p-Coumaric Acid Attenuates Lead Acetate-induced Neurotoxicity in Rats by Improving Behavioral Dysfunction and Suppressing Oxidative Stress, Neuroinflammation, Apoptosis, and Plasticity-related Molecular Alterations.

Protective Effects of p-Coumaric Acid Against Lead-Induced Hepatic Oxidative Stress, Inflammation, and Apoptosis: Integrated Molecular and Machine Learning-Based Analysis.

Overall, PCA alleviates Pb-induced hepatotoxicity by restoring antioxidant defenses, suppressing inflammatory signalling, and inhibiting mitochondrial apoptotic pathways.

Investigating the molecular mechanisms underlying the neuroprotective potential of ellagic acid in scopolamine-induced learning and memory dysfunction

Scopolamine-induced memory impairment is widely used as an experimental model of cognitive dysfunction. Natural compounds with antioxidant and anti-inflammatory properties, such as ellagic acid (EA), have shown neuroprotective potential; however, their effects on cholinergic signaling and neurotrophic factors remain underexplored. This study aimed to investigate the effects of EA on cognitive performance, oxidative stress, neuroinflammation, and cholinergic markers in scopolamine-treated rats. Fifty adult male Wistar rats were divided into control, scopolamine (Scop, 2 mg/kg, i.p.), Scop + EA (25 or 50 mg/kg, orally), and Scop + donepezil (2 mg/kg, orally) groups. Cognitive functions were assessed using the MWM and PA tests. Biochemical assays measured hippocampal and cortical levels of MDA, thiols, SOD, CAT, and AChE activity. In addition, hippocampal BDNF concentration and mRNA expression of pro-inflammatory cytokines, AChE, and CHRM1 were quantified. Scopolamine administration significantly impaired learning and memory in both MWM and PA tests, increased oxidative stress markers, reduced antioxidant enzyme activities, decreased hippocampal BDNF levels, and upregulated pro-inflammatory cytokines, AChE mRNA levels, and decreased CHRM1 mRNA expression. EA treatment (particularly at 50 mg/kg) significantly improved behavioral performance, restored antioxidant balance, enhanced BDNF expression, reduced AChE activity, and downregulated cytokine and AChE mRNA expression, while increasing CHRM1 mRNA expression, with effects comparable to those of donepezil. EA attenuates scopolamine-induced memory deficits, accompanied by improvements in oxidative stress markers, neuroinflammatory gene expression, and cholinergic parameters. These findings suggest a potential neuroprotective role of EA; however, the underlying mechanisms remain speculative.

Neuroprotective effects of zingerone on the thioacetamide-induced hepatic encephalopathy in rats. Insights from oxidative stress, ER stress, BDNF signaling and apoptosis

Overall, ZIN exhibited dose-dependent hepatoprotective and neuroprotective effects in TAA-induced hepatic encephalopathy, as evidenced by attenuation of oxidative stress, inflammation, ER stress, and apoptosis.

Erucic acid arbitrates neuroprotection in streptozotocin-induced memory deficit via improving oxidative stress/neuroinflammatory indicators/cholinergic activity in rodents.

BACKGROUND Erucic acid (EA), a monounsaturated omega-9 fatty acid derived from Raphanus sativus L. seeds, has antioxidant and anti-inflammatory properties. This study investigated its neuroprotective effects against streptozotocin (STZ)-induced diabetes-associated cognitive dysfunction in rats. METHODS Male Wistar rats were randomly assigned to five groups: normal control, STZ control (60 mg/kg), STZ + EA (10 mg/kg), STZ + EA (20 mg/kg), and EA (20 mg/kg) per se. EA was administered orally for 38 days. Blood glucose and body weight were measured before STZ administration and at the end of the study. Cognitive function was assessed using the Y-maze and Morris water maze (MWM). Cholinergic function, oxidative stress, neurotransmitters, inflammatory mediators, apoptosis, and cellular energy status were evaluated biochemically, and hippocampal histopathology was performed. RESULTS EA treatment significantly reduced hyperglycemia and attenuated diabetes-induced body weight loss. EA improved spontaneous alternation in the Y-maze and spatial learning and memory in the MWM, reducing escape latency and increasing target-quadrant time. EA decreased acetylcholinesterase activity while increasing choline acetyltransferase activity, restored antioxidant defenses, and reduced MDA, ROS, and NO levels. It also normalized neurotransmitter levels, suppressed TNF-α, IL-1β, IL-6, NF-κB, and caspase-3, increased IL-10, and improved the ATP/ADP ratio. Histopathology demonstrated preservation of hippocampal neuronal architecture. CONCLUSIONS EA ameliorated diabetes-associated cognitive dysfunction by improving learning and memory, preserving cholinergic neurotransmission, reducing oxidative stress and neuroinflammation, inhibiting neuronal apoptosis, and restoring cellular energy metabolism. These findings support the therapeutic potential of EA for managing cognitive impairment associated with diabetes.

Barbaloin Attenuates Cisplatin‐Induced Hippocampal Neurotoxicity by Suppressing Oxidative Stress, Neuroinflammation, and Apoptosis: In Vivo and In Silico Evidence

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.

Ferulic acid attenuates early life stress induced behavioral and neurochemical alterations via modulating HPA axis, oxidative stress, and NF-κB mediated neuroinflammation