TL;DR
Overall, PLD effectively reduced neurodegeneration in the hippocampus of diabetic rats via inhibiting oxidative stress, inflammation, and Aβ1−42 accumulation and may act as a promising multi-target anti-neurodegenerative candidate.
Objective(s): Brain injury is one of the most predominant complications following excessive alcohol consumption. Oxidative, inflammatory, and apoptotic processes are the essential mechanisms involved in alcohol-induced brain damage. Trigonelline is a natural compound that has a variety of pharmacologic activities. The present study investigated the protective effect of trigonelline in alcohol-induced brain injury and its underlying mechanisms. Materials and Methods: Adult male mice (C57BL/6) were exposed to binge ethanol (6 g/kg/day, by gavage) and treated with trigonelline (50 and 100 mg/kg/day, orally) for 6 days. Mice were sacrificed and the brain tissues were dissected for experimental assessments. Results: The results showed that trigonelline alleviated alcohol-induced locomotor impairment and brain oxidative damage by decreasing lipid peroxidation and protein oxidation. Trigonelline restored the levels of protective antioxidants (GSH, SOD, and HO-1) and reduced the levels of ICAM-1 and MPO in the brains of mice exposed to alcohol. Trigonelline significantly reduced alcohol-induced brain inflammation by the inhibition of iNOS/NO, TLR4, NF-κB, and proinflammatory cytokines (TNF-α, IL-6, IL-1β, and TGF-β1). Moreover, trigonelline treatment reduced the levels of caspase-3, cytochrome c, and TUNEL positive cells in the brains of alcohol-exposed mice. Conclusion: These findings suggest that trigonelline protects brain against alcohol intoxication by inhibition of oxidative and inflammatory and apoptotic responses. Therefore, trigonelline may serve as a potential therapeutic approach for the protection of brain damage associated with binge alcohol consumption.
This study investigates the neuroprotective effects of zinc sulfate (ZnSO4) against diabetic encephalopathy in an aged female rat model of Type 2 diabetes mellitus (T2DM). T2DM was induced using a 4-week high-fat diet followed by a single 25 mg/kg STZ injection. Diabetic rats were treated with 10 mg/kg/day ZnSO4 for 4 weeks. We evaluated serum lipids, hippocampal oxidative stress (MDA, GSH), gene expressions (SIRT-1, GLUT3, BDNF, Bax, Bcl-2), and structural injuries (Nissl, PAS, GAP43, NGF) in the hippocampus and cerebral cortex. Results demonstrated that ZnSO4 significantly ameliorated systemic dyslipidemia. In the diabetic hippocampus, ZnSO4 mitigated oxidative stress by decreasing MDA and elevating depleted GSH levels. Molecularly, ZnSO4 upregulated the suppressed expressions of SIRT-1, GLUT3, BDNF, and Bcl-2, while downregulating pro-apoptotic Bax. Histopathological and immunohistochemical findings confirmed that ZnSO4 reduced neuronal degeneration and vascular pathologies (PAS positivity), preserving neuroplasticity (elevated GAP43 and NGF) in both brain regions. In conclusion, ZnSO4 supplementation provides potent, multifaceted neuroprotection against T2DM-associated neurodegeneration by regulating systemic dyslipidemia, restoring redox homeostasis, activating the SIRT-1/BDNF anti-apoptotic pathway, and preserving structural integrity.
