Polarity-resolved Ziziphus fruit extracts as multifunctional leads: GC-MS and UHPLC-MS/MS profiling, MIC-based bioactivity, and MD/MM/GBSA support.

Antimicrobial resistance and oxidative-stress-associated disorders motivate the search for edible, multi-component botanical matrices with measurable redox and anti-infective potential. Here, fruits of Ziziphus lotus and Ziziphus jujuba were investigated through an integrated chemistry-to-bioactivity-to-mechanism workflow combining polarity-guided Soxhlet extraction, GC-MS profiling of hexane fractions, UHPLC-MS/MS fingerprinting of acetone/methanolic fractions, total phenolic/flavonoid quantification, DPPH/ABTS antioxidant assays, and antimicrobial benchmarking using inhibition zones and resazurin-based MIC/MBC/MFC assays. The Z. lotus acetone fraction displayed the strongest phenolic enrichment (TPC = 124.33 ± 13.45 mg GAE g- 1 extract) and the lowest IC50 values (DPPH = 0.77 ± 0.02; ABTS = 0.19 ± 0.02 mg mL- 1). The lowest antibacterial MICs were observed for the Z. jujuba acetone fraction (0.415 mg mL- 1 against S. aureus, M. luteus and P. aeruginosa), whereas Rhodotorula glutinis was the most susceptible fungus (MIC/MFC = 0.415/5.20 mg mL- 1 with Z. jujuba methanol). Because the MIC values remain in the mg mL- 1 range, the extracts are interpreted as preliminary, moderate-potency anti-infective matrices. Redocking-validated docking, 100 ns molecular dynamics, PCA/free-energy landscape analysis, and 100-snapshot MM/GBSA were used as hypothesis-generating tools and identified stable conformational basins for D3R-4FS3, K3HDH-5JLC and UA-4UYL, with ensemble ΔGbind estimates of - 45.01, - 38.78 and - 46.06 kcal mol- 1, respectively. Overall, the work defines polarity-resolved Ziziphus chemotypes, cautiously links them to bioactivity patterns, and prioritizes fractions and compounds for direct enzyme assays, synergy testing, and formulation-oriented validation.