Search Results (28)

Background/Objectives: To evaluate the neuromodulative effects of oral intake of a fixed combination of citicoline 500 mg plus homotaurine 50 mg plus vitamin B3 54 mg plus pyrroloquinoline quinone (CIT/HOMO/B3/PPQ) or of citicoline 800 mg alone (CIT800) on retinal ganglion cell (RGC) function in glaucoma patients by pattern electroretinogram (PERG) and to investigate the effects on quality of life and visual function. Methods: Consecutive patients with primary open-angle glaucoma with controlled IOP (<18 mmHg) receiving prostaglandin analogues as monotherapy; with two reliable visual fields (Humphrey 24-2 SITA Standard) per year in the last 2 years; and an early to moderate visual field defect (MD < −12 dB) were randomized to: arm A. topical therapy + CIT/HOMO/B3/PPQ for 4 months, followed by 4 months of topical therapy + CIT800; and arm B. topical therapy + CIT800 for 4 months, then topical therapy + CIT/HOMO/B3/PPG for 4 months. Patients were examined at month 0, 4, and 8. Complete ocular examination, visual field test, PERG, and quality of life assessment (NEI-VFQ25) were performed at each visit. Results: Forty patients were selected and completed the study, and none developed or reported an adverse event. The overall mean age was 64.2 (±7.7) years, 27 were male. At the end of the intake period of both products, patients exhibited higher P50 and N95-wave amplitudes and shorter latencies compared to baseline. The crossover analysis found that PERG parameters were better when patients received the CIT/HOMO/B3/PQQ combination with a statistically significant shorter peak time of 1.24 ms (95% CI, 0.37 to 2.10; p = 0.006) in the central P50 wave, 1.32 ms (95% CI, 0.44 to 2.22; p = 0.004) in the inferior P50 wave, and 1.70 ms (95% CI, 0.09 to 3.31; p = 0.038) in the inferior N95 wave; and a statistically significant increase of 0.35 µV (95% CI, 0.10 to 0.60; p = 0.006) in the superior N95 amplitude. The crossover analysis did not reveal any significant differences between the intake of CIT800 and CIT/HOMO/B3/PQQ in terms of visual acuity or IOP. During the intake of CIT/HOMO/B3/PQQ, a significant improvement was observed in the total mean score (p = 0.004), in the general health scale (GH, p = 0.01), in the color vision scale (p = 0.006), and in the peripheral vision scale (p = 0.001). Conclusions: The present study has shown that the addition of CIT/HOMO/B3/PQQ in early glaucoma improves PERG parameters and quality of life, likely by slowing down RGC aging and enhancing mitochondrial function more significantly than citicoline 800 mg alone. Full article

Menopause leads to a decline in estrogen levels, resulting in significant metabolic alterations that increase the risk of developing metabolic syndrome—a cluster of conditions including central obesity, insulin resistance, dyslipidemia, and hypertension. Traditional interventions such as hormone replacement therapy carry potential adverse effects, and lifestyle modifications alone may not suffice for all women. This review explores the potential role of palmitoylethanolamide (PEA), an endogenous fatty acid amide, in managing metabolic syndrome during the postmenopausal period. PEA primarily acts by activating peroxisome proliferator-activated receptor-alpha (PPAR-α), influencing lipid metabolism, energy homeostasis, and inflammation. Evidence indicates that PEA may promote the browning of white adipocytes, enhancing energy expenditure and reducing adiposity. It also improves lipid profiles by boosting fatty acid oxidation and decreasing lipid synthesis, potentially lowering low-density lipoprotein cholesterol and triglyceride levels while increasing high-density lipoprotein cholesterol. Additionally, the anti-inflammatory properties of PEA enhance insulin sensitivity by reducing pro-inflammatory cytokines that interfere with insulin signaling. PEA may aid in weight management by influencing appetite regulation and improving leptin sensitivity. Furthermore, its neuroprotective effects may address the mood disturbances and cognitive decline associated with menopause. Given these multifaceted biological activities and a favorable safety profile, PEA may represent a promising non-pharmacological supplement for managing metabolic syndrome in postmenopausal women. However, further large-scale clinical studies are necessary to establish its efficacy, optimal dosing, and long-term safety. If validated, PEA could become an integral part of strategies to improve metabolic and neuropsychological health outcomes in this population. Full article

