Inhibition of levodopa metabolism to dopamine by honokiol short-chain fatty acid derivatives may enhance therapeutic efficacy in Parkinson's disease. Sci Rep 2025 Jun 06;15(1):20004
Date
06/07/2025Pubmed ID
40481059Pubmed Central ID
PMC12144245DOI
10.1038/s41598-025-05072-3Scopus ID
2-s2.0-105007531272 (requires institutional sign-in at Scopus site) 3 CitationsAbstract
This study investigates the antimicrobial properties of honokiol (HNK), a naturally occurring polyphenol, when conjugated with short-chain fatty acids (SCFAs) such as butyrate. We examined the effects of HNK-SCFA ester conjugates on Enterococcus faecalis, a gut bacterium that metabolizes levodopa, a drug used to manage Parkinson's disease symptoms. Our findings indicate that HNK-SCFA-esters (e.g., HNK-acetate, HNK-propionate, HNK-butyrate, and HNK-hexanoate) inhibit E. faecalis growth in a dose-dependent manner, followed by a temporary recovery period during which levodopa remains intact and unmetabolized. Notably, HNK-SCFAs exhibit enhanced cellular permeability and are hydrolyzed within bacterial cells, releasing HNK and SCFAs. These results suggest that HNK-SCFAs may reversibly modulate the gut metabolism of levodopa to dopamine, potentially enhancing its therapeutic efficacy in treating Parkinson's disease.
Author List
Cheng G, Hardy M, Feix JB, Kalyanaraman BAuthors
Gang Cheng PhD Assistant Professor in the Biophysics department at Medical College of WisconsinJimmy B. Feix PhD Emeritus Professor in the Biophysics 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
Allyl CompoundsBiphenyl Compounds
Dopamine
Fatty Acids, Volatile
Humans
Levodopa
Lignans
Parkinson Disease
Phenols
