Chemical investigation of isihlambezo or traditional pregnancy-related medicines.

Abstract

This study was undertaken to redress the scant knowledge regarding the chemistry and mode of action of pregnancy-related traditional medicines, or isihlambezo (Zulu), which are used by 60 to 80% of women in South Africa. The three selected plants are among the six most frequently cited species from the approximately 90 used by traditional healers. The purpose of the study was to identify components which could cause uterine contractions, those with nutritional value for the foetus and mother, and those with any toxic effects. Plant root extracts were purified via silica gel column chromatography and bioassays were carried out on the fractions, using isolated rat uterine tissue. Purified compounds were identified via spectral techniques, and some were characterised by comparison to authentic standards using HPLC, and others by matching their GC-MS spectra to library standards. Thirty-eight compounds were identified in total, the majority of these being novel to the species concerned. Those isolated from Combretum kraussii were 1 sitosterol, 2 combretastatin, 3 3',4-tri-O-methylellagic acid, 4 combretastatin B-1, 5 combretastatin A-1, 6 3,3'-di-O-ellagic acid lactone, 7a ellagic acid lactone, 7b ellagic acid, 8 and 9 a mixture of combretastatin B-1 and A-1 glucosides, 10 and 11 partly characterised glucosides of ellagic acid. Those isolated from Gunnera perpensa were 12 3',4-tri-methylellagic acid, 13 ellagic acid lactone, 14 1,1'-biphenyl-4,4'-diacetic acid, 15 p-hydroxybenzaldehyde, 16 Z-methyl lespedezate, 17 and 18 partly characterized higher glucosides of Z-methyllespedezate. Those isolated rom Rhoicissus tridentata were 19 (-)-epigallocatechin, 20 (+)-gallocatechin, 21 procyanidin B3, 22 procyanidin B4, 23 (+)-catechin hydrate, 24 (+)-mollisacacidin, 25 (+)-epicatechin, 26 fisetinidol-(4a-8) catechin, 27 (-)-fisetinidol, 28 fisetinidol-(4b-8)catechin, 29 gallic acid, 30 epicatechin-3-0-gallate, 31 partly characterized hydrogel of glucose, 32 sitosterol, 33 sitosterolin, 34 y-sitosterol, 35 oleanolic acid, 36 lupen-3-one, 37 20-epi-y-taraxastananol and 38 triacontanol. The compounds with the greatest in vitro uteroactivity were predominantly proanthocyanidins or phenolic glucosides. It is proposed that effects of phenolic glucosides could be due to the interaction of the sugar moiety as well as the phenolic moiety with the receptor site in muscle tissue. The corresponding phenolic aglycones isolated were only moderately uterotonic, or unreactive by comparison. Non-polar compounds such as sitosterol and sitosterolin showed minimal enhancement of the uterine response at low concentrations, and inhibition at higher concentrations. Aqueous root extracts of the plants were all found to be non-toxic according to cell-viability tests using monkey vero cells and human fibroblasts. Extracts are therefore considered safe for human consumption, although it is recommended that Rhoicissus tridentata be used with caution because it showed the lowest cell viability of the three species, and uterine hyperstimulation has been attributed to this species, as well as CNS depression and respiratory arrest. Ions which could be nutritionally beneficial in pregnancy, calcium, iron, and phospate, were present in low in aqueous extracts. Levels of calcium and potassium ions were considered to be too low to directly stimulate uterine muscle. Proanthocyanidins, combretastatins, ellagic acid derivatives and phytosterols, with health-promoting properties, were also identified.