Multi-target neuroprotection of carbon dots derived from Crinis Carbonisatus in multiple acute epilepsy model

Background Epilepsy remains a prevalent neurological disorder characterized by spontaneous, recurrent seizures. Despite available treatments, there is a critical lack of safe and effective strategies for long-term management and control. Crinis Carbonisatus (CrCi), the carbonized product of human hair, has been utilized for millennia to manage epilepsy and hemorrhagic disorders in Traditional Chinese Medicine. In our previous work, we successfully isolated Carbon Dots (CrCi-CDs) from CrCi and demonstrated their neuroprotective activity against ischemic stroke. Extending this rationale to seizure management, the present study investigates the potential antiepileptic efficacy of CrCi-CDs in acute epilepsy models. Methods CrCi-CDs were synthesized via the calcination of human hair at 350 °C, followed by aqueous extraction and purification. To evaluate their antiepileptic potential, acute epilepsy models were established in mice using three distinct chemoconvulsants: Pentylenetetrazole (PTZ), Pilocarpine (PILO), and Penicillin (PNC). We systematically assessed the ability of CrCi-CDs to attenuate seizure severity by modulating neuronal excitability, suppressing neuroinflammation, and mitigating oxidative stress. Furthermore, the PTZ-induced model was specifically selected as a representative paradigm to elucidate the underlying molecular mechanisms. Results and conclusion This study successfully synthesized spherical CrCi-CDs rich in surface functional groups (hydroxyl, amino, and carboxyl groups), which exhibited excellent dispersibility in aqueous solutions. In vivo evaluations using PTZ, PILO, and PNC models demonstrated that CrCi-CDs significantly reduced the severity of epileptic seizures and attenuated seizure-induced spatial learning and memory deficits. Brain histopathology revealed that CrCi-CDs treatment effectively mitigated hippocampal neuronal damage. Mechanistically, CrCi-CDs exerted neuroprotective effects through multiple pathways: restoring homeostasis by correcting pathological imbalances of neurotransmitters (Glu/GABA), alleviating oxidative stress (SOD/MDA), and suppressing proinflammatory cytokine release (TNF-α, IL-1β, IL-6, IL-18). Further investigations suggest these effects may be mediated by regulating glutamate transporters, inhibiting the NF-κB inflammatory cascade, and modulating neuronal apoptosis pathways. This study confirms that bio-derived CrCi-CDs exhibit potent antiepileptic and neuroprotective properties. By simultaneously targeting neurotransmission, inflammation, and oxidative stress, CrCi-CDs emerge as a highly promising therapeutic candidate with a favorable safety profile, providing a scientific rationale for the development of biomass-derived nanomedicines in epilepsy management.