Mitigating gut microbial degradation of levodopa and enhancing brain dopamine: Implications in Parkinson's disease. Commun Biol 2024 May 30;7(1):668
Date
05/31/2024Pubmed ID
38816577Pubmed Central ID
PMC11139878DOI
10.1038/s42003-024-06330-2Scopus ID
2-s2.0-85194991828 (requires institutional sign-in at Scopus site) 1 CitationAbstract
Parkinson's disease is managed using levodopa; however, as Parkinson's disease progresses, patients require increased doses of levodopa, which can cause undesirable side effects. Additionally, the oral bioavailability of levodopa decreases in Parkinson's disease patients due to the increased metabolism of levodopa to dopamine by gut bacteria, Enterococcus faecalis, resulting in decreased neuronal uptake and dopamine formation. Parkinson's disease patients have varying levels of these bacteria. Thus, decreasing bacterial metabolism is a promising therapeutic approach to enhance the bioavailability of levodopa in the brain. In this work, we show that Mito-ortho-HNK, formed by modification of a naturally occurring molecule, honokiol, conjugated to a triphenylphosphonium moiety, mitigates the metabolism of levodopa-alone or combined with carbidopa-to dopamine. Mito-ortho-HNK suppresses the growth of E. faecalis, decreases dopamine levels in the gut, and increases dopamine levels in the brain. Mitigating the gut bacterial metabolism of levodopa as shown here could enhance its efficacy.
Author List
Cheng G, Hardy M, Hillard CJ, Feix JB, Kalyanaraman BAuthors
Gang Cheng PhD Assistant Professor in the Biophysics department at Medical College of WisconsinJimmy B. Feix PhD Professor in the Biophysics department at Medical College of Wisconsin
Micael Joel Hardy PhD Visiting Assistant Professor in the Biophysics department at Medical College of Wisconsin
Cecilia J. Hillard PhD Associate Dean, Center Director, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
Balaraman Kalyanaraman PhD Professor in the Biophysics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsAntiparkinson Agents
Biphenyl Compounds
Brain
Carbidopa
Dopamine
Enterococcus faecalis
Gastrointestinal Microbiome
Humans
Levodopa
Male
Mice
Mice, Inbred C57BL
Organophosphorus Compounds
Parkinson Disease
