Synergistic Interaction Between Alkanna tinctoria (L.) Tausch and Cefixime Enhances Antibacterial Activity Against Resistant Bacterial Strains
摘要
Antimicrobial resistance hinders effective antibiotic treatment; therefore, it necessitates not only the development of new antimicrobial agents and but to increase the effectiveness of existing agents. This study evaluated the synergistic antimicrobial activity of Alkanna tinctoria (L.) Tausch (A. tinctoria) root extracts with cefixime against resistant bacterial strains including methicillin resistant Staphylococcus aureus (MRSA), resistant Escherichia coli (E. coli), and resistantAcinetobacter baumannii. Extracts of A. tinctoria roots were prepared, followed by phytochemical analysis total phenolic content (TPC), total flavonoid content (TFC) and RP-HPLC standardization. Antioxidant potential was assessed via total antioxidant capacity (TAC), free radical scavenging assay (FRSA), and ferric reducing antioxidant power (FRAP). Initially, susceptibility testing by using disc diffusion and microbroth dilution assays was performed. Synergistic activity was evaluated by checkerboard method, time-kill kinetics, and protein estimation. Hemolytic assay determined hemocompatibility. Results showed that ethyl acetate extract yielded the highest recovery (4.25%). Methanol extract had the highest TPC and TFC (23.7 ± 0.02 µg QE/mg and 19.5 ± 0.18 µg GAE/mg, respectively), with rutin, catechin, and myricetin as major polyphenols. It also showed strong antioxidant activity: TAC (130.67 ± 0.08 µg AAE/mg), FRSA (17.3 ± 0.08%), and FRAP (121.46 ± 0.04 µg AAE/mg). All extracts exhibited antibacterial activity (MIC: 500 µg/ml). Ethyl acetate extract combined with cefixime showed total synergism with 8- to 16-fold MIC reduction against all strains. Time-kill studies indicated a bacteriostatic effect, supported by bacterial protein inhibition. All samples were hemocompatible at 500 µg/ml (3.66 ± 0.36% hemolysis). In conclusion, A. tinctoria extracts especially in combination with cefixime demonstrated significant antimicrobial potential and could enhance antibiotic efficacy against resistant pathogens.