BACKGROUND:Vascular dementia (VD) is a major cause of cognitive decline associated with cerebrovascular dysfunction, and effective therapeutic strategies remain limited. Ligusticum wallichii is a traditional medicinal herb with neuroprotective activity. METHODS:This study investigated the protective effects of L. wallichii against VD by combining network pharmacology with experimental validation. Active constituents and putative targets of L. wallichii were identified using the TCMSP database and SwissTargetPrediction platform, whereas VD-related genes were collected from GeneCards, DisGeNET and OMIM. Protein-protein interaction analysis, Gene Ontology annotation, KEGG pathway enrichment and molecular docking were used to prioritize targets and pathways. The extract used for animal studies was profiled by HPLC. A rat model of VD induced by permanent bilateral common carotid artery occlusion was used for in vivo validation. RESULTS:Seven database-derived compounds and 450 putative targets were identified, of which 177 overlapped with VD-related genes. Network analysis highlighted AKT1, TNF, EGFR, BCL2 and CASP3 as hub targets associated with oxidative stress- and apoptosis-related signalling. HPLC detected ferulic acid, senkyunolide H, senkyunolide I, senkyunolide A and Z-ligustilide in the extract. In vivo, L. wallichii reduced neurological deficit scores, improved spatial learning and memory, alleviated hippocampal neuronal injury, restored cholinergic balance and increased antioxidant indices. Western blotting showed restoration of AKT phosphorylation, increased Bcl-2 expression, reduced Bax and Caspase-3 expression, and recovery of the Bcl-2/Bax ratio after treatment. CONCLUSIONS:These findings associate the neuroprotective effects of L. wallichii in VD with AKT activation, attenuation of oxidative stress and inhibition of Bcl-2/Bax/Caspase-3-related apoptosis.
BACKGROUND:Systemic lipopolysaccharide (LPS)-induced inflammation can disrupt cerebral redox homeostasis and nicotinamide adenine dinucleotide (NAD)-related metabolism, but the extent to which a multimodal nutritional intervention can attenuate these changes remains unclear. OBJECTIVE:This study compared the effects of phycocyanin-derived oligopeptides (PC-O), zinc (Zn), selenium (Se), and their combined administration on whole-brain NAD-related metabolites, oxidative status, antioxidant enzyme activities, selected mRNA markers, and the protein abundance of representative neurotrophic, synaptic, astroglial, and inflammatory markers after low-dose LPS exposure. METHODS:Forty-two male BALB/c mice were allocated to six groups (n = 7/group). PC-O, Zn, Se, or PC-O + Zn + Se was administered orally for 14 days before intraperitoneal LPS challenge (0.04 mg/kg). RESULTS:LPS was associated with lower concentrations of the four NAD-related analytes and lower antioxidant enzyme activities, higher MDA, reduced BDNF, NGF, Synapsin-1, PGC-1α, and TFAM transcripts, and increased GFAP, IL-1β, and IL-6 transcripts (p < 0.05). Western blot analysis further showed lower BDNF and Synapsin I protein abundance and higher GFAP, IL-1β, and IL-6 protein abundance following LPS exposure (p < 0.05). The single-supplements produced endpoint-dependent changes, whereas the PC-O + Zn + Se group showed the most consistent attenuation across the biochemical, transcript, and selected protein outcomes. CONCLUSION:Low-dose LPS was associated with coordinated disturbances in brain NAD-related metabolism, redox balance, and inflammatory signaling. The combined intervention produced a broader biochemical and molecular response than the single interventions; however, mechanistic, histological, behavioral, and translational studies are required before clinical relevance can be inferred.
