{"doi":"10.1038/s41598-025-05072-3","title":"Inhibition of levodopa metabolism to dopamine by honokiol short-chain fatty acid derivatives may enhance therapeutic efficacy in Parkinson’s disease","abstract":"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.","journal":"Scientific Reports","year":2025,"id":532495,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9578,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":349889,"name":"Micaël Hardy","orcid":"0000-0003-2976-7785","position":1,"is_corresponding":false},{"id":386321,"name":"Jimmy B. Feix","orcid":null,"position":2,"is_corresponding":false},{"id":254811,"name":"Balaraman Kalyanaraman","orcid":"0000-0002-9180-8296","position":3,"is_corresponding":false},{"id":604421,"name":"Gang Cheng","orcid":"0000-0002-1760-9539","position":0,"is_corresponding":true}],"reference_count":69,"raw_metadata":null,"created_at":"2026-07-19T02:51:23.237536Z","pmid":"40481059","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}