The Bifunctional Dimer Caffeine-Indan Attenuates α-Synuclein Misfolding, Neurodegeneration and Behavioral Deficits after Chronic Stimulation of Adenosine A1 Receptors.

We previously found that chronic adenosine A1 receptor stimulation with N6-Cyclopentyladenosine increased α-synuclein misfolding and neurodegeneration in a novel α-synucleinopathy model, a hallmark of Parkinson's disease. Here, we aimed to synthesize a dimer caffeine-indan linked by a 6-carbon chain to cross the blood-brain barrier and tested its ability to bind α-synuclein, reducing misfolding, behavioral abnormalities, and neurodegeneration in our rodent model. Behavioral tests and histological stains assessed neuroprotective effects of the dimer compound. A rapid synthesis of the 18F-labeled analogue enabled Positron Emission Tomography and Computed Tomography imaging for biodistribution measurement. Molecular docking analysis showed that the dimer binds to α-synuclein N- and C-termini and the non-amyloid-ß-component (NAC) domain, similar to 1-aminoindan, and this binding promotes a neuroprotective α-synuclein "loop" conformation. The dimer also binds to the orthosteric binding site for adenosine within the adenosine A1 receptor. Immunohistochemistry and confocal imaging showed the dimer abolished α-synuclein upregulation and aggregation in the substantia nigra and hippocampus, and the dimer mitigated cognitive deficits, anxiety, despair, and motor abnormalities. The 18F-labeled dimer remained stable post-injection and distributed in various organs, notably in the brain, suggesting its potential as a Positron Emission Tomography tracer for α-synuclein and adenosine A1 receptor in Parkinson's disease therapy.

Potential of Coffee Cherry Pulp Extract against Polycyclic Aromatic Hydrocarbons in Air Pollution Induced Inflammation and Oxidative Stress for Topical Applications.

Airborne particulate matter (PM) contains polycyclic aromatic hydrocarbons (PAHs) as primary toxic components, causing oxidative damage and being associated with various inflammatory skin pathologies such as premature aging, atopic dermatitis, and psoriasis. Coffee cherry pulp (CCS) extract, rich in chlorogenic acid, caffeine, and theophylline, has demonstrated strong antioxidant properties. However, its specific anti-inflammatory effects and ability to protect macrophages against PAH-induced inflammation remain unexplored. Thus, this study aimed to evaluate the anti-inflammatory properties of CCS extract on RAW 264.7 macrophage cells exposed to atmospheric PAHs, compared to chlorogenic acid (CGA), caffeine (CAF), and theophylline (THP) standards. The CCS extract was assessed for its impact on the production of nitric oxide (NO) and expression of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). Results showed that CCS extract exhibited significant antioxidant activities and effectively inhibited protease and lipoxygenase (LOX) activities. The PAH induced the increase in intracellular reactive oxygen species, NO, TNF-α, IL-6, iNOS, and COX-2, which were markedly suppressed by CCS extract in a dose-dependent manner, comparable to the effects of chlorogenic acid, caffeine, and theophylline. In conclusion, CCS extract inhibits PAH-induced inflammation by reducing pro-inflammatory cytokines and reactive oxygen species (ROS) production in RAW 264.7 cells. This effect is likely due to the synergistic effects of its bioactive compounds. Chlorogenic acid showed strong antioxidant and anti-inflammatory activities, while caffeine and theophylline enhanced anti-inflammatory activity. CCS extract did not irritate the hen's egg chorioallantoic membrane. Therefore, CCS extract shows its potential as a promising cosmeceutical ingredient for safely alleviating inflammatory skin diseases caused by air pollution.

Temporal and Potential Predictive Relationships between Sleep Spindle Density and Spike-and-Wave Discharges.