OBJECTIVES:Many studies have explored whether targeting gut microbiota (GM) could improve health outcomes in neurodevelopmental conditions. In this way, this systematic review examined whether pre- and/or probiotic interventions could modulate GM and reduce gastrointestinal (GI) and behavioral symptoms in individuals with autism spectrum disorder (ASD). METHODS:A comprehensive search was conducted in PubMed, Scopus, and Embase. Eligible studies included participants with ASD diagnosis who received prebiotic and/or probiotic treatment, with outcomes assessing GM- and ASD-related symptoms. From 8795 records identified, 15 studies met the inclusion criteria, totaling 1015 participants. RESULTS:Most probiotic formulations used Bifidobacterium and Lactobacillus strains, and prebiotics, such as galactooligosaccharides. Reported effects included microbiota changes and improvements in GI symptoms, such as reduced abdominal pain. Behavioral benefits were described in some studies, but less consistently. DISCUSSION:Microbiota-targeted interventions were considered safe and, in most cases, effective in alleviating GI symptoms. However, behavioral improvements were variable and possibly influenced by strain specificity, treatment duration, and concurrent dietary factors. Despite the potential as an adjunctive strategy for managing GI comorbidities, their role in addressing core ASD symptoms is unclear, and current evidence is more consistent for GI symptoms than for behavior. Some reported benefits may reflect combined interventions rather than probiotics or prebiotics specifically. Additionally, most participants were children, with limited representation of older individuals. Larger, long-term trials with rigorous designs are needed to clarify clinical relevance, uncover underlying mechanisms, and identify which patients are most likely to benefit from these interventions.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by β-amyloid (Aβ) plaques, hyperphosphorylated tau tangles, cognitive decline, neuroinflammation, and neuronal-glial dysfunction, yet effective disease-modifying therapies remain unavailable. Increasing evidence suggests that preservation of neuronal and glial integrity is critical for mitigating disease progression. In the present study, we investigated the neuroprotective effects of Ficus deltoidea Jack (FD) in a D-galactose and aluminum chloride (D-gal/AlCl₃)-induced rat model of AD-like neurodegeneration. Adult male Wistar rats were treated with FD (50, 100, and 200 mg/kg) for ten weeks and assessed for cognitive performance, cortical neuronal integrity, hippocampal ultrastructure, and neuroinflammatory signaling. FD treatment significantly improved spatial learning and memory in the Morris water maze without affecting locomotor activity. Histopathological analysis demonstrated dose-dependent preservation of pyramidal neurons in prefrontal cortex and hippocampal layers II (p < 0.0001), III (p < 0.0001), and V (p < 0.0001), with the highest dose of FD producing neuronal viability comparable to donepezil. Importantly, transmission electron microscopy demonstrated that FD markedly preserved the ultrastructural integrity of hippocampal microglia and astrocytes, maintaining mitochondrial morphology, rough endoplasmic reticulum organization, and myelin integrity. Consistent with these structural effects, FD significantly suppressed neuroinflammatory cytokine expression (IL-1β, IL-6, and TNF-α) in the prefrontal cortex. Collectively, this study provides the first integrated ultrastructural and molecular evidence that FD confers multi-level neuroprotection across the cortical-hippocampal axis by preserving neuronal-glial architecture and attenuating neuroinflammation. These findings highlight FD as a promising multi-target natural candidate for mitigating neurodegenerative processes associated with AD.
BACKGROUND:Ketogenic dietary therapies, including the medium-chain triglyceride ketogenic diet (MCT KD), are established non-pharmacological treatments for drug-resistant epilepsy (DRE). MCTs may also exert antiseizure effects partly independent of ketosis. This review evaluated the effectiveness, tolerability, safety, and adherence of MCT-based interventions used with or without a ketogenic diet. METHODS:PubMed, Web of Science, Scopus, and the Cochrane Library were searched from inception to April 2025. Randomized controlled trials (RCTs) and cohort studies in patients with DRE were included. Methodological quality was assessed using Joanna Briggs Institute tools and certainty of evidence using GRADE. Owing to substantial heterogeneity, findings were synthesized using a structured Synthesis Without Meta-analysis approach. RESULTS:Twelve studies were included: three RCTs and nine observational studies. One paediatric RCT found no clear difference in seizure outcomes between MCT KD and the classical ketogenic diet (CKD), despite higher ketone levels with CKD; however, equivalence was not established. A small paediatric crossover trial suggested possible benefit from a C10-enriched KD, while a small adult RCT indicated a possible therapeutic signal from MCT supplementation. Observational studies generally reported improvement from baseline but were limited by methodological weaknesses. Gastrointestinal adverse events were common but often manageable. Certainty of evidence was low to very low. CONCLUSION:MCT-based interventions may offer a flexible option for DRE. Low-certainty evidence suggests that MCT KD may achieve seizure outcomes similar to CKD, but equivalence remains unproven. Evidence for MCT supplementation without a strict KD is very uncertain.
