Search Results (74)

Caffeine, one of the most widely consumed bioactive compounds worldwide, is gaining recognition for its potential anticancer properties beyond its well-known neurological and metabolic effects. Mechanistically, caffeine exerts anti-tumor activity by modulating key cellular pathways involved in carcinogenesis, including the inhibition of phosphodiesterases, antagonism of adenosine A2A receptors, and disruption of the DNA damage response through ATR-Chk1 pathway inhibition. These actions collectively promote apoptosis, suppress tumor cell proliferation, and impair metastatic spread. In vitro and in vivo studies have demonstrated that caffeine can enhance the cytotoxic effects of chemotherapeutic agents and radiation therapy, suggesting a synergistic role in conventional cancer treatments. Epidemiological data further supports an inverse association between habitual caffeine consumption and the incidence of several cancers, notably liver, colorectal, breast, and prostate cancers. Among these, the most consistent experimental and clinical evidence exists for liver and colorectal cancer, where caffeine’s modulatory effects on inflammation and cell proliferation have been repeatedly observed. Additionally, caffeine’s anti-oxidant and anti-inflammatory properties may contribute to a microenvironment less conducive to tumor initiation and progression. While promising, the anticancer effects of caffeine are influenced by factors such as dosage, individual genetic variability, and cancer type, underscoring the need for further clinical investigation. This review explores the emerging role of caffeine as a potential chemopreventive and adjuvant therapeutic agent in oncology. Full article

Background: Nedaplatin is a platinum-based anticancer drug that combines the benefits of Cisplatin and Carboplatin, retaining Cisplatin’s anticancer activity while reducing toxicity similar to Carboplatin. After hydrolysis, Nedaplatin targets purines in DNA and forms cross-links that induce cell death via apoptosis. However, it is important to consider how the presence of other chemical compounds with structural similarities to Adenine or Guanine, such as aromatic, purine, or pyrimidine compounds containing a nitrogen atom with a free electron pair, might influence its activity at the cellular level. Alkaloids with structures similar to DNA nucleobases are common, and their influence on Nedaplatin’s activity requires investigation. Methods: In this study, the interactions between Nedaplatin (including its hydrolyzed forms, such as [Pt(NH₃)₂(H₂O)₂]²⁺ and [Pt(NH₃)₂(H₂O)(OH)]⁺) and nucleobases (Adenine and Guanine) and purine alkaloids (Caffeine, Theobromine and Theophylline) were thoroughly investigated using theoretical (density functional theory, DFT) and experimental (UV-Vis spectroscopy) methods. DFT calculations were performed at the B3LYP/6-31G(d,p)/LANL2DZ and MN15/def2-TZVP levels, with structure optimization and harmonic analysis in the gas phase and aqueous solution (modeled using IEF-PCM). UV-Vis spectroscopy was used to verify theoretical findings by examining changes in absorption spectra. Results: Both theoretical and experimental studies confirmed that Nedaplatin forms complexes with both nucleobases and purine alkaloids. Nedaplatin was found to exhibit a higher affinity for nucleobases than for purine alkaloids. Furthermore, this affinity was dependent on the computational method used and on the hydrolyzed form of Nedaplatin. Theoretical calculations showed the formation of stable complexes through bonding with nitrogen atoms in the ligand molecules, which was confirmed by changes in UV-Vis spectra, indicating adduct formation. Conclusions: The results indicate that Nedaplatin readily forms complexes with both nucleobases and purine alkaloids, showing a stronger affinity for nucleobases. This finding highlights the potential importance of Nedaplatin’s interactions with other compounds present in the body, which may influence its effectiveness and mechanism of action in cancer therapy. These studies provide new insights into the molecular mechanisms of Nedaplatin’s action and may contribute to a better understanding of its pharmacological interactions. However, research requires confirmation not only in in vivo studies but also in clinical trials. Full article

