Astragalus Polysaccharide Alleviates Oxidative Stress Injury through Modulation of the Nrf2/HO-1 Axis in the Striatum of Cerebral Ischemic Rats

Cordyceps Polysaccharides Attenuate Post-Ischemic Inflammatory Damage in a Rat Stroke Model with Associated Modulation of the mtDNA/NLRP3 Inflammasome-Related Pyroptosis Pathway

Background: Cordyceps polysaccharides (CSP) have shown neuroprotective potential in models of ischemic stroke, but the underlying mechanisms remain to be clarified. Methods: In this study, the effects of CSP were evaluated in MCAO rats and OGD-exposed BV-2 cells. Results: CSP significantly attenuated ischemic injury and inflammatory responses in both in vivo and in vitro models. Mechanistically, CSP decreased CMPK2 expression, increased TFAM levels, and reduced 8-OHdG expression, suggesting attenuation of oxidative DNA damage and mitochondrial DNA-associated stress. EdU staining further showed that OGD-induced DNA synthesis-related signals were predominantly extranuclear, supporting the possibility of mtDNA-associated alterations under ischemia-like conditions. Moreover, CSP suppressed the upregulation of NLRP3, Caspase-1, N-GSDMD, IL-1β, and IL-18, and reduced LDH release following OGD exposure, suggesting inhibition of inflammasome-associated pyroptotic signaling. Conclusions: These findings suggest that the neuroprotective effects of CSP in ischemic stroke models may be related to the modulation of CMPK2/mtDNA/NLRP3 inflammasome pathway and reduced pyroptosis.

Liquiritigenin attenuates high-salt diet-induced neuroinflammation, mitochondrial dysfunction, and cognitive impairment via NF-κB pathway inhibition.

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.

A combination of Nrf-2 activator, kinetin and zinc provides neuroprotection through NLRP3-NF-ԟB signaling in traumatic brain injury.

Apigenin Protects Against Ischemic Stroke Through Anti- Inflammatory Mechanisms: A Study Combining Comprehensive Network Analysis, Mendelian Randomization and Animal Experiments for Validation

There is a well-established link between inflammation and Ischemic Stroke (IS) pathology. A natural compound, Apigenin (APG), has a neuroprotective effect. However, the specific mechanisms underlying the anti-inflammatory effects of APG and its protective effects on the blood-brain barrier following IS are unclear. This study aimed to explore the mechanisms behind the anti-inflammatory effect of APG in IS. Male Sprague-Dawley rats were used to establish a model of unilateral middle cerebral artery occlusion (MCAO) and were administered APG by oral gavage at doses of 30, 60, or 120 mg/kg for 7 days. On the following day, brain tissues were collected after MCAO. Brain injury was evaluated by measuring brain water content, hematoxylin and eosin (H&E) staining, and Evans blue extravasation. To investigate potential proteins associated with inflammation, methods such as molecular docking, molecular dynamics simulations, Mendelian randomization analysis, immunohistochemistry, and Western blotting were employed. APG therapy has improved neurological deficiencies, lowered brain edema, and improved blood-brain barrier integrity. It has also resulted in decreased levels of inflammatory proteins TLR4, MyD88, NFκB, IL1β, MMP9, and iNOS after IS. Furthermore, IL1R2 was identified as a potential predictive target for IS. APG can repair nerve damage post-IS, with its protective effects mediated by anti-inflammatory mechanisms. The TLR4/myD88/NF-kB signaling pathway is a protective pathway of the body. APG may exert a protective effect on the blood-brain barrier after IS through the TLR4/MyD88/NF-kB signaling pathway. APG can protect against IS by inhibiting the inflammatory response, providing a theoretical basis for clinical translation and further experimental research of APG.

Polydatin inhibits hippocampal neurodegeneration in diabetic rats via modulation of oxidative stress and NF-kB/COX-2/IL-6 inflammatory pathway

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.