Bioassay-Guided Evaluation and LC-MS/MS Characterization of Five Limonia acidissima L. Plant Parts: A Multitarget...

Acne vulgaris is a multifactorial inflammatory disorder involving bacterial colonization, oxidative stress, and lipid-mediated inflammation, necessitating a comprehensive multitarget approach. This study evaluated the anti-acne potential of five morphological parts of Limonia acidissima L. using an integrated in vitro and in silico approach. Ultrasound-assisted extracts were evaluated for antibacterial activity against Cutibacterium acnes and Staphylococcus epidermidis, antioxidant activity using DPPH and ABTS assays, and total phenolic and flavonoid contents (TPC and TFC). TOPSIS was applied to minimize selection bias and identified the leaf extract as the optimal candidate (closeness coefficient = 0.88325). LC-MS/MS tentatively identified major metabolites, including vitexin, quercetin, cyanidin-3-O-galactoside, caffeate, methyleugenol, indole, and linolenic acid. Molecular docking predicted favorable interactions of linolenic acid with C. acnes KAS III (Rerank Score = -78.470) and 15-lipoxygenase (15-LOX) (Rerank Score = -101.025), as well as cyanidin-3-O-galactoside with S. epidermidis (Rerank Score = -109.588) and KEAP1 (Rerank Score = -132.253). SwissADME analysis further suggested favorable drug-likeness and skin-permeation profiles. Collectively, these findings support the potential of L. acidissima leaf extract as a promising multitarget anti-acne candidate.