1. Academic Validation
  2. Intracellular ROS production and apoptotic effect of quinoline and isoquinoline alkaloids on the growth of Trypanosoma evansi

Intracellular ROS production and apoptotic effect of quinoline and isoquinoline alkaloids on the growth of Trypanosoma evansi

  • Acta Trop. 2023 Sep:245:106980. doi: 10.1016/j.actatropica.2023.106980.
Ruma Rani 1 Khushboo Sethi 1 Snehil Gupta 2 Nitin Virmani 1 Sanjay Kumar 1 Rajender Kumar 3
Affiliations

Affiliations

  • 1 ICAR-National Research Centre on Equines, Hisar, Haryana, 125001, India.
  • 2 Department of Veterinary Parasitology, Lala Lajpat Rai University of Veterinary and Animal Sciences, Hisar, Haryana, 125001, India.
  • 3 ICAR-National Research Centre on Equines, Hisar, Haryana, 125001, India. Electronic address: rkg.nrce@gmail.com.
Abstract

Trypanosoma evansi, a hemoflagellate poses huge economic threat to the livestock industry of several countries of Asia, Africa, South America and Europe continents of the world. Limited number of available chemical drugs, incidents of growing drug resistance, and related side effects encouraged the use of herbal substitutes. In the present investigation, the impact of six Alkaloids of quinoline and isoquinoline group was evaluated on the growth and multiplication of Trypanosoma evansi and their cytotoxic effect was examined on horse peripheral blood mononuclear cells in an in vitro system. Quinine, quinindine, cinchonine, cinchonidine, berbamine and emetine showed potent trypanocidal activities with IC50/24 h values 6.631 ± 0.244, 8.718 ± 0.081, 16.96 ± 0.816, 33.38 ± 0.653, 2.85 ± 0.065, and 3.12 ± 0.367 µM, respectively, which was comparable to the standard anti-trypanosomal drug, quinapyramine sulfate (20 µM). However, in the cytotoxicity assay, all the drugs showed dose dependent cytotoxic effect and quinine, berbamine and emetine showed selectivity index more than 5, based of ration of CC50 to IC50. Among the selected Alkaloids, quinidine, berbamine and emetine exhibited higher apoptotic effects in T. evansi. Likewise, drug treated parasites showed a dose-dependent and time-dependent increase in Reactive Oxygen Species (ROS) production. Therefore, increased Apoptosis in combination with ROS generation could be responsible for the observed trypanocidal effect which could be further evaluated in T. evansi-infected mice model.

Keywords

Alkaloids; Apoptosis; Cytotoxicity; HMI-9 medium; ROS generation; Trypanosoma evansi.

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