Spike-and-wave discharges (SWDs) and sleep spindles are characteristic electroencephalographic (EEG) hallmarks of absence seizures and nonrapid eye movement sleep, respectively. They are commonly generated by the cortico-thalamo-cortical network including the thalamic reticular nucleus (TRN). It has been reported that SWD development is accompanied by a decrease in sleep spindle density in absence seizure patients and animal models. However, whether the decrease in sleep spindle density precedes, coincides with, or follows, the SWD development remains unknown. To clarify this, we exploited Pvalb-tetracycline transactivator (tTA)::tetO-ArchT (PV-ArchT) double-transgenic mouse, which can induce an absence seizure phenotype in a time-controllable manner by expressing ArchT in PV neurons of the TRN. In these mice, EEG recordings demonstrated that a decrease in sleep spindle density occurred 1 week before the onset of typical SWDs, with the expression of ArchT. To confirm such temporal relationship observed in these genetic model mice, we used a gamma-butyrolactone (GBL) pharmacological model of SWDs. Prior to GBL administration, we administered caffeine to wild-type mice for 3 consecutive days to induce a decrease in sleep spindle density. We then administered low-dose GBL, which cannot induce SWDs in normally conditioned mice but led to the occurrence of SWDs in caffeine-conditioned mice. These findings indicate a temporal relationship in which the decrease in sleep spindle density consistently precedes SWD development. Furthermore, the decrease in sleep spindle activity may have a role in facilitating the development of SWDs. Our findings suggest that sleep spindle reductions could serve as early indicators of seizure susceptibility.

Motor improvement in Parkinson's disease patients receiving caffeine adjuvants: A double-blind randomized controlled trial in Indonesia.

Parkinson's disease (PD) manifests as a movement and brain function disorder characterized by symptoms such as resting tremors, rigidity, bradykinesia, and postural instability, leading to disability among patients. The use of psychostimulants such as caffeine has been associated with the improvement of motor symptoms in PD patients; however, studies regarding the effect of caffeine adjuvant therapy on motor function among PD patients in the Indonesian population are lacking. The aim of this study was to evaluate motor improvement as measured by the change in scores of the Movement Disorder Society - Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III) among PD patients receiving caffeine adjuvant. A double-blind randomized controlled trial (RCT) was conducted among PD patients at Dr. Soetomo General Academic Hospital and Universitas Airlangga Hospital, Surabaya, Indonesia, from April to August 2023. A total of 27 patients were enrolled and randomly assigned to an intervention (receiving caffeine adjuvant, n=15) and control group (receiving placebo, n=12). Motor improvement was measured using the UPDRS III score prior to intervention and three weeks after. The Chi-squared test was used to analyze the difference in UPDRS III scores between the two groups. Motor improvement, as demonstrated by a reduction in the UPDRS III score, was observed in patients receiving caffeine adjuvant compared to those receiving placebo (80.0% vs 16.7%; p=0.004). Regarding the safety profile, only four out of 15 (26.6%) patients treated with caffeine reported minor adverse events. These conditions improved over time during the intervention. None of the 12 patients in the placebo reported adverse events. This study provides valuable insights into the initial dosage of caffeine that improves motor function in PD patients with minimum adverse effects.

Anti-aging and immunomodulatory role of caffeine in Drosophila larvae.

Drug repurposing is a promising approach to identify new pharmacological indications for drugs that have already been established. However, there is still a limitation in the availability of a high-throughput in vivo preclinical system that is suitable for screening and investigating new pharmacological indications. The aim of this study was to introduce the application of Drosophila larvae as an in vivo platform to screen drug candidates with anti-aging and immunomodulatory activities. To determine whether Drosophila larvae can be utilized for assessing anti-aging and immunomodulatory activities, phenotypical and molecular assays were conducted using wildtype and mutant lines of Drosophila. The utilization of mutant lines (PGRP-LBΔ and Psh[1];;ModSP[KO]) mimics the autoinflammatory and immunodeficient conditions in humans, thereby enabling a thorough investigation of the effects of various compounds. The phenotypical assay was carried out using survival and locomotor observation in Drosophila larvae and adult flies. Meanwhile, the molecular assay was conducted using the RT-qPCR method. In vivo survival analysis revealed that caffeine was relatively safe for Drosophila larvae and exhibited the ability to extend Drosophila lifespan compared to the untreated controls, suggesting its anti-aging properties. Further analysis using the RT-qPCR method demonstrated that caffeine treatment induced transcriptional changes in the Drosophila larvae, particularly in the downstream of NF-κB and JAK-STAT pathways, two distinct immune-related pathways homologue to humans. In addition, caffeine enhanced the survival of Drosophila autoinflammatory model, further implying its immunosuppressive activity. Nevertheless, this compound had minimal to no effect on the survival of Staphylococcus aureus-infected wildtype and immunodeficient Drosophila, refuting its antibacterial and immunostimulant activities. Overall, our results suggest that the anti-aging and immunosuppressive activities of caffeine observed in Drosophila larvae align with those reported in mammalian model systems, emphasizing the suitability of Drosophila larvae as a model organism in drug repurposing endeavors, particularly for the screening of newly discovered chemical entities to assess their immunomodulatory activities before proceedings to investigations in mammalian animal models.

