Preparation and Evaluation of Onjisaponin B-Loaded Liposomes for Drug Delivery to Enhance Mitochondrial Function and Rescue Parkinson’s Disease by Activating Mitophagy

Onjisaponin B (OB) is the main active ingredient of Radix Polygalae with various bioactivities. However, the protective effect of OB in Parkinson’s disease (PD) has not been fully studied. Liposomes are ideal nanocarriers for drugs targeting the brain. In this study, we investigated the therapeutic effect of OB-loaded liposomes (lip OB) on a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- (MPTP-) induced mouse model of PD and 1-methyl-4-phenylpyridinium- (MPP+-) induced cell model of PD. Our results showed that lip OB significantly ameliorated MPTP-induced motor deficits and dopaminergic neuron loss in vivo and prevented MPP+-triggered cell viability reduction and apoptosis in vitro. Lip OB also improved mitochondrial dysfunction in PD models by driving PINK1/Parkin-mediated mitophagy. Furthermore, silencing PINK1 compromised the beneficial effects of lip OB on MPP+-treated PC12 cells. These findings suggested lip OB mitigates Parkinsonism in vivo and in vitro by enhancing mitochondrial dysfunction through the PINK1/Parkin pathway of mitophagy, which provides a new possibility for treating PD.