Background/Objectives: This study investigated the potential of green algae-derived carotenoids as natural inhibitors of the proprotein convertase subtilisin/kexin type 9 (PCSK9), a key regulator of cholesterol metabolism. PCSK9 promotes the degradation of low-density lipoprotein receptors (LDLR), thereby increasing blood cholesterol levels and elevating the risk of cardiovascular diseases. Methods/Results: We screened the pharmacophore fit score of 27 carotenoids with PCSK9 and identified 14 that were analyzed for binding affinity and molecular interactions. Astaxanthin, siphonaxanthin, and prasinoxanthin were identified as the top candidates, demonstrating strong binding affinity (−10.5, −10.3, and −9.4 Kcal/mol, respectively) and stable interactions with several known key residues within the active site of PCSK9, including Pro-331, Arg-357, Cys-358, Val-359, Asp-360, Ile-416, Leu-436, Thr-437, Pro-438, Leu-440, Arg-458, Val-460, Trp-461, Arg-476, Cys-477, Ala-478, Ala-649, Val-650, and Asp-651. Density functional theory analysis confirmed the stability of astaxanthin and its favorable electronic properties, suggesting its potential as an effective inhibitor. Molecular dynamics simulations of the PCSK9–astaxanthin complex revealed sustained structural stability and key interactions critical for maintaining the functional integrity of the protein. Conclusions: These findings provide evidence that specific carotenoids, particularly astaxanthin, may offer a cost-effective alternative to existing PCSK9 inhibitors, providing a potential approach for managing cholesterol levels and reducing cardiovascular risk. Pre-clinical and clinical validations are required to confirm the therapeutic potential of these compounds. Full article

Background: Managing metabolism for optimal training, performance, and recovery in medium-to-high-level endurance runners involves enhancing energy systems through strategic nutrient intake. Optimal carbohydrate intake before, during, and after endurance running can enhance glycogen stores and maintain optimal blood glucose levels, influencing various physiological responses and adaptations, including transitory post-endurance inflammation. This randomized trial investigates the impact of a high-dose 2:1 maltodextrin–fructose supplementation to medium-to-high-level endurance runners immediately before, during, and after a 15 km run at 90% VO_2max intensity on post-exercise inflammatory stress. Methods: We evaluated inflammatory biomarkers and lipidomic profiles before the endurance tests and up to 24 h after. We focused on the effects of high-dose 2:1 maltodextrin–fructose supplementation on white blood cell count, neutrophil number, IL-6, cortisol, and CRP levels, as well as polyunsaturated fatty acids, ω-3 index, and AA/EPA ratio. Results: This supplementation significantly reduced inflammatory markers and metabolic stress. Additionally, it may enhance the post-activity increase in blood ω-3 fatty acid levels and reduce the increase in ω-6 levels, resulting in a lower trend of AA/EPA ratio at 24 h in the treated arm. Conclusions: Adequate carbohydrate supplementation may acutely mitigate inflammation during a one-hour endurance activity of moderate-to-high intensity. These effects could be beneficial for athletes engaging in frequent, high-intensity activities. Full article

The composition of polyunsaturated fatty acids (PUFA) in the cell membrane plays a crucial role in cell signaling and function. Physical activity can induce shifts in PUFA metabolism, potentially altering their membrane composition. Given the multifaceted regulatory and structural roles of PUFA, training-related fluctuations in PUFA concentrations may impact health and athletic performance in both elite and non-elite athletes, highlighting the critical role of these fatty acids’ nutritional intake. The ω-3 index (O3I), a biomarker reflecting the proportion of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in red blood cell membranes, is considered a marker of cardiovascular risk, gaining increasing interest in sports medicine. Dietary interventions aimed at maintaining an optimal O3I may offer several benefits for elite and non-elite athletes, including cardiovascular health performance optimization, recovery, and injury prevention. Here, we discuss emerging evidence on the application of O3I in sports and physical exercise, highlighting its promising role as a biomarker in a wide range of sports practices. Full article

Decreased adult neurogenesis, or the gradual depletion of neural stem cells in adult neurogenic niches, is considered a hallmark of brain aging. This review provides a comprehensive overview of the intricate relationship between aging, adult neurogenesis, and the potential neuroregenerative properties of astaxanthin, a carotenoid principally extracted from the microalga Haematococcus pluvialis. The unique chemical structure of astaxanthin enables it to cross the blood–brain barrier and easily reach the brain, where it may positively influence adult neurogenesis. Astaxanthin can affect molecular pathways involved in the homeostasis, through the activation of FOXO3-related genetic pathways, growth, and regeneration of adult brain neurons, enhancing cell proliferation and the potency of stem cells in neural progenitor cells. Furthermore, astaxanthin appears to modulate neuroinflammation by suppressing the NF-κB pathway, reducing the production of pro-inflammatory cytokines, and limiting neuroinflammation associated with aging and chronic microglial activation. By modulating these pathways, along with its potent antioxidant properties, astaxanthin may contribute to the restoration of a healthy neurogenic microenvironment, thereby preserving the activity of neurogenic niches during both normal and pathological aging. Full article