Caffeine, but not paracetamol (acetaminophen), enhances muscular endurance, strength, and power.

BACKGROUND: Caffeine is one of the most popular ergogenic aids consumed by athletes. Caffeine's ergogenic effect has been generally explained by its ability to bind to adenosine receptors, thus modulating pain and reducing perceived exertion. Another pharmacological agent that may improve performance due to its analgesic proprieties is paracetamol. This study aimed to explore the effects of caffeine, paracetamol, and caffeine + paracetamol consumption on muscular endurance, strength, power, anaerobic endurance, and jumping performance. METHODS: In this randomized, crossover, double-blind study, 29 resistance-trained participants (11 men and 18 women) ingested either a placebo, caffeine (3 mg/kg), paracetamol (1500 mg) or caffeine + paracetamol 45 min before the testing sessions. The testing sessions included performing the bench press exercise with 75% of one-repetition maximum to momentary muscular failure, isokinetic knee extension and flexion at angular velocities of 60°/sec and 180°/sec, Wingate, and countermovement jump (CMJ) tests. RESULTS: Compared to placebo, isolated caffeine ingestion increased the number of repetitions performed in the bench press (p = 0.005; d = 0.42). Compared to placebo, isolated caffeine ingestion and/or caffeine + paracetamol consumption was ergogenic for strength (torque), muscular endurance (total work), or power in the isokinetic assessment, particularly at slower angular velocities (p = 0.027 to 0.002; d = 0.16 to 0.26). No significant differences between the conditions were observed for outcomes related to the Wingate and CMJ tests. CONCLUSION: This study provided novel evidence into the effectiveness of caffeine, paracetamol, and their combination on exercise performance. We found improvements in muscular endurance, strength, or power only when caffeine was consumed in isolation, or in combination with paracetamol. Isolated paracetamol consumption did not improve performance for any of the analyzed outcomes, thus calling into question its ergogenic potential.

Matcha Does Not Affect Electroencephalography during Sleep but May Enhance Mental Well-Being: A Randomized Placebo-Controlled Clinical Trial.

Although theanine in matcha improves sleep quality and cognitive function, the caffeine in green tea is thought to worsen sleep quality. Therefore, this study investigated the factors behind the observed improvements in subjective sleep quality in matcha. A placebo-controlled randomized double-blind parallel-group study was conducted on healthy Japanese men and women aged 27-64 years. After 4 weeks of consuming 2.7 g of matcha daily (containing 50.3 mg theanine, 301.4 mg catechins, and 71.5 mg caffeine), no significant differences were observed between the control and matcha groups on total sleep time, sleep latency, wake after sleep onset, or sleep efficiency measured by electroencephalography (EEG). However, the sleep questionnaire Oguri-Shirakawa-Azumi Sleep Inventory, the Middle-age and Aged version (OSA-MA), administered immediately after waking showed a trend toward increased satisfaction with sleep time (p < 0.1), and EEG measurements indicated significantly shortened wake-up times after waking with matcha intake (p < 0.05). The Beck Depression Inventory-II scores also tended to decrease (p < 0.1). The continuous intake of matcha may offer improved subjective sleep quality and emotional stability despite not offering significant changes in objective sleep parameters.

Impact of Coffee Intake on Measures of Wellbeing in Mice.

