Oleanolic Acid Alleviates Neuronal Ferroptosis in Subarachnoid Hemorrhage by Inhibiting KEAP1‐Nrf2 and NF‐κB Pathways

Drug Development Research, Journal Year: 2025, Volume and Issue: 86(3)

Published: May 1, 2025

ABSTRACT Oleanolic acid (OA) is a pentacyclic triterpenoid compound, and we previously report that it ameliorates neurological injury in subarachnoid hemorrhage (SAH) model. However, the underlying mechanism not clear. The aim of this study was to explore effect OA on SAH. In study, network pharmacology applied screen targets SAH treatment. Based these targets, protein‐protein interaction constructed, k‐means cluster analysis used core vitro model constructed with hemin‐induced neuron HT22 microglia BV2. Then cell counting Kit 8, flow cytometry, western blot, qPCR were performed evaluate effects neurons microglia. 93 identified as Notably, are closely related neuroinflammation oxidative stress responses. had good binding activity KEAP1, NFKB1 IKBA. significantly alleviated inhibitory hemin viability. inhibited expression CD86, promoted CD206, transformation from M1 type M2 type. Additionally, could inhibit activation NF‐κB KEAP1/Nrf2 pathways. conclusion, inflammatory response, ferroptosis SAH, suppresses neuronal by inhibiting

Language: Английский

The association between serum klotho protein and stroke: a cross-sectional study from NHANES 2007–2016

Frontiers in Neurology, Journal Year: 2025, Volume and Issue: 16

Published: May 16, 2025

Objective Serum klotho protein is a with anti-aging effects. Since the relationship between serum and Stroke remains rather ambiguous, this research probed into potential correlation concentration Stroke. Methods This study employed cross-sectional design incorporated population data from NHANES 2007 to 2016. Weighted univariate multivariate logistic regression models were utilized inspect Stratified analyses interaction tests carried out explore latent Finally, fitted smooth curve was adopted depict non-linear relationship. Results In study, after excluding all missing data, total of 12,414 participants encompassed, including 450 individuals. After adjusting for covariates, higher associated lower prevalence According subgroup tests, age, gender, race, BMI, hypertension, diabetes mellitus, family members, drinker smoker not significantly correlated influence stroke [OR: 0.68, 95% CI: 0.47–0.99]. Conclusion disclosed negative levels Further prospective studies are requisite investigate impact on determine causal

Language: Английский

FTO promotes post-stroke neuroprotection by m ⁶ A demethylation of c-Jun

Journal of Cerebral Blood Flow & Metabolism, Journal Year: 2025, Volume and Issue: unknown

Published: May 15, 2025

N 6 -methyladenosine (m A) is a critical epitranscriptomic regulator of neuronal function. Cerebral ischemia induces m A hypermethylation due to decreased expression demethylase fat mass and obesity-associated (FTO) protein. Previously, we showed that cerebral overexpression FTO with an adeno-associated virus (AAV) 9 protects the post-stroke brain. We presently evaluated mechanistic basis for FTO-dependent demethylation in post-ischemic neuroprotection using mice transient middle artery occlusion model experimental stroke. Based on bioinformatic predictions abundance, pro-apoptotic transcription factor Jun proto-oncogene (c-Jun) 19 sites was chosen as exemplary target. normalized c-Jun without altering its transcript levels. suppressed translation c-Jun. Consequently, several target genes are transcriptionally repressed, apoptosis decelerated, seen by cleaved caspase-3 levels TUNEL + neurons AAV9 treated group compared control group. Moreover, replenishing precluded FTO-mediated functional recovery. Collectively, this study demonstrated FTO/m A/c-Jun axis ameliorates brain damage, leading better outcomes.

Language: Английский