Huperzine A improves neurological function in mice with intracerebral hemorrhage by alleviating neuroinflammation and ferroptosis.

Abstract

Intracerebral hemorrhage (ICH) is a devastating neurological condition that is characterized by high morbidity and long-term disability, which frequently results in severe neurological deficits. Given the limited therapeutic options, pharmacological neuroprotection has emerged as a crucial area of research. This study explored the neuroprotective potential of huperzine A (HupA) in a murine model of collagenase-induced ICH in the caudate nucleus. Three experimental groups-Sham, ICH, and ICH + HupA-were assessed at multiple timepoints (1, 3, 7, and 14 days post-ICH) for neurological function, neuroinflammatory responses, and ferroptosis-related markers. Our findings reveal that HupA exerts significant neuroprotection through dual mechanisms: (1) attenuating neuroinflammation via the suppression of IL-1β/IL-6 release and inhibition of glial activation, and (2) mitigating ferroptosis by reducing iron accumulation and upregulating glutathione peroxidase 4 (GPX4) expression, and thereby preserving neuronal viability. These results highlight the therapeutic potential of HupA in alleviating ICH-induced brain injury, and thereby offers a promising multi-target strategy for ICH treatment.