Ischemic stroke currently lacks evidence-based neuroprotective agents, primarily due to the challenge of timely intervention, which often occurs after the onset of irreversible neuronal damage. To address this, this study investigates the PARthanatos pathway, a form of regulated cell death triggered by DNA damage. Utilizing MNNG-induced cellular PARthanatos models, we screened a library of 2,939 traditional Chinese medicine monomers and identified Bruceine E, a natural product derived from Bruce