The biological complexity of sarcopenia presents a major challenge for therapeutic intervention due to the wide range of degenerative changes it induces in skeletal muscle. This study demonstrates the potential of liposomal controlled release systems to address these challenges by combining two bioactive agents with complementary actions: caffeine (CAF), encapsulated in DMPC-based liposomes, and hyaluronic acid methacrylate (HAMA), encapsulated in DOPC-based liposomes. A hybrid system was also developed to deliver both substances simultaneously, aiming to restore tissue function through combined metabolic, anti-inflammatory, and regenerative effects. The liposomes exhibited nanoscale dimensions, spherical morphology, and intact membrane structure, as confirmed by electron microscopy. DLS analysis indicated good colloidal stability and monodisperse size distribution across all formulations, with improved stability observed in the hybrid system. Drug release studies showed a time-dependent profile, with HAMA releasing rapidly and CAF releasing gradually, supporting a dual-action therapeutic approach tailored to the multifactorial pathology of sarcopenia. The biological assays, performed in an established in vitro sarcopenia model, revealed the potential of liposomes co-delivering caffeine and HAMA to mitigate oxidative stress, preserve mitochondrial function, and reduce apoptosis in H₂O₂-damaged myotubes. Full article

Background/Objectives: The ergogenic effects of caffeine in team sports, particularly volleyball, have received significant research attention. This study sought to examine the effects of caffeine on both volleyball-specific and general performance outcomes. Methods: This systematic review comprises 11 studies, each utilizing a blinded crossover experimental design. A meta-analysis was conducted using a random-effect model to determine the standardized mean difference (SMD), estimated by Hedges’ g, with a 95% confidence interval (CI). Results: Caffeine supplementation improved volleyball-specific outcomes, including attack and serve accuracy (SMD: 0.50; 95% CI: 0.11–0.90; p = 0.01). Regarding nonspecific outcomes, caffeine increased single-jump performance (SMD: 0.23; 95% CI: 0.02–0.44; p = 0.03), repeated-jump performance (SMD: 0.51; 95% CI: 0.05–0.96; p = 0.03), and handgrip strength (SMD: 0.23; 95% CI: 0.03–0.42; p = 0.02), while decreasing agility test completion time (SMD: −0.32; 95% CI: −0.60–0.03; p = 0.03). Furthermore, caffeine increased the frequency of positive game actions during simulated volleyball matches (SMD: 0.84; 95% CI: 0.26–1.43; p < 0.01). Conclusions: Caffeine supplementation enhances physical performance and volleyball-specific actions during competition, supporting its role as an effective ergogenic aid for volleyball players. Full article

Glioblastoma (GBM) is one of the most invasive central nervous system tumors, with rising global incidence. Therapy resistance and poor prognosis highlight the urgent need for new anticancer drugs. Plant alkaloids, a largely unexplored yet promising class of compounds, have previously contributed to oncology treatments. While past reviews provided selective insights, this review aims to collectively compare data from the last decade on (1) plant alkaloid-based anticancer drugs, (2) alkaloid transport across the blood–brain barrier (BBB) in vitro and in vivo, (3) alkaloid mechanisms of action in glioblastoma models (in vitro, in vivo, ex vivo, and in silico), and (4) cytotoxicity and safety profiles. Additionally, innovative drug delivery systems (e.g., nanoparticles and liposomes) are discussed. Focusing on preclinical studies of single plant alkaloids, this review includes 22 botanical families and 28 alkaloids that demonstrated anti-GBM activity. Most alkaloids act in a concentration-dependent manner by (1) reducing glioma cell viability, (2) suppressing proliferation, (3) inhibiting migration and invasion, (4) inducing cell death, (5) downregulating Bcl-2 and key signaling pathways, (6) exhibiting antiangiogenic effects, (7) reducing tumor weight, and (8) improving survival rates. The toxic and adverse effect analysis suggests that alkaloids such as noscapine, lycorine, capsaicin, chelerythrine, caffeine, boldine, and colchicine show favorable therapeutic potential. However, tetrandrine, nitidine, harmine, harmaline, cyclopamine, cocaine, and brucine may pose greater risks than benefits. Piperine’s toxicity and berberine’s poor bioavailability suggest the need for novel drug formulations. Several alkaloids (kukoamine A, cyclovirobuxine D, α-solanine, oxymatrine, rutaecarpine, and evodiamine) require further pharmacological and toxicological evaluation. Overall, while plant alkaloids show promise in glioblastoma therapy, progress in assessing their BBB penetration remains limited. More comprehensive studies integrating glioma research and advanced drug delivery technologies are needed. Full article