Coffee intake is increasingly recognized as a life-style factor associated with the preservation of health, but there is still a debate on the relative effects of caffeinated and decaffeinated coffee. We now tested how the regular drinking of caffeinated and decaffeinated coffee for 3 weeks impacted on the behavior of male and female adult mice. Males drinking caffeinated coffee displayed statistically significant lower weight gain, increased sensorimotor coordination, greater motivation in the splash test, more struggling in the forced swimming test, faster onset of nest building, more marble burying and greater sociability. Females drinking caffeinated coffee displayed statistically significant increased hierarchy fighting, greater self-care and motivation in the splash test and faster onset of nest building. A post-hoc two-way ANOVA revealed sex-differences in the effects of caffeinated coffee (p values for interaction between the effect of caffeinated coffee and sex) on the hierarchy in the tube test (p = 0.044; dominance), in the time socializing (p = 0.044) and in the latency to grooming (p = 0.048; selfcare), but not in the marble burying test (p = 0.089). Intake of decaffeinated coffee was devoid of effects in males and females. Since caffeine targets adenosine receptors, we verified that caffeinated but not decaffeinated coffee intake increased the density of adenosine A1 receptors (A1R) and increased A1R-mediated tonic inhibition of synaptic transmission in the dorsolateral striatum and ventral but not dorsal hippocampus, the effects being more evident in the ventral hippocampus of females and striatum of males. In contrast, caffeinated and decaffeinated coffee both ameliorated the antioxidant status in the frontal cortex. It is concluded that caffeinated coffee increases A1R-mediated inhibition in mood-related areas bolstering wellbeing of both males and females, with increased sociability in males and hierarchy struggling and self-care in females.

Risperidone suppresses caffeine-induced hyperthermia and hyperactivity in rats.

Caffeine, a methylxanthine alkaloid, works as a nonselective adenosine receptor antagonist. It is the most widely used psychostimulant drug worldwide. However, caffeine overdose can lead to acute intoxication, posing a clinical problem. Hyperthermia and hyperactivity are associated issues with acute caffeine intoxication; however, no definitive treatment exists. This study aimed to assess the ability of risperidone to attenuate caffeine-induced hyperthermia and hyperactivity while elucidating the unknown mechanisms of caffeine intoxication. The rats received intraperitoneal injections of saline, risperidone (0.25 mg/kg, 0.5 mg/kg), WAY-100635, ketanserin, haloperidol, sulpiride, or SCH 23390, 5 min after the administration of caffeine (25 mg/kg). Subcutaneous temperature and activity counts were measured using nano tag ® for up to 90 min. In vivo microdialysis was used to determine the effect of risperidone on caffeine-induced elevation of dopamine (DA), serotonin (5-HT), and noradrenaline (NA) concentrations in the anterior hypothalamus. Rats were injected with caffeine (25 mg/kg), followed by saline or risperidone (0.5 mg/kg) 5 min later. The levels of DA, 5-HT, and noradrenaline were measured every 15 min for up to 90 min after caffeine administration. Risperidone and 5-HT2A receptor antagonist ketanserin attenuated caffeine-induced hyperthermia and hyperactivity. Haloperidol and dopamine D1 antagonist SCH-23390 exacerbated hyperthermia without any effect on the hyperactivity. In the microdialysis study, risperidone treatment further attenuated caffeine-induced 5-HT elevation, but not DA and NA. Our results indicate that risperidone attenuates caffeine-induced hyperthermia and hyperactivity by blocking 5-HT2A receptor activity and may be potentially useful for treating caffeine intoxication.

Examining the effects of caffeine during an auditory attention task.

Participants completed two sessions of an auditory attention task and intermittently responded to thought probes asking about their level of mind-wandering. After the first session one group received 200 mg of caffeinated chewing gum (n = 61) and another group received regular (placebo) chewing gum (n = 66). The gum was chewed for 20-minutes and then disposed of before beginning the second session. Participants who received caffeine showed a performance benefit as well as reported being more on task and fewer instances of spontaneous mind-wandering compared to those in the placebo group. Participants who received caffeine also reported greater positive affect and arousal, as well as less feelings of boredom, sleepiness, and mental effort required to stay on task compared to those who received placebo. These results suggest that caffeine may benefit attentional engagement as well as performance during a sustained attention task.

Caffeine weakens the astringency of epigallocatechin gallate by inhibiting its interaction with salivary proteins.

