Sesquiterpene Lactone-Rich Extract of Tithonia diversifolia (Hemsley) A. Gray (Asteraceae) suppresses Trypanosoma brucei brucei in both In Vivo and In Vitro Experimental Models doi.org/10.26538/tjnpr/v6i8.18

Abstract

Tithonia diversifolia has continued to play vital roles in phytomedicine due to its ethnopharmacological relevance, medicinal properties and agricultural applications. Its richness in sesquiterpene lactones has also continued to generate interest due to its diverse pharmacological activities, structure-activity relationships, and pharmacokinetics. The study evaluated the anti-trypanosomal and cytotoxic activities of the sesquiterpene lactone (STL) constituents of Tithonia diversifolia using in vivo mouse and in vitro experimental models. The T. diversifolia methanol extract was fractionated by solvent-solvent partitioning in n-hexane, EtOAc, and n-butanol and further separated by the vacuum liquid chromatographic (VLC) method. The in vitro anti-trypanosomal and cytotoxic activities were evaluated using resazurin- based cell viability assays. The in vivo anti-trypanosomal activity was determined using a hematocrit-based packed cell volume analysis and rapid matching counting of Trypanosoma brucei brucei inhibition methods in a mouse model. The two STL-enriched sub-fractions (VLC- 3 and VLC-4) obtained from the VLC separation displayed significant (p < 0.05) in vitro activity against Trypanosoma brucei with IC50 values of 0.88 and 0.52 µg/mL respectively and SI of 44 and 165 respectively. In the in vivo mouse model, a 400 mg/kg dose of VLC-3 and VLC-4 elicited a 100% clearance of the parasites within 16 and 14 days post-induction of parasitemia compared with a similar effect of the positive control drug, diminazene aceturate on day 12. The strong in vivo/in vitro anti-trypanosomal activity of T. diversifolia STL represents a promising starting point for discovering potent trypanocidal agents against T.b. brucei, the major cause of animal African trypanosomiasis.