An approved herbal medicinal preparation of Salvia officinalis as potential source of new agents against Trypanosoma brucei rhodesiense

Sleeping sickness, Chagas disease and Leishmaniasis, are infectious diseases caused by unicellular eukaryotic parasites (“protozoans”). They are classified as Neglected Tropical Diseases by World Health Organization. These life-threatening diseases, due to the lack of vaccines as well as safe medicines and in view of the lack of industrial interest, urgently require development of new therapies.

The aim of our ongoing study is to investigate the potential of legally approved and marketed herbal medicinal products (HMPs) as antiprotozoal agents.

Up to now, 66 extracts from 53 HMPs have been assayed by a Multiple-Target-Screening (MTS) against protozoan parasites of the genera Trypanosoma, Leishmania and Plasmodium. 19 HMPs showed in vitro activity against at least one of the pathogens (IC₅₀< 10 µg/mL). In particular, a preparation of Salvia officinalis exhibited promising activity against T.b. rhodesiense (East African Sleeping Sickness) with 100% of growth inhibition (GI) at 10 µg/mL, IC₅₀= 1.86 µg/mL and SI = 17. Separation on Sephadex LH-20 afforded fractions that were assayed in vitro against the parasite and analyzed by UPLC/ESI-QqTOF-MS to generate the analytical fingerprints. Fractions 18, 19, 20, 22 and 24 exhibited significant trypanocidal activity ranging from 75.6 to 100% of GI at 10 µg/mL. Partial Least Squares regression models (PLS) were constructed to correlate the activity of the fractions and their LC-MS profiles in order to localize those compounds most likely responsible for the biological activity. The obtained PLS models explained about 98% of the variance in the biological data with 2 – 3 latent variables. Targeted isolation of the most important compounds highlighted by the PLS models is in progress.

Acknowledgements: NLM is grateful for a fellowship from Heinrich-Böll-Stiftung. Financial support by Apothekerstiftung Westfalen-Lippe is gratefully acknowledged. We thank R. Brun and M. Kaiser, Swiss TPH, Basle, for performing the bioassays.