Search Results (4,755)

This paper presents a review of studies on SGLT protein inhibitors, based on literature published between 2000 and 2025, sourced from the Scopus, ScienceDirect, Google Scholar and PubMed databases. The individual isoforms of SGLT proteins are briefly described, with attention to their distribution in the body and biological functions. Representative inhibitors and their potential biological effects are also discussed. Beyond the well-established glucose-lowering properties, characteristic of the extensively studied SGLT2 inhibitors, this review explores additional effects, including anticancer, anti-inflammatory, antioxidant, and neuroprotective activities. The analysis encompasses synthetic SGLT inhibitors, computer-designed molecules, and a wide range of naturally derived compounds, including medicinal plants and food-based substances. Importantly, the review deliberately excludes SGLT2 inhibitors, such as the well-known gliflozin class due to the abundance of existing reviews focused specifically on them. This review focuses on potential inhibitors of the SGLT1, SGLT3, SGLT4, SGLT5, and SGLT6 isoforms, emphasizing their diverse physiological roles beyond diabetes and cardiovascular disease, including applications in cancer therapy and neuroprotection. Particular attention is given to the SGLT1 isoform, for which numerous synthetic inhibitors with promising therapeutic potential have been identified. Additionally, natural compounds, especially those derived from medicinal plants and dietary sources, are extensively documented for their inhibitory effects. For the remaining isoforms (SGLT3–SGLT6), all available data on selective inhibitors were examined, alongside an evaluation of their possible therapeutic applications in light of current scientific knowledge. Full article

The aging process is closely linked to cognitive decline, and numerous studies have demonstrated a decrease in both the quality and quantity of sleep in the general population. Melissa officinalis (lemon balm) is a plant rich in bioactive compounds, including flavonoids, phenolic acids, and essential oils, which are responsible for its neuroprotective and antidepressant properties. Its positive effects on the sleep quality are probably, at least in part, attributable to the presence of rosmarinic acid, which modulates γ-aminobutyric acid transaminase activity. This review aimed to investigate the effects of M. officinalis on cognition and sleep quality in human clinical trials. For cognition, studies have shown that the plant improved cognitive performance and mood. In elderly individuals with mild cognitive impairment or early Alzheimer’s disease, extracts standardized in rosmarinic acid stabilized cognitive functions and reduced neuropsychiatric symptoms such as agitation. Regarding sleep, a combination of lemon balm and valerian significantly improved sleep quality in postmenopausal women. Isolated lemon balm extracts also reduced sleep disorders in cardiac patients. When compared to citalopram, lemon balm enhanced the quality of life, including sleep quality. It is concluded that lemon balm has the potential to improve cognition and sleep quality; however, robust evidence is needed, as more rigorous trials are required. Full article

Objective: To implement a neonatal iron deficiency (ID) guideline as part of a neuroprotective strategy using reticulocyte hemoglobin content (RET-He) for neonates born <33 weeks postmenstrual age (PMA) and small for gestational age (SGA) neonates ≥33 weeks PMA, to achieve ≥80% screening rate by June 2024. Methods: An interdisciplinary team conducted a quality improvement initiative in a level III neonatal intensive care unit (NICU) from April 2022 to August 2024. RET-He is a validated, sensitive marker of early iron deficiency reflecting recent iron supply for erythropoiesis and providing a more reliable measure than ferritin. The primary outcome was RET-He screening at 30 ± 7 days for neonates <33 weeks PMA or pre-discharge for SGA neonates ≥33 weeks PMA. Exclusion criteria were death or transfer before eligibility. Process measures included ID screening failure rate (RET-He level < 29 pg). Results: Of 345 eligible neonates, P-chart analysis showed screening rates for premature neonates <33 weeks PMA declined during PDSA 1–2, before improving to 85.9% in PDSA 3. ID screening failure was 12.6% at one month, increasing to 32.1% at two months. For SGA neonates ≥33 weeks PMA, screening rates remained low, peaking at 36% in PDSA 3, with a 2.2% failure rate. Conclusions: Implementation of a RET-He based ID guideline improved screening rates for premature neonates but was less effective for SGA neonates. Despite improved guideline adherence, ID prevalence remained high at NICU discharge, indicating a further need to improve nutritional prevention and treatment strategies. Full article

