Screening North American plant extracts in vitro against Trypanosoma brucei for discovery of new antitrypanosomal drug leads

Surendra Jain; Melissa Jacob; Larry Walker; Babu Tekwani

doi:10.1186/s12906-016-1122-0

Screening North American plant extracts in vitro against Trypanosoma brucei for discovery of new antitrypanosomal drug leads

BMC Complement Altern Med. 2016 May 18:16:131. doi: 10.1186/s12906-016-1122-0.

Authors

Surendra Jain^{1

2}, Melissa Jacob¹, Larry Walker^{1

2}, Babu Tekwani^{3

4}

Affiliations

¹ National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, MS, 38677, USA.
² Department of BioMolecular Sciences, School of Pharmacy, University of Mississippi, University, MS, 38677, USA.
³ National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, MS, 38677, USA. btekwani@olemiss.edu.
⁴ Department of BioMolecular Sciences, School of Pharmacy, University of Mississippi, University, MS, 38677, USA. btekwani@olemiss.edu.

Abstract

Background: Human African Trypanosomiasis (HAT) is a protozoan parasitic disease caused by Trypanosoma brucei. The disease is endemic in regions of sub-Saharan Africa, covering 36 countries and more than 60 million people at the risk. Only few drugs are available for the treatment of HAT. Current drugs suffer from severe toxicities and require intramuscular or intravenous administrations. The situation is further aggravated due to the emergence of drug resistance. There is an urgent need of new drugs that are effective orally against both stages of HAT. Natural products offer an unmatched source for bioactive molecules with new chemotypes.

Methods: The extracts prepared from 522 plants collected from various parts of the North America were screened in vitro against blood stage trypamastigote forms of T. brucei. Active extracts were further screened at concentrations ranging from 10 to 0.4 μg/mL. Active extracts were also investigated for toxicity in Differentiated THP1 cells at 10 μg/mL concentration. The results were computed for dose-response analysis and determination of IC50/IC90 values.

Results: A significant number (150) of extracts showed >90 % inhibition of growth of trypomastigote blood forms of T. brucei in primary screening at 20 μg/mL concentration. The active extracts were further investigated for dose-response inhibition of T. brucei growth. The antitrypansomal activity of 125 plant extracts was confirmed with IC50 < 10 μg/mL. None of these active extracts showed toxicity against differentiated THP1 cells. Eight plants extracts namely, Alnus rubra, Hoita macrostachya, Sabal minor, Syzygium aqueum, Hamamelis virginiana, Coccoloba pubescens, Rhus integrifolia and Nuphar luteum were identified as highly potent antitrypanosomal extracts with IC50 values <1 μg/mL.

Conclusions: Limited phytochemical and pharmacological reports are available for the lead plant extracts with potent antitrypanosomal activity. Follow up evaluation of these plant extracts is likely to yield new antitrypanosomal drug-leads or alternate medicines for treatment of HAT.

Keywords: Human African trypanosomiasis; Natural products; North American plants; Trypanosoma brucei.

MeSH terms

Cell Line, Transformed
Drug Evaluation, Preclinical
Humans
Plant Extracts / pharmacology*
Plant Extracts / toxicity
Trypanocidal Agents / pharmacology*
Trypanocidal Agents / toxicity
Trypanosoma brucei brucei / drug effects*
United States

Substances

Plant Extracts
Trypanocidal Agents