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Ethnopharmacological Relevance: The twigs of Elytropappus rhinocerotis are widely used in the Cape region of South Africa to treat foot odour, perspiration and also itchy, chilblained and burning feet. However, no antimicrobial studies have hitherto been published on this popular Cape herbal medicine, which is also used for a wide range of ailments., Aims of the Study: To determine the antimicrobial activity of the extracts, essential oil and two major labdane diterpenes isolated from E. rhinocerotis against micro-organisms associated with foot odour and other conditions associated with skin infections., Materials and Methods: Leafy stems were harvested from three individual plants at three separate geographical localities, giving a total of nine plant samples. The samples were air-dried, powdered and extracted with a 1:1 mixture of methanol and dichloromethane, and also with sterile distilled water. A portion of each sample was also hydrodistilled to obtain nine samples of essential oil. Isolation of the major labdane diterpenes was performed using silica and ethyl acetate in hexane (3:7 v/v) as the mobile phase. Minimum inhibitory concentrations (MIC) were determined for nine crude extracts, as well as three essential oil samples and two labdane diterpenes obtained from a bulk sample. The test organisms used in this study were from Deutsche Sammlung von Mikrooganismen (DSM) and American type culture collection (ATCC) strains and included five bacterial species (Brevibacterium agri ATCC 51663, B. epidermidis DSM 20660, B. linens DSM 20425, Staphylococcus aureus ATCC 25923, S. epidermidis ATCC 12228) and one fungal species (Trichophyton mentagrophytes ATCC 9533) associated with the skin., Results: The presence of essential oil is reported for the first time. Organic extracts and essential oil samples showed moderate to noteworthy activity against selected test organisms. For the Brevibacteria, the lowest MIC values for phenolic extracts were several times lower than the corresponding values for the positive control zinc (shown in brackets): 0.0031 mg/mL against Brevibacterium agri (0.33 mg/mL), 0.17 mg/mL against B. epidermidis (3.91 mg/mL) - both for sample 2 of Vanwyksdorp; 0.13 mg/mL against B. linens (2.28 mg/mL) - for sample 3 of Vanwyksdorp. Two isolated labdane diterpenoids (one of which is here first reported) were also antimicrobially tested and showed moderate activity but had high abundance in the extracts. Two major monoterpenes and four sesquiterpenes in the essential oil were identified as 1,8-cineole (4.6-12.3%), terpinen-4-ol (9.2-24.3%), germacrene A (3.9-15.6%), (-)-spathulenol (1.7-37.8%), viridiflorol (0.3-100%), and silphiperfol-6-en-5-one (4.5-26.8%)., Conclusion: The antimicrobial results particularly for the essential oils and against the Brevibacteria support the traditional topical use of Elytropappus rhinocerotis twigs to treat foot perspiration, foot odour and other related skin conditions., (Copyright © 2018 Elsevier B.V. All rights reserved.)