The recent attention to the risk of potential permanent eye damage triggered by ocular infections has been leading to a deeper investigation of the current antimicrobials. An antimicrobial agent used in ophthalmology should possess the following characteristics: a broad antimicrobial spectrum, prompt action even in the presence of organic matter, and nontoxicity. The objective of this study is to compare the antimicrobial efficacy of widely used ophthalmic antiseptics containing povidone-iodine, chlorhexidine, and liposomes containing ozonated sunflower oil. We determined the minimum inhibitory concentration (MIC) on various microbial strains: Staphylococcus aureus (ATCC 6538), methicillin-resistant Staphylococcus aureus (ATCC 33591), Staphylococcus epidermidis (ATCC 12228), Pseudomonas aeruginosa (ATCC 9027), and Escherichia coli (ATCC 873). Furthermore, we assessed its efficacy in controlling antibiotic resistance, biofilm formation, and bacterial adhesion. All three antiseptic ophthalmic preparations showed significant anti-microbicidal and anti-biofilm activity, with the liposomes containing ozonated sunflower oil with the highest ability to control antibiotic resistance and bacteria adhesion to human corneal cells. Full article

Vitamin D is a pleiotropic hormone that plays a vital role in regulating bone growth, maintaining calcium and phosphate homeostasis, modulating immune function, and a wide range of other pleiotrophic actions in humans, which have increased the attention for its clinical applications. Despite its importance, vitamin D deficiency is prevalent worldwide and is related to a range of pathophysiological conditions, including an increased risk of osteoporosis and chronic and autoimmune diseases. The recommended daily doses of vitamin D vary depending on genetics, age, sex, and health status, with specific doses recommended for infants, children, adults, and those at increased risk of deficiency or specific health conditions. Maintaining adequate vitamin D levels is essential for optimal health, and together with sun exposure, appropriate supplementation strategies can help achieve this goal. Vitamin D supplementation is commonly used to maintain adequate levels, and the optimal administration strategy, such as a daily dose vs. a bolus, is still being investigated. This review aims to understand vitamin D physiology and the impact of relevant vitamin D polymorphisms and to evaluate the role of a daily dose versus a bolus in maintaining optimal vitamin D levels and clinical health outcomes. It also provides suggested clinical guidelines for clinicians based on the most recent scientific evidence. Full article

Estrogen deficiency is a major cause of loss of postmenopausal bone mineral density (BMD). This study aimed to evaluate the effects of equol and resveratrol on bone turnover biomarkers in postmenopausal women. Sixty healthy postmenopausal women were randomly assigned to receive 200 mg fermented soy containing 10 mg equol and 25 mg resveratrol or a placebo for 12 months. Whole-body BMD and bone turnover biomarkers, such as deoxypyridinoline (DPD), tartrate-resistant acid phosphatase 5b (TRACP-5b), osteocalcin, and bone-specific alkaline phosphatase (BAP), were measured at baseline and after 12 months of treatment. At the end of treatment, DPD, osteocalcin, and BAP significantly improved in the active group (p < 0.0001 for all) compared to the placebo group. Conversely, TRACP-5b levels were unaffected by supplementation (p = 0.051). Statistically significant changes in the concentrations of DPD (p < 0.0001), osteocalcin (p = 0.0001), and BAP (p < 0.0001) compared to baseline were also identified. Overall, the intervention significantly increased BMD measured in the whole body (p = 0.0220) compared with the placebo. These data indicate that the combination of equol and resveratrol may positively modulate bone turnover biomarkers and BMD, representing a potential approach to prevent age-related bone loss in postmenopausal women. Full article