Background: Coffea arabica, commonly known as Arabica coffee, has garnered attention in recent years for its potential applications in dermato-cosmetic formulations. This review aims to critically evaluate the emerging role of Coffea arabica as an active ingredient in skin care products, focusing on its bioactive compounds derived from both the leaves and beans, mechanisms of action, and efficacy in dermatological applications. A comparative analysis between the bioactive profiles of the leaves and beans is also presented to elucidate their respective contributions to dermato-cosmetic efficacy. Results: This review synthesizes findings from various studies that highlight the presence of key bioactive compounds in Coffea arabica, including caffeine, chlorogenic acids, and flavonoids. Notably, the leaves exhibit a higher concentration of certain phenolic compounds compared to the beans, suggesting unique properties that may enhance skin health. These compounds have demonstrated significant anticellulite, anti-inflammatory, antioxidant, photoprotective, anti-aging, antibacterial, and moisturizing properties. Discussion: This article delves into the biochemical pathways through which bioactive compounds derived from both the leaves and beans of Coffea arabica exert their beneficial effects on skin and hair health. Furthermore, this review highlights the growing trend of incorporating natural ingredients in cosmetic formulations and the consumer demand for products with scientifically substantiated benefits. Conclusions: The findings of this review underscore the potential of Coffea arabica as a valuable active ingredient in dermato-cosmetic applications. Its multifaceted bioactivity suggests that it can contribute significantly to skin health and cosmetic efficacy. Future research should focus on clinical trials to further validate these benefits and explore optimal formulation strategies for enhanced delivery and stability in cosmetic products. Full article

The aim of this study was to investigate the effects of caffeine, vanillin, and epigallocatechin gallate on salivation and swallowing and to find ways to correct their negative effects. Solutions of these substances with an equivalent intensity of bitter taste were compared for this purpose. To compensate for their effect, solutions of adenosine monophosphate, saliva substitute, and their combination were used. The results of the sialometric and surface electromyographic analyses demonstrate that all of the bitter substances studied exert a significant influence on the physiology of salivation and swallowing while exhibiting distinct modes of action. Caffeine has been shown to increase the area under the swallowing electromyographic curve, which is indicative of an increase in maximal amplitude. Epigallocatechin gallate has been linked to a reduction in salivation rate, an increase in duration, and a decrease in maximal intensity of the sEMG curve. Vanillin is demonstrated to reduce the area under the swallowing electromyographic curve due to a decline in both duration and maximal intensity. The addition of adenosine monophosphate to solutions of all substances under study resulted in a convergence of the salivary secretion and swallowing profile toward a profile that is characteristic of water. The findings can be utilized to modify the physiological responses to bitter-tasting substances when developing novel food formulations. Full article

