Plants have been long scrutinized in the quest for new antibiotics, but no strong antibiotic molecule was ever found. Evidences exist that most phytochemicals have a regulatory or adjuvant effect on other antibacterial compounds, thus promoting a greater therapeutic effect. The current study assessed twenty-eight plants from different families for their antibacterial activity and as adjuvants in antibiotic therapy against Staphylococcus aureus, including methicillin-resistant S. , respectively. Non-antibacterial plants were assessed in combination with ampicillin, oxacillin, ciprofloxacin, erythromycin and tetracycline by a modified disc diffusion test. Methanolic extracts of Acacia dealbata, Prunus spp. plants, Centaurea nigra, Eupatorium cannabium and Buxus sempervirens showed a potentiating effect mostly of ciprofloxacin, erythromycin and tetracycline. B. sempervirens was selected for its potentiating activity and applied against S. aureus biofilms. B.sempervirens (1 g L -1 ) was able to cause an 88% reduction of S. aureus within 1 h exposure. Further phytochemical investigation of B. sempervirens allowed to identify betulinic acid as a major component, together with other triterpenoids. Betulinic acid and other common terpernoids -lupeol, betulin, hederagenin, ursolic acid and oleanolic acid, were tested for antibacterial and antibiotic-potentiating activities. Among the tested compounds, oleanolic acid and ursolic acid -were highlighted, showing MIC of 62.5 and 15.6 mg L -1 , respectively, against S. aureus. Additionally, oleanolic acid showed synergism when combined with tetracycline and erythromycin and caused biofilm reductions of 70, 81 and 85% when applied at ½ MIC, MIC and 2 × MIC, respectively.
IntroductionTwo major circumstances have accentuated the quest for new antibacterial agents and alternative therapies in the last decades. Primarily, because microbes, due to their incredible and innate adaptability, seem to have at least equal chances for survival as scientists and pharmaceutical industries develop methods to kill them. 3 Multidrug-resistant (MDR) bacteria are responsible for a large number of nosocomial but also community-acquired infections and are spreading all over the globe. 4 Additionally, the limitation of our current arsenal of effective antibiotics accompanied by the lack of new antimicrobial alternatives are prompting the beginning of the "post-antibiotic era", which threats all the achievements of modern medicine.Since the beginning of mankind plants were undoubtedly the most important source of therapeutic remedies with an enormous range of applications. The earliest records of natural products were depicted from Mesopotamia (2600 B.C.) and included oils from cypress (Cupressus sempervirens) and myrrh (Commiphora species), which are still used today to treat coughs, colds and inflammation. 5 Many plant extracts and their phytochemical constituents are known to have antimicrobial activities. 6 However, it can be rapidly established that this effort of finding individual active anti...