Antibacterial phytocomplexes and compounds from Psychotria sycophylla (Rubiaceae) against drug-resistant bacteria

In this study, we examined the antibacterial and antibiotic-resistance reversal properties of methanol (MeOH) and ethyl acetate (EtOAc) extracts and compounds from Psychotria sycophylla aerial parts against drug-resistant bacteria. The tests were performed using the microdilution method. The mechanisms of action were investigated on growth kinetic and proton pumps of Escherichia coli. The structures of isolated compounds including oleanolic acid (1), ursolic acid (2), lupeol (3), betulinic acid (4), beta-sitosterol glucoside (5), and stigmasterol (6), were established based on nuclear magnetic resonance (NMR) and electrospray ionization-mass spectrometry (ESI-MS). The extracts displayed noteworthy antibacterial activities, with recorded minimal inhibitory concentrations (MIC) ranging from 4 to 1024 mu g/mL. Significant activities (MIC < 100 mu g/mL) were obtained with the MeOH extract against Providencia stuartii PS2636 and Staphylococcus aureus MRSA9 (MIC of 16 mu g/mL) as well as the EtOAc extract against S. aureus MRSA3 (MIC of 32 mu g/mL) and Enterobacter aerogenes EA27 (MIC of 4 mu g/mL). MeOH extract displayed a broad-spectrum antibacterial activity, acting against 21 out of 22 studied bacteria. The MICs of compounds (1-6) varied from 16 to 256 mu g/mL. Oleanolic acid (1) appeared to be the most effective, preventing the growth of 100% of studied bacteria. The MeOH extract significantly enhanced the efficacy of conventional antibiotics against selected multidrug-resistant Gram-negative bacteria. The mechanistic investigations showed interference of MeOH with bacterial growth kinetic (by extending the lag phase) and inhibition of proton pumps. The current study provides a strong experimental baseline to consider P. sycophylla extracts and compounds as potent antibacterial natural products.