Phytochemical Composition, Antibacterial Activity, Modes of Action, and Antibiotic Resistance–Modifying Effects of <i>Harungana madagascariensis</i> (Hypericaceae) Against Multidrug‐Resistant <i>Pseudomonas aeruginosa</i>

<i>Harungana madagascariensis</i> is a plant used in African traditional medicine to treat a wide range of human diseases, including microbial infections. The aim of this study was to evaluate the phytochemical composition, antibacterial activity, modes of action, and antibiotic resistance-modifying effects of the leaf, bark and root extracts of <i>H</i>. <i>madagascariensis</i> against multidrug-resistant <i>Pseudomonas aeruginosa</i>. The broth microdilution method was used to evaluate the antibacterial activity and antibiotic resistance-modifying effects of extracts. Phytochemical composition of extracts was carried out using known qualitative and quantitative methods. The action of the most active extract was evaluated on the bacteria cell membrane and catalase activity. The phytochemical results indicated that all the extracts contain alkaloids, terpenoids, saponins, phenols, flavonoids, tannins, and anthocyanins. Moreover, <i>H</i>. <i>madagascariensis</i> leaf extract (HMLE) had the highest phenolic (107.41 ± 9.66 mg GAE/g of extract) and flavonoid (53.67 ± 5.09 mg QE/g of extract) contents. The extracts had a wide range of antibacterial activity, with MICs ranging from 16 to 2048 μg/mL. HMLE identified as the most active extract affected the cytoplasmic membrane integrity and inhibited the catalase activity of <i>P</i>. <i>aeruginosa</i>. Moreover, HMLE at its subinhibitory concentration (MIC/8) improved the antibiotic activity by 2- to 16-fold. The MICs of tetracycline and doxycycline deceased from 32 to ≤ 2 <i>μ</i>g/mL and that of kanamycin from 256 to 32 μg/mL against the tested MDR <i>P</i>. <i>aeruginosa</i>. In conclusion, this study indicates that extracts from <i>H. madagascariensis</i>, particularly from its leaves, could serve as valuable assets in the discovery of new treatment option of infections due to MDR <i>P</i>. <i>aeruginosa</i>.