Biomol Ther.  2024 Sep;32(5):523-530. 10.4062/biomolther.2024.075.

Coadministration of 6-Shogaol and Levodopa Alleviates Parkinson’s Disease-Related Pathology in Mice

• Kim JH
• Kim JS
• Ju IG
• Huh E
• Choi Y
• Lee S
• Cho JY
• Park BY
• Oh MS

• KMID: 2559241
• DOI: http://doi.org/10.4062/biomolther.2024.075

Abstract

Parkinson’s disease (PD) is a neurodegenerative disease caused by the death of dopaminergic neurons in the nigrostriatal pathway, leading to motor and non-motor dysfunctions, such as depression, olfactory dysfunction, and memory impairment. Although levodopa (L-dopa) has been the gold standard PD treatment for decades, it only relieves motor symptoms and has no effect on non-motor symptoms or disease progression. Prior studies have reported that 6-shogaol, the active ingredient in ginger, exerts a protective effect on dopaminergic neurons by suppressing neuroinflammation in PD mice. This study investigated whether cotreatment with 6-shogaol and L-dopa could attenuate both motor and non-motor symptoms and dopaminergic neuronal damage. Both 6-shogaol (20 mg/kg) and L-dopa (80 mg/kg) were orally administered to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid-induced PD model mice for 26 days. The experimental results showed that L-dopa alleviated motor symptoms, but had no significant effect on non-motor symptoms, loss of dopaminergic neuron, or neuroinflammation. However, when mice were treated with 6-shogaol alone or in combination with L-dopa, an amelioration in both motor and non-motor symptoms such as depressionlike behavior, olfactory dysfunction and memory impairment was observed. Moreover, 6-shogaol-only or co-treatment of 6-shogaol with L-dopa protected dopaminergic neurons in the striatum and reduced neuroinflammation in the striatum and substantia nigra. Overall, these results suggest that 6-shogaol can effectively complement L-dopa by improving non-motor dysfunction and restoring dopaminergic neurons via suppressing neuroinflammation.

Keyword

6-shogaol; Levodopa; Parkinson’s disease; Non-motor symptom; Dopaminergic neuron; Neuroinflammation