BACKGROUND:The role of diet in modulating inflammation has garnered attention, particularly regarding anti-inflammatory dietary interventions rooted in complementary medicine. The present study examined the clinical manifestations through which anti-inflammatory diets may influence MS, providing insights for clinician researchers. METHODS:A thorough search was performed in Scopus, MEDLINE (PubMed), ScienceDirect, EMBASE, Google Scholar, Central Cochrane Library, and the Web of Science, covering trials published until December 2025. Random-effects models were used to analyze the quantitative data through STATA14. RESULTS:After analyzing 246 entries, we found 10 Randomized Controlled Trials (RCTs) with a total of 332 participants, who had an average disease duration of 8.7 years. The combined effect size revealed a decrease in fatigue severity (Weighted Mean Difference [WMD] = -7.10; 95% Confidence Interval [CI] = -13.61, -0.59; P = 0.032) and an increase in physical health score (WMD = 2.59; 95% Confidence Interval [CI] = 0.17, 5.00; P = 0.036). CONCLUSION:Anti-inflammatory diets may improve MS clinical manifestations, especially fatigue and disability; therefore, more research is needed to confirm the present findings.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder with limited disease-modifying therapies. Chronic aluminum exposure, a well-recognized environmental risk factor, exacerbates AD pathogenesis by driving oxidative stress and neuroinflammation. Schisandrin A (SchA), a bioactive lignan from the medicinal and edible plant Schisandra chinensis, exhibits promising antioxidant and anti-inflammatory properties, yet its nutritional relevance for AD intervention remains undefined. This study evaluated SchA's neuroprotective potential in an AlCl₃/D-galactose-induced cognitive impairment model. We found that SchA significantly ameliorated learning and memory impairments in Morris water maze, novel object recognition, open field and Y-maze tests, alleviated neuronal damage in the hippocampus and cortex, and reduced cerebral amyloid-β (Aβ) production in AlCl₃/D-galactose-treated mice. Mechanistically, SchA mitigated neuroinflammation via inhibiting the IKK/NF-κB/iNOS pathway, and alleviated oxidative stress through activating the Nrf2/HO-1 axis. Our findings demonstrate that SchA exerts neuroprotective effects in AlCl₃/D-galactose-treated mice, accompanied by modulation of inflammatory and oxidative-stress-related signalling, supporting its potential as a nutritional intervention for AD.
Neurodegenerative disorders arise from the convergence of oxidative stress, neuroinflammation, synaptic dysfunction, mitochondrial failure, and dysregulated cell death, highlighting the need for therapeutic agents capable of coordinated, multi-target modulation. Luteolin (3',4',5,7-tetrahydroxyflavone), a dietary flavonoid widely present in edible and medicinal plants, has emerged as a promising neuroactive compound with pleiotropic biological actions. Rather than focusing on isolated outcomes, this review presents an integrated summary of how luteolin orchestrates interconnected signaling networks, with receptor-level neuromodulation and neuroimmune regulation to preserve neuronal integrity. Particular emphasis is placed on pathway convergence, cross-talk, and system-level neuroprotection across models of Alzheimer's disease, Parkinson's disease, and related disorders. In parallel, pharmacokinetic behavior, metabolite activity, and emerging delivery strategies are examined in relation to mechanistic efficacy. By linking molecular signaling, neurotransmission and therapeutic feasibility within a unified framework, this review offers a refined perspective on role of luteolin in neurodegenerative disease modulation.