The astringency of green tea is an integrated result of the synergic and antagonistic effects of individual tea components, whose mechanism is highly complex and not completely understood. Herein, we used an epigallocatechin gallate (EGCG)/caffeine (CAF)/saliva model to simulate the oral conditions during tea drinking. The effect of CAF on the interaction between EGCG and salivary proteins was first investigated using molecular docking and isothermal titration calorimetry (ITC). Then, the rheological properties and the micro-network structure of saliva were studied to relate the molecular interactions and perceived astringency. The results revealed that CAF partially occupied the binding sites of EGCG to salivary proteins, inhibiting their interaction and causing changes in the elastic network structure of the salivary film, thereby reducing astringency.

Subclinical brain manifestations of repeated mild traumatic brain injury are changed by chronic exposure to sleep loss, caffeine, and sleep aids.

INTRODUCTION: After mild traumatic brain injury (mTBI), the brain is labile for weeks and months and vulnerable to repeated concussions. During this time, patients are exposed to everyday circumstances that, in themselves, affect brain metabolism and blood flow and neural processing. How commonplace activities interact with the injured brain is unknown. The present study in an animal model investigated the extent to which three commonly experienced exposures-daily caffeine usage, chronic sleep loss, and chronic sleep aid medication-affect the injured brain in the chronic phase. METHODS: Subclinical trauma by repeated mTBIs was produced by our head rotational acceleration injury model, which causes brain injury consistent with the mechanism of concussion in humans. Forty-eight hours after a third mTBI, chronic administrations of caffeine, sleep restriction, or zolpidem (sedative hypnotic) began and were continued for 70 days. On Days 30 and 60 post injury, resting state functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) were performed. RESULTS: Chronic caffeine, sleep restriction, and zolpidem each changed the subclinical brain characteristics of mTBI at both 30 and 60 days post injury, detected by different MRI modalities. Each treatment caused microstructural alterations in DTI metrics in the insular cortex and retrosplenial cortex compared with mTBI, but also uniquely affected other gray and white matter regions. Zolpidem administration affected the largest number of individual structures in mTBI at both 30 and 60 days, and not necessarily toward normalization (sham treatment). Chronic sleep restriction changed local functional connectivity at 30 days in diametrical opposition to chronic caffeine ingestion, and both treatment outcomes were different from sham, mTBI-only and zolpidem comparisons. The results indicate that commonly encountered exposures modify subclinical brain activity and structure long after healing is expected to be complete. CONCLUSIONS: Changes in activity and structure detected by fMRI are widely understood to reflect changes in the functions of the affected region which conceivably underlie mTBI neuropathology and symptomatology in the chronic phase after injury.

Impact of CYP1A2 Genotypes on the Ergogenic Effects and Subjective Mood States of Caffeine Ingestion in Resistance-Trained Women.

Caffeine's metabolism is determined by CYP1A2 genotypes: AC/CC (SLOW) and AA (FAST). This trial evaluated CYP1A2 genotypes' impact on exercise and cognitive effects in 36 resistance-trained females assessed under placebo (PL) and caffeine (6 mg/kg bw anhydrous caffeine-CAF) conditions, before ingestion and throughout the session. 23andMe® (San Francisco, CA, USA) determined genotypes using saliva. Data were analyzed using two-way RMANOVA and paired-samples t-tests (p < 0.05). A significant main effect for genotype existed for leg press repetitions to failure (RTF) for CAF (p = 0.038), with the FAST group performing more repetitions than the SLOW (p = 0.027). There was a significant condition x genotype interaction for the subjective outcome index score (p = 0.045), with significant differences for time (p < 0.01) and between genotype (p < 0.001). Follow-up analysis revealed a higher total score (p = 0.028) following CAF for the FAST group and a lower total score (p < 0.01) in the SLOW group. Dizziness was reported following CAF in the SLOW group (p = 0.014; Cohen's d = 0.725). Aside from leg press RTF, subjective outcome index score, and dizziness, the genotype groups experienced similar responses to resistance exercise performance and subjective mood states following caffeine ingestion.

A novel open-access artificial-intelligence-driven platform for CNS drug discovery utilizing adult zebrafish.

