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Neuropsychiatric dysfunction is increasingly being acknowledged as a disabling complication of non-alcoholic steatohepatitis (NASH), but there are no therapeutic approaches. We investigated in the present study the neuroprotective effectiveness of naringenin, a citrus flavonoid with known anti-inflammatory and neurotrophic effects, in a murine NASH model induced by an 8-week methionine-choline-deficient (MCD) diet. Male C57BL/6 mice (n = 8/group) were treated with naringenin (50 mg/kg/day, i.p.) during the final 4 weeks. In behavioral tests, naringenin counteracted cognitive impairment in novel object recognition, reduced anxiety in both open field and elevated plus maze paradigms, and decreased immobility in the forced swim test, indicating antidepressant-like activity. Mechanistically, naringenin restored hippocampal apoptotic balance, normalizing the MCD diet-induced Show less

Obesity and excessive weight gain have emerged as significant global health concerns in recent years and are often comorbid with numerous contemporary diseases, including cardiovascular disorders, diabetes, and cognitive impairments. L-carnitine, a vital cofactor in mitochondrial energy metabolism, possesses potent antioxidant and anti-inflammatory properties that merit investigation for mitigating obesity-associated neuronal damage. Consequently, this study investigated the potential neuroprotective effects of L-carnitine on anxiety- and depression-like behaviors in adolescent rats subjected to neonatal monosodium glutamate (MSG) exposure, a model known to induce obesity and associated neurobehavioral alterations. Neonatal rats received MSG (4 g/kg, s.c.) on alternate postnatal days (PND) 2-10. Subsequently, L-carnitine (200 mg/kg) was administered via oral gavage daily from PND 60 to 81 (subchronic treatment). Anxiety- and depression-like behaviors were assessed using the Forced Swim Test (FST), Elevated Plus Maze (EPM), and Open Field Test (OFT). All molecular and histological analyses were conducted in the prefrontal cortex (PFC), a region selected for its susceptibility to excitotoxicity and critical role in emotional regulation. Oxidative stress was evaluated through measurements of total oxidant and antioxidant levels. To elucidate the underlying molecular mechanisms, gene expression analyses focused on neuronal survival and apoptosis (BDNF, Bax, Bcl-2), while immunohistochemical evaluations targeted neuroinflammation and cell death pathways (TNF-α, Caspase-3, IL-1β, and Bcl-2). The findings reveal that neonatal MSG exposure leads to pronounced anxiety- and depression-like behaviors, accompanied by metabolic dysregulation, oxidative stress, neuroinflammation, and apoptosis. Although L-carnitine treatment did not reverse obesity-related metabolic alterations, it exhibited notable sustained anxiolytic effects. The neuroprotective potential of L-carnitine was further supported by its ability to reduce cortical neuroinflammation and neurodegerenative damage through suppression of proinflammatory cytokines and restoration of antioxidant balance. Overall, this study offers valuable insights into the cognitive, genetic, and histological outcomes associated with obesity-related mood disturbances and contributes to understanding the complex biological mechanisms underlying these conditions. Show less

Coenzyme Q10 (CoQ10) is an endogenous lipid-soluble molecule with antioxidative and anti-inflammatory properties. Chronic environmental stress can induce neuroinflammation, leading to posttraumatic stress disorder (PTSD)-like behaviors and cognitive deficits. However, therapeutic options that achieve high efficacy with minimal adverse effects remain limited. Here, we investigated the effects of ubiquinol, the reduced form of CoQ10, administered via oral mucosal absorption on behavioral and molecular changes in mice subjected to social disruption (SD). Our results showed ubiquinol administration ameliorated SD-induced social avoidance and anxiety-like behaviors, accompanied by increased hippocampal brain-derived neurotrophic factor (BDNF) and decreased monoamine oxidases A and B (MAO-A and MAO-B). Additionally, ubiquinol suppressed SD-induced upregulation of inducible nitric oxide synthase (iNOS), lipocalin 2, and interleukin-6 (IL-6) in the hippocampus. In microglial cells, CoQ10 effectively attenuated lipopolysaccharide (LPS)-induced increases in iNOS and lipocalin 2 as well. Notably, CoQ10 restored the downregulated expression of peroxisome proliferator-activated receptor alpha (PPARα) observed under SD mice and microglial cells stimulated by LPS. The protective effects of ubiquinol were abrogated by inhibiting PPARα, resulting in reduced BDNF and elevated MAOs and pro-inflammatory mediators. Collectively, these findings demonstrate that ubiquinol mitigates neuroinflammation and behavioral impairments through PPARα-dependent mechanisms, thereby promoting BDNF expression and suppressing upregulation of monoamine oxidases in the hippocampus. The current study provides mechanistic insight into the potential therapeutic application of CoQ10 for chronic stress-induced behavioral and cognitive deficits. Show less

