Antitrypanosomal Activities and Mechanisms of Action of Novel Tetracyclic Iridoids from Morinda lucida Benth

Abstract

Trypanosoma brucei parasites are kinetoplastid protozoa that devastate the health and economic well-being of millions of people in Africa through the disease human African trypanosomiasis (HAT). New chemotherapy has been eagerly awaited due to severe side effects and the drug resistance issues plaguing current drugs. Recently, there has been an emphasis on the use of medicinal plants worldwide. Morinda lucida Benth. is a popular medicinal plant widely distributed in Africa, and several research groups have reported on the antiprotozoal activities of this plant. In this study, we identified three novel tetracyclic iridoids, molucidin, ML-2-3, and ML-F52, from the CHCl3 fraction of M. lucida leaves, which possess activity against the GUTat 3.1 strain of T. brucei brucei. The 50% inhibitory concentrations (IC50) of molucidin, ML-2-3, and ML-F52 were 1.27 μM, 3.75 μM, and 0.43 μM, respectively. ML-2-3 and ML-F52 suppressed the expression of paraflagellum rod protein subunit 2, PFR-2, and caused cell cycle alteration, which preceded apoptosis induction in the bloodstream form of Trypanosoma parasites. Novel tetracyclic iridoids may be promising lead compounds for the development of new chemotherapies for African trypanosomal infections in humans and animals.

In vitro antiprotozoan activity and mechanisms of action of selected Ghanaian medicinal plants against Trypanosoma, Leishmania, and Plasmodium parasites

“…Regarding the components of mango, although it has been suggested that the most important constituent in mango‐related antiparasitic activity is mangiferin having the C‐glucosyl xanthone structure (Wauthoz & Balde, ), the active component is still unknown. In this regard, we intend to employ the bioassay‐guided fractionation techniques to determine the active components of the promising anti‐ Plasmodium active extracts as in the case of M. lucida (Kwofie et al, ).…”

“…The Alamar Blue assay (Alamar Blue®, Life Technologies™, USA) was used to determine the antitrypanosomal and antileishmanial activities of plant extracts. Assays were carried out in a 96‐well plate following manufacturer's instructions with modifications (Kwofie et al, ). Either 1.5 × 10 4 Trypanosoma parasites per well or 1.25 × 10 5 Leishmania parasites per well were seeded with varied concentrations of crude extracts ranging from 0 to 200 μg/ml.…”

“…Cytotoxicity was calculated as the percentage of life cells relative to the control culture. The selectivity index (SI) was expressed as the ratio of the IC 50 value obtained for mammalian cells to the IC 50 values obtained for parasites (Kwofie et al, ).…”

“…Seeding and incubation of parasites with crude extracts were done under the same conditions of in vitro antiparasitic screening assay as described above. After 24 hr incubation, 10% Nexin reagent (Millipore, USA) was added to the Trypanosome culture and then subjected to FACS analysis (Guava EasyCyte 5HT, Millipore, USA) following the manufacture's instruction (Kwofie et al, ).…”

Secochiliolide ester derivatives: Preparation and evaluation of their antitrypanosomal and antimalarial efficacy

“…Moreover, there is little commercial interest in the development of new or improved therapeutics for these poor affected populations. [8,9] In a previous work, SA and some derivatives exhibited IC 50 values against Trypanosoma cruzi epimastigotes similar to that of the commercial drug benznidazole (IC 50 about 2 μg/ ml -5.8 μm). [5] Secochiliolide acid (1, SA) is the major secondary metabolite present in the Patagonian endemic shrub Nardophyllum bryoides.…”