The neurotoxicity of cisplatin (CIS) in the hippocampal leads to cognitive effects caused by oxidative stress, neuroinflammation, apoptosis, and dysfunction of neurotransmitters. The major bioactive phytonutrient in Aloe vera is barbaloin (BLN), which has been shown to have antioxidant and anti‐inflammatory effects, but its neuroprotective ability against CIS‐induced neurotoxicity has not been investigated. To assess the neuroprotective action of BLN in CIS‐induced hippocampal neurotoxicity in rats and to understand the molecular interactions between BLN and major neuroinflammatory and apoptotic proteins. A total of 24 male Wistar rats were split into 4 groups (n = 6): control, CIS (5 mg/kg), CIS + BLN 25 mg/kg, and CIS + BLN 50 mg/kg over 21 days. Cognitive ability (Morris water maze), oxidative stress indicators (MDA, GSH, SOD, CAT), neuroinflammatory cytokines (TNF‐α, IL‐1β, IL‐6, NF‐κB, TGF‐β1), caspase‐3, neurotransmitters, and hippocampal histopathology were measured. Molecular docking and 100‐ns molecular dynamics simulations (MDS) with MM‐GBSA analysis were done with TNF‐α, TGF‐β1, NF‐κBp65, and caspase‐3. BLN significantly reduced cognitive impairment, oxidative stress, neuroinflammation, and apoptosis, and restored neurotransmitter homeostasis and hippocampal cytoarchitecture (all p < 0.0001). Molecular docking demonstrated positive binding energies (− 7.226 to −8.566 kcal/mol), and MDS revealed the presence of stable BLN–protein complexes (ΔGbind = −56.07 kcal/mol for TGF‐β1). BLN exhibits considerable neuroprotective properties against CIS‐induced neurotoxicity in the hippocampus, suggesting its potential as a natural dietary phytonutrient supplement to ameliorate chemotherapy‐induced cognitive impairment.
Liquiritigenin (LG), a flavonoid compound extracted from licorice, possesses diverse pharmacological activities, including anti-inflammatory and antioxidant effects. A high-salt diet (HSD) is a common dietary risk factor associated not only with hypertension but also with central nervous system injury. However, the underlying mechanisms and potential therapeutic interventions remain insufficiently explored. In this study, we investigated the neuroprotective effects of LG against HSD-induced brain pathology and cognitive impairment in mice. The mechanism of action was further examined using NaCl-treated HT22 cells with LG intervention. By establishing HSD-related mouse and cellular models, administering different doses of LG, and performing neurobehavioral assessments, we evaluated its effects on brain tissue structure, cognitive performance, neuroinflammation, and mitochondrial function. The results demonstrated that in HSD-fed mice, LG attenuated hippocampal neuronal atrophy and death, thereby improving brain tissue morphology. Behavioral testing further revealed that LG enhanced motor performance and exploratory behavior, alleviating cognitive deficits. At the molecular level, LG reduced the expression of pro-inflammatory mediators while upregulating anti-inflammatory cytokines, effectively suppressing neuroinflammation. In addition, LG decreased cytoplasmic expression of mitochondrial DNA-related genes (d-loop, cox1, non-numt), increased ATP production, and improved mitochondrial function. Mechanistic studies further indicated that LG inhibits HSD-induced nuclear factor kappa-B p65 phosphorylation, reducing neuroinflammation and mitochondrial dysfunction, whereas NF-κB p65 overexpression abrogated these protective effects. In summary, LG protects against neuroinflammation and mitochondrial impairment by suppressing NF-κB signaling, thereby mitigating neurological dysfunction. These findings suggest that LG holds promise as a potential therapeutic agent for the prevention and treatment of HSD-related neurological disorders.
Alzheimer’s disease (AD) is one of the neurodegenerative diseases that is marked by deterioration in cognitive functioning and behavioral capacities in a progressive manner. It is the most prevalent cause of dementia in the aging population and imposes a high social and economic cost on the global population. In this study, we have examined Santonin, which can prevent the brain damage caused by aluminum chloride (AlCl 3 ) in rats, a typical method used to simulate the effects of AD in the laboratory. We administered AlCl 3 (100 mg/kg) to the rats to induce changes in them that resembled Alzheimer’s and tested their behavior using the open field and elevated plus maze tests. Then, we analyzed their brains in terms of the presence of inflammation, oxidative stress, enzyme activities, and tissue damage. The rats receiving AlCl 3 had reduced motility and an increase in acetylcholinesterase, malondialdehyde, and inflammatory cytokines, including cyclooxygenase-2, tumor necrosis factor-alpha, and interleukin-6. Their antioxidant defense mechanisms, glutathione, superoxide dismutase, and catalase, also decreased. However, these effects were changed positively when we treated rats with Santonin. Their movement was better, and they responded quicker, and their brains became less inflamed and less oxidatively stressed. Santonin reduced levels of harmful proteins and enzymes and restored antioxidant activity in a dose-dependent manner. Santonin helps reverse the brain changes and behavior problems caused by AlCl 3 in rats. It looks promising as a neuroprotective agent for AD.
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