BACKGROUND: Although zebrafish are increasingly utilized in biomedicine for CNS disease modelling and drug discovery, this generates big data necessitating objective, precise and reproducible analyses. The artificial intelligence (AI) applications have empowered automated image recognition and video-tracking to ensure more efficient behavioral testing. NEW METHOD: Capitalizing on several AI tools that most recently became available, here we present a novel open-access AI-driven platform to analyze tracks of adult zebrafish collected from in vivo neuropharmacological experiments. For this, we trained the AI system to distinguish zebrafish behavioral patterns following systemic treatment with several well-studied psychoactive drugs - nicotine, caffeine and ethanol. RESULTS: Experiment 1 showed the ability of the AI system to distinguish nicotine and caffeine with 75 % and ethanol with 88 % probability and high (81 %) accuracy following a post-training exposure to these drugs. Experiment 2 further validated our system with additional, previously unexposed compounds (cholinergic arecoline and varenicline, and serotonergic fluoxetine), used as positive and negative controls, respectively. COMPARISON WITH EXISTING METHODS: The present study introduces a novel open-access AI-driven approach to analyze locomotor activity of adult zebrafish. CONCLUSIONS: Taken together, these findings support the value of custom-made AI tools for unlocking full potential of zebrafish CNS drug research by monitoring, processing and interpreting the results of in vivo experiments.

Effects of coffee on cognitive function.

This chapter thoroughly examines coffee's impact on cognitive function. It synthesizes research findings involving animals and humans, investigating coffee's influence on various memory and cognitive aspects, including short-term/working memory, long-term memory, attention, vigilance, executive functions, and processing speed. The chapter also discusses moderating factors, such as dose-response relationships, individual differences, age, and habitual consumption patterns, that influence the cognitive effects of coffee. Additionally, it addresses the potential risks and adverse effects associated with coffee intake, memory, and cognitive function, including stress and anxiety, sleep disturbances, cardiovascular effects, and addiction. Studies suggest moderate coffee intake improves attention, processing speed, decision-making, and certain executive functions. However, the effects vary depending on factors like dosage, individual traits, age, and sleep habits. Despite potential benefits, coffee consumption may lead to adverse effects such as anxiety, sleep issues, cardiovascular concerns, and dependency. Future research should address methodological concerns, incorporate neuroimaging methods, explore interactions with other substances, and investigate long-term effects and therapeutic uses. Understanding coffee's neuroscience can shed light on its role in daily life and health.

Molecular targets of caffeine in the central nervous system.

Caffeine is an alkaloid obtained from plants and is one of the most consumptive drug in the form of chocolate, coffee and beverages. The potential impact of caffeine within CNS can be easily understood by mechanism of action-antagonism of adenosine receptor, calcium influx, inhibits phosphodiesterases. Adenosine a neuromodulator for adenosine receptors, which are abundantly expressed within the central nervous system. Caffeine antagonized the adenosine receptor, hence stimulate expression of dopamine. It plays pivotal role in many metabolic pathways within the brain and nervous system, it reduced the amyloid-ß-peptide (Aß) accumulation, downregulation of tau protein phosphorylation, stimulate cholinergic neurons and inhibits the acetylcholinestrase (AChE). It also possess antioxidant and antiapoptotic activity. Caffeine act as nutraceutical product, improves mental health. It contains antioxidants, vitamins, minerals and dietary supplements, by reducing the risk factor of several neurodegenerations including Alzheimer's disease, migraine, gallstone, cancer, Huntington's disease and sclerosis. This act as a stimulant and have capability to increase the effectiveness of certain pain killer. Beside positive affects, over-consumption of caffeine leads to negative impact: change in sleep pattern, hallucinations, high blood pressure, mineral loss and even heartburn. This chapter highlights pros and cons of caffeine consumption.

Coffee and mental disorders: How caffeine affects anxiety and depression.

