound profiles of Arabica Kalosi Enrekang with different postharvest processing

Abstract: This work aimed to understand and evaluate the impacts of postharvest procedures on physicochemical characteristics and bioactive compounds (CQAs and alkaloids) of green bean and roasted bean. Arabica green bean of kalosi Enrekang was obtained from different procedures: natural, honey and full-washed, and followed with medium roasting, powdered, and extracted using boiling water. A single-factor ANOVA and t-test was arranged to evaluate data, and OPLS-DA was applied to produce mapping. As the results, full washed processed green beans demonstrated a high lightness, while honey processed green beans showed a high chromaticity a*. Natural processed green beans contained a high CQAs, whereas honey processed green beans contained the highest quantity of alkaloids. In terms of caffeine, natural and honey processed green beans exhibited equal levels. In addition, honey roasted beans contained a high content of 3-CQA and 4-CQA, while full-washed processed roasted beans contained a high level of theobromine. The roasting process was reported to reduce the content of total CQAs and alkaloids.

Neuroprotective Effects of Theobromine in permanent bilateral common carotid artery occlusion rat model of cerebral hypoperfusion

Abstract: Cerebral hypoperfusion (CH) is a common underlying mechanism of dementia disorders linked to aberrations in the neurovascular unit. Hemodynamic disturbances adversely affect cellular energy homeostasis that triggers a sequence of events leading to irrevocable damage to the brain and neurobehavioral discrepancies. Theobromine is a common ingredient of many natural foods consumed by a large population worldwide. Theobromine has shown health benefits in several studies, attributed to regulation of calcium homeostasis, phosphodiesterase, neurotransmission, and neurotrophins. The current study evaluated the neuroprotective potential of theobromine against CH in the permanent bilateral common carotid artery occlusion (BCCAO) prototype. Wistar rats were distributed in Sham-operated (S), S + T100, CH, CH + T50, and CH + T100 groups. Animals received permanent BCCAO or Sham treatment on day 1. Theobromine (50, 100 mg/kg) was given orally in animals subjected to BCCAO for 14 days daily. CH caused neurological deficits (12-point scale), motor dysfunction, and memory impairment in rats. Treatment with theobromine significantly attenuated neurological deficits and improved sensorimotor functions and memory in rats with CH. In biochemistry investigation of the entire brain, findings disclosed reduction in brain oxidative stress, inflammatory intermediaries (tumor necrosis factor-α, interleukin-1β and - 6, nuclear factor-κB), markers of cell demise (lactate dehydrogenase, caspase-3), acetylcholinesterase activity, and improvement in γ-aminobutyric acid quantity in rats that were given theobromine for 14 days daily after CH. Histopathological analysis substantiated attenuation of neurodegenerative changes by theobromine. The findings of this study indicated that theobromine could improve neurological scores, sensorimotor abilities, and memory in CH prototype.