SMS: A new screening method for synergism to test multi-herbal drug interactions for their antimicrobial activity

Effective strategies for management of antimicrobial resistant pathogens include revitalizing already existing antimicrobials and combination therapies. As previously reported, oregano and thyme ct. thymol essential oils (EOs) provide synergistic antimicrobial activities. The most common method to explore multiple drug interactions is the checkerboard assay creating FICIs by pairwise comparisons. As investigations of Thymus oils could show, checkerboard assays are experimentally costly even for a pairwise interaction test. By increasing the number of herbal drugs interacting with each other and by taking into account multi-herbal drug interactions, the number of experimental settings needed is increasing exponentially. In our study we fractionated oregano and thyme ct. thymol EOs to five fractions each. We developed a screening method for synergism (SMS) for multi-herbal drugs by sampling the diagonal of experiments and deleting single components instead of adding them. By this we could confirm the synergism of thymol and carvacrol and outrun the limitation of pairwise interaction testing of other methods. This is a major advantage decreasing costs and time needed to test multiple drug interactions for any number of components. SMS provides information if a specific component works synergistic, additive or antagonistic.