Chemotherapeutic potentials of β-ionone against Trypanosoma congolense infection: Inhibition of parasite proliferation, anemia development, trans-sialidase (TconTS3 and TconTS4) gene expressions, and phospholipase A2

Chem Biol Drug Des. 2022 Jun;99(6):908-922. doi: 10.1111/cbdd.14048. Epub 2022 Apr 8.

Abstract

Trypanosoma congolense is a pathogenic African animal trypanosome species causing devastating conditions leading to death of an infected host. The drawbacks of the existing trypanocidal drugs have led to the search for new drug candidates. In this study, β-ionone at 15 and 30 mg/kg body weight (BW) was orally administered to T. congolense infected rats for 14 days followed by an assessment of anemia, organ damages, and the expression of T. congolense trans-sialidase gene variants. A significant decrease in parasitemia (p < .05) was observed in the animals treated with 15 mg/kg BW β-ionone besides increased animal survival rate. A trypanosome-induced decrease in packed cell volume (PCV) and histopathological changes across tissues was significantly (p < .05) ameliorated following treatment with both doses of β-ionone. This is in addition to reversing the parasite-induced upsurge in free serum sialic acid (FSA) and expression of T. congolense trans-sialidase gene variants (TconTS1, TconTS3, and TconTS4). Correlation analysis revealed a positive correlation (p > .05) between FSA with the TconTS gene expressions. In addition, the compound inhibited partially purified T. congolense sialidase and phospholipase A2 via mixed inhibition pattern with inhibition binding constants of 25.325 and 4.550 µM, respectively, while molecular docking predicted binding energies of -5.6 kcal/mol for both enzymes. In conclusion, treatment with β-ionone suppressed T. congolense proliferation and protected the animals against some of the parasite-induced pathologies whilst the effect on anemia development might be due to inhibition of sialidase and PLA2 activities as well as the expression levels of TconTS3 and TconTS4.

Keywords: Trypanosoma congolense; anemia; gene expression; phospholipase A2; trans-sialidase; β-Ionone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia* / drug therapy
  • Anemia* / parasitology
  • Animals
  • Cell Proliferation
  • Gene Expression
  • Glycoproteins
  • Molecular Docking Simulation
  • Neuraminidase
  • Norisoprenoids* / pharmacology
  • Phospholipases A2 / genetics
  • Rats
  • Trypanosoma congolense* / genetics
  • Trypanosomiasis, African* / drug therapy
  • Trypanosomiasis, African* / parasitology

Substances

  • Glycoproteins
  • Norisoprenoids
  • beta-ionone
  • Phospholipases A2
  • trans-sialidase
  • Neuraminidase