Although autism spectrum disorder (ASD) is a multifaceted neurodevelopmental syndrome, accumulating evidence indicates that oxidative stress and inflammation are common features of ASD. Flavonoids, one of the largest and best-investigated classes of plant-derived compounds, are known to exert antioxidant, anti-inflammatory, and neuroprotective effects. This review used a systematic search process to assess the available evidence on the effect of flavonoids on ASD. A comprehensive literature search was carried out in PubMed, Scopus, and Web of Science databases following the PRISMA guidelines. A total of 17 preclinical studies and 4 clinical investigations met our inclusion criteria and were included in the final review. Most findings from animal studies suggest that treatment with flavonoids improves oxidative stress parameters, reduces inflammatory mediators, and promotes pro-neurogenic effects. These studies also showed that flavonoids ameliorate the core symptoms of ASD, such as social deficits, repetitive behavior, learning and memory impairments, and motor coordination. However, there are no randomized placebo-controlled trials that support the clinical efficacy of flavonoids in ASD. We only found open-label studies and case reports/series, using only two flavonoids such as luteolin and quercetin. These preliminary clinical studies indicate that flavonoid administration may improve specific behavioral symptoms of ASD. Overall, this review is the first one to systematically report evidence for the putative beneficial effects of flavonoids on features of ASD. These promising preliminary results may provide the rationale for future randomized controlled trials aimed at confirming these outcomes. Full article

Aging results from the progressive dysregulation of several molecular pathways and mTOR and AMPK signaling have been suggested to play a role in the complex changes in key biological networks involved in cellular senescence. Moreover, multiple factors, including poor nutritional balance, drive immunosenescence progression, one of the meaningful aspects of aging. Unsurprisingly, nutraceutical and pharmacological interventions could help maintain an optimal biological response by providing essential bioactive micronutrients required for the development, maintenance, and the expression of the immune response at all stages of life. In this regard, many studies have provided evidence of potential antiaging properties of resveratrol, as well as rapamycin and metformin. Indeed, in vitro and in vivo models have demonstrated for these molecules a number of positive effects associated with healthy aging. The current review focuses on the mechanisms of action of these three important compounds and their suggested use for the clinical treatment of immunosenescence and aging. Full article

Astaxanthin (AST) is a dietary xanthophyll predominantly found in marine organisms and seafood. Due to its unique molecular features, AST has an excellent antioxidant activity with a wide range of applications in the nutraceutical and pharmaceutical industries. In the past decade, mounting evidence has suggested a protective role for AST against a wide range of diseases where oxidative stress and inflammation participate in a self-perpetuating cycle. Here, we review the underlying molecular mechanisms by which AST regulates two relevant redox-sensitive transcription factors, such as nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor κB (NF-κB). Nrf2 is a cellular sensor of electrophilic stress that coordinates the expression of a battery of defensive genes encoding antioxidant proteins and detoxifying enzymes. Likewise, NF-κB acts as a mediator of cellular stress and induces the expression of various pro-inflammatory genes, including those encoding cytokines, chemokines, and adhesion molecules. The effects of AST on the crosstalk between these transcription factors have also been discussed. Besides this, we summarize the current clinical studies elucidating how AST may alleviate the etiopathogenesis of oxidative stress and inflammation. Full article

Recent evidence suggests that diet modifies key biological factors associated with the development of depression. It has been suggested that this could be due to the high flavonoid content commonly found in many plant foods, beverages and dietary supplements. Our aim was to conduct a systematic review to evaluate the effects of dietary flavonoids on the symptoms of depression. A total of 46 studies met the eligibility criteria. Of these, 36 were intervention trials and 10 were observational studies. A meta-analysis of 36 clinical trials involving a total of 2788 participants was performed. The results showed a statistically significant effect of flavonoids on depressive symptoms (mean difference = −1.65; 95% C.I., −2.54, −0.77; p < 0.01). Five of the 10 observational studies included in the systematic review reported significant results, suggesting that a higher flavonoid intake may improve symptoms of depression. Further studies are urgently required to elucidate whether causal and mechanistic links exist, along with substantiation of functional brain changes associated with flavonoid consumption. Full article

Spirulina microalgae contain a plethora of nutrient and non-nutrient molecules providing brain health benefits. Numerous in vivo evidence has provided support for the brain health potential of spirulina, highlighting antioxidant, anti-inflammatory, and neuroprotective mechanisms. Preliminary clinical studies have also suggested that spirulina can help to reduce mental fatigue, protect the vascular wall of brain vessels from endothelial damage and regulate internal pressure, thus contributing to the prevention and/or mitigating of cerebrovascular conditions. Furthermore, the use of spirulina in malnourished children appears to ameliorate motor, language, and cognitive skills, suggesting a reinforcing role in developmental mechanisms. Evidence of the central effect of spirulina on appetite regulation has also been shown. This review aims to understand the applicative potential of spirulina microalgae in the prevention and mitigation of brain disorders, highlighting the nutritional value of this “superfood”, and providing the current knowledge on relevant molecular mechanisms in the brain associated with its dietary introduction. Full article