From Detoxified Yam to Bioactive Extracts: Integrated Extraction and In Silico Evidence of Anti-Biofilm Activity of Dioscorea hispida Extracts Against Cutibacterium acnes

The increasing prevalence of biofilm-associated infections caused by Cutibacterium acnes has stimulated interest in food-derived natural products as alternative sources of anti-biofilm agents. This study investigated the effects of processing and extraction conditions on the phytochemical composition, antibacterial activity, and anti-biofilm properties of Dioscorea hispida Dennst. Reflux extraction of dried yam with 80% ethanol produced the crude extracts with the highest yields (1.39–1.80%), whereas fresh yam yielded 0.51–0.97% extract. Using Gas–liquid chromatography–mass spectrometry (GLC-MS) analysis, linoleic acid ethyl ester, n-hexadecanoic acid, 9,12-octadecadienoic acid (Z,Z)-, and stigmasterol were identified as the major constituents. Among the tested extracts, DH-W-F-H (D. hispida-water washing-fresh-hexane) and DH-W-F-E (D. hispida-water washing-fresh-ethanol) were extracted from fresh yam using hexane and ethanol, respectively, while DH-W-D-E (D. hispida-water washing-dry-ethanol) was isolated from dried yam using ethanol and exhibited the strongest antibacterial activity, with minimum inhibitory concentrations (MIC) ranging from 64 to 2048 µg/mL. These extracts demonstrated pronounced concentration-dependent inhibition of biofilm formation by Staphylococcus epidermidis, Staphylococcus aureus, and Cutibacterium acnes. The strongest anti-biofilm activity was observed against C. acnes, with biofilm formation nearly eliminated at MIC concentrations. Moreover, all three extracts significantly reduced established C. acnes biofilms, with DH-W-F-H exhibiting greater eradication efficacy than vancomycin under the tested conditions. To elucidate the underlying mechanism, major fatty acid derivatives were evaluated against C. acnes lipase (CALipase), a virulence factor associated with biofilm development, using molecular docking, molecular dynamics simulations, and the Molecular Mechanics-Generalized Born Surface Area (MM-GBSA) binding free-energy calculations. The compounds exhibited favorable interactions with CALipase, with linoleic acid ethyl ester (FA2) showing the strongest binding affinity, stable protein–ligand interactions throughout a 200 ns simulation, and the most favorable binding free energy. Collectively, the biological and computational findings suggest that fatty acid-rich extracts from processed D. hispida suppress biofilm formation through an antivirulence mechanism involving CALipase inhibition. These results highlight the potential of D. hispida as a source of metabolites for the development of functional food ingredients and value-added cosmetic and dermatological applications.