Background: Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder with limited treatment options. Emerging evidence reveals bidirectional crosstalk between gut and brain through inflammatory signaling, leading us to hypothesize that anti-neuroinflammatory agents may concurrently ameliorate intestinal inflammation. The scorpion venom-derived heat-resistant synthetic peptide (SVHRSP), a bioactive peptide initially identified in scorpion venom and subsequently synthesized by our laboratory, possesses neuroprotective, anti-inflammatory, and antioxidative activities. Its properties make SVHRSP a promising candidate for investigating the therapeutic potential of anti-neuroinflammatory strategies in mitigating intestinal inflammation. Methods: Using a chronic dextran sodium sulfate (DSS)-induced colitis model in wild-type and α7 nicotinic acetylcholine receptor (α7nAChR) knockout mice, along with lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages, we assessed SVHRSP’s effects on inflammation, histopathology, gut permeability, oxidative stress markers, and α7nAChR-Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling. Results: SVHRSP treatment significantly ameliorated colitis symptoms in wild-type mice by reducing inflammation, repairing histological damage, restoring gut barrier function, and attenuating oxidative stress, with these effects abolished in α7nAChR knockout mice. Mechanistically, SVHRSP activated JAK2/STAT3 signaling through α7nAChR engagement, suppressing proinflammatory cytokine production in macrophages. Conclusion: These results demonstrated that SVHRSP alleviated intestinal inflammation via α7nAChR-dependent JAK2/STAT3 activation. Combined with its known neuroprotective properties, our findings support the repurposing of this neuroactive peptide, SVHRSP, for treating intestinal inflammatory disorders. Full article

Various clinical studies aimed at modifying the progression of idiopathic Parkinson’s disease have been unsuccessful. Similarly, several nutritional trials using bioactive compounds have shown positive effects for patients but have also failed to slow or reduce the disease’s progression. This repeated failure is likely because these studies ignore the extremely slow neurodegenerative process, which unfolds over many years. The molecular mechanism behind the loss of neuromelanin-containing dopaminergic neurons in the nigrostriatal system in idiopathic Parkinson’s disease remains unclear. This is a conceptual/theoretical review based mainly on mechanistic and preclinical evidence, with no direct clinical data. However, research suggests that aminochrome, an endogenous neurotoxin, may trigger the degeneration of these neurons through a single-neuron degeneration model. In this model, aminochrome selectively destroys individual neurons without spreading to neighboring cells. Aminochrome is produced during neuromelanin synthesis, a process that is normally harmless because protective enzymes like DT-diaphorase and glutathione transferase M2-2 neutralize aminochrome’s neurotoxic effects. Increasing the levels of these enzymes could offer neuroprotection. The KEAP1/NRF2 signaling pathway is critical for regulating antioxidant enzymes, such as DT-diaphorase and glutathione transferase M2-2. Importantly, specific bioactive compounds from food can activate this pathway, increasing the production of these protective enzymes. For instance, the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), along with astaxanthin—a compound present in cold-water fish like salmon—have been demonstrated to enhance enzyme expression. This connection leads to a compelling question: Could dietary interventions help prevent idiopathic Parkinson’s disease? Answering this will require further research. Full article

Essential oils from the genus Piper are recognized for their chemical diversity and biological potential, yet Piper platylobum has been scarcely investigated. This study aimed to characterize the chemical composition of the leaf essential oil of P. platylobum and evaluate its antimicrobial, antioxidant, and anticholinesterase activities. The oil was obtained by steam distillation and analyzed through gas chromatography–mass spectrometry (GC-MS) and gas chromatography equipped with a flame ionization detector (GC-FID), leading to the identification of 35 compounds that accounted for 91.11% of the volatile fraction. Dillapiole (42.0%) was the principal constituent, followed by α-(E)-bergamotene (5.69%), (E)-caryophyllene (5.01%), and (E)-isocroweacin (3.75%). Biological assays revealed selective antimicrobial activity, with inhibition observed only against Enterococcus faecium (MIC = 1000 µg/mL), while no effect was detected against other bacterial or fungal strains tested. Antioxidant evaluation showed moderate activity in the ABTS assay (SC₅₀ = 335.71 ± 1.43 µg/mL; TEAC = 45.85 ± 1.68 µM Trolox/g EO), but no activity in the DPPH assay. The essential oil also displayed moderate inhibition of acetylcholinesterase (IC₅₀ = 76.86 ± 1.00 µg/mL), suggesting a potential role in neuroprotective applications. This study constitutes the first report on the chemical composition and biological activities of P. platylabum essential oil, highlighting its potential as a novel source of bioactive compounds. Full article

This study investigates the neuroprotective and anxiolytic effects of Solanum macrocarpon L. leaf n-butanol extract (SMB) in a zebrafish model of scopolamine (SCOP; 100 μM)-induced cognitive and behavioral impairments. SCOP, a muscarinic receptor antagonist, is commonly used to mimic memory deficits and anxiety-like behaviors associated with neurodegenerative conditions. Zebrafish were chronically exposed to SMB at concentrations of 1, 3, and 6 mg/L. Behavioral assessments included anxiety-related paradigms, such as novel tank diving (NTT), novel approach (NA), and light–dark transition (LD) tests, as well as cognitive assays, including the Y-maze and novel object recognition (NOR) tests. SMB significantly mitigated SCOP-induced anxiety-like behaviors and cognitive deficits in a dose-dependent manner. Biochemical analyses demonstrated that SMB inhibited acetylcholinesterase (AChE) overactivity, indicating restoration of cholinergic function. Furthermore, SMB enhanced the activity of endogenous antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) and significantly reduced oxidative stress biomarkers, including malondialdehyde (MDA) and protein carbonyls. These findings suggest that SMB may exert neuroprotective effects through modulation of cholinergic signaling and oxidative stress. Overall, SMB represents a promising phytotherapeutic candidate for mitigating cognitive and anxiety-related symptoms linked to oxidative damage. Further investigations are warranted to characterize its active constituents and assess long-term efficacy and safety in models of neurodegeneration. Full article

The distinctive geographical environment of the Qinghai–Tibet Plateau has nurtured a variety of anthocyanin-rich berry plants. This review systematically summarizes the current state of research on anthocyanins obtained from Lycium ruthenicum Murr. (LRAs), Nitraria tangutorun Bobr (NTAs), and Rubus idaeus (RAs) for their potential health benefits and use. The anthocyanins found in these three berries have attracted considerable interest for their significant biological effects, such as their antioxidant, anti-aging, hypoglycemic, anti-inflammatory, and neuroprotective activities, as well as their ability to regulate the gut microbiota and inhibit cancer cells. These anthocyanins have potential applications as natural colorants, packaging materials and smart labels, as well as functional food and health supplements in the food industry. They have diverse molecular architectures with glycosylation and acylation profiles. The structural features of anthocyanins are closely related to their biological activities. This review provides a detailed overview of the chemical structures, synthesis pathways, biological activities, and applications in the food industry of LRAs, NTAs, and RAs. This summary offers a theoretical foundation for exploring plant resources characteristic of the Qinghai–Tibet Plateau and for the development and utilization of high-value-added functional foods, pharmaceuticals, and cosmetics. Full article

Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) such as erlotinib are widely used in non-small-cell lung cancer treatment, and accumulating evidence indicates they can markedly increase ocular toxicity. Nonetheless, whether erlotinib causes optic nerve injury has not been investigated before and remains a subject worth investigating. This study aimed to examine the impact of erlotinib on oxidative stress, inflammation, and histopathological changes in rat optic nerve tissue and evaluate the potential neuroprotective role of thiamine pyrophosphate (TPP). Methods: Twenty-four male Wistar rats were randomly assigned to four groups: healthy control, TPP alone, erlotinib alone, and erlotinib + TPP. Erlotinib (10 mg/kg, orally, on alternate days) and TPP (20 mg/kg, intraperitoneally, daily) were administered for two consecutive weeks. Optic nerve samples were analyzed for malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), catalase (CAT), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α), followed by histopathological examination. Results: Erlotinib treatment significantly increased MDA, IL-1β, and TNF-α levels while reducing tGSH, SOD, and CAT activity, demonstrating oxidative stress and an inflammatory response. Co-administration of TPP ameliorated these changes by lowering reactive oxygen species, restoring antioxidant capacity, and attenuating inflammation. Histopathological alterations, including astrocyte degeneration, edema, and vascular congestion, were evident after erlotinib exposure but were significantly alleviated when TPP was administered concurrently. Conclusions: Erlotinib induces oxidative and inflammatory optic nerve injury, while TPP co-treatment offers significant neuroprotection. These findings support TPP as a potential adjunct to reduce EGFR-TKI-related ocular toxicity and highlight importance of redox modulation in limiting treatment-associated side effects. Full article