Caffeine has recently attracted attention as a potential remedy for hair loss. In the present review, we look into the molecule’s possible mechanisms of action and pharmacodynamics. At the molecular level, it appears that the physiological effects of caffeine are mainly due to the molecule’s interaction with adenosine pathways which leads to an increase in cAMP level and the stimulation of metabolic activity in the hair follicle. Moreover, caffeine also acts as an antioxidant and may prevent degenerative processes. While the intact stratum corneum seems virtually impenetrable to caffeine and a range of physical and chemical methods have been proposed to facilitate its penetration, hair follicles seem to be both a main entry route into the skin and target structures for caffeine at the same time. Caffeine readily forms bonds with water and other molecules which may influence its bioavailability and should be taken into account when engineering future hair products. The results of clinical studies published so far seem promising; however, the majority of the studies of caffeine-based hair loss products offer a very low level of evidence due to considerable flaws in study designs. Nevertheless, the metabolic activity of caffeine and its ability to enter and accumulate in the hair follicles combined with the results of available clinical trials seem to indicate that caffeine could indeed prove as an effective and safe option in the management of hair loss. Full article

Background: Intestinal aging is characterized by declining protein homeostasis via reduced proteasome activity, which are hallmarks of age-related diseases. Our previous study showed that caffeine intake improved intestinal integrity with age by reducing vitellogenin (VIT, yolk protein) in C. elegans. In this study, we investigated the regulatory mechanisms by which caffeine intake improves intestinal integrity and reduces vitellogenin (VIT) production in aged Caenorhabditis elegans. Methods: We performed RNA-seq analysis, and qRT-PCR to validate and confirm the RNA-seq results. Transgenic worms with VIT-2::GFP and VIT-6::GFP were used for measuring VIT production. dsRNAi was conducted to elucidate the roles of pas-1 and pas-3 genes. Results: pas-1 and pas-3, a C. elegans ortholog of human PASM4, was upregulated by caffeine intake. They reduced VIT production by repressing unc-62, a transcriptional activator of vit expression. Interestingly, vit-2 was required for pas-1 and pas-3 expression, and RNAi of pas-1 and pas-3 promoted intestinal atrophy and colonization, suggesting a balancing mechanism for VIT levels in intestinal health. Additionally, lifespan was extended by caffeine intake (2 ± 0.05 days), however, this effect was not observed by pas-1 but not pas-3 RNAi, suggesting that the mode of action for an anti-aging effect of caffeine through pas-1 and pas-3 is distinctive. The lifespan extended by pas-1 was mediated by SKN-1 activation. Conclusions: Caffeine intake enhances intestinal health through proteasome activity and extends lifespan in aged C. elegans by upregulating pas-1 and pas-3. These findings suggest that caffeine consumption mitigates age-related proteasome impairment and maintains intestinal integrity during aging. Full article

Alzheimer’s disease (AD) is a complex multifactorial neurodegenerative disease. With the escalating aging of the global population, the societal burden of this disease is increasing. Although drugs are available for the treatment of AD, their efficacy is limited and there remains no effective cure. Therefore, the identification of safe and effective prevention and treatment strategies is urgently needed. Functional factors in foods encompass a variety of natural and safe bioactive substances that show potential in the prevention and treatment of AD. However, current research focused on the use of these functional factors for the prevention and treatment of AD is in its initial stages, and a complete theoretical and application system remains to be determined. An increasing number of recent studies have found that functional factors such as polyphenols, polysaccharides, unsaturated fatty acids, melatonin, and caffeine have positive effects in delaying the progression of AD and improving cognitive function. For example, polyphenols exhibit antioxidant, anti-inflammatory, and neuroprotective effects, and polysaccharides promote neuronal growth and inhibit inflammation and oxidative stress. Additionally, unsaturated fatty acids inhibit Aβ production and Tau protein phosphorylation and reduce neuroinflammation, and melatonin has been shown to protect nerve cells and improve cognitive function by regulating mitochondrial homeostasis and autophagy. Caffeine has also been shown to inhibit inflammation and reduce neuronal damage. Future research should further explore the mechanisms of action of these functional factors and develop relevant functional foods or nutritional supplements to provide new strategies and support for the prevention and treatment of AD. Full article

