South African traditional medicinal plants and their synergistic interactions with azithromycin

Traditional medicinal plants are frequently purchased from traditional muthi markets in South Africa. The Faraday market in Johannesburg (JHB), Gauteng and the Warwick market in Durban, KwaZulu-Natal (KZN), are two of the largest muthi markets in South Africa, responsible for traditional medicinal plant trading. Our previous studies on medicinal plants from these two markets showed some interesting interactive antimicrobial profiles with conventional antibiotics. Here we explore 22 of the 34 plants investigated, which were found to be antimicrobially synergistic against Staphylococcus aureus (ATCC 25923) when combined with azithromycin ([ Fig. 1 ]). The minimum inhibitory concentrations were determined for the medicinal plants and azithromycin and the fractional inhibitory concentration index (ΣFIC) calculated for the combinations. The highest synergy was found for azithromycin: Hypoxis hemerocallidea Fisch., C.A.Mey. & Avé-Lall. against S. aureus (ΣFIC 0.06). Synergistic interactions were calculated at varied concentrations for a dose-response analysis, against S. aureus (ATCC 25923 ). Further, the ΣFIC calculations were used for interactive profiling of nine varied combination ratios (9:1, 8:2, 7:3, 6:4, 5:5, 4:6, 3:7, 2:8, 1:9) and isobolograms constructed. The brine shrimp lethality assay (BSLA) allowed for further in vitro toxicity analysis of synergistic ratios. Findings confirmed that synergism was dose-dependent, with ratios exhibiting varied antimicrobial profiles, and potential for toxicity. This research highlights the need for further dose-dependent investigations, inclusive of biofilm activity, mechanism of action studies and in vivo antimicrobial and toxicity analysis, using a varied dose-response approach. Fig. 1 Overview of the plant sample: azithromycin combinations and applied methods for investigating interactive antimicrobial and toxicity profiles of varied ratio concentrations. Publication History Article published online: 05 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany