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Background: Iranian (Lahijan) black tea caffeine has been previously shown to have antifungal activity against Candida albicans. The aim of this study was to investigate whether the combination of caffeine and fluconazole (FLU) has an effective antifungal activity on a FLU-resistant (MIC >64mgL^-1) C. albicans PTCC5027. Materials and Methods: Caffeine from Lahijan black tea was extracted and its pharmacological effects against 20 clinical isolates of FLU-sensitive and resistant C. albicans was evaluated by Colony Forming Units (CFU) method. Furthermore, the synergistic effect of caffeine and FLU against PTCC-5027strain was investigated. Results: Our results indicate the antifungal efficacy of Lahijan black tea caffeine on C. albicans isolates and subsequent identification of caffeine in combination with FLU againstPTCC-5027 strain. The concentrations of caffeine causing 90% growth inhibition (MIC₉₀) for  PTCC-5027 strain, FLU-resistant and -sensitive C. albicans isolates were 25mgL^-1, 24.4mgL^-1 and 37.2mgL^-1,respectively. The combination of caffeine with FLU showed stronger antifungal activity against C. albicans PTCC5027. The addition of 12.5mgL^-1 caffeine to FLU 10-50 mgL^-1 (below MIC₉₀) inhibited the growth of C. albicans PTCC5027 by 99.3%–99.7%, the concentrations at which neither caffeine nor FLU alone affected the growth. Conclusion: It can be concluded that caffeine has antifungal effect on C. albicans and in combination with FLU can enhance the antifungal activity of FLU against C. albicans. The synergism of the combination of caffeine and FLU induces multiple antifungal effects, resulting in the use of lower doses of the FLU. It suggests that this can decrease the side effects of antifungal drugs.

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Reactive oxygen species (ROS) at low concentrations effectively regulates intracellular pathways such as gene expression. Whereas their high concentrations are involved in the pathogenesis of many diseases by causing oxidative stress and damaging vital macromolecules. Each cell is equipped with an antioxidant defense system to neutralize high levels of ROS. Peroxidase, as an essential antioxidant enzyme, catalyzes the oxidation of various substrates using hydrogen peroxide which is a reactive oxygen species. Since, the caffeine and theobromine are widely consumed daily in the world, and their concentrations affect the activity of many enzymes. Therefore, in the present study, the inhibitory effect of these methylxanthines on peroxidase activity has been examined. The peroxidase activity is measured by a spectrophotometer at 510 nm for 3 minutes with following absorption due to the oxidation of 4-aminoantipyrine in the presence and absence of caffeine and theobromine. In this study, it was observed that both compounds had an inhibitory effect on peroxidase activity. The values of IC₅₀ for theobromine and caffeine were obtained as 0.5 and 0.6 mmol, respectively. Moreover, the values of K_m and V_max showed that both inhibitors acted by an un-competitive mechanism of inhibition. Also, K_i values for theobromine and caffeine were calculated 0.03 and 0.08 mM, respectively. The values of K_i and IC₅₀ for theobromine was lower than those of caffeine indicating that theobromine has a higher inhibition strength and binding affinity to the enzyme-substrate complex. Therefore, it can be concluded that theobromine has a stronger inhibitory effect on peroxidase activity.

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In this study, chitosan-coated nanoliposomes in ratios of 9-1, 8-2, 7-3 and 6-4 lecithin-cholesterol, were prepared using thin-film hydration method, as a practical delivery system for encapsulation of caffeine. Then, the particle size and zeta potential were measured to determine the characteristics of the produced particles. Average particle size (average hydrodynamic diameter) and particle size distribution for different lecithin-cholesterol ratios were in the range of 135.5-533.5 nm and 0.31-0.41, respectively. Zeta potential values were also obtained in the range of +40.96 to +50.5. After determining the encapsulation efficiency, FTIR method was used to investigate possible reactions between caffeine and nanoliposome wall materials. The morphology of chitosome with 9-1 ratio of lecithin-cholesterol loaded with caffeine, was shown by scanning electron microscopy (SEM). The stability of the chitosomal sample with a ratio of 1-9 lecithin-cholesterol was evaluated through visual observation of precipitation formation and calculation of the amount of release of encapsulated caffeine during 60 days of storage at ambient temperature. The results obtained in this research showed that nanochitosomes are an efficient system in maintaining and releasing caffeine.

