Use of SCFAs Conjugated to a Polyphenol May Improve Parkinson's Disease Treatment
Findings from a recent study by scientists in the Department of Biophysics at 抖阴短视频 and Aix-Marseille University suggest that the use of short-chain fatty acids (SCFAs)—such as butyrate, propionate, and acetate—conjugated to the naturally occurring polyphenol honokiol (HNK) may improve the therapeutic efficacy of levodopa in treating Parkinson’s disease. SCFAs are major microbial fermentation-induced metabolites in the human gut.
Parkinson’s disease is a progressive neurodegenerative disorder characterized by motor dysfunction and non-motor symptoms. Parkinson’s disease often is treated with levodopa; however, the oral bioavailability of levodopa decreases over time due to increased metabolism of levodopa by gut bacteria, Enterococcus faecalis. Pharmacological approaches are needed to manage symptoms as they progress.
HNK has demonstrated neuroprotective effects in several mouse models of Parkinson’s disease. In this study, the authors examined the effects of esterase-cleavable HNK-SCFA ester conjugates (e.g., HNK-butyrate) on the inhibition of E. faecalis. They found that HNK-SCFAs inhibit the growth of E. faecalis in a dose-dependent manner. HNK-SCFAs exhibit enhanced cellular permeability and are hydrolyzed within bacterial cells, releasing HNK and SCFAs. This novel strategy is a significant step toward the development of pro-SCFA drugs targeting the gut microbiome in Parkinson’s disease.
This study, titled “,” was published in Scientific Reports and was supported by the National Institutes of Health, Advancing a Healthier Wisconsin Endowment, Harry R. and Angeline E. Quadracci Professor in Parkinson’s Research Endowment, and International Research Project SuperO2.
Authors of the study are Gang Cheng, PhD; Jimmy B. Feix, PhD; and Balaraman Kalyanaraman, PhD, in the Department of Biophysics, and Micael Hardy, PhD, from Aix-Marseille University.