Eerdun Wurile, a Mongolian medicine, alleviates neuronal damage and improves neurological dysfunction after cerebral hemorrhage by activating the PI3K/AKT signaling pathway.

Abstract

Background: This study aims to evaluate the neuroprotective effects of the Mongolian medicine Eerdun Wurile (EW) against intracerebral hemorrhage (ICH) and explore its underlying mechanisms. ICH, a severe subtype of stroke, is characterized by a complex pathological process, with no specific treatments currently available. EW, a traditional Mongolian medicinal formula, has a long history of use in treating central nervous system disorders, but its mechanism of action in ICH remains poorly understood.

Methods: A mouse model of ICH was induced through stereotactic intracerebral injection of Collagenase Type IV. Behavioral assessments, histological examinations, and RNA sequencing were conducted to assess the effects of EW and elucidate its mechanism of action in mitigating neuronal injury post-cerebral hemorrhage.

Results: EW administration improved a range of ICH-induced deficits, including neurological and neurofunctional impairments, anxiety-like behaviors, and cognitive dysfunction. EW protected neurons from injury and apoptosis in both in vitro and in vivo models. Additionally, EW treatment suppressed the activation of astrocytes and microglia, reducing neuroinflammation, preserving blood-brain barrier integrity, and alleviating synaptic damage. RNA-seq analysis revealed that the PI3K/AKT signaling pathway plays a key role in EW's neuroprotective effects. EW activates this pathway, modulating the balance of Bcl-2 family proteins, thereby reducing neuronal apoptosis.

Conclusion: EW confers neuroprotection through multiple mechanisms. These findings provide strong experimental evidence supporting the potential clinical application of EW as a therapeutic agent for ICH.