Immunomodulatory principles of Pelargonium sidoides

Extracts and isolated constituents (coumarins and phenols) of Pelargonium s idoides DC, a plant species used in folk medicine by the Southern African n ative population, were evaluated for their effects on nonspecific immune fu nctions. Although this herbal medicine is also successfully employed in mod ern phytotherapy in Europe to cure infectious diseases of the respiratory t ract, the scientific basis of its remedial effects is still unclear. Thus, functional bioassays including an in vitro model for intracellular infectio n with Leishmania parasites, an extracellular Leishmania growth assay, a fi broblast-virus protection assay (IFN activity), a fibroblast-lysis assay (T NF activity) and a biochemical assay for inorganic nitric oxides (iNO) were employed. None of the test samples revealed significant activity against e xtracellular, promastigote Leishmania donovani, the causative agent of huma n visceral leishmaniasis. In contrast, apart from the coumarin samples, all the Pelargonium extracts (EC50 <0.1-3.3 <mu>g/mL), gallic acid EC50 4.4 mu g/mL) and its methyl eater (EC50 12.5 mug/mL) significantly reduced the int racellular survival of L. donovani amastigotes within murine macrophages. T hese data indicate that the samples acted indirectly on Leishmania parasite s, possibly by activating leishmanicidal macrophage functions. Macrophage a ctivation was confirmed by detection of tumour necrosis factor (TNF-alpha) and inorganic nitric oxides (iNO) in supernatants of sample-treated macroph age cultures. Synthesis of iNO is a well-known effector mechanism of macrop hages against microorganisms such as Leishmania. Interestingly, blocking iN O-synthase with L-NMMA had no substantial effect on sample-induced intracel lular Leishmania kill, From bioassay-guided fractionation, gallic acid and its methyl ester present in large amounts in P, sidoides and in its active extracts, were identified as the prominent immunomodulatory principle for t his herbal medicine. The results, when taken together with recent reported antibacterial activity, provide a rational basis for both the traditional a nd the present utilization of P. sidoides in the claimed conditions. Copyri ght (C) 2001 John Wiley & Sons, Ltd.