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<p>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 <i>Enterococcus faecalis</i>, 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 <i>E. faecalis</i> 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.</p>

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Inhibition of levodopa metabolism to dopamine by honokiol short-chain fatty acid derivatives may enhance therapeutic efficacy in Parkinson’s disease

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年6月6日

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  • Gang Cheng,
  • Micael Hardy,
  • Jimmy B. Feix,
  • Balaraman Kalyanaraman

摘要

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.