Global warming is attributed to an increased frequency of high ambient temperatures and humidity, elevating the prevalence of high-temperature-related illness and death. Evidence over recent decades highlights that tailored nutritional strategies are essential to improve performance and optimise health during acute and chronic exertional-heat exposure. Therefore, the purpose of this review is to discuss the efficacy of various nutritional strategies and ergogenic aids on responses during and following acute and chronic exertional-heat exposure. An outline is provided surrounding the application of various nutritional practices (e.g., carbohydrate loading, fluid replacement strategies) and ergogenic aids (e.g., caffeine, creatine, nitrate, tyrosine) to improve physiological, cognitive, and recovery responses to acute exertional-heat exposure. Additionally, this review will evaluate if the magnitude and time course of chronic heat adaptations can be modified with tailored supplementation practices. This review highlights that there is robust evidence for the use of certain ergogenic aids and nutritional strategies to improve performance and health outcomes during exertional-heat exposure. However, equivocal findings across studies appear dependent on factors such as exercise testing modality, duration, and intensity; outcome measures in relation to the ergogenic aid’s proposed mechanism of action; and sex-specific responses. Collectively, this review provides evidence-based recommendations and highlights areas for future research that have the potential to assist with prescribing specific nutritional strategies and ergogenic aids in populations frequently exercising in the heat. Future research is required to establish dose-, sex-, and exercise-modality-specific responses to various nutritional practices and ergogenic aid use for acute and chronic exertional-heat exposure. Full article

Precision in dosing is crucial for optimizing therapeutic outcomes and preventing overdosing, especially in preterm infants. Traditional manual adjustments to adapt the dose often lead to inaccuracies, contamination risks, and reduced precision. To overcome these challenges, semi-solid extrusion 3D printing was used to create personalised gel-based caffeine dosage forms. The hydrogels, made from agar and hydroxypropyl methylcellulose, demonstrated excellent rheological properties, ensuring uniform extrusion and accurate shape retention during and after printing. This gel formulation allowed for precise adjustments of caffeine volume and content tailored to a neonate weighing 1.36 kg, achieving a recovery of 103.46%, well within acceptable limits. Additionally, three production batches confirmed the process’s reproducibility with minimal variability. Forced degradation studies showed that both pure caffeine and caffeine in the gel matrix exhibited similar stability profiles, confirming the drug’s chemical integrity. The printed gel dosage forms also displayed immediate-release characteristics, with over 80% of caffeine released within 45 min, highlighting their suitability for rapid therapeutic action. These findings emphasise the potential of SSE 3DP and gel-based formulations to produce personalised drug delivery systems with high precision, reproducibility, and reliability. Full article

Background: The evidence about the synergy of combining caffeine (CAF) and nitrates on exercise performance has not been summarized, although there is a possibility of additive/synergistic effects of the co-ingestion of these substances given their different mechanisms of action in central (CAF) and peripheral tissues (nitrates). Objectives: The aim was to analyze the effects of co-supplementation of CAF and nitrates on sports performance in comparison to the isolated ingestion of these substances. Methods: The databases of PubMed, Web of Science, Medline, CiNAHL and SPORTDiscus were used until June 2024 following PRISMA guidelines. Randomized controlled trials, at least one single-blind trial, conducted in adults were considered. A meta-analysis was performed using the random effects model to calculate the standardized mean difference estimated by Hedges’ g and 95% confidence intervals (CIs) for studies with four arms. Results: Six studies were included (N = 95). The meta-analysis revealed that caffeine and nitrates supplementation (CAF+nitrates) did not enhance performance in time trials (TTs) over the CAF alone (g = −0.06; 95% CI = −0.46 to 0.35; p = 0.78) or nitrates alone (g = 0.29; 95% CI = −0.12 to 0.70; p = 0.17). CAF+nitrates did not affect heart rate during submaximal exercise trials over CAF alone (g = 0.04; 95% CI = −0.31 to 0.40; p = 0.80) or nitrates alone (g = −0.15; 95% CI = −0.50 to 0.20; p = 0.40). Likewise, CAF+nitrates did not affect oxygen uptake during submaximal exercise trials over CAF alone (g = −0.04; 95% CI = −0.45 to 0.37; p = 0.84) or nitrates alone (g = −0.29; 95% CI = −0.70 to 0.12; p = 0.16). Conclusions: CAF+nitrates did not offer further benefits on exercise performance or physiological variables from the isolated intake of CAF and nitrates. Full article