Oxidative stress-induced mitochondrial dysfunction and apoptosis are critical factors in the pathogenesis of neurodegenerative diseases. This study investigated the synergistic neuroprotective effects of anthocyanin-enriched Morus alba L. extract combined with vitamin C (MAC) against hydrogen peroxide (H₂O₂)-induced oxidative stress in SH-SY5Y neuronal cells. Exposure to H₂O₂ triggered excessive reactive oxygen species (ROS) production and apoptosis, whereas treatment with MAC markedly alleviated these effects. Biochemical analyses revealed that MAC significantly reduced malondialdehyde (MDA) and enhanced the activities of antioxidant enzymes, including catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px), thereby contributing to improved redox balance. Furthermore, MAC modulated apoptosis-related signaling by upregulating extracellular signal-regulated kinase (ERK), cAMP response element-binding protein (CREB), and the anti-apoptotic protein B-cell lymphoma 2 (Bcl-2), while downregulating the pro-apoptotic protein Bcl-2-associated X (BAX) and cleaved caspase-3. Collectively, these findings demonstrate that MAC acts synergistically as a promising nutraceutical ingredient, supporting the development of functional foods for the prevention or mitigation of oxidative stress-related neurodegenerative disorders. Full article

Hydroxytyrosol (HXT), a phenolic compound from olive, shows great potential as a neuroprotective agent and a translational target for claim-ready nutrition and food products. Human studies increasingly report benefits for vascular function, inflammatory tone, and early cognitive/psychomotor outcomes, consistent with engagement of redox and signalling pathways (Keap1–Nrf2–ARE, PI3K/Akt–ERK, and AMPK–SIRT1–PGC-1α). HXT is rapidly absorbed and likely reaches the brain, acting on endothelial and microglial targets. On the neurovascular axis, it reduces oxidative stress, preserves nitric-oxide bioavailability, lower inflammatory markers, and favourable intrinsic connectivity. For product development, bitterness from oleuropein-rich inputs can be mitigated by hydrolysis, followed by structure-guided delivery to balance sensory quality with exposure. Viable formats include cyclodextrin inclusion, microencapsulation, and (micro)emulsions in lipid matrices, plus stability engineering for aqueous systems (acidification, chelation, low-oxygen handling, or barrier packaging). Matrix effects are consequential; some proteins and fibers may decrease HXT bioaccessibility, whereas lipid phases and microstructured carriers often enhance it. Clinically, recommended doses are ~7–15 mg/day chronically and ~30–60 mg acutely. As conclusions of this review, future work should prioritize harmonized pharmacokinetics–pharmacodynamics readouts, cognition anchored to a compact neurovascular/blood–brain barrier biomarker core, and head-to-head comparisons of manufacturable delivery formats. Full article

An overproduction of reactive oxygen species (ROS) creates oxidative stress that disrupts neuronal activity and contributes to the pathogenesis of neurodegenerative diseases. Arecoline, the predominant alkaloid component of Areca catechu L., is known for multiple biological activities, yet its involvement in neuronal oxidative injury has not been fully clarified. This study investigated arecoline’s effect on hydrogen peroxide (H₂O₂)-induced toxicity in SH-SY5Y human neuroblastoma cells (SH-SY5Y). Arecoline pretreatment significantly improved cell viability and preserved plasma membrane integrity, accompanied by reduced lipid peroxidation and restoration of cellular antioxidant enzyme activities. Moreover, arecoline maintained mitochondrial membrane potential and suppressed apoptotic progression. At the molecular level, Arecoline stimulated nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) protein expression, concurrently diminishing Kelch-like ECH-associated protein 1 (Keap1) levels. In parallel, it altered the apoptosis profile by increasing B-cell lymphoma 2 (Bcl2) levels and decreasing Bcl-2-associated X protein (Bax) and total cysteine aspartate protease-3 (Caspase-3) protein expression. Collectively, the findings suggest that arecoline safeguards neurons against oxidative stress by simultaneously activating antioxidant defenses and restraining apoptosis. This study adds novel molecular evidence supporting the potential neuroprotective relevance of arecoline in oxidative stress-related neuropathology. Full article

