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

Summary

This research investigated how hispidin, a natural compound found in medicinal mushrooms, could protect brain cells from damage related to Parkinson’s disease. The study found that hispidin helps protect neurons by reducing oxidative stress and maintaining proper mitochondrial function, potentially offering a new therapeutic approach for Parkinson’s disease prevention or treatment. Impacts on everyday life: • Identifies a natural compound from mushrooms that could help prevent or treat Parkinson’s disease • Demonstrates the potential therapeutic value of traditional medicinal mushrooms • Provides new hope for developing safer treatments for neurodegenerative diseases • Highlights the importance of antioxidants in brain health • Shows how natural compounds might complement existing treatments for Parkinson’s disease

Background

Parkinson’s disease (PD) is the second most frequent neurodegenerative disorder that predominantly influences dopamine production areas of substantia nigra. Most cases occur sporadically, with 10-15% having family histories. The main features include resting tremors, bradykinesia, stiffness, and postural instability. Current therapies aim to relieve symptoms and slow progression but can have harmful motor complications. Oxidative stress plays a key role in dopaminergic neuron degeneration, resulting from disrupted balance between reactive oxygen species generation and cellular antioxidant defenses.

Objective

To investigate the neuroprotective effects of hispidin, a polyphenol compound found in medicinal fungi Inonotus and Phellinus, against MPP+-induced cell damage in a Parkinson’s disease cell model and elucidate the underlying protective mechanisms.

Results

Hispidin protected MES23.5 cells from MPP+-induced cytotoxicity by reducing ROS production, preserving antioxidant enzyme activities (SOD, CAT, GSH-Px), maintaining dopamine levels, and preventing mitochondrial dysfunction. It also attenuated MPP+-induced activation of the JNK signaling pathway and subsequent mitochondrial-dependent apoptotic cascades. The protective effects were comparable to JNK inhibitors JNK-IN-8 and SR3576.

Conclusion

Hispidin demonstrates neuroprotective effects against MPP+-induced cell damage through restoration of mitochondrial complex respiratory chain I activity, antioxidant properties, and downregulation of oxidation-dependent JNK signaling that suppresses caspase cascade activation. These findings suggest hispidin may represent a potential therapeutic strategy for preventative and complementary Parkinson’s disease treatment.
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