ArticleCNS neuroscience & therapeutics2024
Betulin ameliorates neuronal apoptosis and oxidative injury via DJ-1/Akt/Nrf2 signaling pathway after subarachnoid hemorrhage.
Article in CNS neuroscience & therapeutics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed.
- Microglia Attenuate Neuroinflammation After Subarachnoid Hemorrhage by Modulating Astrocyte Phenotypic Transformation via the RARα/Mafb/Msr1 Pathway.Molecular neurobiology · 2026Article
- Optimization of Extraction of Total Terpenoids fromMolecules (Basel, Switzerland) · 2026Article
- Sestrin2 Mitigates Neuronal Ferroptosis Following Subarachnoid Hemorrhage via Orchestration of the AMPK/PGC1α/Nrf2 Signaling Axis.CNS neuroscience & therapeutics · 2026Article
- Integrative Analysis Identifies PANoptosis-Associated Molecular Patterns and Immune Alterations in Rat Cerebral Ischemic-Reperfusion Injury.Cellular and molecular neurobiology · 2026Article
- Betulinic Acid Attenuates Lipopolysaccharide-Induced Kidney Inflammatory Injury by Suppressing PANoptosis in Weaned Piglets.Veterinary sciences · 2026Article
- Systematic evaluation of cerebral injury stimulating by underwater infrasound.Frontiers in physiology · 2026Article
- Neuroprotective Potential of Betulin and Its Drug Formulation with Cyclodextrin-In Vitro Assessment.International journal of molecular sciences · 2025Article
- Loss of DJ-1 alleviates microglia-mediated neuroinflammation in Parkinson's disease via autophagy-lysosomal degradation of NLRP3.Frontiers in immunology · 2025Article
- Betulin ameliorates neuronal apoptosis and oxidative injury via DJ-1/Akt/Nrf2 signaling pathway after subarachnoid hemorrhage.CNS neuroscience & therapeutics · 2024Article
- DJ-1-Binding Compound Improves Peripheral Nerve Injury in the Spinal Dorsal Horn by Restraining STAT3-Mediated Neurotoxic Reactive Astrocytes.Dose-response : a publication of International Hormesis SocietyArticle
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7 authors.
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Abstract
aimsWe aimed to resolve the uncertainty as to whether betulin exerted neuroprotection on early brain injury (EBI) caused by subarachnoid hemorrhage (SAH), and to investigate the related molecular mechanisms.
methodsBioinformatic analysis was performed to pre-study the differently expressed genes (DEGs) and the possible signaling pathways. Rat and cellular model of SAH were introduced in this study, and betulin, an activator of DJ-1 protein, was administered to reveal the effect. Gross assessment regarding mortality, neurofunctions, SAH grade, brain water content (BWC) along with multiple cellular and molecular studies in vivo or/and in vitro such as immunofluorescence (IF) staining, western blot (WB), reactive oxygen species (ROS) assay, and flow cytometry (FCM) were all conducted after SAH induction to verify the protective effect and the relevant mechanisms of DJ-1 in diverse levels. In addition, MK2206 (selective inhibitor of Akt) and iRNADj-1 (interfering RNA to Dj-1) were utilized to confirm the mechanisms of the effect.
resultsThe data from our study showed that DJ-1 protein was moderately expressed in neurons, microglia, and astrocytes; its level in brain tissue elevated and peaked at 24-72 h after SAH induction. Betulin could efficaciously induce the expression of DJ-1 which in turn activated Akt and Bcl-2, and anti-oxidative enzymes SOD2 and HO-1, functioning to reduce the activation of cleaved caspase-3 (c-Casp-3) and reactive oxygen species (ROS). The induced DJ-1 could upregulate the expression of Nrf2. However, Akt seemed no direct effect on elevating the expression of Nrf2. DJ-1 alone could as well activate Akt-independent antiapoptotic pathway via suppressing the activation of caspase-8 (Casp-8).
conclusionsBetulin which was a potent agonist of DJ-1 had the ability to induce its expression in brain tissue. DJ-1 had neuroprotective effect on EBI through comprehensive mechanisms, including facilitating intrinsic and extrinsic antiapoptotic pathway, and reducing oxidative injury by upregulating the expression of redox proteins. Betulin as an inexpensive drug showed the potential for SAH treatment.
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