Valproic acid (VPA) is recognized for its neurotrophic properties and is widely used in psychiatric and peripheral disorders, while dextromethorphan (DM) has demonstrated anti-inflammatory and neuroprotective effects. This study examined whether adjunctive DM provides additional benefits on cognitive or immunomodulatory beyond standard VPA treatment in bipolar disorder (BD). BD aged 20-65 received open-label VPA (500-2500 mg/day; target blood level 50-100 μg/dl) for one week and were then randomized to VPA plus placebo (BDVPA) or VPA plus extended-release DM (BDVPA + DM; 30 or 60 mg/day) for twelve weeks. Neuropsychological measures (Continuous Performance Test, CPT; Wechsler Memory Scale-Revised, WMS-R), symptom severity, cytokines, and BDNF were assessed at baseline and post-treatment. A total of 109 participants (mean age 31.04 years, SD = 10.04) were enrolled; 96 completed cognitive testing and blood sampling (66 BD Show less

Statins are a class of cholesterol-lowering agents widely used in clinical practice to reduce plasma levels of low-density lipoprotein cholesterol in hyperlipidemic patients. Beyond their lipidlowering roles, statins exhibit several additional effects. In the current review, we searched PubMed, ScienceDirect, and Google Scholar databases using the keywords "Statins," "HMG-CoA reductase inhibitors," "Anti-inflammatory," "Antioxidant," and "Anticancer" to provide an overview of the effects of statins. Articles published on these topics between 1990 and 2025 were included. The retrieved records were imported into EndNote, and duplicates were removed. Multiple potential therapeutic benefits of statins have been described, including suppression of apoptosis, antioxidant, anti-inflammatory and anticancer effects, immunomodulation and neuroprotection. NADPH oxidases (NOX) play a crucial role in the development of various diseases through excessive production of reactive oxygen species (ROS) and the creation of oxidative stress conditions. Stimulation of BDNF/Nrf2, inhibition of NOX pathways, and reduction of intracellular ROS via enhanced antioxidant activity represent possible mechanisms through which statins exert their effects. Interestingly, ROS and inflammatory cytokines activate nuclear factor kappa B (NF-κB), a critical factor in the development of malignant tumors, which induces the expression of genes involved in cell proliferation and carcinogenesis. Furthermore, statins inhibit NF-κB activity, a key transcriptional regulator in inflammatory responses. Clinical evidence suggests that statins may reduce the risk of various cancers and disease recurrence due to their anti-inflammatory and antioxidant properties. These findings form the basis for new therapeutic avenues in cancer treatment, potentially offering a more promising strategy than statin monotherapy. Show less

Aging-related cognitive decline is a major concern in aging societies. Theobromine (TB), a cacao-derived methylxanthine, exerts neuroprotective effects through anti-inflammatory, antioxidant, and neurotrophic mechanisms; however, its efficacy in aging models remains unclear. This study investigated the mechanisms underlying neuroprotective effects of chronic TB administration in senescence-accelerated mouse prone 8 (SAMP8), a model of age-related memory impairment. SAMP8 and SAMR1 mice were fed either a control diet or a diet supplemented with 0.05% TB for 50 d. Cognitive performance was evaluated by the novel object recognition (NOR) test. Neurotrophic factors (BDNF and NT-3), synaptic proteins (PSD95 and synaptophysin), and plasticity-related signaling molecules (phosphorylated CREB and TrkB) were analyzed in the prefrontal cortex and hippocampus. Inflammatory cytokines, lipid peroxides, and antioxidant enzymes were quantified. Molecular docking was used to assess TB's interaction with phosphodiesterase (PDE) enzymes. TB improved short-term memory in SAMP8, increasing discrimination index in the NOR test. This was accompanied by increased BDNF, NT-3, PSD95, and synaptophysin levels and enhanced CREB and TrkB phosphorylation. Furthermore, TB lowered the levels of pro-inflammatory cytokines (IL-1β, TNF-α) and phosphorylated NF-κB, reduced lipid peroxidation, and increased the levels of antioxidant markers (HO-1, GSH). These effects were minimal in SAMR1. No adverse effects on body weight or blood parameters were observed. Molecular docking indicated that TB binds to PDE enzymes with weaker inhibitory activity than selective inhibitors. TB enhances short-term memory and synaptic function in aged mice via neurotrophic, antioxidant, and anti-inflammatory mechanisms, supporting its potential as a safe dietary intervention for age-related cognitive decline. Show less