Background/Aims: Parkinson’s disease (PD) is a progressive neurodegenerative disorder caused by the degeneration of dopaminergic neurons, leading to motor and non-motor symptoms that significantly impair quality of life (QoL). Oxidative stress (OS) and neuroinflammation play a key role in its progression. The ketogenic diet (KD) may have neuroprotective effects by reducing these factors through ketosis. The primary aim of this narrative review is to examine the impact of the ketogenic diet on the quality of life and symptomatology of patients with PD, evaluating its effects on motor and non-motor symptoms, as well as on certain metabolic parameters. Secondary aims included assessing the feasibility of and adherence to the diet, as well as its tolerability and safety. Methods: A search of PubMed, Scopus, Embase, CINAHL and Cochrane databases up to June 2025 was performed. Eligible studies included adults with PD following a KD regimen. Data were extracted regarding QoL outcomes, adverse events, and risk of bias included for synthesis. Results: A total of 152 patients were included across 6 studies. KD showed a small to moderate effect size on QoL improvements, particularly in non-motor domains such as fatigue and sleep quality. However, findings were inconsistent across studies. Risk of bias was rated moderate to high due to small sample sizes, heterogeneous methodologies, and lack of blinding. The most frequently reported adverse events were gastrointestinal disturbances (nausea, constipation), weight loss, and transient fatigue. Conclusions: Although preliminary evidence suggests a potential benefit of KD on QoL in PD patients, the small number of participants, short follow-up, and high heterogeneity significantly limit generalizability. Further large, controlled trials with rigorous methodology are warranted before relevant conclusion benefits can be drawn. Full article

Background/Objectives: Low vitamin D levels are associated with an elevated risk of Alzheimer’s disease (AD). Given the rising prevalence of diabetes and its association with AD, this study investigated whether vitamin D modulates amyloidogenesis and inflammation in the brains of diabetic mice. Methods: Five-week-old male C57BLKS/J-m+/m+(con) and C57BLKS/J-db/db (db) mice received diets with low or high vitamin D (LVD or HVD) for 8 weeks. Hippocampal neuronal morphology was assessed using H&E and Nissl staining, and Aβ levels, along with the mRNA expression of genes related to amyloidogenesis, amyloid degradation, inflammation, antioxidation, and neurotrophic factors, were measured in the hippocampus and prefrontal cortex (PFC). Results: High dietary vitamin D levels attenuated neuronal necrosis in db/db mice. Hippocampal App and Bace1 expression levels were higher in db/db mice; however, amyloidogenic gene (App, Bace1, Ps1) expression levels in both the hippocampus and PFC were significantly lower in db_HVD group compared with those in db_LVD group (all p < 0.05). Among control mice, PFC App and Ps1 expression levels were lower in con_HVD group than in con_LVD group. Nonetheless, Aβ42 protein levels were not affected by either diabetes or dietary vitamin D levels. Furthermore, lower hippocampal Iκbα and PFC Mcp-1 expression levels in db_HVD group than those in db_LVD group were observed, both upregulated in diabetic mice. Amyloid degradation-related gene or Vdr expression was not altered by dietary vitamin D levels. Conclusions: These findings suggest that vitamin D may exert neuroprotective effects on the hippocampus and PFC in diabetic mice by mitigating neuronal damage and suppressing amyloidogenic and inflammatory gene expression. Full article

Neopyropia (N.) yezoensis is a widely cultivated red alga in East Asia and valued worldwide for its rich bioactive constituents recognized for their health benefits, including polsaccharides, porphyrans, pigments, phenolic compounds, phycobiliproteins, polyunsaturated fatty acids, myosporin-like amino acids, and both synthetic and recombinant peptides. This review summarizes the current knowledge regarding the therapeutic potential of N. yezoensis extracts and their bioactive compounds. Based on in vitro, ex vitro, and in vivo experimental data (including those on Drosophila melanogaster larvae), this review comprehensively discusses its antioxidant, anti-inflammatory, neuroprotective, anti-atopic dermatitis, anti-colitis, anticancer, anti-aging, anti-atrophy, metabolic health-promoting effects, improving renal health, proliferating, anti-osteoarthritic, anti-allergic, antibacterial, and antivirus activities. The prebiotic effect of N. yezoensis porphyran through modulation of the gut microbiota was also investigated. Studies have indicated that protein hydrolysates and peptides derived from N. yezoensis with low molecular weights and aromatic and/or hydrophobic amino acids contribute significantly to these diverse bioactivities. Although N. yezoensis has shown promising bioactivity in preclinical models, validated clinical data in humans are currently lacking. Future research should prioritize the design and implementation of well-controlled human clinical trials to fully explore their therapeutic potential. Full article