Synergy Awardee Stephanie Leigh-de Rapper, Witwatersrand University, South Africa

The first GA synergy award, inaugurated in 2023, is aiming to create awareness for the exciting research on methods to prove the synergistic effects of the multiple components making up natural products.

The awardee, Dr. Stephanie Leigh-de Rapper from the Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, University of the Witwatersrand, Johannesburg, South Africa, contributed in an exemplary way to the development of this field with her studies on the synergies of essential oils, which culminated in the development of a formulated essential oil product demonstrating enhanced antimicrobial efficacy. She presented her research in a lecture at the 71. GA Congress, which was hosted by Dr. Gaia Scalabrino and Prof. Dr. Helen Sheridan at Trinity College Dublin´s NatPro Centre from July 2-7, 2023 in Dublin, Ireland

The synergistic effects involved in the action of natural products are key for their medicinal use. Research on these actions has been revolutionized in the past decades by methods quantifying synergy and by genomics techniques.

Dr. Leigh-de Rapper’s ground-breaking PhD work primarily has garnered recognition for its significant contributions exactly in this research field. Through several publications, this work has demonstrated how basic research principles can be developed into advanced predictive tools and validated into pharmaceutical formulations. Her studies on essential oil blends for positive therapeutic outcomes aide in paving the way for future advancements in natural product drug design, exemplifying the promising potential of synergy research in natural products and the vital role it plays in advancing medicinal applications.

The first of four publications that formed the body of this research aimed to provide the context concerning the aromatherapeutic use of essential oils alone and in combination in the management of respiratory tract infections. This publication provided merit to the study indicating the need for further exploratory studies concerning the use of essential oils in combination. The second publication entitled, “The use of chemometric modelling to determine chemical composition-antimicrobial activity relationships of essential oils used in respiratory tract infections”, provided further evidence in support of essential oil synergy between chemical compounds. The research undertaken in chemometrics identified major essential oil compounds that were responsible for the predominant antimicrobial effect of essential oils but also highlighted the interactions needed between compounds for enhanced effect.

Following the investigation into the antimicrobial activity of individual essential oils, an investigation into the combined effect of essential oils was undertaken and reported in the publication, “Essential oil blends: The potential of combined use for respiratory tract infections”. Interestingly, the number of synergistic interactions for antimicrobial effects appears substantial amongst the 369 combinations studied; however, toxic effects predominated in antagonistic potential (more toxic effects). Further investigation of the essential oil blends antimicrobially synergistic and non-toxic to brine shrimp was undertaken to determine the potential of these combinations for anti-inflammatory and non-toxic effects against lung cell lines. The essential oil blends demonstrated positive anti-inflammatory outcomes. Five distinct combinations (Cupressus sempervirens with Melaleuca alternifolia, Hyssopus officinalis with Salvia rosmarinus, Origanum marjorana with M. alternifolia, Myrtus communis with M. alternifolia and Origanum vulgare in combination with M. alternifolia) were found to be the most promising. This study was the first to identify these five combinations for synergistic antimicrobial, anti-inflammatory and non-toxic effects.

These combinations were then optimised in the study, “Optimizing the antimicrobial synergism of Melaleuca alternifolia (tea tree) essential oil combinations for application against respiratory related pathogens”. The use of computer-aided software to quantify synergy for drug design and development has been in use within the pharmaceutical industry for a number of years, with great success. The use of this technology in essential oil antimicrobial research is novel, with limited data available to validate its potential for use in this field of study. The use of this technology and the determination of essential oils interactions was explored and further elaborated on in this publication.

The essential oil combination of H. officinalis and S. rosmarinus demonstrated broad-spectrum antimicrobial potential with a Bliss model synergy score of 9.76 at ratios of between 49.57% of H. officinalis to 50.43% of S. rosmarinus. The findings of this study proved that isobolograms and computational modelling tools such as SynergyFinder can work collaboratively to pin-point optimum antimicrobial potential for synergy. The study then finally culminated with a formulated essential oil product demonstrating enhanced antimicrobial efficacy when compared to the neat essential oils.