Cimifugin Improves Motor Function Through Suppression of the NLRP3 Inflammasome in an Animal Model of Parkinson's Disease

Abstract

Objective: Parkinson's disease (PD) is a neurodegenerative disease characterized by the loss of dopaminergic neurons and persistent neuroinflammation in the substantia nigra (SN), triggering a dopamine deficiency that can lead to movement disorders. Neuroinflammation is a common feature of aging brains and neurodegenerative diseases. Inflammasome-related neuroinflammation is involved in the progression of PD. Methods: The effects of cimifugin was investigated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. Cimifugin is one of the main components of Saposhnikovia divaricata (Turcz.) Schischkin. Behavioral tests, such as the rotarod, pole, and traction tests, were conducted to measure the recovery effects of Parkinson-related motor deficiencies. Results: Our analyses showed that cimifugin treatment mitigates motor dysfunction in a dose-dependent manner. In addition, cimifugin conferred neuroprotection by increasing the survival of dopaminergic neurons, as measured by tyrosine hydroxylase immunostaining. Neuroinflammation was reduced by cimifugin by inhibiting NLR family pyrin domain-containing 3 (NLRP3)/caspase-1/interleukin 1β signaling in the MPTP-insulted SN. Moreover, monosodium urate crystals, an NLRP3 agonist, reversed cimifugin-induced improvement in motor function in the PD model. Conclusion: These results suggest that cimifugin administration is a potential therapeutic strategy for mitigating PD.