The increasing incidence of drug- resistant pathogens raises an urgent need to identify and isolate new bioactive compounds from medicinal plants using standardized modern analytical procedures. Medicinal plant-derived compounds could provide novel straightforward approaches against pathogenic bacteria. This review explores the antimicrobial activity of plant-derived components, their possible mechanisms of action, as well as their chemical potential. The focus is put on the current challenges and future perspectives surrounding medicinal plants antimicrobial activity. There are some inherent challenges regarding medicinal plant extracts and their antimicrobial efficacy. Appropriate and optimized extraction methodology plant species dependent leads to upgraded and selective extracted compounds. Antimicrobial susceptibility tests for the determination of the antimicrobial activity of plant extracts may show variations in obtained results. Moreover, there are several difficulties and problems that need to be overcome for the development of new antimicrobials from plant extracts, while efforts have been made to enhance the antimicrobial activity of chemical compounds. Research on the mechanisms of action, interplay with other substances, and the pharmacokinetic and/or pharmacodynamic profile of the medicinal plant extracts should be given high priority to characterize them as potential antimicrobial agents.

It is accepted that the medicinal use of complex mixtures of plant-derived bioactive compounds is more effective than purified bioactive compounds due to beneficial combination interactions. However, synergy and antagonism are very difficult to study in a meticulous fashion since most established methods were designed to reduce the complexity of mixtures and identify single bioactive compounds. This study represents a critical review of the current scientific literature on the combined effects of plant-derived extracts/bioactive compounds. A particular emphasis is provided on the identification of antimicrobial synergistic or antagonistic combinations using recent metabolomics methods and elucidation of approaches identifying potential mechanisms that underlie their interactions. Proven examples of synergistic/antagonistic antimicrobial activity of bioactive compounds are also discussed. The focus is also put on the current challenges, difficulties, and problems that need to be overcome and future perspectives surrounding combination effects. The utilization of bioactive compounds from medicinal plant extracts as appropriate antimicrobials is important and needs to be facilitated by means of new metabolomics technologies to discover the most effective combinations among them. Understanding the nature of the interactions between medicinal plant-derived bioactive compounds will result in the development of new combination antimicrobial therapies.

Plants have long been thought to contribute to health promotion due to their fiber and phenolic content, as well as their inherent biological potential. The bioactive derivatives of medicinal plants are a valuable resource in the fight against serious diseases all around the world. The present review focuses on the current state of knowledge on the usage and medicinal applications of plant bioactives. Issues concerning the effect of aromatic plant derivatives on human gut microbiota and their antimicrobial and anti-inflammatory potentials are discussed and worth further exploring.

Natural products (NPs) serve as a crucial source for leading bioactive compounds in drug discovery research. Numerous drugs currently utilized as therapeutic agents have been derived from natural origins, with medicinal plant (MP) sources being particularly significant. Despite the advancement of synthetic chemistry, the importance of NPs persists due to their distinct chemical structures and varied biological activities. Moreover, recent advancements in technology have significantly aided in overcoming challenges, primarily due to inherent complexity. This review explores the potential of NPs in the process of drug discovery and development, placing emphasis on the blend of traditional knowledge with modern drug discovery techniques. A brief history of the development of NP drug discovery and examples of significant NPs developed in recent decades are also provided. The focus is on the various methods employed in authentication, selection, extraction/isolation, and bioactivity screening through the application of modern drug-development principles for NPs. Several cutting-edge techniques, such as genetic engineering, metabolic engineering, plant cell culture and synthetic biology utilizing “omics” technologies and computational methodologies enhancing research in NP drug discovery, are also highlighted. There are several problems and inherent challenges regarding NP drug discovery that need to be overcome. Despite the challenges that exist, NPs will be crucial for the future development of new therapeutic drugs, and it is expected that continuous research and the effective utilization of new approaches will further enhance drug discovery efforts.

The development of antibiotic resistance is a major public health issue, as infections are increasingly unresponsive to antibiotics. Emerging antimicrobial resistance has raised researchers’ interest in the development of alternative strategies using natural compounds with antibacterial activity, like honey, which has emerged as an agent to treat several infections and wound injuries. Nevertheless, the antibacterial effect of honey was mostly evaluated against Gram-positive bacteria. Hence, the objective of our study was to evaluate the antibacterial activity, as well as the physicochemical parameters, of genuine Greek honeys against multidrug-resistant Gram-negative pathogenic bacteria. In this vein, we aimed to study the in vitro antibacterial potential of rare Greek honeys against Verona integron-encoded metallo-β-lactamase (VIM)- or Klebsiella pneumoniae carbapenemase-producing multidrug-resistant Gram-negative pathogens. Physicochemical parameters such as pH, hydrogen peroxide, free acidity, lactonic acid, total phenols total flavonoids, free radical scavenging activities, tyrosinase enzyme inhibitory activity and kojic acid were examined. Moreover, the antimicrobial activity of 10 different honey types was evaluated in five consecutive dilutions (75%, 50%, 25%, 12.5% and 6.25%) against the clinical isolates by the well diffusion method, as well as by the determination of the minimum inhibition concentration after the addition of catalase and protease. Almost all the physicochemical parameters varied significantly among the different honeys. Fir and manuka honey showed the highest values in pH and H₂O₂, while the free acidity and lactonic acid levels were higher in chestnut honey. Total phenols, total flavonoids and free radical scavenging activities were found higher in cotton, arbutus and manuka honey, and finally, manuka and oregano honeys showed higher tyrosinase inhibition activity and kojic acid levels. The antimicrobial susceptibility depended on the type of honey, on its dilution, on the treatment methodology and on the microorganism. Arbutus honey was the most potent against VIM-producing Enterobacter cloacae subsp. dissolvens in 75% concentration, while fir honey was more lethal for the same microorganism in the 25% concentration. Many honeys outperformed manuka honey in their antibacterial potency. It is of interest that, for any given concentration in the well diffusion method and for any given type of honey, significant differences were not detected among the four multidrug-resistant pathogens, which explains that the damaging effect to the bacterial cells was the same regardless of the bacterial species or strain. Although the antimicrobial potency of different honey varieties dependents on their geographical origin and on their compositional differences, the exact underlying mechanism remains yet unclear.

The rising demand for novel antibiotic agents prompts an investigation into natural resources, notably plant-derived compounds. In this study, various extracts (aqueous, ethanolic, aqueous-ethanolic, and enzymatic) of Rosa damascena and Hypericum perforatum were systematically evaluated against bacterial strains isolated from dental lesions (n = 6) and food sources (raw milk and broiler carcass, n = 2). Minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC), antibiofilm activity, and time-kill kinetics were assessed across a range of extract concentrations, revealing a dose-responsive effect. Notably, some extracts exhibited superior antibacterial efficacy compared to standard clinical antibiotics, and the time-kill kinetics demonstrated a rapid elimination of bacterial loads within 24 h. The susceptibility pattern proved strain-specific, contingent upon the extract type, yet all tested pathogens exhibited sensitivity. The identified extracts, rich in phenolic and polyphenolic compounds, as well as other antioxidant properties, contributed to their remarkable antibiotic effects. This comprehensive investigation not only highlights the potential of Rosa damascena and Hypericum perforatum extracts as potent antibacterial agents against diverse bacterial strains including caries pathogens, but also underscores their rapid action and dose-dependent efficacy. The findings suggest a promising avenue for harnessing plant-derived compounds in the development of novel antimicrobial strategies against dental caries and other oral inflammations, bridging the gap between natural resources and antibiotic discovery.