Background and Objectives: Obesity and related disorders are an increasing global health problem. Achieving and maintaining long-term weight loss through lifestyle changes and/or pharmacological interventions have not met expectations. Dietary supplements and alternative treatments have also shown limited effectiveness in this regard. The consumption of green tea in general has been shown to benefit obese patients, with effects attributed to caffeine, catechins, polyphenols and other components. However, the potential of white tea to prevent and treat the negative effects of obesity has not been addressed so far. In this study, the effect of white tea (WT) consumption in obese individuals was anthropometrically and biochemically investigated. Materials and Methods: Based on anthropometric and biochemical assessments, the patients were assigned to the control, orlistat, metformin and WT groups. Patients were given a diet and exercise program and one of either orlistat, metformin or WT for 12 weeks. At the end of the 12th week, the anthropometric and biochemical measurements were reassessed. Results: Body weight, waist circumference and BMI parameters decreased significantly in all groups. TNF-α, IL-6, IL-1β and MMP-9 levels decreased significantly in the WT group. In addition, contrary to a significant elevation in HDL-C, the serum cholesterol, LDL-C and TG levels decreased significantly. Furthermore, leptin, ghrelin and asprosin levels decreased significantly. Serum glucose levels decreased significantly in all groups except for the control. In the WT group, while there was a significant decrease in the levels of serum PL MDA and 8-OHdG, the opposite was true for GSH. Conclusions: The oral consumption of WT, its availability and its potency in obesity treatment and prevention pave the way for further delineation of the mechanisms of actions of its bioactive compounds at the cellular and endocrinological levels. Full article

Traumatic brain injuries (TBIs) constitute a significant public health issue and a major source of disability and death in the United States and worldwide. TBIs are strongly associated with high morbidity and mortality rates, resulting in a host of negative health outcomes and long-term complications and placing a heavy financial burden on healthcare systems. One promising avenue for the prevention and treatment of brain injuries is the design of TBI-specific supplementation and dietary protocols centred around nutraceuticals and biochemical compounds whose mechanisms of action have been shown to interfere with, and potentially alleviate, some of the neurophysiological processes triggered by TBI. For example, evidence suggests that creatine monohydrate and omega-3 fatty acids (DHA and EPA) help decrease inflammation, reduce neural damage and maintain adequate energy supply to the brain following injury. Similarly, melatonin supplementation may improve some of the sleep disturbances often experienced post-TBI. The scope of this narrative review is to summarise the available literature on the neuroprotective effects of selected nutrients in the context of TBI-related outcomes and provide an evidence-based overview of supplementation and dietary protocols that may be considered in individuals affected by—or at high risk for—concussion and more severe head traumas. Prophylactic and/or therapeutic compounds under investigation include creatine monohydrate, omega-3 fatty acids, BCAAs, riboflavin, choline, magnesium, berry anthocyanins, Boswellia serrata, enzogenol, N-Acetylcysteine and melatonin. Results from this analysis are also placed in the context of assessing and addressing important health-related and physiological parameters in the peri-impact period such as premorbid nutrient and metabolic health status, blood glucose regulation and thermoregulation following injury, caffeine consumption and sleep behaviours. As clinical evidence in this research field is rapidly emerging, a comprehensive approach including appropriate nutritional interventions has the potential to mitigate some of the physical, neurological, and emotional damage inflicted by TBIs, promote timely and effective recovery, and inform policymakers in the development of prevention strategies. Full article