Caffeine, the main psychoactive component in coffee, has garnered significant attention for its potential impact on the most prevalent mental health conditions like anxiety and depression. This chapter comprehensively examines the neurobiological effects of caffeine, its influence on anxiety and depression, and relevant clinical studies. Caffeine exerts its psychostimulant effects primarily through antagonizing adenosine receptors, modulating neurotransmitter systems, and influencing intracellular calcium signaling in the brain. Caffeine exhibits dose-dependent effects. While moderate caffeine consumption is safe in healthy adults and may offer benefits for mental health, excessive intake is linked to adverse effects on neurological and psychiatric health and can aggravate symptoms, highlighting the importance of adjusting consumption patterns. High caffeine intake correlates with elevated anxiety levels, especially in individuals predisposed to anxiety disorders. However, the relationship between caffeine consumption and the risk of depression is intricate, with some studies suggesting a potential protective effect of moderate intake, while others find no significant association. Individual variations in caffeine metabolism, sensitivity, and genetic factors considerably impact responses to caffeine. The chapter also explores the therapeutic potential of caffeine as an adjunct treatment and outlines challenges and future research directions in elucidating caffeine's multifaceted role in mental health.

Bioactive potential and chemical compounds of coffee.

For decades, coffee has held the distinction of being the most commercially prominent food product and the most universally consumed beverage worldwide. Since the inauguration of the inaugural coffee house in Mecca toward the conclusion of the 15th century, coffee consumption has experienced exponential growth across the globe. Coffee, renowned globally as a beloved beverage, contains a diverse array of compounds known to benefit health. Its prominent phytochemistry contributes to its favorable reputation. Caffeine, a primary constituent, leads this intricate blend of bioactive substances, each exerting various physiological effects. Coffee is rich in potassium, magnesium, and vitamin B3. It encompasses lactones, diterpenes (such as cafestol and kahweol), niacin, and trigonellin, serving as a precursor to vitamin B3. This chapter aims to review and investigate the bioactive potential and chemical compounds of coffee. In the current study, different compounds are discussed. In conclusion, coffee is containing different compounds that can be impacted by different factors such as geographical condition, processing condition, etc.

Coffee and sleep: Benefits and risks.

Consuming coffee, a widely enjoyed beverage with caffeine, can impact the central nervous system and disturb sleep if taken too close to bedtime. Caffeine impacts sleep by slowing the onset, blocking adenosine receptors, lowering deep sleep levels, disrupting sleep patterns, and lessening rapid eye movement sleep. Although coffee can help with alertness in the morning, it may disturb sleep in the evening, particularly for individuals who are sensitive to caffeine. To enhance the quality of sleep, reduce the consumption of caffeine in the afternoon and evening, refrain from drinking caffeine before going to bed, and choose decaffeinated drinks instead. Variables such as personal reactions, ability to handle caffeine, and engagement with other compounds also influence the impact of coffee on sleep. Keeping track of how much caffeine you consume and your sleeping habits can assist in recognizing any disturbances and making needed changes. Furthermore, taking into account variables such as metabolism, age, and the timing of coffee consumption can assist in lessening the effects of coffee on sleep. In general, paying attention to the amount of caffeine consumed from different sources and consuming it at the right times can assist in preserving healthy sleep patterns even while enjoying coffee.

Coffee and Parkinson's disease.

Parkinson's disease (PD) is a prevalent neurodegenerative disease marked by dopaminergic neuronal loss and misfolded alpha-synuclein (α-syn) accumulation, which results in both motor and cognitive symptoms. Its occurrence grows with age, with a larger prevalence among males. Despite substantial study, effective medicines to reduce or stop the progression of diseases remain elusive. Interest has grown in examining dietary components, such as caffeine present in coffee, for potential medicinal effects. Epidemiological studies imply a lower incidence of PD with coffee drinking, attributable to caffeine's neuroprotective abilities. Beyond caffeine, coffee constituent like chlorogenic acid and cafestol have anti-Parkinsonian benefits. Moreover, coffee use has been related with variations in gut microbiota composition, which may reduce intestinal inflammation and prevent protein misfolding in enteric nerves, perhaps through the microbiota-gut-brain axis. This review gives a summary of the neuroprotective effects of coffee, investigating both its motor and non-motor advantages in individuals with PD as well as in experimental models of PD. We reviewed some bioactive constituents of coffee, their respective interactions with misfolded α-syn accumulation, and its emerging mechanisms associated to the gut microbiome.