Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Coadministration of 6-Shogaol and Levodopa Alleviates Parkinson's Disease-Related Pathology in Mice

  • Jin Hee Kim (Department of Biomedical and Pharmaceutical Sciences, Graduate School, Kyung Hee University) ;
  • Jin Se Kim (Department of Biomedical and Pharmaceutical Sciences, Graduate School, Kyung Hee University) ;
  • In Gyoung Ju (Department of Oriental Pharmaceutical Science and Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University) ;
  • Eugene Huh (Department of Oriental Pharmaceutical Science and Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University) ;
  • Yujin Choi (Department of Biomedical and Pharmaceutical Sciences, Graduate School, Kyung Hee University) ;
  • Seungmin Lee (Department of Biomedical and Pharmaceutical Sciences, Graduate School, Kyung Hee University) ;
  • Jun-Young Cho (Department of Fundamental Pharmaceutical Science, Kyung Hee University) ;
  • Boyoung Y. Park (Department of Fundamental Pharmaceutical Science, Kyung Hee University) ;
  • Myung Sook Oh (Department of Biomedical and Pharmaceutical Sciences, Graduate School, Kyung Hee University)
  • Received : 2024.05.10
  • Accepted : 2024.06.04
  • Published : 2024.09.01
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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 depression-like 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.

Keywords

Acknowledgement

This study was supported by the National Research Foundation of Korea Grant and Commercialization Promotion Agency for R&D Outcomes (COMPA) (2021M3A9G1015618). This research was also supported by grants from the National Research Foundation of Korea, funded by the Korean government (grant number 2022M3A9B6017813).

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