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Aims: Exercise activity and the use of herbal supplements are effective in regulating vascular contraction by influencing on angiogenesis factors. The purpose of this study was to investigate the effect of caffeine and genistein supplement on cardiac levels of nitric oxide (NO) and vascular endothelial growth factor (VEGF) in wistar rats, following an acute swimming exercise.
Materials and Methods: In this experimental study, 49 male Wistar 8-10-week rats were randomly divided into 7 groups of control, saline, acute exercise, caffeine, genistein, acute swimming exercise plus caffeine, and acute swimming exercises plus genistein (7 rats in each group). Acute exercise included 90 minutes swimming. Dietary supplement groups, taked the caffeine at a rate of 5mg/kg of body weight by gavage and Genistein in the amount of 100mg/kg of body weight by intra peritoneal injection. Two hours after the end of the training session, the levels of NO and VEGF were measured by ELISA. Data were analyzed by SPSS 20 software using one-way ANOVA.
Findings: 90 minutes swimming exercise caused a significant increase in cardiac levels of NO and VEGF in acute exercise, acute exercise plus caffeine, acute exercise plus genistein in comparison to the control and saline groups (p=0.01), while supplementation of caffeine or genistein alone did not significantly increase the levels of cardiac level of these factors compared to control and saline groups.
Conclusion: The supplementation of caffeine and genistein increases the levels of NO and VEGF of the heart tissue of rats following an acute swimming session.

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Consumption of caffeine for reasons such as increasing alertness, reducing fatigue, increasing energy, and reducing drowsiness, as a drink and additive has many fans among consumers. Therefore, adding caffeine to cheese as a Dairy product containing caffeine. In addition, the consumption of caffeine causes weight loss by reducing appetite, and for this reason, its use in the formulation of food supplements has been considered. Therefore, the consumption of ultrafiltrated (UF) cheese containing caffeine, in addition to being a very good source of nutrients and useful substances needed by the children, increases energy and reduces fatigue, and makes a person more energetic. In this study, caffeine with different concentrations of 0 (control sample), 0.2, 0.4, and 0.6% was added to cheese, and its color values (L*, a*, b* indexes) and textural characteristics (hardness, cohesiveness, adhesiveness, gumminess, and springiness) were studied during the 45 days of storage period. The results of color evolution showed that the L* index decreased with the increase of caffeine concentration (p< 0.05) and passing the storage period (p< 0.001). In addition, no significant effect was observed by adding caffeine to UF-cheese on a* and b* indices, but the storage time caused a significant decrease (p< 0.01) in both parameters. The degree of hardness, cohesiveness and gumminess of the UF-cheeses decreased significantly with the increase of caffeine concentration from 0.2 to 0.6% and with the passage of storage time (p< 0.01). Adhesiveness and springiness values also decreased with increasing caffeine concentration and storage time, but these changes were not significant (p> 0.05). Based on color and texture quality, there were no significant differences between control and sample containing 0.4% caffeine. Therefore, by using the concentration of 0.4% caffeine, it is possible to produce an energizing and invigorating UF-cheese. 

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Tea, after water, is one of the most consumed beverages in the world due to its chemical compounds such as polyphenols, antioxidant compounds, and caffeine, which are beneficial. Factors such as tea leaf processing, harvest time, and cultivation region can affect the composition of tea leaves. This research was conducted in a factorial design and as a completely randomized design, with independent variables including raw green tea leaves, processed green tea, and black tea, and dependent variables in this design include measuring the amount of polyphenols, antioxidant activity, and The amount of caffeine and soil properties have been carried out in two harvest seasons: spring (May) and summer (July) and two cultivation zones in the east of Guilan (Lahijan) and west of Guilan (Fouman). According to the results, the interaction effects were, the moisture content of spring green tea in Fouman region (78.83%) was at its highest and summer green tea in Fouman region (6.22%) had the lowest value. The highest amount of solid matter was reported in summer green tea from the Fuman region (93.76%), while the lowest amount was found in spring green tea leaves from Fuman (21.20%) Additionally, the highest caffeine content was observed in spring green tea from Fuman (2.65%), and the lowest amount was in summer green tea leaves from Lahijan (1.87%) The highest and lowest levels of antioxidant compounds were also seen in both spring and summer green tea leaves from Lahijan, as well as in summer black tea from Fuman (57.27%). Furthermore, the highest amount of polyphenols was observed in the spring green tea from Fouman (12.37%), while the lowest amount was found in the summer green tea from Fouman (12.29%).