Hispidin in the Medicinal Fungus Protects Dopaminergic Neurons from JNK Activation-Regulated Mitochondrial-Dependent Apoptosis in an MPP+-Induced In Vitro Model of Parkinson's Disease

Degenerative diseases of the brain include Parkinson's disease (PD), which is associated with moveable signs and is still incurable. Hispidin belongs to polyphenol and originates primarily from the medicinal fungi Inonotus and Phellinus, with distinct biological effects. In the study, MES23.5 cells were induced by 1-methyl-4-phenylpyridinium (MPP⁺) to build a cell model of PD in order to detect the protective effect of hispdin and to specify the underlying mechanism. Pretreatment of MES23.5 cells with 1 h of hispdin at appropriate concentrations, followed by incubation of 24 h with 2 μmol/L MPP⁺ to induce cell damage. MPP⁺ resulted in Reactive Oxygen Species production that diminished cell viability and dopamine content. Mitochondrial dysfunction in MS23.5 cells exposed to MPP⁺ was observed, indicated by inhibition of activity in the mitochondrial respiratory chain complex I, the collapse of potential in mitochondrial transmembrane, and the liberation of mitochondrial cytochrome c. Enabling c-Jun N-terminal kinase (JNK), reducing Bcl-2/Bax, and enhancing caspase-9/Caspase-3/PARP cleavage were also seen by MPP⁺ induction associated with increased DNA fragmentation. All of the events mentioned above associated with MPP⁺-mediated mitochondrial-dependent caspases cascades were attenuated under cells pretreatment with hispidin (20 µmol/L); similar results were obtained during cell pretreatment with pan-JNK inhibitor JNK-IN-8 (1 µmol/L) or JNK3 Inhibitor SR3576 (25 µmol/L). The findings show that hispidin has neuroprotection against MPP⁺-induced mitochondrial dysfunction and cellular Apoptosis and suggest that hispidin can be seen as an assist in preventing PD.

1-methyl-4-phenylpyridinium; MS23.5 cells; Parkinson’s disease; hispidin; medicinal fungus.