Wolfberry glycopeptides alleviate levodopa-induced dyskinesia

Abstract Levodopa-induced dyskinesia is a prevalent and almost inevitable complication of long-term levodopa therapy in Parkinson’s disease, significantly impairing patients’ quality of life. Despite its clinical significance, levodopa-induced dyskinesia remains insufficiently understood, and effective therapeutic strategies are still limited. Wolfberry glycopeptides, bioactive components extracted from Lycium barbarum L. have recently been widely reported to possess neuroimmune activities. In this study, levodopa-induced dyskinesia was induced through chronic levodopa administration in multiple Parkinson’s disease animal models, including synuclein alpha-overexpressing mice and glutathione peroxidase 4 conditional knockdown mice, and then treated with wolfberry glycopeptides. Behavioral assessment using abnormal involuntary movements scoring showed that wolfberry glycopeptides significantly alleviated levodopa-induced dyskinesia-like symptoms across these models. Mechanistically, wolfberry glycopeptides preserved nigral dopaminergic neurons by restoring membrane lipid oxidative homeostasis, thereby delaying neuronal loss, and modestly improving dopamine metabolic homeostasis in the brain. Collectively, these findings demonstrate that wolfberry glycopeptides effectively mitigate levodopa-induced dyskinesia through dopaminergic neuroprotection and support their use as an integrative strategy in combination with levodopa to reduce levodopa-induced dyskinesia development and improve Parkinson’s disease symptom management.