title: Plants traditionally used individually and in combination to treat sexually transmitted infections in northern Maputaland, South Africa: antimicrobial activity and cytotoxicity.
abstract: BACKGROUND
  Although medicinal plants are used extensively to treat sexually transmitted infections (STIs) in rural northern Maputaland, KwaZulu-Natal, the efficacy and safety of these plants have not previously been evaluated.
  
  
  OBJECTIVE
  A study was designed to investigate the in vitro antimicrobial activity and cytotoxicity profiles of a selection (individual plants and selected combinations) of traditionally used plants in this study area.
  
  
  METHODS
  Aqueous and organic (dichloromethane: methanol, 1:1) extracts were prepared. Antimicrobial activity was assessed using the minimum inhibitory concentration (MIC) assay against the STI associated pathogens; Candida albicans ATCC 10231, Ureaplasma urealyticum clinical strain, Oligella ureolytica ATCC 43534, Trichomonas vaginalis clinical strain, Gardnerella vaginalis ATCC 14018 and Neisseria gonorrhoeae ATCC 19424. For the combination study, interactions were assessed using the fractional inhibitory concentration (ΣFIC). The plant species were assessed for safety using the 3-[4,5-dimethyl-2-thiazol-yl]-2,5-diphenyl-2H-tetrazolium bromide (MTT) cellular viability assay on the human embryonic kidney epithelial (Graham, HEK-293) cell line.
  
  
  RESULTS
  For the antimicrobial studies, U. urealyticum was the most sensitive of the six test organisms, with the aqueous extract of Ranunculus multifidus (0.02mg/ml) and the organic extract of Peltophorum africanum (0.04mg/ml) being the most antimicrobially active plant species studied. Sclerocarya birrea was found to have the broadest spectrum of activity (mean MIC of 0.89mg/ml). The only plant species to exhibit some degree of cytotoxicity against the kidney epithelial cell line was Kigelia africana (100µg/ml), with 22% and 16% cell death for the aqueous and organic extracts, respectively. Of the 13 combinations studied, several synergistic combinations were evident, the most prominent being the combination of Albizia adianthifolia and Trichilia dregeana (aqueous extract) with an ΣFIC value of 0.15 against O. ureolytica. Synergistic interactions were observed regardless of the ratio of the aqueous mixtures of the two plants. Syzygium cordatum and S. birrea (aqueous extract) was also a combination of interest, demonstrating synergistic (ΣFIC=0.42) interactions against O. ureolytica. This combination, however, also displayed some cytotoxicity towards the human epithelial cell line.
  
  
  CONCLUSIONS
  This study demonstrated that anecdotal evidence of plant use does not always correlate with in vitro activity. Furthermore, the toxicological profiling is of utmost importance as if not combined in its correct ratio can lead to potential adverse effects.
authors.affiliation: Department of Pharmacy and Pharmacology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, 2193, South Africa.
authors.forename: D
authors.initials: D
authors.lastname: Naidoo
authors.forename: S F
authors.initials: SF
authors.lastname: van Vuuren
authors.forename: R L
authors.initials: RL
authors.lastname: van Zyl
authors.forename: H
authors.initials: H
authors.lastname: de Wet
mesh_terms: D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D057809:HEK293 Cells; D006801:Humans; D016488:Medicine, African Traditional; D008826:Microbial Sensitivity Tests; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D010946:Plants, Medicinal / Q000737:chemistry*; D012749:Sexually Transmitted Diseases / Q000188:drug therapy* / Q000382:microbiology*; D013019:South Africa; D016896:Treatment Outcome
chemical_list: D000890:Anti-Infective Agents; D010936:Plant Extracts
keywords: 1:1 mixture of dichloromethane and methanol; 3-[4,5-dimethyl-2-thiazol-yl]-2,5-diphenyl-2H-tetrazolium bromide; Ad; An; Antimicrobial; CFU/ml; Combination; Cytotoxicity; D:M; DMSO; INT; MIC; MTT; Medicinal plants; Ni; S; STIs; Sexually transmitted infection; TSB; additive; antagonistic; colony forming units/ml; dimethyl sulfoxide; iodonitrotetrazolium chloride; minimum inhibitory concentration; non-interactive; sexually transmitted infections; synergistic; the sum of the fractional inhibitory concentration; tryptone soya broth.; ΣFIC