OBJECTIVE:Given the global aging intensification, age-related chronic diseases like Alzheimer's disease (AD) severely harm the elderly's health, with unclear pathogenesis and no effective drugs. Thus, this study intervened in APP/PS1 mice with docosahexaenoic acid (DHA) feeds of different doses to explore DHA's effects on the mice's cognitive function and nerve cell apoptosis, aiming to find the ways to prevent or delay the elderly's cognitive decline. METHODS:Six-month-old APP/PS1 mice were divided into 4 groups: wild control (WT), model control (Con), low-dose DHA (DHA-L), and high-dose DHA (DHA-H). After intervention, the study evaluated mice's cognitive function, determined brain AD-related protein and free fatty acid levels, assessed neuronal degeneration and apoptosis, measured telomere oxidative damage, telomere length, and brain oxidative stress levels. RESULTS:(1) DHA shortened water maze escape latency, increased platform crossings and target quadrant residence time, and reduced the expression of AD-related proteins (APP, Aβ, etc.) (P < 0.05); (2) It improved brain neuronal degeneration and apoptosis (P < 0.05); (3) It enhanced brain antioxidant capacity, regulated SOD, LPO, and MDA levels, and reduced DNA and telomere oxidative damage (P < 0.05); (4) It prolonged brain telomere length (P < 0.05). CONCLUSION:DHA supplementation can improve cognitive decline in AD model mice, and the mechanism may be that DHA supplementation alleviates oxidative stress-mediated telomere wear in brain tissue, thereby inhibiting apoptosis of neuronal cells. These conditions provide a scientific basis for the elderly and people with cognitive impairment to prevent or alleviate cognitive impairment with reasonable intake of DHA.
BACKGROUND:Depression is a global health issue linked to gut-microbiota-dysbiosis, which influences brain function through the gut-brain axis. Dietary biotics offer a promising therapeutic avenue. OBJECTIVE:This systematic review and meta-analysis aimed to evaluate the efficacy of biotic interventions in managing depression. METHODOLOGY:Five databases were searched for randomized controlled trials (RCTs) from 2016 to 2024. 27 RCTs with a control group and standard depression rating scales were included. Data extraction and risk-of-bias assessment were conducted independently by two reviewers, with certainty-of-evidence appraised using GRADE. Meta-analyses employed standardized mean differences, with subgroup analyses by intervention duration (short: <6 weeks, medium: 6-12 weeks, and long: >12 weeks), respectively. RESULTS:Probiotic interventions showed no significant effects in short and medium-duration subgroups (6 and 12 studies, respectively), both of which demonstrated substantial heterogeneity. A significant effect was observed in the long-duration subgroup (2 studies) with no observed heterogeneity, although based on limited evidence. Prebiotic interventions showed no significant effects, while postbiotic interventions demonstrated no clear effects across durations, with variable heterogeneity. Sensitivity analyses were generally consistent with the main findings. Overall certainty of evidence was rated as moderate due to inconsistency across studies. CONCLUSION:Probiotics administered over longer durations may be associated with improvements in depressive symptoms, although this finding is based on limited evidence. Evidence for prebiotic and postbiotic interventions remains inconclusive. Overall, substantial heterogeneity was observed across studies, and findings should be interpreted cautiously. Further well-designed randomized controlled trials are needed to clarify the effects of microbiome-targeted interventions in depression.
OBJECTIVE:Global aging is increasing the incidence of Alzheimer's disease (AD) and mild cognitive impairment (MCI). This network meta-analysis evaluates the effects of dietary supplements on cognitive function in AD/MCI patients. METHODS:We systematically searched PubMed, Embase, Cochrane Library, and Web of Science for randomized controlled trials up to July 2024. Study quality was assessed using risk-of-bias tools, and a network meta-analysis was performed using R and STATA. RESULTS:Analysis of 29 trials (n = 2000) demonstrated that several supplements significantly improved Mini-Mental State Examination (MMSE) scores compared to placebo. Cosmos caudatus increased MMSE scores (MD = 1.02, 95% CI 0.41-1.63, intervention vs placebo). In comparisons where placebo was the reference group, the following supplements were superior: plant extraction (MD = -1.54, 95% CI -1.88 to -1.19), probiotics with selenium (MD = -1.7, 95% CI -2.34 to -1.05), phosphatidylserine-100 mg (MD = -1.14, 95% CI -1.86 to -0.41), spirulina (MD = -0.68, 95% CI -1.23 to -0.13), and vitamin B (MD = -0.88, 95% CI -1.67 to -0.09). Probiotics with selenium showed the strongest effect. No supplement produced significant improvements on the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog). CONCLUSION:Specific supplements, including Cosmos caudatus, probiotic-selenium combinations, and plant extracts, are associated with improvements in MMSE scores among AD/MCI patients. The absence of effects on ADAS-Cog scores underscores the importance of assessment tool selection. This study provides evidence for considering nutritional interventions in cognitive support strategies.
OBJECTIVES:To investigate whether dietary behavior-derived nutritional profiles and proteomic analysis of dried blood spots (DBS) could identify patterns associated with autism spectrum disorder (ASD). METHODS:A total of 29 children with ASD (mean age, 56.0 ± 8.7 months; 23 boys) and 27 control children (mean age, 60.6 ± 9.5 months; 20 boys) participated in the study. Three-day food records were used to assess nutrient and food group intakes. Blood samples were collected as DBS. To evaluate group separation, partial least squares discriminant analysis was applied to food group data, nutrient intake, and proteomic data. Balanced accuracy (average of sensitivity and specificity) was estimated using 5-fold cross-validation (100 repeats). Candidate markers were selected based on variable importance in projection (VIP) scores, followed by pathway enrichment analysis of proteomic candidates. Tripartite relationships among candidate nutritional and proteomic markers and clinical measures (Childhood Autism Rating Scale; Aberrant Behavior Checklist; Social Responsiveness Scale; Full-Scale IQ; Vineland Adaptive Behavior Scales) were explored using correlation heatmaps. RESULTS:We prioritized 18 candidate nutritional markers and 10 proteomic markers. The proteins were significantly enriched in nervous system pathways. Correlation analyses revealed several tripartite relationships among nutritional markers, proteomic markers, and clinical measures, including an S100A6-(omega-6 intake or meat intake)-clinical measures relationship and an ALDH18A1-nuts/seeds intake-clinical measures relationship. DISCUSSION:Specific combinations of nutritional profiles and DBS-derived proteomic signatures were associated with symptom severity and functional outcomes in children with ASD. Dietary intake may help interpret these molecular and clinical patterns. Future studies are necessary to elucidate these interrelationships.
Background: This investigation aimed to evaluate the relationship between ultra-processed foods (UPFs) intake and indicators of depression and quality of life (QoL) in community-dwelling older adults.Methods: In this community-based cross-sectional study, 368 community-dwelling older adults (mean age 67.11 ± 6.21 years; 55.2% women) were recruited from local health centers. Body composition was measured using a bioelectrical impedance analyzer and physical activity was evaluated with a validated short-form questionnaire. Dietary intake was captured through a self-administered 147-item semi-quantitative food frequency questionnaire, with UPFs classified according to the NOVA system and categorized into tertiles.Results: A clear, stepwise increase in depression prevalence was observed across ascending tertiles of UPFs intake (P < 0.001). After multivariable adjustment, higher UPFs intake remained significantly associated with greater odds of depression in the overall population (T2 vs. T1: OR = 2.13; 95% CI, 1.43-3.17; P < 0.001 and T3 vs. T1: OR = 1.50; 95% CI, 1.01-2.22; P = 0.041). Sex-stratified analyses revealed that these associations were significant among women (T2 vs. T1: OR = 3.27; 95% CI, 1.85-5.77; P < 0.001 and T3 vs. T1: OR = 2.10; 95% CI, 1.22-3.59; P = 0.007), whereas no significant associations emerged in men. In contrast, UPFs intake was not significantly associated with low QoL.Conclusion: Higher UPF intake is significantly associated with an elevated prevalence of depression among community-dwelling older adults, with women appearing particularly susceptible. Further longitudinal studies are warranted to clarify causal pathways.
